nhs r&d hta programme hta · 2012-10-07 · the assumptions made for the model were used to...

Article

A systematic review of repetitive task training with modelling of resource use, costs and effectiveness

French, Beverley, Leathley, Michael John, Sutton, Chris J, McAdam, Joanna, Thomas, Lois Helene, Forster, A, Langhorne, P, Price, C, Walker, A and Watkins, Caroline Leigh

Available at http://clok.uclan.ac.uk/4764/

French, Beverley, Leathley, Michael John, Sutton, Chris J ORCID: 0000000264061318, McAdam, Joanna ORCID: 0000000189637240, Thomas, Lois Helene ORCID: 0000000152186546, Forster, A, Langhorne, P, Price, C, Walker, A et al (2008) A systematic review of repetitive task training with modelling of resource use, costs and effectiveness. Health Technology Assessment, 12 (30). pp. 1117. ISSN 13665278

It is advisable to refer to the publisher’s version if you intend to cite from the work.http://dx.doi.org/10.3310/hta12300

For more information about UCLan’s research in this area go to http://www.uclan.ac.uk/researchgroups/ and search for <name of research Group>.

For information about Research generally at UCLan please go to http://www.uclan.ac.uk/research/

All outputs in CLoK are protected by Intellectual Property Rights law, includingCopyright law. Copyright, IPR and Moral Rights for the works on this site are retained by the individual authors and/or other copyright owners. Terms and conditions for use of this material are defined in the http://clok.uclan.ac.uk/policies/

CLoKCentral Lancashire online Knowledgewww.clok.uclan.ac.uk

http://clok.uclan.ac.uk/policies/

http://www.uclan.ac.uk/research/

http://www.uclan.ac.uk/researchgroups/

A systematic review of repetitive functional task practice with modellingof resource use, costs and effectiveness

B French, M Leathley, C Sutton, J McAdam,L Thomas, A Forster, P Langhorne, C Price,A Walker and C Watkins

Health Technology Assessment 2008; Vol. 12: No. 30

HTAHealth Technology AssessmentNHS R&D HTA Programmewww.hta.ac.uk

The National Coordinating Centre for Health Technology Assessment,Alpha House, Enterprise RoadSouthampton Science ParkChilworthSouthampton SO16 7NS, UK.Fax: +44 (0) 23 8059 5639 Email: [email protected]://www.hta.ac.uk ISSN 1366-5278

FeedbackThe HTA Programme and the authors would like to know

your views about this report.

The Correspondence Page on the HTA website(http://www.hta.ac.uk) is a convenient way to publish

your comments. If you prefer, you can send your comments to the address below, telling us whether you would like

us to transfer them to the website.

We look forward to hearing from you.

August 2008

Health Technology Assessm

ent 2008;Vol. 12: No. 30

Repetitive functional task practice

Copyright notice

© Queen's Printer and Controller of HMSO 2008 HTA reports may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising Violations should be reported to [email protected] Applications for commercial reproduction should be addressed to HMSO, The Copyright Unit, St Clements House, 2–16 Colegate, Norwich NR3 1BQ

How to obtain copies of this and other HTA Programme reports.An electronic version of this publication, in Adobe Acrobat format, is available for downloading free ofcharge for personal use from the HTA website (http://www.hta.ac.uk). A fully searchable CD-ROM isalso available (see below).

Printed copies of HTA monographs cost £20 each (post and packing free in the UK) to both public andprivate sector purchasers from our Despatch Agents.

Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is£2 per monograph and for the rest of the world £3 per monograph.

You can order HTA monographs from our Despatch Agents:

– fax (with credit card or official purchase order) – post (with credit card or official purchase order or cheque)– phone during office hours (credit card only).

Additionally the HTA website allows you either to pay securely by credit card or to print out yourorder and then post or fax it.

Contact details are as follows:HTA Despatch Email: [email protected]/o Direct Mail Works Ltd Tel: 02392 492 0004 Oakwood Business Centre Fax: 02392 478 555Downley, HAVANT PO9 2NP, UK Fax from outside the UK: +44 2392 478 555

NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30–40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current orforthcoming volume.

Payment methods

Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltdand drawn on a bank with a UK address.

Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard,Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email.

Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK.We cannot at present accept purchase orders from commercial companies or from outside the UK.

How do I get a copy of HTA on CD?

Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (seecontact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.

The website also provides information about the HTA Programme and lists the membership of the variouscommittees.

HTA

A systematic review of repetitivefunctional task practice with modellingof resource use, costs and effectiveness

B French,1 M Leathley,1 C Sutton,1 J McAdam,1

L Thomas,1 A Forster,2 P Langhorne,3 C Price,4

A Walker3 and C Watkins1*

1 University of Central Lancashire, Preston, UK2 University of Leeds, UK3 Faculty of Medicine, University of Glasgow, UK4 Northumbria Healthcare NHS Trust, Newcastle University,

Newcastle upon Tyne, UK

* Corresponding author

Declared competing interests of authors: none

Published August 2008

This report should be referenced as follows:

French B, Leathley M, Sutton C, McAdam J, Thomas L, Forster A, et al. A systematicreview of repetitive functional task practice with modelling of resource use, costs andeffectiveness. Health Technol Assess 2008;12(30).

Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE,Excerpta Medica/EMBASE and Science Citation Index Expanded (SciSearch®) and Current Contents®/Clinical Medicine.

NIHR Health Technology Assessment Programme

The Health Technology Assessment (HTA) Programme, part of the National Institute for HealthResearch (NIHR), was set up in 1993. It produces high-quality research information on the

effectiveness, costs and broader impact of health technologies for those who use, manage and providecare in the NHS. ‘Health technologies’ are broadly defined as all interventions used to promote health,prevent and treat disease, and improve rehabilitation and long-term care.The research findings from the HTA Programme directly influence decision-making bodies such as theNational Institute for Health and Clinical Excellence (NICE) and the National Screening Committee(NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in thatthey form a key component of the ‘National Knowledge Service’.The HTA Programme is needs-led in that it fills gaps in the evidence needed by the NHS. There arethree routes to the start of projects. First is the commissioned route. Suggestions for research are actively sought from people working in theNHS, the public and consumer groups and professional bodies such as royal colleges and NHS trusts.These suggestions are carefully prioritised by panels of independent experts (including NHS serviceusers). The HTA Programme then commissions the research by competitive tender. Secondly, the HTA Programme provides grants for clinical trials for researchers who identify researchquestions. These are assessed for importance to patients and the NHS, and scientific rigour.Thirdly, through its Technology Assessment Report (TAR) call-off contract, the HTA Programmecommissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.Some HTA research projects, including TARs, may take only months, others need several years. They cancost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence,undertaking a trial, or other research collecting new data to answer a research problem.The final reports from HTA projects are peer-reviewed by a number of independent expert refereesbefore publication in the widely read journal series Health Technology Assessment.

Criteria for inclusion in the HTA journal seriesReports are published in the HTA journal series if (1) they have resulted from work for the HTAProgramme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search,appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit thereplication of the review by others.

The research reported in this issue of the journal was commissioned by the HTA Programme as projectnumber 05/17/04. The contractual start date was in November 2005. The draft report began editorialreview in February 2007 and was accepted for publication in February 2008. As the funder, by devising acommissioning brief, the HTA Programme specified the research question and study design. The authorshave been wholly responsible for all data collection, analysis and interpretation, and for writing up theirwork. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and wouldlike to thank the referees for their constructive comments on the draft document. However, they do notaccept liability for damages or losses arising from material published in this report.The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme or the Department of Health.

Editor-in-Chief: Professor Tom WalleySeries Editors: Dr Aileen Clarke, Dr Peter Davidson, Dr Chris Hyde,

Dr John Powell, Dr Rob Riemsma and Professor Ken SteinProgramme Managers: Sarah Llewellyn Lloyd, Stephen Lemon, Kate Rodger,

Stephanie Russell and Pauline Swinburne

ISSN 1366-5278

© Queen’s Printer and Controller of HMSO 2008This monograph may be freely reproduced for the purposes of private research and study and may be included in professional journals providedthat suitable acknowledgement is made and the reproduction is not associated with any form of advertising.Applications for commercial reproduction should be addressed to: NCCHTA, Alpha House, Enterprise Road, Southampton Science Park,Chilworth, Southampton SO16 7NS, UK.Published by Gray Publishing, Tunbridge Wells, Kent, on behalf of NCCHTA.Printed on acid-free paper in the UK by St Edmundsbury Press Ltd, Bury St Edmunds, Suffolk. G

Objectives: To determine whether repetitivefunctional task practice (RFTP) after stroke improveslimb-specific or global function or activities of dailyliving and whether treatment effects are dependent onthe amount of practice, or the type or timing of theintervention. Also to provide estimates of the cost-effectiveness of RFTP.Data sources: The main electronic databases weresearched from inception to week 4, September 2006.Searches were also carried out on non-English-languagedatabases and for unpublished trials up to May 2006. Review methods: Standard quantitative methodswere used to conduct the systematic review. Themeasures of efficacy of RFTP from the data synthesiswere used to inform an economic model. The modelused a pre-existing data set and tested the potentialimpact of RFTP on cost. An incremental cost perquality-adjusted life-year (QALY) gained for RFTP wasestimated from the model. Sensitivity analyses aroundthe assumptions made for the model were used to testthe robustness of the estimates.Results: Thirty-one trials with 34 intervention–controlpairs and 1078 participants were included. Overall, itwas found that some forms of RFTP resulted inimprovement in global function, and in both arm andlower limb function. Overall standardised meandifference in data suitable for pooling was 0.38 [95%confidence interval (CI) 0.09 to 0.68] for global motorfunction, 0.24 (95% CI 0.06 to 0.42) for arm functionand 0.28 (95% confidence interval 0.05 to 0.51) forfunctional ambulation. Results suggest that training maybe sufficient to have an impact on activities of dailyliving. Retention effects of training persist for up to

6 months, but whether they persist beyond this isunclear. There was little or no evidence that treatmenteffects overall were modified by time since stroke ordosage of task practice, but results for upper limbfunction were modified by type of intervention. Theeconomic modelling suggested that RFTP was cost-effective. Given a threshold for cost-effectivenessof £20,000 per QALY gained, RFTP is cost-effective so long as the net cost per patient is less than £1963.This result showed some sensitivity to the assumptionsmade for the model. The cost-effectiveness of RFTPtends to stem from the relatively modest costassociated with this intervention. Conclusions: The evidence suggests that some form of RFTP can be effective in improving lower limbfunction at any time after stroke, but that the durationof intervention effect is unclear. There is as yetinsufficient good-quality evidence to make any firmrecommendations for upper limb interventions. If task-specific training is used, adverse effects should bemonitored. While the effectiveness of RFTP is relativelymodest, this sort of intervention appears to be cost-effective. Owing to the large number of ongoing trials,this review should be updated within 2 years and anyfuture review should include a comparison againstalternative treatments. Further research shouldevaluate RFTP upper limb interventions and inparticular constraint-induced movement therapy,address practical ways of delivering RFTP interventions,be directed towards the evaluation of suitable methodsto maintain functional gain, and be powered to detectwhether RFTP interventions are cost-effective.


iii

© Queen’s Printer and Controller of HMSO 2008. All rights reserved.

Abstract

A systematic review of repetitive functional task practice withmodelling of resource use, costs and effectiveness

B French,1 M Leathley,1 C Sutton,1 J McAdam,1 L Thomas,1 A Forster,2

P Langhorne,3 C Price,4 A Walker3 and C Watkins1*

1 University of Central Lancashire, Preston, UK2 University of Leeds, UK3 Faculty of Medicine, University of Glasgow, UK4 Northumbria Healthcare NHS Trust, Newcastle University, Newcastle upon Tyne, UK* Corresponding author


v

List of abbreviations .................................. vii

Executive summary .................................... ix

1 Introduction ............................................... 1Description of the condition ...................... 1Description of the intervention ................. 1Scope of the review .................................... 1Scope of the cost-effectiveness analysis ...... 2Objectives ................................................... 2

2 Review methods ......................................... 3Search strategy for identification of studies 3Inclusion criteria ........................................ 4Exclusion criteria ....................................... 5Types of outcome measure ......................... 5Data extraction and assessment of studyvalidity ........................................................ 6

3 Description of studies ................................ 9Description of studies ................................ 10Included studies ......................................... 10Participants ................................................. 11Interventions .............................................. 11Comparison interventions ......................... 13Primary outcomes ...................................... 14Secondary outcomes ................................... 14Excluded studies ........................................ 15Ongoing studies ......................................... 15Studies not assessed at report completion ................................................. 15Quality of included studies ........................ 15

4 Results of the review ................................. 19Primary outcomes ...................................... 19Secondary outcomes ................................... 42

5 Economic analysis ...................................... 45Background ................................................ 45Methods ...................................................... 45Results ........................................................ 47

6 Discussion ................................................... 51Summary of main results ........................... 51Overall completeness and applicability ofevidence ...................................................... 52Quality of evidence .................................... 54Potential limitations in the review process ........................................................ 55

Agreement or disagreement with previousreviews ........................................................ 55Economic analysis ...................................... 56

7 Conclusions ................................................ 59Implications for practice ............................ 59Recommendations for future research ....... 59

Acknowledgements .................................... 61

References .................................................. 63

Appendix 1 Included studies: repetitive task training ............................................... 71

Appendix 2 Included studies: constraint-induced movement therapy ....................... 87

Appendix 3 Included studies: treadmilltraining ....................................................... 99

Appendix 4 Characteristics of excluded studies ......................................................... 107

Appendix 5 Characteristics of ongoing studies ......................................................... 109

Appendix 6 Criteria for subgroup analyses ....................................................... 111

Appendix 7 Summary of baselinecharacteristics of patients from the cohort in the patient data set who survived to 3 years ........................................................ 113

Appendix 8 Numbers of patients and costs in the baseline and new groups ......... 115

Appendix 9 Cost-effectiveness at 3 years per QALY gained for RFTP on outcomemeasures that were significant in the systematic review ........................................ 117

Health Technology Assessment reportspublished to date ....................................... 119

Health Technology Assessment Programme ................................................ 137

Contents

ADL activity of daily living

ARAT Action Research Arm Test

BBT Box and Block Test

BI Barthel Index

CI confidence interval

CIMT constraint-induced movementtherapy

df degrees of freedom

EQ-5D EuroQol-5 Dimensions

FAC Functional Ambulation Classification

FIM Functional Independence Measure

FM Fugl–Meyer Assessment

FTHUE Functional Test of the HemipareticUpper Extremity

9HPT Nine Hole Peg Test

10HPT Ten Hole Peg Test

ICER incremental cost-effectiveness ratio

IQR interquartile range

MAL Motor Activity Log

MAS Motor Assessment Scale

mCIMT modified constraint-inducedmovement therapy

5MWS Five Metre Walk Speed

6MWS Six Metre Walk Speed

6MWT Six Minute Walk Test

10MWS Ten Metre Walk Speed

NHP Nottingham Health Profile

PSS Personal Social Services

QALY quality-adjusted life-year

RCT randomised controlled trial

RFTP repetitive functional task practice

RMA Rivermead Motor Assessment

RTT repetitive task training

SD standard deviation

SMD standardised mean difference

SMES Sodring Motor Evaluation Scale

TEMPA Test Evaluant des MembresSuperieurs des Personnes Agées

TM treadmill training

TUG Timed Up and Go

WMD weighted mean difference

WMFT Wolf Motor Function Test


vii


List of abbreviations

All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices in which case the abbreviation is defined in the figure legend or at the end of the table.


ix


BackgroundThe repetitive practice of functional tasks is acomponent of current approaches to strokerehabilitation. Practice may be augmented bystrategies to enhance learning as used inmovement science approaches, by mechanicalmeans such as treadmills, or by strategies toencourage use of the affected limb in daily life byrestraining the unaffected limb.

All these approaches have a core mechanism basedon the repeated practice of functional tasks. Thishas the potential to be a resource-efficientcomponent of stroke rehabilitation, includingdelivery in a group setting, or instructed practicein the home environment. This review considersthe effectiveness and cost-effectiveness of all formsof repetitive functional task practice (RFTP).

ObjectivesThe aims of this study were:

● to determine whether RFTP after strokeimproves limb-specific or global function oractivities of daily living

● to determine whether treatment effects aredependent on the amount of practice, or thetype or timing of the intervention

● to provide cost-effectiveness estimates for RFTP.

MethodsData sourcesThe following searches were undertaken:

● electronic searches of Cochrane Stroke TrialsRegister, the Cochrane Library, MEDLINE,EMBASE, CINAHL, AMED, SportDiscus, ISIScience Citation Index, Index to Theses,ZETOC, PEDro and OT Seeker (all frominception to week 4, September 2006)

● electronic searches on non-English-languagedatabases and for unpublished trials onMetaRegister, BioMed Central, CRISP,Centerwatch, National Research Register,ReFeR, Stroke Trials Directory, REHABDATAand CIRRIE (to May 2006)

● searches of conference proceedings, referencelists of existing systematic reviews, citationsearching, publication on bulletin boards andauthor contact for all relevant trials.

Study selectionThe review included randomised and quasi-randomised trials in adults after stroke, whichincluded an intervention where an active motorsequence was performed repetitively within asingle training session, where the practice aimedtowards a clear functional goal and where theamount of task practice could be quantified.Studies using mechanical or behavioural strategiesto facilitate or encourage functional task practicewere also included. Primary outcomes includedlimb-specific or global functional measures.Secondary outcomes included measures ofactivities of daily living and adverse events.

Data extractionTwo reviewers independently screened titles andabstracts, extracted data and critically appraisedthe trials. Assessment of methodological qualitywas undertaken for allocation concealment,blinding, loss to follow-up, trial size andequivalence of treatment. Trialists were contactedfor additional information.

Data synthesisStandard Cochrane quantitative systematic review methods were used. A fixed-effect modelwas used, and results were expressed as weighted or standardised mean differences, with 95% confidence interval. Subgroup analyses were conducted for amount, timing and type of intervention, and for adequacy of allocation concealment, type of comparisongroup, equivalence of therapy time and trial size.

The measures of efficacy of RFTP from the datasynthesis were used to inform an economic model.The model used a pre-existing data set and testedthe potential impact of RFTP on cost. From themodel an incremental cost per quality-adjustedlife-year (QALY) gained for RFTP was estimated.Sensitivity analyses around the assumptions madefor the model were used to test the robustness ofthe estimates.

Executive summary

x

ResultsThirty-one trials with 34 intervention–controlpairs and 1078 participants were included.Overall, it was found that some forms of RFTPresulted in improvement in global function, andin both arm and lower limb function. Overallstandardised mean difference in data suitablefor pooling was 0.38 [95% confidence interval(CI) 0.09 to 0.68] for global motor function,0.24 (95% CI 0.06 to 0.42) for arm functionand 0.28 (95% confidence interval 0.05 to 0.51)for functional ambulation. Results suggest thattraining may be sufficient to have an impact onactivities of daily living. Retention effects oftraining persist for up to 6 months, but whetherthey persist beyond this is unclear. There waslittle or no evidence that treatment effectsoverall were modified by time since stroke ordosage of task practice, but results for upperlimb function were modified by type ofintervention. The economic modellingsuggested that RFTP was cost-effective. Given athreshold for cost-effectiveness of £20,000 perQALY gained, RFTP is cost-effective so long asthe net cost per patient is less than £1963. Thisresult showed some sensitivity to theassumptions made for the model. The cost-effectiveness of RFTP tends to stem from therelatively modest cost associated with thisintervention.

ConclusionsImplications for practiceThe evidence suggests that some form of RFTPcan be effective in improving lower limb functionat any time after stroke, but that the duration ofintervention effect is unclear. There is as yetinsufficient good-quality evidence to make anyfirm recommendations for upper limbinterventions. If task-specific training is used,adverse effects should be monitored. While theeffectiveness of RFTP is relatively modest, this sortof intervention appears to be cost-effective.

Recommendations for future researchOwing to the large number of ongoing trials, thisreview should be updated within 2 years. Anyfuture review should include a comparison against alternative treatments. Further researchshould:

● evaluate RFTP upper limb interventions and inparticular constraint-induced movementtherapy

● address practical ways of delivering RFTPinterventions

● be directed towards the evaluation of suitablemethods to maintain functional gain

● be powered to detect whether RFTPinterventions are cost-effective, include abaseline activities of daily living measure,include indirect costs and use quality of life asan outcome measure to facilitate economicanalysis.

Executive summary

Description of the conditionThe annual incidence of first ever stroke in theUK is approximately 100,000 people per year.1

Although the incidence of stroke is falling,2 strokeis still the major cause of long-term neurologicaldisability in adults.3 The prevalence of disabilityand impairment varies according to sampling ofcohorts, but approximately half of all strokesurvivors are left with severe functional problems,4

and 53% are dependent on others for help withdaily activities at 6 months after their stroke.5 Only5–20% of people with initial upper limbimpairment fully regain arm function, and30–66% regain no functional use at 6 months.6–9

At 3 weeks and 6 months after stroke, 40% and15% of people are unable to walk independentlyindoors,5 with only 18% regaining unrestrictedwalking ability.10 Initial grade of paresis is themost important predictor for motor recovery, witha longer recovery period for people with severestroke.11

Stroke is thus a leading cause of disability, and assuch contributes to 4% of NHS costs.12 Whilestroke is a costly condition in the acute stage, over40% of the 5-year cost of stroke is likely to beincurred subsequent to discharge, with 18% of the total cost being due to institutional care.13

If the disability and subsequent need forinstitutional care can be reduced, there is apotential for the long-term care costs to besubstantially lowered.

Description of the interventionSystematic reviews of treatment interventions forthe paretic upper limb suggest that patientsbenefit from exercise programmes in whichfunctional tasks are directly trained, with lessbenefit if the intervention is focused on theimpairment, such as muscle strengthening.14

Although individual studies do not agree whetherincreased therapy intensity improves overalloutcome, a recent meta-analysis15 has shown thatmore intensive therapy may at least improve therate of recovery of activities of daily living (ADLs),particularly if a direct functional approach isadopted.16

Repetitive practice of goal-directed, functionalmovement under varying conditions for procedurallearning is a feature of many forms of interventionin stroke rehabilitation. The use of intensiverepetition is grounded in neurophysiologicalhypotheses about the reasons for loss of movementafter stroke. Repeated motor practice enhancesmotor strength, speed and endurance, whilesensorimotor coupling contributes to theadaptation and recovery of neuronal pathways.17

Repetitive task training (RTT) is common as aspecific rehabilitation technique, but it is oftencombined with techniques to enhance cognitiveinvolvement in the relearning of motor skills, suchas functional relevance and knowledge ofperformance, thereby forming the underlyingprinciples in the motor relearning or movementscience physiotherapy approach.18

Intensive periods of task practice using shapingtechniques (progressively increasing the difficultyof a task in small steps and providing frequentfeedback and positive encouragement) to build upto completion of a functional task are also a majorfeature of constraint-induced movement therapy,19

where they are combined with restricted use of theunaffected limb to overcome learned non-use oradaptive strategies.

Intensive practice of functional movement can alsobe assisted by treadmills,20 gait trainers21 orrobotics.22 Mechanical assistance is used toovercome impairment which restricts the ability toparticipate, but also serves to deliver an intensityof training sufficient to develop the amount andpower of movement required for functionalperformance.

Scope of the reviewThis study will consider the impact and cost-effectiveness of all three of the major forms oftherapy that have repeated, functional taskpractice as a major component, namely repetitivetask training (RTT), constraint-induced movementtherapy (CIMT) and treadmill training (TM). Incombination, these three forms of therapy will bereferred to as repetitive functional task practice(RFTP).


1


Chapter 1

Introduction

Systematic reviews of TM20 and CIMT23 havealready been published. To provide an overallpicture of the relative effectiveness and cost-effectiveness of all the common forms of RFTP,the references from the systematic reviews for TMand CIMT were followed up and data wereextracted from those primary studies that also metthe inclusion criteria for this study. A systematicreview of RTT studies has already been submittedto The Cochrane Collaboration by the authors ofthis report. This review therefore presents theresults of these three interventions combined. Thecharacteristics, quality and results of the trials foreach intervention are reviewed and presentedseparately to ensure clarity, until combined insubgroup analysis to present a between-intervention overall estimate of efficacy andcomparison of effect.

Scope of the cost-effectivenessanalysisAn economic model will be developed from anexisting data set. The data set containsinformation on the natural recovery and resourceuse of a cohort of stroke patients, which allows

estimates to be made on outcomes and costs. Theefficacy of RFTP and hence its potential impact onoutcomes will be obtained from the review; thecost of RFTP will be estimated by considering staffand equipment costs. Using certain assumptions,which will be clearly outlined in the methods, themodel data and the efficacy of RFTP from thereview will be used to estimate the cost-effectiveness of RFTP. Uncertainty in the estimatewill be considered by varying the parameters ofany assumptions that are made.

ObjectivesThe objectives of this study were to carry out asystematic review and cost-effectiveness analysis todetermine:

● whether RFTP improves global or limb-specificfunctional ability and ADL function in adultsafter stroke

● the factors that could influence primaryoutcome measures for RFTP, including theeffect of amount, type and timing ofintervention

● estimates of the cost-effectiveness of RFTP.

Introduction

2

Search strategy for identificationof studiesElectronic searchesThe Cochrane Stroke Group Trials Register wassearched in October 2006, using the followingparameters: Intervention Type: “Physiotherapy” or“Occupational Therapy”, without restriction ofintervention code.

In addition, the following databases were searchedas follows: The Cochrane Library (2006 Issue 3),MEDLINE (1966 to September week 4, 2006),EMBASE (1980 to week 40, 2006), CINAHL (1982to October week 1, 2006), AMED (1985 to week40, 2006), SportDiscus (1980 to October week 1,2006), ISI Science Citation Index (1973 to 14October 2006), Index to Theses (1970 toSeptember 2006), ZETOC (to 14 October 2006),PEDro (to 3 October 2006), OT Seeker (to 21April 2006) and OT Search (to March 2006).

The main search design was reviewed by theCochrane Stroke Group Trials Search Co-ordinator. The MEDLINE search given below wasused and adapted for other databases.

MEDLINE (OVID)1 cerebrovascular disorders/ or exp basal ganglia

cerebrovascular disease/ or exp brain ischemia/or exp carotid artery diseases/ orcerebrovascular accident/ or exp braininfarction/ or exp cerebrovascular trauma/ orexp hypoxia-ischemia, brain/ or expintracranial arterial diseases/ or intracranialarteriovenous malformations/ or exp"Intracranial Embolism and Thrombosis"/ orexp intracranial hemorrhage/ or vasospasm,intracranial/ or vertebral artery dissection/

2 (stroke or poststroke or post-stroke orcerebrovasc$ or brain vasc$ or cerebral vasc$or cva$ or apoplex$ or SAH).tw.

3 ((brain$ or cerebr$ or cerebell$ or intracran$or intracerebral) adj5 (isch?emi$ or infarct$ orthrombo$ or emboli$ or occlus$)).tw.

4 ((brain$ or cerebr$ or cerebell$ orintracerebral or intracranial or subarachnoid)adj5 (haemorrhage$ or hemorrhage$ orhaematoma$ or hematoma$ or bleed$)).tw.

5 hemiplegia/ or exp paresis/

6 (hemipleg$ or hemipar$ or paresis orparetic).tw.

7 or/1-6 8 *cerebrovascular disorders/rh or exp *basal

ganglia cerebrovascular disease/rh or exp*brain ischemia/rh or exp *carotid arterydiseases/rh or *cerebrovascular accident/rh orexp *brain infarction/rh or exp *cerebrovasculartrauma/rh or exp *hypoxia-ischemia, brain/rhor exp *intracranial arterial diseases/rh or*intracranial arteriovenous malformations/rhor exp *"Intracranial Embolism andThrombosis"/rh or exp *intracranialhemorrhage/rh or *vasospasm, intracranial/rhor *vertebral artery dissection/rh

9 *hemiplegia/rh or exp *paresis/rh 10 exp *gait Disorders, neurologic/rh or *motor

skills disorders/rh11 rehabilitation/ or "activities of daily living"/ or

exercise therapy/ or occupational therapy/12 Physical Therapy Modalities/ 13 Exercise Movement Techniques/ or exercise

therapy/ or walking/14 Robotics/15 exp Psychomotor Performance/ 16 movement/ or gait/ or exp locomotion/ or exp

motor activity/ 17 "Range of Motion, Articular"/ or "Task

Performance and Analysis"/ or "Practice(Psychology)"/

18 "Recovery of Function"/ 19 ((motor or movement$ or task$ or skill$ or

performance) adj5 (repetit$ or repeat$ ortrain$ or re?train$ or learn$ or re?learn$ orpractic$ or practis$ or rehears$ or rehers$)).tw.

20 ((motor or movement$ or task$ or skill$ orperformance) adj5 (schedule$ or interventionor therap$ or program$ or regim$ orprotocol$)).tw.

21 (functional adj5 (task$ or movement)).tw. 22 or/8-2123 7 and 22

The search above was combined with theCochrane Stroke Review Group search forrandomised controlled trials.

A similar search (Search 2), given below, wasconducted without limits of study type and/orclient group, to check for trials incorrectly


3


Chapter 2

Review methods

indexed, and to trace trials of RFTP in other clientgroups for citation tracking.

MEDLINE OVID1 *hemiplegia/rh or exp *paresis/rh 2 exp *gait Disorders, neurologic/rh or *motor

skills disorders/rh 3 1 or 24 Physical Therapy Modalities/ 5 Exercise Movement Techniques/ or exercise

therapy/ or walking/ 6 Robotics/7 rehabilitation/ or "activities of daily living"/ or

occupational therapy/ 8 exp Psychomotor Performance/ 9 "Task Performance and Analysis"/ or "Practice

(Psychology)"/ 10 ((motor or movement$ or task$ or skill$ or

performance) adj5 (repetit$ or repeat$ ortrain$ or re?train$ or practic$ or practis$ orrehears$ or rehers$)).tw.

11 (functional adj5 (task$ or movement)).tw. 12 or/4-1113 movement/ or gait/ or exp locomotion/ or exp

motor activity/ 14 "Recovery of Function"/ 15 13 and 1416 3 and (12 or 15)

Unpublished trial data were searched for onnational and international databases to May 2006as follows: MetaRegister of Controlled Trials,BioMed Central, CRISP, Centerwatch, NationalResearch Register, ReFeR, Stroke Trials Directory,REHABDATA and CIRRIE, using simple terms forstroke and rehabilitation or physical therapy.

Physiotherapy, occupational therapy and roboticsconference proceedings were searched as follows:

● Australian Physiotherapy AssociationConference 2000, 2002, 2004

● Australian Physiotherapy Association Neurologyand Gerontology Physiotherapy Conference 2005

● American Physical Therapy Congress AnnualConference 2005

● Canadian Physiotherapy Conference 2005● UK College of Occupational Therapists

Conference 2002, 2003, 2005● National Association of Neurological

Occupational Therapists Conference 2005● World Confederation for Physical Therapy 1st

International Congress 1953, 4th InternationalCongress 1963

● World Confederation of Physiotherapy Europe:First Congress, Copenhagen 1994:Physiotherapy in Stroke Management

● Chartered Society of Physiotherapy AnnualCongress 2000, 2001, 2002, 2003, 2004, 2005

● ICORR Rehabilitation Robotics InternationalConferences 1999, 2001, 2005

Non-English-language literature was identified bysearching Chinese, Russian and Indian databasesvia Eastview, Panteleimon and Indmed, usingbroad descriptors for stroke, rehabilitation andphysical therapy. The China National Knowledgedatabase was searched in both English andChinese. Searching and translation of Chineseabstracts were undertaken by personnel from theSecond Military Medical University, Shanghai.

Other sourcesRTTThe reference lists of systematic reviews relevant tophysical or occupational therapy in strokerehabilitation were searched.11,14–16,24–45 Referencelists of publications and literature reviews relevantto RTT identified by the search were combed toidentify further relevant trials.46–48 In addition,forward citation searching was undertaken on ISIWeb of Knowledge for all included trials, and theauthors were contacted to ask for details of anyother possible relevant trials, either published orunpublished. A request for information was alsoposted to the bulletin boards of World Congress ofPhysical Therapy and PHYSIO JISCmail.

CIMT and TMStudies relevant to CIMT and TM were sourcedfrom the search identified above, and also fromexisting systematic reviews.20,23 Only those trials ofCIMT and TM that met the requirements of thisreview (i.e. RFTP intervention with suitablecomparison) were included.

Inclusion criteriaTypes of studyRandomised and quasi-randomised trials (such asthose allocating by date or alternation) wereincluded in the review. Only the first period ofcross-over trials was included.

One arm of the trial had to include RFTP,compared against usual practice (including ‘notreatment’) or an attention-control group. Fortrials of TM or CIMT, comparison groups usingalternative forms of training were included.

Examples of attention-control treatment arecomparable time spent receiving therapy on adifferent limb or participating in an activity with no

Review methods

4

potential motor benefits. Usual-practice comparisongroups were accepted when the interventionreceived by the control group was considered anormal or usual component of stroke rehabilitationpractices, including neurophysiological ororthopaedic approaches. Early after stroke it wasassumed that usual practice would mean thatpatients would receive some therapy.

Types of participantAdults (presumed 18 years and older) who hadsuffered a stroke were included. Stroke was definedaccording to the World Health Organization(WHO) definition as “a syndrome of rapidlydeveloping symptoms and signs of focal, and attimes global, loss of cerebral function lasting morethan 24 hours or leading to death, with noapparent cause other than that of vascularorigin”.49 Trials starting at any time after an acutestroke and in any setting were included.

Types of interventionTrials were required to include an interventionwhere an active motor sequence was performedrepetitively within a single training session, wherethe practice aimed towards a clear functional goal.Functional goals could involve complex wholetasks, or pretask movements for a whole limb orlimb segment such as grasp, grip or movement ina trajectory to facilitate an ADL. To be included,trials of repetitive activity were required to involvecomplex multijoint movement with functionalmeasurement of outcome, rather than the exerciseof a single joint or muscle group orientated tomotor-performance outcomes.

Any intensity and duration of task trainingschedule was included. However, trials wereincluded only if the duration or number ofrepetitions within a session of practice, and thenumber of sessions delivered, could be identified.Trials clearly using motor relearning as a wholetherapy approach were included if the amount oftask-specific training received could be identified.

Trials using person-delivered, mechanical orrobotic movement assistance were included if thepurpose of the assistance was to facilitate a task-related repetition. Trials combining repetitive taskpractice with constraint of the unaffected limbwere also included.

Exclusion criteriaTrials were excluded if they combined RFTP with other interventions such as electrical

stimulation virtual environments, biofeedback,bilateral movement, or mental rehearsal. Trials were also excluded if the intervention used mechanical means simply to increaseendurance through the intensity of practicewithout monitoring or adjustment according tothe quality of movement, such as the use of slotmachines.

Trial authors were contacted for clarification of the nature of the intervention if it was unclearwhether the trial met the definition.

Types of outcome measurePrimary outcomesThe primary outcomes chosen were global andlimb-specific functional measures. Owing to thelarge range of measures used across trials,selection of outcome measures was done by the review authors to maximise quantitativepooling. If more than one measure was available in an outcome category, measures offunctional motor ability used in the primary trialswere prioritised as follows in the differentcategories. Items marked with an asterisk aremeasures where a low score equals a positiveoutcome. In all other measures, a high scoreindicates a good outcome.

Upper limb function/reach● Arm function: Action Research Arm Test

(ARAT), Motor Assessment Scale (MAS) – upperlimb component, Frenchay Arm Test, WolfMotor Function Test (WMFT), Functional Testof the Hemiparetic Upper Extremity (FTHUE),Box and Block Test (BBT), Test Evaluant desMembres Supérieurs des Personnes Agées(TEMPA), University of Maryland ArmQuestionnaire for Stroke, Motor Activity Log(MAL).

● Hand function: MAS hand, Jebsen Test of HandFunction*, Peg Test*, Purdue Pegboard.

● Sitting balance/reach: Reaching PerformanceScale, Functional Reach.

Lower limb function/balance● Lower limb function: walking distance, walking

speed, functional ambulation, sit-to-stand*,measures of lower limb function, e.g.Rivermead Mobility Index, Sodring MotorEvaluation Scale (SMES), Step Test.

● Standing balance/reach: Berg Balance Scale.

Overall functional abilityMAS, Rivermead Motor Assessment (RMA) Scale.


5


Secondary outcomesADLBarthel Index (BI), Functional IndependenceMeasure (FIM), Modified Rankin Scale, GlobalDependency Scale.

Adverse outcomePain, injury, falls.

Timing of outcome assessmentPrimary outcome timing was at the end of theintervention period. Where the end of theintervention period was not clearly defined,outcome measures at 3 months post-stroke werechosen as primary. Data are presented for follow-up less than 6 months post-stroke, and between6 months and 1 year post-stroke.

Data extraction and assessment ofstudy validitySelection of studiesOne reviewer (BF) performed the searches. Fromthe initial references, 4443 obviously irrelevantitems were excluded on title and abstract by onereviewer (BF) and checked by a second reviewer(JM). All reviewers (BF, JM, ML and LT)undertook screening on the same titles andabstracts until an acceptable level of inter-raterreliability was achieved (kappa = 0.63). From thatpoint, two reviewers (from BF, JM, ML and LT)independently screened references.

In total, 447 full papers considered potentiallyrelevant were retrieved, including 71 items inlanguages other than English. For non-English-language papers, decisions about exclusion weremade on English abstract or machine translationof the abstract via WorldLingo or TranslationBooth, if adequate. Where machine translation wasinadequate, or where inclusion was unclear fromEnglish abstracts, the methods sections of fullpapers were commercially translated by nativespeakers. Seventeen methods sections of papersand three full non-English-language papers thatwere screened as potentially relevant were alsocommercially translated. Two reviewersindependently screened all full papers andmethods section translations for non-Englishstudies. Altogether, 121 papers were progressed tomore detailed filtering by two reviewers (from ML,LT, BF and JM).

Data extraction and managementAll reviewers (BF, JM, ML and LT) undertook dataextraction and critical appraisal on eight studies.

Using unweighted multiple kappa, inter-raterreliability of judgement of seven criteria for qualityassessment was median kappa = 0.67 (range0.48–0.85). Disagreements were reviewed andinstructions for critical appraisal gradings revised.From that point, two reviewers independentlyconducted data extraction and review of themethodological quality of the eligible trials.Disagreements were resolved by discussion andreferral to a third reviewer. Data were recorded ona standardised checklist, incorporating details ofrandomisation method, study population,intervention methods and delivery, reason forlosses to follow-up, and post-therapy and follow-upoutcome measures. In addition, informationrelating to treatment monitoring, acceptability andadherence was extracted where available.

Assessment of methodological qualityItems were evaluated as adequate, inadequate orunclear, and quality assessment was undertakenusing the following criteria:

● selection bias– random allocation– allocation concealment– baseline comparability of groups

● performance bias– equal treatment of groups

● attrition bias– description of withdrawals, dropouts and

those lost to follow-up– intention-to-treat analysis– percentage loss to follow-up

● detection bias– blinding of outcome assessors.

AnalysesThe primary comparison to be undertaken was toestimate the overall effect of RFTP. Secondarycomparisons were designed to determine whethertreatment effects differed for type of intervention(RTT, CIMT or TM), or the timing or amount ofintervention.

Measures of treatment effectFor continuous outcomes using similarmeasurement scales, the weighted mean difference(WMD) with 95% confidence interval (CI) wasused. Where similar outcomes were measuredusing different outcome scales, results werecombined using standardised mean difference(SMD) with 95% confidence interval. Outcomesmeasured using both dichotomous and continuousmeasurement units were analysed using thegeneric inverse variance method. For continuousoutcomes, means of post-therapy scores and their

Review methods

6

respective standard deviations were extracted.Changes from baseline outcome data wereextracted if available across all trials.

Unit of analysis issuesStudies with multiple treatment groupsTwo RTT trials50–52 compared upper versus lowerlimb training, so are included as fourintervention–control pairs. In the subgroupanalyses, these intervention–control pairs are notincluded as separate trials, as it was consideredthat the impacts of the interventions on upper andlower limb function in the same person would notbe independent. Results for primary outcome ofthe lower limb training groups were selected, asstudies were showing that treatment effects weregreater for lower limbs. This strategy may have theeffect of inflating effect sizes, but the effect shouldnot bias the tests of subgroup effects. One RTTtrial53 compared upper and lower limb traininggroups against the same control group. To avoidthe control group being included twice, and to usea limb-specific rather than a global or an ADLmeasure, the lower limb training versus splintcontrol comparison was selected for the subgroupanalyses.

Dealing with missing dataIf data were not in a form suitable for quantitativepooling, trial authors were contacted foradditional information. Attempts were made toobtain post-therapy scores from trial authors whohad reported median and interquartile ranges(IQRs).

Assessment of heterogeneityThe degree of heterogeneity for each outcome wasassessed by the I2 statistic. If less than or equal to50%, any heterogeneity was deemed insubstantialand a fixed-effects meta-analysis was used. If the I2

statistic was greater than 50%, the individual trialcharacteristics were explored to identify potentialsources of heterogeneity. Meta-analysis was thenperformed using both fixed- and random-effectsmodelling to assess sensitivity to the choice ofmodelling approach and reported accordingly.

Clinical and methodological diversity wasaddressed by incorporation of subgroup analysesfor type of participant (time from stroke),intervention (type and amount of intervention)and study design (allocation concealment,comparison group, equivalence of treatment, lossto follow-up and trial size).

To test for subgroup effects data were stratified bysubgroup and the Q-statistic was partitioned from

the unstratified analysis into ‘within subgroups’and ‘between subgroups’. A �2 test of the resultingbetween-subgroups Q-statistic was performed,using a 10% significance level.54

Assessment of reporting biasesAssessment of the potential for reporting bias waschecked by performing a subgroup analysis basedon the trial size (number of participants) andproducing a funnel plot of the standard error (ofeffect estimate) against effect estimate.

Subgroup analysis and investigation ofheterogeneityPlanned subgroup analyses for upper and lowerlimb functional outcomes were undertaken asfollows.

● Type of intervention: trials were classified asRTT, CIMT or TM.

● Dosage of task practice: this was calculated bymultiplying the number of weeks by the numberof sessions per week by the session duration inhours. Trials were divided into those providingup to and including 20 hours’ training andthose providing more than 20 hours’ training intotal. The division at 20 hours was based on themedian value for dosage of task practice fromall included trials, and the average length ofstay in the National Sentinel Stroke Audit55

after the first 7 days of acute care, presumingthe provision of 1 hour of training per day inthe inpatient rehabilitation period.

● Time since stroke: mean time since stroke atrecruitment was used to classify trials as within0–6 months post-stroke or more than 6 monthspost-stroke. The division at 6 months was basedon the interpretation of this as the main periodof active rehabilitation. Because a number oftrials recruited very early post-stroke, a post hocanalysis grouping was included for trialsrecruiting within 14 days of stroke.

It had been intended to consider whether effectsizes were related to whether training was basedon pre-functional or functional activities or pre-intervention level of disability. In the event,most pre-functional trials were excluded becausethey contained passive or active-assistedmovement, and levels of disability proved toodifficult to classify because of mixed groups ofparticipants and unsuitable measures and data forthis purpose. Therefore, these planned subgroupanalyses are not presented.

The selection of outcome measure for subgroupanalysis was complicated by the fact that few trials


7


used similar outcome measures. Subgroup analyseswere performed separately for upper and lowerlimb interventions. Outcomes for subgroupanalyses were limited to measures of walking forlower limbs and arm function for upper limbs. Ifmore than one measure was available, lower limboutcomes were prioritised in the following order:(1) walking speed, (2) walking distance and (3) functional ambulation/walking scales; andupper limb outcomes were prioritised as follows:(1) ARAT, (2) MAS – upper extremity (MAS-UE),(3) WMFT and (4) BBT. Outcome selection wasbased on evidence for correlation and similarresponsiveness to change for walking distance,speed and functional ambulation.56 For measuresof arm function, there is evidence for correlationand similar responsiveness to change for the MAS-UE and ARAT,57,58 and for correlationbetween ARAT and BBT.59 There is less evidencefor correlation between WMFT and other tests,but ARAT, BBT and WMFT all correlate well withthe Fugl–Meyer measure of arm impairment.59,60

Four trials61–64 were omitted from the subgroupanalyses because data were unsuitable for pooling.

Of the remaining 27 trials, 26 presented meansand standard deviations, so SMD could be used asthe effect measure. One trial65 was excluded fromthe subgroup analyses because it used adichotomous main outcome. This trial wasexcluded rather than using generic inversevariance, because SMD is easier for clinicians tointerpret.

Planned subgroup analyses were also carried outfor allocation concealment (adequate orinadequate/unclear). In addition, post hocsubgroup analyses were included to consider theimpact of different comparison groups (attention-control, usual care), equivalence of therapy time(equivalent time, additional time) and trial size(under 25 participants, 25 participants and over),based on the median value. Planned subgroupanalyses for intervention delivery (therapist versusself-administered, group versus individual) andintervention setting (home versus community)were not undertaken, because of insufficientnumbers of trials.

Review methods

8

For the RTT search, 1366 records wereidentified from the Cochrane Stroke Trials

Registry and 18,241 records from the maindatabase searches, totalling 19,607. A further 772records were added from unpublished trialdatabases, conference proceedings, and hand andcitation searching, totalling 20,379. After removalof duplicates, 14,978 records progressed tofiltering.

Figure 1 illustrates that, of the 447 papersretrieved, 360 studies were excluded as irrelevantwhen full-text details were seen. Thirty-four

potentially relevant CIMT and TM studies wereidentified from existing systematic reviews,totalling 121 potentially relevant studies. Forty-four studies were excluded after more detailedfiltering, leaving 77 studies identified aspotentially appropriate for inclusion. Of these,eight are ongoing studies, of which one wasidentified from the Cochrane Stroke TrialsRegistry, four from handsearching, two fromsecondary referencing, and one from authorcontact. Thirty-eight studies are still awaitingassessment, because available information isinsufficient to be able to make a decision. Seven of


9


Chapter 3

Description of studies

Potentially relevant titles identified by RTT search (n = 14,978)

Full text papers retrieved for more detailed evaluation

(n = 447)

Potentially relevant studies identified

from CIMT and TM systematic reviews

(n = 34)

Studies excluded as not relevant

(n = 360)

Potentially appropriate studies to be included in the

meta-analysis (n = 77)

Studies included in meta-analysis (n = 31)

Studies excluded (n = 44)• not functional, no functional outcome (n = 9)• mixed/exercise interventions (n = 11)• not repetition (n = 3)• passive movement (n = 1)• unsuitable comparison (n = 11)• methodological or reporting reasons (n = 9)

• Ongoing studies (n = 8)• Awaiting assessment: insufficient information (n = 38)

FIGURE 1 Flowchart of included and excluded studies

these were identified from the Cochrane StrokeTrials Registry, 20 from handsearching, three fromdatabase searching, five from secondary referencesand three from author contact.

Unpublished data were sourced from the trialauthors for 11 RTT trials50,51,53,65–72 and twoCIMT trials.73,74

All of the included studies for RTT were identifiedfrom the Cochrane Stroke Trials Registry. ForCIMT and TM, all of the included studies wereidentified from existing systematic reviews, exceptfor one recent CIMT trial identified from theCochrane Stroke Trials Registry.75

Description of studiesThirty-one studies were included in total,including 34 intervention–control pairs and datafrom 1078 participants relevant to this review. Adescription of included studies is presentedseparately for each of the three forms of RFTP,namely RTT, CIMT and TM. A summary of thecharacteristics of the included studies is given inAppendices 1–3.

Included studiesRTTFourteen trials were identified, comprising 17intervention–control pairs, which met theinclusion criteria. Three trials included tworelevant intervention–control pairs: Kwakkel andcolleagues53 refer to a trial with twointervention–control pairs: a lower limb traininggroup versus splint control, and an upper limbtraining group versus splint control.Blennerhassett and Dite50 also include twointervention–control pairs: an upper limb traininggroup versus lower limb attention-control, and alower limb training group versus an upper limbtraining attention-control. Two papers report ontwo intervention–control pairs of the same trial:Salbach and colleagues51 refer to a lower limbtraining group versus upper limb trainingattention-control, and Higgins and colleagues52

refer to an upper limb training group versus lowerlimb training attention-control.

In one trial71 there were three arms, consisting ofa functional task practice group, a strengthtraining group and a usual-care group. Only thedata for the intervention–control pair of functionaltask practice versus control are included here.

DesignThe 14 trials considered comprised 13 randomisedcontrolled trials (RCTs)50,51,53,65–68,70–72,76–78 andone quasi-randomised trial.69 Four of the trialswere identified as pilot RCTs67,71,76,77 and three ofthe trials were multicentre.51,53,77 Three of thetrials were stratified for randomisation: one forbaseline level of walking deficit,51 one for genderand side of stroke,68 and one for severity ofdeficit.71

Sample sizeFour trials had 25 participants or fewer,66,67,69,76

six trials had between 25 and 49participants,50,65,71,72,77,78 and five trials had 50participants or more.51,53,68,70,71

SettingOf the 14 trials, three were carried out inCanada,51,65,67 three in Australia,50,66,78 three inthe UK,69,70,77 one in Taiwan,72 one in the USA,71

one in The Netherlands53 and one in France.76

CIMTEleven trials met the inclusion criteria. In fourtrials61,62,79,80 there were three arms consisting of amodified CIMT group, a traditional rehabilitationgroup and a no-treatment control group. In two ofthese trials the traditional rehabilitation groupalso received RTT, with the only differencebetween groups being constraint.79,80 In these trials,therefore, the no-treatment group was included asthe comparison group. In the remaining two trialsthe data for the modified CIMT and traditionalrehabilitation groups were included.61,62

DesignAll 11 trials were identified as RCTs, of which twowere identified as pilot81,82 and two aspreliminary,61,83 and one trial was labelled a‘feasibility and efficacy’ study.80 All trials weresingle centre.

Sample sizeTen trials had 25 participants or fewer.61,62,73,74,79–84

One trial had 50 participants or more.64

SettingNine trials were carried out in theUSA,61,62,73,74,80–84 one in Saudi Arabia79 and onein Thailand.64

TMSix trials were identified which met the eligibilitycriteria. One trial with three arms consisted of twoTM interventions, speed-dependent TM andlimited progressive TM, compared with


10

conventional gait training.85 The limitedprogressive TM group was used in this review, asspeed-dependent TM was judged to comprise twomechanisms of action.

DesignOne study was a cross-over trial,63 of which onlythe first phase was used. The remaining fivestudies were RCTs. Of these five trials, one wasidentified as a pilot controlled trial.86 All of thetrials were single centre. Three of the trials werestratified for randomisation, one for walkingspeed,87 one for deficit severity and age,88 and onefor initial time to walk 10 m without assistance.85

Sample sizeTwo trials had 25 participants or fewer,63,86 onetrial had between 26 and 49 participants,87 andthree trials had 50 participants or more.85,88,89

SettingOf the six trials, two were carried out in theUSA,86,88 three in Germany;63,85,89 and one inAustralia.87

ParticipantsRTTThe 14 trials included 680 participants, of which659 were included in the 17 intervention–controlpairs relevant to this review. All of the trialsincluded both genders, with three trials havingmore than 60% male participants.51,65,66 In twotrials, the participants had a mean age of less than6050,69 and in five trials the mean age was over70 years.51,68,70,77,78

Six trials included only participants after a firststroke53,67,68,71,72,76 and two trials includedparticipants with either first or recurrentstroke.50,51 In the remaining trials, it was unclearwhether inclusion was limited to first stroke only.

Mean time since strokeThree trials recruited within 14 days of stroke.53,68,70

A further four trials recruited within the firstmonth post-stroke,65,71,76,77 one trial recruitedwithin 3 months of stroke,50 two trials recruited within 6 months of stroke,69,78 two trials recruited within 12 months of stroke51,72

and two trials recruited participants in the chronic phase of stroke.66,67

CIMTThe 11 trials included 203 participants, and datafrom 190 participants were relevant to this review.

Thirteen participants were not included fromstudies where there was more than onecomparison group.61,62,79,80 All of the studiesincluded both genders, with six studies havingmore than 60% male participants.61,62,64,74,82,84 Infour trials, participants had a mean age of lessthan 60 years;62,64,79,80 no trials had a mean ageover 70 years.

Three trials included only subjects after a firststroke.64,74,83 In the remaining trials, it was unclearwhether inclusion was limited to first stroke only.

Mean time since strokeThree trials recruited within 19 days ofstroke,81,82,84 three trials recruited between 1 and6 months post-stroke,61,79,80 and one trial recruitedbetween 3 and 9 months post-stroke.83 Theremaining trials recruited 12 months or morepost-stroke.62,64,73,74

TMThe six studies included 254 participants, of whichdata from 229 participants were relevant to thisreview. Five of the studies included both genders,as participants in one study were all male.86 Fivestudies had more than 60% maleparticipants.63,85–87,89 Two trials had a mean ageless than 60;85,86 no trials had a mean age morethan 70 years.

Three trials included only subjects after a firststroke,63,87,89 one trial included subjects with eitherfirst or recurrent stroke,85 and in the remainingtwo trials86,88 it was unclear whether inclusion waslimited to first stroke only.

Mean time since strokeOne trial recruited within the first month ofstroke,86 one trial recruited within 3 months post-stroke,89 one trial recruited within 6months post-stroke85 and three trials recruited in the chronic phase of stroke recovery.63,87,88

InterventionsRTTTwo trials used whole therapy motorapproaches,68,70 and four trials trained singletasks, all related to balance, reach or sit-to-stand.65,66,76,77 The remaining trials consisted ofmixed functional task training. Of these, threeused a circuit-training approach.50,51,67 While all ofthe remaining trials included some functional taskpractice, this was sometimes mixed with othercomponents, including strengthening exercise and


11


TM,53 upper limb exercise,69 lower limb exercise78

and shaping training.72

Of the 17 intervention–control pairs relevant tothis review, four included lower limb or mobilitytraining,50,51,53,67 one trained sit-to-standmovements,65 two trained balance in sitting andstanding,76,77 one trained functional reach insitting,66 and one trained standing balance andmobility.78 Six intervention–control pairs wereupper limb training.50,52,53,69,71,72 Twointervention–control pairs used whole therapyapproaches, training global function.68,70

SettingFour trials were carried out solely in an inpatientsetting,50,65,76,77 four trials included both inpatientand outpatient care,53,68,70,71 four trials were carriedout in outpatient or community settings51,66,67,72

and two trials were in the home environment.69,78

In three trials, the intervention was additional tousual care, of which two were during inpatientrehabilitation71,77 and one was after dischargefrom inpatient therapy, but additional tooutpatient therapy.69

Amount of task practiceThe number of hours of training variedconsiderably across the interventions. Three trialsprovided less than 10 hours’ training intotal,66,70,77 seven trials provided between 10 and21 hours’ training,50,51,65,67,68,71,76 two trialsprovided more than 40 hours’ training53,72 andtwo trials prescribed more than 40 hours’ home-exercise therapy.69,78

Duration of trainingThe length of time over which training was spreadvaried from 2 to 4 weeks for seventrials.50,66,67,71,72,76,77 For two trials, the length oftime was estimated as 3 weeks of hospital inpatienttherapy, with therapy for some patients in anoutpatient setting if required.68,70 The interventionin four trials was over 6–8 weeks51,65,69,78 and inone trial the intervention was over 20 weeks.53

Intervention deliveryAll of the interventions were delivered by trainedphysiotherapists or occupational therapists, exceptfor the self-monitored home-exerciseprogrammes,69,78 where trained staff input wasrestricted to prescription and programme review,one trial where trained physiotherapy assistantsprovided balance training77 and one trial whereregistered practical nurses delivered sit-to-standtraining.65 Three of the interventions were

delivered in a group setting of between four andseven participants per group.50,65,67

Of those programmes delivered in a circuit-classformat, trial authors reported between 70 and80% compliance.50,51,67 For the self-administeredprogrammes in a home setting, trial authorsreported 68–75% self-monitored adherence to theprescribed exercise programme.69,78

CIMTTrials were divided into those evaluatingCIMT64,73,74,83,84 and those evaluating modifiedCIMT (mCIMT).61,62,79–82 CIMT interventionsincluded wearing a padded mitten and/or sling toreduce use of the unaffected arm, together with aprogramme for improving task performance of theaffected limb using techniques such as ‘shaping’(progressively increasing the difficulty of a task insmall steps and providing frequent feedback andpositive encouragement) and repetitive taskpractice. Typically, therapy sessions lasted for6 hours with participants attending 5 days perweek. mCIMT comprised similar interventions, buttherapy time was reduced to typically 1 hour perday with participants attending 3 days per week.

SettingTwo trials were carried out solely in an inpatientsetting,81,82 and one trial included both inpatientand outpatient care.84 Seven trials were conductedin outpatient clinic settings,61,62,64,73,74,79,80 and thefinal study83 did not specify a setting, but giventhat participants were 3–9 months post-stroke it islikely to be an outpatient clinic setting.

Amount of task practiceThe number of hours of training varied acrosstrials, with those evaluating CIMT typicallyproviding a larger number of hours, with aminimum of 42 hours84 and a maximum of75 hours.74 Modified CIMT trials typically provided30 hours’ training;61,62,79,80 with the exceptions ofone trial where 15 hours’ training was provided,82

and another providing 20 hours’ training.81

Duration of trainingAll CIMT trials spread training over 2 weeks, withthe exception of one trial84 where trainingspanned 2.5 weeks. Trials evaluating mCIMTspread training over a longer period, typically10 weeks,61,62,79,80,82 with the exception of onetrial81 where training lasted for 2 weeks.

Intervention deliveryInterventions in eight trials were delivered bytrained physiotherapists and/or occupational


12

therapists,61,62,79–84 with one trial also includingdelivery by ‘therapy assistants’.84 In three trials itis unclear who delivered the intervention.64,73,74

In the majority of trials, it is not clear whetherinterventions were delivered on a one-to-one orgroup basis. Exceptions are one trial wheretreatment was on a one-to-one basis,83 and onetrial where participants were treated in groups ofthree to four.64

TMTwo studies evaluated unsupported TM,87,88 andfour studies evaluated bodyweight-supportedtreadmill training.63,85,86,89 One trial supportedbodyweight to a maximum of 15%,89 one trial onlyallowed bodyweight support in the first threetraining sessions,85 and one trial progressivelydecreased bodyweight support as participantsacquired greater self-support.86

Two trials practised walking training with either adefined training heart rate89 or a target heart rateof 60–70%.88 The other trials did not specify adefined heart rate.

Five trials increased the belt speed of the treadmillduring the intervention. One trial identifies theuse of a treadmill with a variable belt speed, butdoes not specify how this was used.63

SettingFour trials were carried out in an inpatientsetting63,85,86,89 and two trials in an outpatientsetting.87,88 The four trials in the inpatient settingwere in addition to usual care.

Amount of task practiceOnly one trial provided more than 20 hours’ taskpractice.88

Duration of trainingThe length of time over which training was spreadvaried from 2 to 4 weeks for four studies.63,85–87

For one study the length of time was 6 weeks89 andfor one study it was 6 months.88

Intervention deliveryAll of the interventions were delivered by trainedphysiotherapists or occupational therapists.

Comparison interventionsRTTTen intervention–control pairs compared theintervention against an attention-control: two

intervention–control pairs used a recreation orcognitive therapy control group,65,66 twointervention–control pairs from the same trialused a splint control53 and six (four from twotrials) used a comparison training programme forthe upper or lower limb.50,51,67,78

Seven intervention–control pairs compared theintervention against usual care. Of these, threewere during inpatient rehabilitation and providedequivalent hours of therapy,68,70,76 and oneprovided additional hours of therapy.71 The otherthree intervention–control pairs were afterdischarge from inpatient rehabilitation, andadditional to any outpatient treatment.69,72,78 It isunclear whether the duration of therapy for theintervention–control pair was equivalent for one ofthese trials.72

CIMTThree studies compared the intervention againstan attention-control. One trial used a bimanualneurodevelopmental therapy control group,64 onetrial used procedures designed to focus attentionon the affected limb without providing training inactive movement,73 and one trial used a controldesigned to be less intense and designed toimprove task performance with the unaffectedside.74

Three trials compared the intervention againstusual care only.81,82,84 Control groups received anequal frequency of therapy time in two trials,81,84

and in one trial control participants received halfthe amount of therapy time compared withintervention participants.82

A further three trials had two comparison groups,one receiving usual care and one receiving notreatment.61,62,80 Usual-care participants in allthree trials received an equal amount of therapy tothe intervention group; the no-treatment groupreceived no interventions during the same period.Another trial also had two comparison groups, onereceiving no treatment, the other an attention-control group that received the interventionwithout the restraint component.79

The trial by Alberts and colleagues83 comparedthe intervention to no treatment, with participantsrandomised to the latter receiving the intervention1 year later.

TMOne trial compared the intervention against an attention-control consisting of a home-exerciseprogramme to lengthen and strengthen


13


muscles.87 Two trials compared against analternative intervention.88,89 One of theseinterventions was individual physiotherapyconcentrated on walking rehabilitation,89 and onewas based on common components ofconventional therapy which would not normallyhave been received as participants were late post-stroke.88 Three trials compared the interventionagainst usual care.63,85,86 These trials were duringinpatient rehabilitation and provided equivalenthours of therapy.

Primary outcomesThe 31 included trials used a wide range ofdifferent outcome measures, measurementstatistics and time intervals for follow-up. Measuresselected post-intervention are detailed below.

Upper limb functional outcomemeasuresArm● RTT: ARAT,53 WMFT,72 MAS – arm,50,68,70

BBT,52 FTHUE71 and Southern Motor GroupAssessment – upper limb activity.69

● CIMT: Action Research Arm Test61,62,64,79,80,82

and WMFT.61,73,74,79–81,83

Hand function● RTT: Nine Hole Peg Test (9HPT),52 Ten Hole

Peg Test (10HPT),69 MAS – hand.50,68,70

● CIMT: Grooved Pegboard Test,84 a key-turningtask,83 and hand grip and pinch strength.64

Sitting balance/reach● RTT: reaching distance,66 Sitting Equilibrium

Index,76 MAS – balanced sitting,68,70 and lateralreach – time to return to quiet sitting.77

Lower limb functional outcomemeasuresWalking distance ● RTT: Six Minute Walk Test (6MWT).50,51,67

● TM: 6MWT87–89 and Five Minute Walk Test.86

Measures of walking distance over 5 minuteswere converted to distance over 6 minutes, onthe assumption that participants could maintaineffort equivalently over such similar periods.

Walking speed● RTT: Ten Metre Walk Speed (10MWS) with

walking aid,53,66,67 Five Metre Walk Speed(5MWS) at comfortable speed51 and Six MetreWalk Speed (6MWS).70

● TM: 5MWS,86 10MWS85,87,89 and walking speedover 30 feet (9.1 m).88

Functional ambulation● RTT: Functional Ambulation Classification

(FAC)53,76 and MAS – walking.68,70,78

● TM: FAC.85,86

Sit-to-stand● RTT: Timed Up and Go (TUG),50,51,67

MAS – sit-to-stand,68,70 sit-to-stand time inseconds,77 and number of people able to stand safely and independently on twooccasions.65

Lower limb functional measures● RTT: SMES trunk, balance and gait subscale,68

Step Test,50,67 and Rivermead Leg and Trunk.70

Standing balance and reach● RTT: Upright Equilibrium Index,76 Functional

Reach78 and Berg Balance Scale.51

● TM: measures of standing balance using aninstrumented balance assessment system88

which was not used.

Global motor function● RTT: MAS68 and RMA score for gross

functions.70

● CIMT: none● TM: RMA score for gross functions.63,88,89

Secondary outcomesADL measures● RTT: BI51,53,68,70 and FIM.76 Two trials used the

BI scoring out of 20,53,70 while the other trialsused the scoring out of 100.

● CIMT: The BI.81

● TM: none.

Adverse events● RTT: number of falls.65

● CIMT: levels of stiffness and discomfort on theaffected side.73

● TM: no trials reported quantitative data foradverse events. Narrative reports and reasonsfor withdrawal are summarised.

Timing of outcome measurement● RTT: within the 0–6-month period post-stroke:

one trial77 measured outcome at 1 month post-intervention and three trials at 2 monthspost-intervention.67,76,78 Within the 6–12-monthpost-stroke period, one trial measured outcomeat 6 months post-intervention,50 one trial at9 months post-intervention,71 one trial at6 months post-randomisation,70 and one trial at1 year post-stroke.68


14

● CIMT: one trial measured outcome 3–4 monthspost-stroke84 and one trial measured outcome6 months post-intervention.74

● TM: two trials measured outcome at 3 monthspost-intervention.87,89

Excluded studiesThere is a large number of excluded studies(n = 44), described in Appendix 4. Because of thedifficulties in determining whether trialinterventions included task-specific functionalrepetition, the authors have attempted to be astransparent as possible about the basis on whichtrials were excluded. The reasons for exclusion were:

● not functional, or no functional outcome: ninestudies

● mixed interventions, or interpreted as focusingpredominantly on exercise: 11 studies

● not repetition, or unable to determine amountof practice: three studies

● passive movement: one study● comparison group also includes some form of

repetitive functional intervention: 11 studies● methodological or reporting reasons: nine studies.

The excluded studies included three trials thathad been either partially or fully translated fromChinese to English. While translation wasundertaken by native-speaking health-serviceworkers, there is the possibility that informationwas misinterpreted or misunderstood.

Ongoing studiesThere are eight ongoing studies, where theinformation available is sufficient to say that theinterventions include an element of RFTP. Theseare detailed in Appendix 5. Three trials involvetraining for standing, balance or sit-to-stand,90–92

two trials are of lower limb circuit training93,94 andone trial is of upper limb task-specific training.95

One trial uses a motor relearning approach(Langhammer B, Oslo University College, Oslo,Norway: personal communication, November2006) and one trial is of CIMT.96 All are withparticipants in the early stages of stroke recovery,except for the trial by Langhammer.

Studies not assessed at reportcompletionRTTOf the 17 studies categorised as unable to beassessed, 12 were ongoing studies identified from

trials registers, where the information availablewas insufficient to be able to exclude them at thisstage.97–108 Two studies are unpublished, and thereviewers are awaiting data.109,110 One study waspublished as a conference proceeding, and thereviewers were unable to contact the authors.111

Two studies are published, and attempts are beingmade to contact the authors to determine theexact content of the intervention.112,113

CIMTOf the seven studies awaiting assessment, three areongoing114,115 (Page S, University of CincinnatiAcademic Medical Centre, Ohio, USA: personalcommunication, February 2007). One recentlypublished study was not in the date range forsearching.75 Two related studies have recentlycompleted and been submitted for publication.116

The reviewers were unable to contact the authorsof one study to assess for eligibility.117

TMOf the 14 studies awaiting assessment, theinformation available for seven ongoing studies isinsufficient to be able to exclude them at thisstage.118–124 Three studies requiretranslation.125–127 One study is recentlycompleted128 as a follow-up to an included study,86

and three studies could not be traced.129–131

Quality of included studiesAllocationRTTAllocation concealment was adequate in eighttrials.50,51,53,67,70,71,77,78 In five trials, allocationconcealment was unclear; of these, three trialsstated that random allocation was used, butprovided no description of the procedure for itsconcealment from those recruitingparticipants;68,72,76 one trial used coin flipping torandomise participants with no further descriptionof the procedure,65 and one trial attemptedconcealment with a procedure involvingparticipants drawing cards out of a box containingten control group and ten experimental groupcards, but the procedure for ensuring that thoserecruiting participants remained unaware ofassignments is not described.66 One trial was quasi-randomised, allocating participants to interventionor control groups in alternate runs of five.69

CIMTThe procedure for allocation concealment wasunclear in all trials. Seven trials stated that randomallocation was used, but provided no description


15


of the procedure.61,62,73,79,80,83,84 Four trials stateduse of tables of random numbers to allocateparticipants to intervention or control groups, withno description of the procedure.64,74,81,82

TMAllocation concealment was adequate in fourtrials.86–89 In two trials, allocation concealment wasunclear. One trial stated that participants wereassigned to groups by block randomisation on thebasis of walking speed, but provided nodescription of the procedure for concealing theallocation, or the block length.85 One trial statedrandomisation, with no description of theprocedure.63

Blinding of outcome assessorsRTTBlinding of primary outcome assessment wasstated in all but two trials.69,71 Of the studies thatstated observer blinding, three gave no details ofhow this was done.68,72,78 Four trials checkedwhether the outcome assessor had becomeunblinded,51,53,67,70 and out of these, three trialsreported that some degree of unmasking mighthave occurred.51,53,67

CIMTBlinding of outcome assessment was attempted inall trials with the exception of one trial,79 wherethere was no mention of blinding. In two trials73,84

action taken at blinding was judged likely to havebeen effective, for example employing personnelfrom outside the hospital who were blind totreatment assignment. Eight trials stated thatoutcome assessment was blinded, but did notdescribe the procedure.61,62,64,74,80–83 No trialreported checking for the possibility thatunblinding had occurred.

TMBlinding of primary outcome assessment wasstated in two trials.85,87 Neither trial describedchecks for unblinding. Two trials attemptedblinding, but report that this may not have beensuccessful,88,89 for example one trial stated that asa result of staffing limitations and institutionalsafety regulations, treadmill exercise testing wasconducted by the same staff who providedtraining,88 hence metabolic fitness tests wereunblinded. In one trial, physiotherapists notinvolved in the therapy were responsible for theassessment of the RMA Scale, but disclosure bypatients and team-mates could not be fullyexcluded.89 One trial did not mention blinding ofoutcome assessors to participants’ treatmentstatus.86

Owing to the nature of the interventions, blindingof participants, intervention providers or usualcare providers was not assessed, as it is essentiallyimpractical in this type of study.

Follow-up and exclusionsRTTAll trials provided information about numbers ofwithdrawals and reasons for withdrawal. All trialsaccounted for all participants at the end of thetrial, except for one, which included participantsin the analysis only if they completed thetreatment programme.71 Of the 14 trials in total,three trials had 10–20% loss53,68,78 and two trialshad more than 20% loss.67,70 The remaining ninetrials had less than 10% loss to follow-up.

CIMTNine trials had no withdrawals.61,62,64,73,74,79,80,82,83

One trial provided information about numbers ofwithdrawals and reasons for withdrawal;84 and onetrial81 states overall numbers of withdrawals, butnot by intervention group. All except one trial81

accounted for all participants at the end of thetrial. All trials had no loss to follow-up, except forone trial with 13% loss81 and one trial with 29%.84

TMFive trials provided information about numbers ofwithdrawals and reasons for withdrawal, andaccounted for all participants at the end of thetrial. Withdrawals and follow-up were unclear inone trial.63 Two trials had less than 10% loss tofollow-up post-treatment,87,89 two trials had11–20% loss to follow-up post-treatment85,86 andone trial had more than 20% loss to follow-uppost-treatment.88

Other potential sources of biasTo detect systematic differences in care providedto participants in comparison groups other thanthe intervention under investigation, trials wereassessed to determine whether groups were treatedequally during the intervention and during usualcare.

RTTDuring the intervention, groups were treatedequally in all trials, with the following exceptions:in one trial70 there was no significant difference inthe amount of treatment; however, the authorsstate in a supplementary paper that there mayhave been differences in elements of treatmentsuch as detailed feedback and socialconversation;132 in one trial it is not clear whethergroups were treated equally72 and in two trialsparticipants in the intervention group received


16

additional hours of therapy.71,77 During usual care,groups were treated equally in eighttrials.50,53,65–69,77 In four trials no information isprovided70–72,76 and in a further two trials52,78

there was no usual-care group.

CIMTDuring the intervention, comparison groupsreceiving therapy were treated equally in all excepttwo trials. In one trial,73 participants in theintervention group spent 7 hours at therehabilitation centre each weekday for 2 weeks;the comparison group received only four 10-minute periods encouraging them to focus onperforming new activities with the affected upperextremity at home and two sessions of ‘physicaltherapy’, plus a range of exercises to carry out athome. (As it was unknown how long control groupparticipants practised, equivalence of therapy timewas assumed for subgroup analyses.) In another

trial,74 participants in the intervention arm of thetrial similarly received longer periods of therapy(6 hours per day over 8 weekdays and 4 hours perday over 2 weekend days) than the comparisongroup (3 hours per day over 8 weekdays and2 weekend days of rest). Groups were treatedequally in all trials with a usual-care comparison.

TMDuring the intervention, other than theintervention provided, groups were treated equallyin all except one trial,87 where the control groupwas given a home-exercise programme to carryout for the same number of sessions as in theintervention group. However, this programme wasnot prescribed in sufficient number or intensity toprovide a training effect and instead aimed toprovide a credible sham programme. Groups weretreated equally in all trials with a usual-carecomparison.


17


Primary outcomesResults are presented separately for upper andlower limb outcomes and global function,concluding with an overall treatment effect for allforms of RFTP on functional outcome. All resultsare post-therapy, except for Langhammer andStanghelle,68 which are 3 months post-stroke, andVan Vliet and colleagues,70 which are 3 monthspost-baseline.

Upper limb function: post-therapyResults are presented for arm function, handfunction, and sitting balance and reach.

Arm functionEighteen trials recruiting 634 participantsmeasured arm function, with data suitable forpooling available for 76% (n = 485) (Figure 2).There was some heterogeneity of treatment effects


19


Chapter 4

Results of the review

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 02 Upper limb functionOutcome: 01 Arm function

Study Treatment Control SMD (fixed) Weight (SMD (fixed)or subcategory N Mean (SD) N Mean (SD) (95% CI) (%) (95% CI)

01 RTTBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)

Subtotal (95% CI) 205 207 87.66 0.17 (–0.03 to 0.36)Test for heterogeneity: �2 = 3.18, df = 7 (p = 0.87), I2 = 0%Test for overall effect: Z = 1.67 (p = 0.09)

02 CIMTAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.85 0.03 (–1.94 to 2.00) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69)

Subtotal (95% CI) 38 35 12.34 0.77 (0.26 to 1.29)Test for heterogeneity: �2 = 10.18, df = 6 (p = 0.12), I2 = 41.0%Test for overall effect: Z = 2.93 (p = 0.003)

Total (95% CI) 243 242 100.00 0.24 (0.06 to 0.42)Test for heterogeneity: �2 = 17.99, df = 14 (p = 0.21), I2 = 22.2%Test for overall effect: Z = 2.59 (p = 0.010)

–10 –5 0 5 10 Favours control Favours treatment

FIGURE 2 Arm function

(I2 = 22.2%), although not sufficient to merit theuse of a random-effects approach.

Eight RTT trials recruited 467participants,50,52,53,68–72 with data available for 88%(n = 412) of participants. Ten CIMT trialsrecruiting 167 participants measured armfunction.61,62,64,73,74,79–83 In three of the CIMTtrials with 91 participants in total, data wereunsuitable for pooling.61,62,64 Page and colleagues(2002)61 included outcome data for nineparticipants, and provided means with nostandard deviations (ARAT: CIMT group meanchange +11.5, traditional therapy group meanchange +1.4). Page and colleagues (2004)62

included data for 13 participants, and alsoprovided means with no standard deviations(ARAT: CIMT group mean change +11.4,traditional therapy group mean change +7.1).Suputtitada and colleagues64 reported median andranges for 69 participants (ARAT: CIMT group

n = 33, median 55, range 30–57, control groupn = 36, median 47.5, range 15–54). Of theremaining seven CIMT trials with 76 participants,data were available for 96% (n = 73).

The pooled effect for the impact of RFTP on armfunction across all trials showed a small effect size,which was statistically significant: (SMD 0.24, 95% CI 0.06 to 0.42).

Hand functionSeven trials recruiting 357 participants measuredhand function, with data available for 86%(n = 307) (Figure 3). Five RTT trials recruited 324participants,50,52,68–70 with data available for 87%(n = 281) of participants. Two CIMT trials83,84

recruited 33 participants, with data available for79% (n = 26). The pooled effect for RFTP onhand function across all trials was small, andmarginally statistically non-significant (SMD 0.19,95% CI –0.03, 0.42).


20 FIGURE 3 Hand function

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 02 Upper limb functionOutcome: 02 Hand function

Studyor subcategory

Treatment Control SMD (fixed)(95% C)

Weight (%)

SMD (fixed)(95% CI)N Mean (SD) N Mean (SD)

01 RTT Blennerhassett, 200450

Higgins, 200652

Langhammer, 200068

Turton, 199069

Van Vliet, 200570

Subtotal (95% CI)Test for heterogeneity: �2 = 1.66, df = 4 (p = 0.80), I2 = 0%Test for overall effect: Z = 1.36 (p = 0.18)

02 CIMT Alberts, 200483

Boake, 200684

Subtotal (95% CI)Test for heterogeneity: �2 = 0.00, df = 1 (p = 0.99), I2 = 0%Test for overall effect: Z = 1.36 (p = 0.17)

Total (95% CI)Test for heterogeneity: �2 = 2.50, df = 6 (p = 0.87), I2 = 0%Test for overall effect: Z = 1.69 (p = 0.09)

9.9029.7117.10 7.19

28.04 91.93

3.11

8.07 4.96

100.00

–0.08 (–0.80 to 0.63) 0.28 (–0.13 to 0.70) 0.33 (–0.21 to 0.87)–0.11 (–0.95 to 0.73) 0.09 (–0.33 to 0.52) 0.16 (–0.07 to 0.40)

0.55 (–0.72 to 1.83) 0.55 (–0.47 to 1.56) 0.55 (–0.24 to 1.34)

0.19 (–0.03 to 0.42)

–4 –2 0 2 4

Favourscontrol

Favourstreatment

15 4.70 (2.50) 15 4.90 (2.10) 47 –9.00 (3.00) 44 –10.00 (4.00) 29 4.60 (1.90) 24 3.90 (2.30) 12 –43.50 (20.80) 10 –41.10 (20.10) 42 4.30 (2.41) 43 4.07 (2.56)145 136

5 –32.10 (49.90) 5 –65.40 (58.20) 9 0.08 (0.06) 7 0.04 (0.08) 14 12

159 148


21


Sitting balance/reachFive trials (all RTT) recruiting 256 participantsmeasured sitting balance or functional reach(Figure 4).66,68,70,76,77 Data were available for 82%(n = 210). There was some heterogeneity oftreatment effects (I2 = 32%), although notsufficient to merit the use of a random-effectsapproach.

The impact on sitting balance/reach showed asmall effect size that was not statistically significant(SMD 0.23, 95% CI –0.05 to 0.50).

Upper limb function: follow-upUnder 6 months post-therapyOne CIMT trial measuring hand function84 andtwo RTT trials measuring sitting balance,76,77

recruiting 78 participants in total, measured forretention effects between post-therapy and under 6 months post-therapy (Figure 5). Data were available for 86% (n = 67) and effects across trials were homogeneous

(I2 = 0%). There was a moderate effect size, which was statistically significant (SMD 0.55, 95% CI 0.06 to 1.04).

Between 6 and 12 months post-therapyFour trials50,68,70,71 (all RTT) recruiting 254participants measured arm function for retentioneffects between 6 and 12 months post-therapy(Figure 5). Data were available for 76% (n = 195).Effects across trials were homogeneous (I2 = 0%).Results showed no effect of treatment (SMD –0.02,95% CI –0.31 to 0.26).

Subgroup analysis: upper limb functionSubgroup analyses for upper limb interventionsare based on trials providing measures of armfunction. Trials that only provide measures ofhand function84 or sitting balance/reach66,76,77 aretherefore excluded. Subgroup analyses arepresented for type, amount and timing ofintervention, and to consider the impact of

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 02 Upper limb function Outcome: 03 Sitting balance/reach

Study Treatment Control SMD (fixed) Weight SMD (fixed)or subcategory N Mean (SD) N Mean (SD) (95% CI) (%) (95% CI)

01 RTTde Sèze 200176 10 3.30 (0.80) 10 3.00 (0.80) 9.61 0.36 (–0.53 to 1.24)Dean 199766 10 12.00 (0.95) 9 10.80 (0.90) 7.49 1.24 (0.23 to 2.24)Howe 200577 15 –1.90 (0.80) 18 –2.10 (0.70) 15.89 0.26 (–0.43 to 0.95)Langhammer 200068 29 5.40 (0.90) 24 5.00 (1.50) 25.38 0.33 (–0.22 to 0.87)Van Vliet 200570 42 4.54 (1.49) 43 4.63 (1.42) 41.63 –0.06 (–0.49 to 0.36)

Subtotal (95% CI) 106 104 100.00 0.23 (–0.05 to 0.50)Test for heterogeneity: �2 = 5.88, df = 4 (p = 0.21), I2 = 32.0%Test for overall effect: Z = 1.61 (p = 0.11)

Total (95% CI) 106 104 100.00 0.23 (–0.05 to 0.50)Test for heterogeneity: �2 = 5.88, df = 4 (p = 0.21), I2 = 32.0%Test for overall effect: Z = 1.61 (p = 0.11)


FIGURE 4 Sitting balance/reach

specific trial features on the results. Theclassification of trials for each subgroup analysis isgiven in Appendix 6.

Type of interventionSubgroups compared the treatment effects foreight RTT trials recruiting 467 participants, andseven CIMT trials recruiting 76 participants(Figure 6). The impact of RTT on upper limb

function post-treatment just failed to reachstatistical significance (SMD 0.17, 95% CI –0.03 to0.36). The impact of CIMT on arm functionshowed some heterogeneity (I2 = 41%), but notsufficient to necessitate the use of a random-effectsapproach. There was a large and statisticallysignificant effect size (SMD 0.77, 95% CI 0.26 to1.29). The difference between effect sizes for CIMTand RTT was statistically significant (p = 0.03).


22

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 02 Upper limb function Outcome: 04 Follow-up


01 Under 6 months post-therapyBoake, 200684 9 0.16 (0.06) 7 0.10 (0.10) 5.65 0.71 (–0.32 to 1.74)de Sèze, 200176 10 3.60 (0.50) 10 3.40 (0.60) 7.62 0.35 (–0.54 to 1.23)Howe, 200577 15 2.50 (1.30) 16 1.90 (0.50) 11.43 0.60 (–0.12 to 1.32)

Subtotal (95% CI) 34 33 24.70 0.55 (0.06 to 1.04)Test for heterogeneity: �2 = 0.32, df = 2 (p = 0.85), I2 = 0%Test for overall effect: Z = 2.19 (p = 0.03)

02 6–12 months post-therapyBlennerhassett, 200450 10 –23.60 (12.20) 11 –31.00 (33.20) 8.04 0.28 (–0.58 to 1.14)Langhammer, 200068 27 3.90 (2.50) 27 3.50 (2.80) 20.90 0.15 (–0.39 to 0.68)Van Vliet, 200570 42 3.45 (2.40) 45 3.77 (2.37) 33.65 –0.13 (–0.55 to 0.29)Winstein, 200471 17 9.67 (5.80) 16 10.98 (6.20) 12.72 –0.21 (–0.90 to 0.47)

Subtotal (95% CI) 96 99 75.30 –0.02 (–0.31 to 0.26)Test for heterogeneity: �2 = 1.42, df = 3 (p = 0.70), I2 = 0%Test for overall effect: Z = 0.17 (p = 0.86)

–10 –5 0 5 10

Favours control Favours treatment

FIGURE 5 Arm function: follow-up at 0–6 months and more than 6 months post-therapy


23


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limb Outcome: 01 Type of intervention


01 RTTBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60)Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47)Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00)Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82)Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07)Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51)Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64)Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)


02 CIMTAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08)Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.85 0.03 (–1.94 to 2.00)Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89)Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25)Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12)Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50)Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69)


Total (95% CI) 243 242 100.00 0.24 (0.06, 0.42)Test for heterogeneity: �2 = 17.99, df = 14 (p = 0.21), I2 = 22.2%Test for overall effect: Z = 2.59 (p = 0.010)


FIGURE 6 Subgroup analysis: type of intervention – upper limb trials

Dosage of task practiceSeven trials (five RTT, two CIMT) with 399participants provided up to 20 hours’ taskpractice. Eight trials (three RTT, five CIMT) with163 participants provided more than 20 hours’task practice (Figure 7). There was substantialheterogeneity (I2 = 50.8%) in the trials providing

up to 20 hours’ task practice, Using a random-effects model to combine the effects fromindividual trials, while the estimated effect was greater for the subgroup with more than 20 hours of task practice, the difference betweensubgroups failed to reach statistical significance(p = 0.18).


24

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limbOutcome: 02 Dosage of task practice

Study Treatment Control SMD (random) Weight SMD (random)or subcategory N Mean (SD) N Mean (SD) (95% CI) (%) (95% CI)

01 0–20 hoursBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 7.47 –0.11 (–0.83 to 0.60) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 4.80 0.95 (0.01 to 1.89) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 15.53 0.06 (–0.36 to 0.47) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.12 0.28 (–0.27 to 0.82) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.82 3.70 (1.28 to 6.12) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 14.97 0.08 (–0.34 to 0.51) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 9.28 0.02 (–0.60 to 0.64)


02 More than 20 hoursAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.92 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 1.23 0.03 (–1.94 to 2.00) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 11.99 0.48 (–0.03 to 1.00) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 1.08 0.14 (–1.97 to 2.25) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.60 1.79 (0.07 to 3.50) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 5.76 0.23 (–0.61 to 1.07) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 4.14 0.67 (–0.35 to 1.69) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 7.28 0.36 (–0.37 to 1.09)




FIGURE 7 Subgroup analysis: dosage of task practice – upper limb trials

Time since strokeNine trials (four RTT, five CIMT) with 364participants measured arm function in participants up to 6 months post-stroke. Six trials(four RTT, two CIMT) with 189 participantsincluded participants more than 6 months

post-stroke (Figure 8). There was someheterogeneity in trials 0–6 months post-stroke (I2 = 34.8%), but not sufficient to warrant using a random-effects model. The differencebetween subgroups did not reach statisticalsignificance (p = 0.65).


25


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limb Outcome: 03 Time since stroke


01 0–6 monthsAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.85 0.03 (–1.94 to 2.00) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64)


02 More than 6 monthsBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)




FIGURE 8 Subgroup analysis: time since stroke – upper limb trials

Allocation concealmentTrials were grouped according to whetherallocation concealment was judged to be adequate(five RTT trials) or inadequate/unclear (ten trials:three RTT, seven CIMT) (Figure 9). There wassome heterogeneity observed in the

‘inadequate/unclear’ subgroup (I2 = 27.3%). The difference between subgroups was statistically significant (p = 0.08), indicating thatthe effect of RFTP was greater for trials whereallocation concealment was either inadequate orunclear.


26

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limb Outcome: 04 Allocation concealment


01 AdequateBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64)


02 Inadequate/unclearAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.85 0.03 (–1.94 to 2.00) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)




FIGURE 9 Subgroup analysis: allocation concealment – upper limb trials

Post hoc analysis: type of comparison groupSeven trials (five RTT, two CIMT) were classified as usual care or alternative treatment,and eight trials (three RTT, five CIMT) wereclassified as attention-control or no treatment

(Figure 10), with some heterogeneity observed in trials with usual care/alternative treatmentcontrols (I2 =46.1%). There was no statisticallysignificant difference between subgroups(p = 0.84).


27


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limbOutcome: 05 Comparison group


01 Usual care/alternative treatmentDromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)


02 Attention control/no treatmentAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 1.50 (10.50) 0.85 0.03 (–1.94 to 2.00) Blennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69)




FIGURE 10 Subgroup analysis: type of comparison group – upper limb trials

Post hoc analysis: equivalence of therapy timeOne subgroup comprised seven trials (two RTT,five CIMT) which gave, additional therapy time tothe experimental group, and the other containedeight trials (six RTT, two CIMT) where therapytime for experimental and control groups wasequivalent (Figure 11). There was someheterogeneity of treatment effects in eachsubgroup, but not sufficient to merit the use of arandom-effects meta-analysis. There was nosignificant difference between the two subgroups (p = 0.92).

Post hoc analysis: trial size The median number of participants in the trialswas 23. A post hoc analysis was thereforeundertaken for trials with under 25 participants

versus those with 25 or more participants(Figure 12). Some heterogeneity was observed intrials with under 25 participants (I2 = 38.2%), but not enough to warrant the use of a random-effects model. The difference between effect sizesin the small trial sub-group (<25 participants) andthe larger trial sub-group (�25 participants) wasstatistically significant (p = 0.06). As the effect inthe small trial subgroup (SMD 0.62, 95% CI 0.18to 1.07) is significantly larger than in the largertrial subgroup (SMD 0.16, 95% CI –0.04 to 0.36),this may indicate some degree of reporting bias inupper limb trials. This is supported by the funnelplot in Figure 13, which has some apparentasymmetry indicating a potential lack of reporting of small negative trials with largestandard errors.


28

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limbOutcome: 06 Equivalence of therapy time


01 Additional therapy timeAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.85 0.03 (–1.94 to 2.00) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69)


02 Equivalent therapy timeBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)




FIGURE 11 Subgroup analysis: equivalence of therapy time – upper limb trials


29


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limbOutcome: 07 Trial size


01 Under 25 participantsAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 2.14 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.85 0.03 (–1.94 to 2.00) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 3.75 0.95 (0.01 to 1.89) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.74 0.14 (–1.97 to 2.25) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.56 3.70 (1.28 to 6.12) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 1.13 1.79 (0.07 to 3.50) Turton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 4.66 0.23 (–0.61 to 1.07) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 3.16 0.67 (–0.35 to 1.69)


02 25 or more participantsBlennerhassett, 200450 15 4.90 (1.90) 15 5.10 (1.50) 6.45 –0.11 (–0.83 to 0.60) Higgins, 200652 47 29.00 (17.00) 44 28.00 (19.00) 19.58 0.06 (–0.36 to 0.47) Kwakkel, 199953 27 20.00 (22.00) 34 10.00 (19.00) 12.59 0.48 (–0.03 to 1.00) Langhammer, 200068 29 4.70 (2.00) 24 4.10 (2.30) 11.21 0.28 (–0.27 to 0.82) Van Vliet, 200570 42 3.88 (2.23) 43 3.69 (2.38) 18.30 0.08 (–0.34 to 0.51) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 8.62 0.02 (–0.60 to 0.64) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 6.24 0.36 (–0.37 to 1.09)




FIGURE 12 Subgroup analysis: trial size – upper limb trials

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 03 Subgroup analyses: upper limb Outcome: 08 Trial size

–10 –5 0 5 10

0.0

0.4

0.8

1.2

1.6

SE (S

MD

)

SMD (fixed)

FIGURE 13 Funnel plot of precision versus effect size – upper limb trials


30

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb functionOutcome: 01 Walking distance

Study Treatment Control WMD (random) Weight WMD (random)or subcategory N Mean (SD) N Mean (SD) (95% CI) (%) (95% CI)

01 RTTBlennerhassett, 200450 15 221.00 (65.40) 15 107.00 (85.60) 9.81 114.00 (59.49 to 168.52) Dean, 200067 5 42.03 (30.42) 4 4.76 (4.90) 20.79 37.27 (10.18 to 64.36) Salbach, 200451 44 40.00 (72.00) 47 5.00 (66.00) 20.04 35.00 (6.56 to 63.44)


02 TMAda, 200387 11 99.00 (70.00) 14 13.00 (27.00) 13.09 86.00 (42.28 to 129.72) da Cunha, 200286 6 107.00 (71.52) 7 51.58 (63.00) 6.19 55.42 (–18.42 to 129.26) Eich, 200489 25 90.60 (43.50) 25 55.70 (32.60) 24.17 34.90 (13.59 to 56.21) Macko, 200588 25 281.03 (120.00) 20 264.57 (136.31) 5.90 16.46 (–59.58 to 92.50)


Total (95% CI) 131 132 100.00 50.05 (29.65 to 70.44)Test for heterogeneity: �2 = 11.79, df = 6 (p = 0.07), I2 = 49.1%Test for overall effect: Z = 4.81 (p < 0.00001)


FIGURE 14 Walking distance

Lower limb function: post-therapyResults are presented for walking distance, walkingspeed, functional ambulation, sit-to-stand, lowerlimb functional measures and standingbalance/reach. All results are post-therapy, exceptfor Langhammer and Stanghelle,68 which is3 months post-stroke, and Van Vliet andcolleagues,70 which is 3 months post-baseline.

Walking distanceSeven trials included a measure of walkingdistance (Figure 14). All results are change frombaseline scores except for Macko and colleagues,88

and are expressed as metres walked in 6 minutes.The degree of heterogeneity (I2 = 49.1%) in theeffect sizes of the seven trials was very close to thestudy criterion for ‘substantial’ heterogeneity, so arandom-effects model was used. Three RTTtrials50,51,67 recruiting 133 participants measuredwalking distance, with outcome data available for98% (n = 130) of participants. Four TM trials86–89

recruiting 155 participants measured walkingdistance, with outcome data available for 96%(n = 149).

For RFTP overall, pooled results showed astatistically significant difference (WMD 50.05 m,95% CI 29.65 to 70.44 m). Owing to the lack ofhomogeneity of standard deviations, resulting in asubstantial impact on the weighting of severaltrials, results were reanalysed using the SMD and arandom-effects model. The result showed a largeeffect size, which remained highly statisticallysignificant (SMD 0.98, 95% CI 0.58 to 1.39,excluding Macko and colleagues,88 which did notprovide ‘change-from-baseline’ data). To improvecomparability with effect sizes for other outcomesand for use in the economic analysis, the SMDbased on the post-treatment data from the seventrials was also computed (SMD 0.45, 95% CI 0.20to 0.70; figure not shown). As expected, the SMDbased on the post-treatment data is considerablysmaller than that based on the change-from-baseline data, primarily owing to its poorersensitivity to change.

Walking speedTen trials included a measure of walking speed(Figure 15). Results were converted into metres per


31


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb functionOutcome: 02 Walking speed


02 RTTDean, 199766 10 –33.80 (18.60) 8 –29.40 (33.90) 4.19 –0.16 (–1.09 to 0.77) Dean, 200067 5 0.80 (0.43) 4 0.88 (0.52) 2.09 –0.15 (–1.47 to 1.17) Kwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 13.22 0.64 (0.12 to 1.16) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 21.13 0.36 (–0.05 to 0.78) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 20.08 –0.05 (–0.48 to 0.37)


03 TMAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 5.49 0.65 (–0.17 to 1.46) da Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 2.47 1.15 (–0.06 to 2.36) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 11.55 0.41 (–0.15 to 0.97) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 10.50 –0.06 (–0.65 to 0.53) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 9.29 0.35 (–0.27 to 0.98)




FIGURE 15 Walking speed

second, with the exception of Dean andShepherd66 and Van Vliet and colleagues,70 whopresented statistics for the number of seconds to walk 10 m and 6 m, respectively. Therewas some heterogeneity of treatment effects (I2 = 8.7%), although not sufficient to merit theuse of a random-effects approach. Five RTT trialsrecruited 311 participants,51,53,66,67,70 withoutcome data available for 85% (n = 263) of participants. Six TM trials recruited 229participants.63,85–89 One TM trial with 30participants provided data unsuitable for pooling,with data for mean distance walked but nostandard deviations.63 Of the five remaining trialswith 199 participants, outcome data were availablefor 87% (n = 173) of participants.

Overall, pooled results for the impact of RFTP onwalking speed showed a small effect size, whichwas statistically significant (SMD 0.28, 95% CI0.09 to 0.47). A subgroup analysis was undertakenfor walking speed measured over short (5 or 6 m)or medium (10 m) distances, with no significantdifference found (p = 0.57).

Functional ambulationFor RFTP overall, seven trials recruiting 368participants measured functional ambulation, withoutcome data available for 79% (n = 291) (Figure 16).Effects across trials were homogeneous (I2 = 0%).Five RTT trials53,68,70,76,78 recruited 295 participants,with outcome data available for 81% (n = 238). TwoTM trials85,86 recruited 59 participants, with outcomedata available for 89% (n = 53).

Pooling the results from seven trials showed RFTPto have a statistically significant but small effect onfunctional ambulation measures (SMD 0.28, 95%CI 0.05 to 0.51), with no significant difference ineffects between RTT and TM (p = 0.66).

Sit-to-standSeven trials (all RTT) recruiting 397 participantsincluded a measure of sit-to-stand,50,51,65,67,68,70,77

with outcome data available for 87% (n = 346)(Figure 17).

Effects across trials were homogeneous (I2 = 0%),showing a small to moderate effect size, which was


32 FIGURE 17 Sit-to-stand

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb functionOutcome: 04 Sit-to-stand

Study TreatmentN

ControlN

(Estimate (fixed)(95% CI)

Weight(%)

Estimate (fixed)(95% CI)or subcategory Estimate (SE)

01 RTTBarreca, 200465 25 23 0.8715 (0.2812) 14.80 0.87 (0.32 to 1.42) Blennerhassett, 200450 15 15 0.7000 (0.3775) 8.21 0.70 (–0.04 to 1.44) Dean, 200067 5 4 0.5700 (0.6900) 2.46 0.57 (–0.78 to 1.92) Howe, 200577 15 15 0.2500 (0.3673) 8.67 0.25 (–0.47 to 0.97) Langhammer, 200068 29 24 0.3000 (0.2800) 14.92 0.30 (–0.25 to 0.85) Salbach, 200451 44 47 0.1600 (0.2091) 26.76 0.16 (–0.25 to 0.57) Van Vliet, 200570 42 43 0.3500 (0.2200) 24.18 0.35 (–0.08 to 0.78)



FIGURE 16 Functional ambulation

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb functionOutcome: 03 Functional ambulation


01 RTTde Sèze, 200176 10 2.60 (1.40) 10 1.60 (1.50) 6.62 0.66 (–0.25 to 1.57) Kwakkel, 199953 25 4.00 (1.00) 34 3.00 (2.00) 19.47 0.60 (0.07 to 1.12) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 18.54 0.11 (–0.43 to 0.65) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 7.15 –0.34 (–1.21 to 0.53) Van Vliet, 200570 42 3.70 (1.62) 43 3.39 (1.93) 29.93 0.17 (–0.25 to 0.60)


02 TMda Cunha, 200286 6 7.93 (3.65) 7 7.07 (4.50) 4.54 0.19 (–0.90 to 1.29) Pohl, 200285 20 4.60 (0.60) 20 4.30 (0.70) 13.75 0.45 (–0.18 to 1.08)


Total (95% CI) 144 147 100.00 0.28 (0.05 to 0.51)Test for heterogeneity: �2 = 4.95, df = 6 (p = 0.55), I2 = 0%Test for overall effect: Z = 2.34 (p = 0.02)


statistically significant (standardised effect size0.39, 95% CI 0.18 to 0.61).

Lower limb functional measuresFour trials (all RTT) recruiting 223 participantsincluded a measure of lower limb function,50,67,68,70

with outcome data available for 79% (n = 177)(Figure 18). Effects across trials were homogeneous(I2 = 0%).

Results overall showed a small effect size, whichwas not statistically significant (SMD 0.20, 95% CI–0.10 to 0.50).

Standing balance and reachThree trials (all RTT) recruiting 137 participantsmeasured standing balance or functionalreach,51,76,78 with outcome data available for 96%(n = 132) (Figure 19).

Effects across trials were homogeneous (I2 = 0%),showing a small effect size, which was not statistically significant (SMD 0.29, 95% CI –0.06 to 0.63).


33


FIGURE 18 Lower limb functional measures

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb functionOutcome: 05 Lower limb functional measures


01 RTTBlennerhassett, 200450 15 11.10 (5.00) 15 8.50 (4.60) 16.59 0.53 (–0.20 to 1.26) Dean, 200067 5 9.80 (4.00) 4 5.80 (4.30) 4.40 0.86 (–0.56 to 2.28) Langhammer, 200068 29 41.00 (18.00) 24 39.00 (21.00) 30.17 0.10 (–0.44 to 0.64) Van Vliet, 200570 42 5.62 (4.02) 43 5.24 (4.30) 48.83 0.09 (–0.34 to 0.52)


Total (95% CI) 91 86 100.00 0.20 (–0.10 to 0.50)Test for heterogeneity: �2 = 1.99, df = 3 (p = 0.58), I2 = 0%Test for overall effect: Z = 1.32 (p = 0.19)


FIGURE 19 Standing balance/reach

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb function Outcome: 06 Standing balance and reach


01 RTTde Sèze, 200176 10 2.40 (1.60) 10 2.00 (0.80) 15.19 0.30 (–0.58 to 1.19) McClellan, 200478 12 21.90 (9.40) 9 17.80 (7.40) 15.36 0.46 (–0.42 to 1.33) Salbach, 200451 44 44.00 (11.00) 47 41.00 (13.00) 69.46 0.25 (–0.17 to 0.66)


Total (95% CI) 66 66 100.00 0.29 (–0.06 to 0.63)Test for heterogeneity: �2 = 0.18, df = 2 (p = 0.91), I2 = 0%Test for overall effect: Z = 1.64 (p = 0.10)


Lower limb: follow-upUnder 6 months post-therapySix trials (four RTT67,76–78 and two TM87,89)recruiting 174 participants measured some aspectof lower limb function for retention effectsbetween post-therapy and under 6 months post-therapy (Figure 20). Outcome data wereavailable for 90% (n = 155). Effects across trials were homogeneous (I2 = 0%). Resultsshowed a small to moderate effect size which wasstatistically significant (SMD 0.37, 95% CI 0.05 to 0.69).

Between 6 and 12 months post-therapyThree RTT trials recruiting 211 participantsmeasured some aspect of lower limb function forretention effects of RTT interventions between 6and 12 months post-therapy (Figure 20).50,68,70

Outcome data were available for 80% (n = 170).

There was some degree of heterogeneity oftreatment effects (I2 = 49.1%), although notsufficient to merit the use of a random-effectsapproach (and the small effect size precludes theneed to perform a sensitivity analysis on the choiceof analytic approach). Results showed no treatmenteffect (SMD –0.01, 95% CI –0.32 to 0.29).

Subgroup analyses: lower limb functionSubgroup analyses for lower limb interventions are based on trials providing measures of walkingfunction (walking distance, walking speed orfunctional ambulation rating). Trials that onlyprovide measures of standing balance/reach76 orsit-to-stand65,77 are therefore excluded. Subgroupanalyses are presented for type, amount andtiming of intervention, and to consider the impact of adequacy of allocation concealment


34

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 04 Lower limb function Outcome: 07 Follow-up


01 Under 6 months post-therapyAda, 200387 13 0.83 (0.26) 13 0.64 (0.29) 7.70 0.67 (–0.13 to 1.46) de Sèze, 200176 10 3.10 (1.20) 10 2.50 (1.20) 6.09 0.48 (–0.41 to 1.37) Dean, 200067 4 84.00 (46.70) 4 81.50 (47.20) 2.52 0.05 (–1.34 to 1.43) Eich, 200489 24 0.77 (0.35) 25 0.58 (0.22) 14.64 0.64 (0.07 to 1.22) Howe, 200577 14 –4.20 (7.30) 15 –2.90 (2.50) 9.07 –0.24 (–0.97 to 0.50) McClellan, 200478 13 20.20 (9.40) 10 17.70 (8.40) 7.06 0.27 (–0.56 to 1.10)


02 6–12 months post-therapyBlennerhassett, 200450 15 416.00 (171.00) 14 313.00 (154.00) 8.67 0.61 (–0.13 to 1.36) Langhammer, 200068 27 3.10 (2.30) 27 3.00 (2.30) 17.04 0.04 (–0.49 to 0.58) Van Vliet, 200570 42 3.24 (1.96) 45 3.70 (1.72) 27.21 –0.25 (–0.67 to 0.17)

Subtotal (95% CI) 84 86 52.92 –0.01 (–0.32 to 0.29)Test for heterogeneity: �2 = 3.93, df = 2 (p = 0.14), I2 = 49.1%Test for overall effect: Z = 0.08 (p = 0.93)


FIGURE 20 Lower limb follow-up at 0–6 months and more than 6 months post-therapy

and type of comparison group. There wereinsufficient trials providing additional therapytime or trials of fewer than 25 participants toundertake subgroup analyses. The classification of trials for each subgroup analysis is given inAppendix 6.

Type of interventionTwelve trials (seven RTT, five TM) included ameasure of walking ability (Figure 21). There wassome heterogeneity of treatment effects withineach subgroup, but not sufficient to merit the useof random-effects analysis.

There was no statistically significant differencebetween RTT and TM interventions (p = 0.62).

Dosage of task practiceNine trials (five RTT, four TM) provided up to20 hours’ training time and three trials (two RTT,one TM) provided more than 20 hours’ trainingtime (Figure 22). There was substantialheterogeneity in the more than 20 hours’ practicesubgroup (I2 = 59.4%), so a random-effects modelwas used. There was no statistically significantdifference between subgroups (p = 0.65).

Time since strokeSix trials (three RTT, three TM) recruited0–6 months post-stroke and six trials (four RTT,two TM) recruited more than 6 months post-stroke(Figure 23). There was some heterogeneity oftreatment effects in both subgroups, but not


35


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 05 Subgroup analyses – lower limb Outcome: 01 Type of intervention


01 RTTBlennerhassett, 200450 15 404.00 (101.00) 15 288.00 (124.00) 5.20 1.00 (0.23 to 1.76) Dean, 200067 5 80.20 (42.80) 4 88.40 (52.20) 1.75 –0.15 (–1.47 to 1.16) Kwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 11.09 0.64 (0.12 to 1.16) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 10.40 0.11 (–0.43 to 0.65) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 4.01 –0.34 (–1.21 to 0.53) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 17.72 0.36 (–0.05 to 0.78) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 16.85 –0.05 (–0.48 to 0.37)


02 TMAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 4.60 0.65 (–0.17 to 1.46) da Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 2.07 1.15 (–0.06 to 2.36) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 9.69 0.41 (–0.15 to 0.97) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 8.81 –0.06 (–0.65 to 0.53) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 7.80 0.35 (–0.27 to 0.98)


Total (95% CI) 260 262 100.00 0.29 (0.11, 0.46)Test for heterogeneity: �2 = 14.73, df = 11 (p = 0.20), I2 = 25.3%Test for overall effect: Z = 3.25 (p = 0.001)


FIGURE 21 Subgroup analysis: type of intervention – lower limb trials

sufficient to merit a random-effects analysis. Therewas no significant difference between subgroups(p = 1.0).

Allocation concealmentTrials were grouped according to whetherallocation concealment was judged adequate (eight trials: six RTT, two TM) or inadequate/unclear (four trials: one RTT, three TM) (Figure24). There was heterogeneity within each

subgroup, but insufficient to warrant using arandom-effects meta-analysis. There was nostatistically significant difference betweensubgroups (p = 0.51).

Post hoc analysis: type of comparison groupSix trials (two RTT, four TM) were classified asusual care or alternative treatment, and six trials(five RTT, one TM) as attention-control or notreatment (Figure 25). There was some


36

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 05 Subgroup analyses – lower limb Outcome: 02 Dosage of task practice

Study Treatment Control SMD (random) Weight SMD (random)or subcategory N Mean (SD) N Mean (SD) (95% CI) (%) (95% CI)

01 0–20 hoursAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 5.58 0.65 (–0.17 to 1.46) Blennerhassett, 200450 15 404.00 (101.00) 15 288.00 (124.00) 6.18 1.00 (0.23 to 1.76) da Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 2.76 1.15 (–0.06 to 2.36) Dean, 200067 5 80.20 (42.80) 4 88.40 (52.20) 2.36 –0.15 (–1.47 to 1.16) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 9.97 0.41 (–0.15 to 0.97) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 10.47 0.11 (–0.43 to 0.65) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 8.50 0.35 (–0.27 to 0.98) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 14.70 0.36 (–0.05 to 0.78) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 14.27 –0.05 (–0.48 to 0.37)


02 More than 20 hoursKwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 10.95 0.64 (0.12 to 1.16) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 9.30 –0.06 (–0.65 to 0.53) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 4.96 –0.34 (–1.21 to 0.53)




FIGURE 22 Subgroup analysis: dosage of task practice – lower limb trials


37


heterogeneity within each subgroup, butinsufficient to warrant the use of a random-effectsmeta-analysis. The difference between subgroupswas marginally non-significant (p = 0.10), with theestimated effect somewhat larger for the attention-control/no treatment subgroup.

Trial sizeNo trials of lower limb interventions had fewerthan 25 participants, so subgroup analysis was notundertaken. The funnel plot in Figure 26 does notsuggest reporting bias.

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 05 Subgroup analyses – lower limbOutcome: 03 Time since stroke


01 0–6 monthsda Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 2.07 1.15 (–0.06 to 2.36) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 9.69 0.41 (–0.15 to 0.97) Kwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 11.09 0.64 (0.12 to 1.16) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 10.40 0.11 (–0.43 to 0.65) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 7.80 0.35 (–0.27 to 0.98) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 16.85 –0.05 (–0.48 to 0.37)


02 More than 6 monthsAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 4.60 0.65 (–0.17 to 1.46) Blennerhassett, 200450 15 404.00 (101.00) 15 288.00 (124.00) 5.20 1.00 (0.23 to 1.76) Dean, 200067 5 80.20 (42.80) 4 88.40 (52.20) 1.75 –0.15 (–1.47 to 1.16) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 8.81 –0.06 (–0.65 to 0.53) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 4.01 –0.34 (–1.21 to 0.53) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 17.72 0.36 (–0.05 to 0.78)




FIGURE 23 Subgroup analysis: time since stroke – lower limb trials


38

FIGURE 24 Subgroup analysis: allocation concealment – lower limb trials

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 05 Subgroup analyses - lower limbOutcome: 04 Allocation concealment


01 AdequateAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 4.60 0.65 (–0.17 to 1.46) Blennerhassett, 200450 15 404.00 (101.00) 15 288.00 (124.00) 5.20 1.00 (0.23 to 1.76) Dean, 200067 5 80.20 (42.80) 4 88.40 (52.20) 1.75 –0.15 (–1.47 to 1.16) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 9.69 0.41 (–0.15 to 0.97) Kwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 11.09 0.64 (0.12 to 1.16) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 4.01 –0.34 (–1.21 to 0.53) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 17.72 0.36 (–0.05 to 0.78) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 16.85 –0.05 (–0.48 to 0.37)


02 Inadequate/unclearda Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 2.07 1.15 (–0.06, 2.36) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 10.40 0.11 (–0.43, 0.65) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 8.81 –0.06 (–0.65, 0.53) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 7.80 0.35 (–0.27, 0.98)

Subtotal (95% CI) 80 71 29.08 0.20 (–0.13, 0.52)Test for heterogeneity: �2 = 3.45, df = 3 (p = 0.33), I2 = 13.0%Test for overall effect: Z = 1.20 (p = 0.23)




39


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 05 Subgroup analyses – lower limbOutcome: 05 Comparison group


01 Usual care/alternative treatmentda Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 2.07 1.15 (–0.06 to 2.36) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 9.69 0.41 (–0.15 to 0.97) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 10.40 0.11 (–0.43 to 0.65) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 8.81 –0.06 (–0.65 to 0.53) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 7.80 0.35 (–0.27 to 0.98) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 16.85 –0.05 (–0.48 to 0.37)


02 Attention control/no treatmentAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 4.60 0.65 (–0.17 to 1.46) Blennerhassett, 200450 15 404.00 (101.00) 15 288.00 (124.00) 5.20 1.00 (0.23 to 1.76) Dean, 200067 5 80.20 (42.80) 4 88.40 (52.20) 1.75 –0.15 (–1.47 to 1.16) Kwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 11.09 0.64 (0.12 to 1.16) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 4.01 –0.34 (–1.21 to 0.53) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 17.72 0.36 (–0.05 to 0.78)




FIGURE 25 Subgroup analysis: type of comparison group – lower limb trials

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 05 Subgroup analyses – lower limbOutcome: 06 Trial size

–10 –5 0 5 10

0.0

0.2

0.4

0.6

0.8

SE (S

MD

)

SMD (fixed)

FIGURE 26 Funnel plot of precision versus effect size – lower limb trials


40

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 06 Global motor functionOutcome: 01 Global motor function scales


01 RTTLanghammer, 200068 29 37.00 (12.00) 24 33.00 (15.00) 29.14 0.29 (–0.25 to, 0.84) Van Vliet, 200570 42 7.85 (3.17) 43 6.69 (3.52) 46.96 0.34 (–0.09 to 0.77)


02 TMMacko, 200588 25 12.00 (0.30) 20 11.80 (0.40) 23.90 0.57 (–0.04 to 1.17)

Subtotal (95% CI) 25 20 23.90 0.57 (–0.04 to 1.17)Test for heterogeneity: not applicableTest for overall effect: Z = 1.84 (p = 0.07)

Total (95% CI) 96 87 100.00 0.38 (0.09 to 0.68)Test for heterogeneity: �2 = 0.49, df = 2 (p = 0.78), I2 = 0%Test for overall effect: Z = 2.55 (p = 0.01)


FIGURE 27 Global motor function

Global motor functionTwo RTT trials68,70 recruiting 181 participantsmeasured global motor function (Figure 27).Outcome data were available for 76% (n = 138).Three TM trials63,88,89 recruiting 105 participantsmeasured global motor function. Data were notsuitable for pooling from two trials.63,89 Standarddeviations were not given for one trial.63 Onetrial89 showed no significant difference in RMAscore for gross functions, but provided medianand IQR scores only: experimental group median11 (IQR 11–11), control group median 11 (IQR10–11).

The trials with outcome data suitable for poolingshowed a small to moderate effect size which wasstatistically significant (SMD 0.38, 95% CI 0.09 to 0.68).

Overall summary analysisThe primary analysis requires an overall estimateof the effect of RFTP on functional outcome(Figure 28). To gain an overall measure of RFTP as a preliminary basis for the economicanalysis, a summary plot was constructed, withsubcategories for the different intervention types. Some RTT trials included both upper

and lower limb intervention–control pairs. Toavoid their being included twice, the lower limbintervention–control group was chosen, as it isknown that lower limb treatment effects are morelikely. By privileging lower limb outcomes, thiswould have the effect of providing a slightlyinflated overall effect size.

Twenty-six intervention–control pairs with 876participants provided data suitable for pooling,with outcome data available for 88% (n = 775).Figure 28 shows that the overall treatment effect ofRFTP (with selection of lower limb functionaloutcomes in studies with multipleintervention–control pairs, or in studies with bothupper and lower limb intervention) was small tomoderate and statistically significant (SMD 0.34,95% CI 0.19 to 0.48).

If selection is based on upper limb functionaloutcomes from trials with multipleintervention–control pairs, or in studies with bothupper and lower limb intervention, the results aresmall and statistically significant (SMD 0.26, 95%CI 0.12 to 0.41), indicating that the findings arenot particularly sensitive to the choice of lowerlimb rather than upper limb outcomes.


41


Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 07 Summary analysis RFTPOutcome: 01 Functional outcomes (inc. lower limb)


01 Upper limb RTTTurton, 199069 12 13.83 (6.00) 10 12.25 (7.20) 2.95 0.23 (–0.61 to 1.07) Winstein, 200471 20 9.58 (5.70) 20 9.47 (6.30) 5.45 0.02 (–0.60 to 0.64) Yen, 200572 13 –2.57 (0.93) 17 –3.06 (1.54) 3.94 0.36 (–0.37 to 1.09)


02 Upper limb CIMTAlberts, 200483 5 –28.89 (24.80) 5 –25.02 (17.96) 1.35 –0.16 (–1.40 to 1.08) Atteya, 200479 2 52.00 (6.00) 2 51.50 (10.50) 0.54 0.03 (–1.94 to 2.00) Boake, 200684 9 0.08 (0.06) 7 0.04 (0.08) 2.04 0.55 (–0.47 to 1.56) Dromerick, 200081 11 52.80 (5.90) 9 44.30 (11.10) 2.37 0.95 (0.01 to 1.89) Page, 200180 2 53.00 (6.00) 2 51.00 (10.00) 0.47 0.14 (–1.97 to 2.25) Page, 200582 5 49.80 (3.27) 5 35.80 (3.56) 0.36 3.70 (1.28 to 6.12) Taub, 199373 4 8.10 (0.42) 5 6.90 (0.70) 0.71 1.79 (0.07 to 3.50) Wittenberg, 200374 9 7.54 (2.04) 7 5.85 (2.79) 2.00 0.67 (–0.35 to 1.69)


03 Lower limb RTTBlennerhassett, 200450 15 404.00 (101.00) 15 288.00 (124.00) 3.57 1.00 (0.23 to 1.76) Dean, 200067 5 80.20 (42.80) 4 88.40 (52.20) 1.20 –0.15 (–1.47 to 1.16) Kwakkel, 199953 26 0.65 (0.46) 34 0.37 (0.41) 7.62 0.64 (0.12 to 1.16) Langhammer, 200068 29 4.00 (1.60) 24 3.80 (2.00) 7.14 0.11 (–0.43 to 0.65) McClellan, 200478 12 4.30 (1.20) 9 4.70 (1.00) 2.75 –0.34 (–1.21 to 0.53) Salbach, 200451 44 0.78 (0.40) 47 0.64 (0.37) 12.17 0.36 (–0.05 to 0.78) Van Vliet, 200570 42 –12.19 (9.05) 43 –11.75 (7.88) 11.57 –0.05 (–0.48 to 0.37)


04 Lower limb TMAda, 200387 11 0.75 (0.26) 14 0.56 (0.30) 3.16 0.65 (–0.17 to 1.46) da Cunha, 200286 6 0.59 (0.29) 7 0.27 (0.23) 1.42 1.15 (–0.06 to 2.36) Eich, 200489 25 0.71 (0.30) 25 0.60 (0.22) 6.65 0.41 (–0.15 to 0.97) Macko, 200588 25 0.74 (0.30) 20 0.76 (0.36) 6.05 –0.06 (–0.65 to 0.53) Pohl, 200285 20 1.22 (0.74) 20 0.97 (0.64) 5.35 0.35 (–0.27 to 0.98)


05 Sitting and standing balance RTTde Sèze, 200176 10 3.30 (0.80) 10 3.00 (0.80) 2.67 0.36 (–0.53 to 1.24) Dean, 199766 10 12.00 (0.95) 9 10.80 (0.90) 2.08 1.24 (0.23 to 2.24) Howe, 200577 15 –1.90 (0.80) 18 –2.10 (0.70) 4.41 0.26 (–0.43 to 0.95)


Total (95% CI) 387 388 100.00 0.34 (0.19 to 0.48)Test for heterogeneity: �2 = 32.31, df = 25 (p = 0.15), I2 = 22.6%Test for overall effect: Z = 4.59 (p < 0.00001)


FIGURE 28 Overall impact of all forms of RFTP on functional outcome

Secondary outcomesADL functionFive RTT trials with seven intervention–controlpairs51,53,68,70,76 and recruiting a total of 399people used a measure of ADL, with data availablefor 81% (n = 325) (Figure 29). One CIMT trial81

recruiting 23 participants used a measure of ADL,with data available for 87% (n = 20). No TM trialsincluded ADL data. For RFTP overall, six trialsrecruiting 422 participants included a measure ofADL, with outcome data available for 82%(n = 345).

Results showed a small statistically significanteffect size (SMD 0.30, 95% CI 0.09 to 0.52).

Adverse effectsOne RTT trial of sit-to-stand training65 presenteddata for the number of falls: intervention group 3/25 (12%) versus control group 4/23

(17.4%), (odds ratio 0.65, 95% CI 0.13 to 3.27).No other trials presented data for adverse events, but two trials narratively reported noadverse effects.76,78 In one trial,51 intervention-related reasons for withdrawal that could beinterpreted as adverse events included one personout of 47 in a mobility-training group whoexperienced the onset of groin pain. Fourparticipants also fell during the mobilityintervention, but did not suffer injury andcontinued to participate in the group. Two fallsalso occurred during evaluation. No other trialsreported intervention-related reasons forwithdrawal.

Eight CIMT trials did not mention adverseevents,61,62,64,74,79,80,82,83 although four of thesetrials stated that participants were highly satisfiedwith the protocol.61,79,80,82 A further two trialsstated there were no adverse events,81,84 with onetrial author commenting further that there was no


42

Review: Repetitive functional task practice (including RTT, CIMT, TM)Comparison: 08 Secondary outcomesOutcome: 01 ADL function

Study Treatment Control SMD (fixed) Weight SMD (fixed)or subcategory N Mean (SD) N Mean (SD) 95% CI (%) (95% CI)

01 RTTde Sèze, 200176 10 99.40 (10.80) 10 101.70 (14.30) 5.98 –0.17 (–1.05 to 0.70) Kwakkel, 199953 54 16.96 (3.66) 34 14.00 (5.00) 23.67 0.69 (0.25 to 1.14) Langhammer, 200068 29 83.00 (25.00) 24 72.00 (34.00) 15.51 0.37 (–0.18 to 0.91) Salbach, 200451 40 93.40 (18.70) 39 90.20 (12.60) 23.62 0.20 (–0.24 to 0.64) Van Vliet, 200570 42 16.02 (3.90) 43 15.78 (4.40) 25.53 0.06 (–0.37 to 0.48)


02 TMSubtotal (95% CI) 0 0 Not estimableTest for heterogeneity: not applicableTest for overall effect: not applicable

03 CIMTDromerick, 200081 11 100.00 (1.10) 9 98.50 (3.77) 5.69 0.54 (–0.36 to 1.44)

Subtotal (95% CI) 11 9 5.69 0.54 (–0.36 to 1.44)Test for heterogeneity: not applicableTest for overall effect: Z = 1.18 (p = 0.24)

Total (95% CI) 186 159 100.00 0.30 ( 0.09 to 0.52)Test for heterogeneity: �2 = 5.98, df = 5 (p = 0.31), I2 = 16.3%Test for overall effect: Z = 2.77 (p = 0.006)


FIGURE 29 ADL function

evidence of excess disability associated withCIMT.81 In one trial, the first three participants toreceive restraint reported stiffness and discomforton the involved side half-way through the 2-weektreatment period.73 These effects were associatedwith overuse of the affected limb and led tomodification of the intervention protocol for thefourth participant, with motor demands increasingmore slowly. The fourth participant reported nomuscle soreness. There were no intervention-related reasons for withdrawal in any CIMT ormCIMT trial. Of the six TM trials, three reportedthat there were no adverse events.85,87,89 There areno reports of adverse events in three trials.63,86,88

None of the trials reported intervention-relatedreasons for withdrawal that could be interpreted asadverse events.

Sensitivity analysisA sensitivity analysis was undertaken to evaluatethe effect on upper limb outcomes of includingcross-over and quasi-randomised trials,63,69 findingno substantive difference between including (SMD0.24, 95% CI 0.06 to 0.42) and not including(SMD 0.24, 95% CI 0.05 to 0.43) these trials. Asensitivity analysis was also undertaken on lowerlimb trials to evaluate the effect of excludingstudies with more than 20% loss to follow-up (onlyone upper limb trial had loss to follow-up ofgreater than 20%). The effect of RFTP wassignificantly greater (p = 0.02) for trials with lossto follow-up of 20% or less (SMD 0.42, 95% CI0.22 to 0.63) than for trials with more than 20% loss to follow-up (SMD –0.06, 95% CI –0.39 to 0.27).


43


BackgroundThe systematic review identified studies that willpotentially alter patient outcomes by using RTT.There were three forms of therapy that had RTTas a major component: RTT, CIMT, and TM. Thetherapies will subsequently be referred to as RFTP.The economic modelling reported below wasdesigned to determine whether RFTP is cost-effective.

Study questionFrom the perspective of the NHS, is RFTP forstroke (in addition to usual care) cost-effective over3 years as judged by the incremental cost perquality-adjusted life-year (QALY) gained?

PerspectiveThe analyses performed took the perspective ofthe NHS and Personal Social Services (PSS). Thecost of stroke tends to be higher in the acute stageowing to the inpatient cost. Once a patient isdischarged from hospital, some of the costs will beborne by the NHS through provision of therapyand aids, and some will be borne by PSS throughprovision of support services. RFTP would takeplace after the acute stage of treatment and hencewill have no effect on these costs; therefore theyare not considered in this analysis.

Current treatmentAt present, the amount of physical therapy inputto post-stroke patients varies widely. In hospital,most patients receive physiotherapy andoccupational therapy. Once their care is transferredinto the community, the provision of therapies ismuch less structured. This means that it is difficultto define a standard package of physical therapyafter stroke. For this analysis usual care was basedon observations of a cohort of patients treated inthe NHS over time with the amount of physicaltherapy varying between patients. For the costanalysis the alternative treatments compared hereare usual care and usual care plus RFTP.

MethodsForm of evaluationA cost–utility approach was adopted, assessinggains in QALYs. The authors believe this to be the

most meaningful outcome measure on which tobase the economic evaluation. The nature of RFTPmeans that it will not directly prevent death,excluding a cost-effectiveness analysis of life-yearsgained. An alternative would be to express theeffects of RFTP in terms of a change in units ofsome measure of function; however, the authorsbelieve that this would be generally lessmeaningful than identifying a cost per QALYgained. The modelling is based over a 3-yearperiod.

Choice of RFTP interventionThe economic analysis is based around the threeforms of therapy described in the systematicreview: RTT, CIMT and TM.

Measures of benefitThe health outcome summary measure is thenumber of QALYs gained. A health outcome wasneeded that could be used across the three formsof therapy described.

The patient data setThe patient data set used for the modelling is alongitudinal data set that contains follow-up datafor a cohort of 539 stroke patients, consecutivelyidentified over a 6-month period in 1996, onstroke registers in two hospitals.134 Data werecollected on admission, at discharge, and at 3 and6 months, and subsequently 1, 2, and 3 years post-stroke. The data collected in hospital includedadmission and discharge dates, basicdemographics, stroke characteristics and scanresults. At each follow-up time patient status (aliveor dead) was identified, and data were collectedregarding residence, function, social service input,therapy input and aids provided. These patientsreceived usual stroke care and their 3-year datawere used as the baseline from which to judge thepotential impact of RFTP. The baselinecharacteristics of these patients can be seen inAppendix 7. The characteristics of the data setcompare favourably with the characteristics of thepatients in the included studies.

Assumptions about health outcomesThe Barthel Activities of Daily Living Index (BI)135

at 3 years post-stroke was used to define outcomegroups, which represented a range of disability


45


Chapter 5

Economic analysis

levels, and such that there were similar numbers ineach group. The choice of the BI was based on itswidespread usage as a global outcome in strokeresearch and because it had been mapped ontothe EuroQol-5 Dimensions (EQ-5D).136 The BI is aten-item scale ranging from 0 (dependent onothers for ADLs) to 20 (independent of others forADLs); the items measured include mobility,transfers, grooming and feeding. The number ofpatients in each Barthel category was 28 (BI � 10); 34 (BI = 11–14); 33 (BI = 15–17), 25(BI = 18 or 19) and 30 (BI = 20).

Efficacy of RFTPA range of different outcome measures was used inthe systematic review. For each outcome theeffectiveness of RFTP was expressed as the SMDwith associated 95% CI. The exception to this wasfor walking distance, which was expressed as WMD.However, for the economic analysis, the SMD willbe used. In the economic analysis the focus was onthose outcomes that showed a significant benefit ofRFTP and where there were at least 250 patients inthe analysis of efficacy, because the estimates basedon such a sample size would be more robust.However, walking speed was not included in theeconomic analysis because it was felt that walkingdistance was the more meaningful of these twooutcomes. To determine the potential impact ofRFTP, it was necessary to estimate how a change inthe SMD would equate to a change on the BI. Itwas estimated that a change in the SMD of 0.2 wasequivalent to a change in 1 point on the BI. Thiswas based on the following assumption: SMD =(treatment mean – control mean)/SD; a ‘typical SD’for the BI in a rehabilitation stroke populationmight be 5 units; therefore, an SMD of 0.2 wouldbe 1 Barthel unit.

Patient values preferencesA study was identified that examined theassociation between the BI and the EQ-5D.136

Although this study was based in TheNetherlands, the characteristics of the patientsincluded in the study are similar to thecharacteristics of those in the present patient dataset (at 6 months). The study136 suggested that 1point on the BI was equivalent to 0.05 of a QALY.

CostThe cost estimates reflect 2005/06 prices. Directcosts have been used, valued from an NHS public-sector perspective. The majority of the costs wereobtained from national figures.137 The exception tothis was the cost for aids, which were obtained froman NHS loan store. The assumptions made aboutthe costs for the RFTP studies are detailed below.

Assumptions about costingPatient data setThe analysis focused on the costs that were likelyto be influenced by RFTP, which included the costof services, therapy and aids post-discharge. Costswere estimated from the following inputs: homecare, meals on wheels, chiropody, physiotherapy,occupational therapy, day centre, day hospital,wheelchair, walking frame, walking stick, toilet seatraiser, chair raiser, bed raiser, toilet frame, trolleyand shopping trolley. The costs that were notincluded were GP attendance, readmission tohospital, clinic attendance or medication. Alsoexcluded were hospital costs for the index strokeand subsequent hotel costs for residence ininstitutions. Although RFTP is likely to promoteindependence in everyday activities, it is unlikelythat it would prevent admission to institutions.Moreover, there was some concern that high hotelcosts of institutions, or even readmissions tohospital, would unduly influence the model andthe authors wished to adopt a conservativeapproach to the estimates of cost-effectiveness.

RFTP studiesThe RFTP studies included in the review exhibitedsome diversity in when and where they wereperformed; some were more than 10 years old andmany were not based in the UK. To estimate thecosts of such studies, an assumption was made thatthey could be performed in a similar manner inthe UK. In addition, although the studies reportedon how much therapy was provided, there were nodata on the impact of the training on subsequentresource use. Therefore, it was assumed that theRFTP training did not result in additional costsowing to readmission or clinic attendance, causedby patients’ conditions worsening.

Because of the diverse nature of studies and thedata reported therein, a somewhat pragmaticapproach to costing methodology was taken. It wasassumed that for all studies the therapy staff costwas £40 per hour and that as well as the cost ofproviding the therapy there would be anadditional 20 hours of staff training per study. Thelack of CIMT data from the UK meant that anestimate of the cost of CIMT equipment had to bemade, of £100 per patient. The TM studies used acost of £25,000 for the equipment plus anadditional £1500 for installation. Within the RTTstudies there were miscellaneous costs for whichthe following cost estimates were made: Bon SaintCôme trunk control and retraining device £1000,videotaped instructions and telephone contacts£500, and instruction booklets £600. In onestudy67 a Kinetron machine was used in one

Economic analysis

46

workstation out of ten. The original cost of thismachine was approximately £32,000. Because this device is no longer manufactured and itcontributed only a small part to the RTT input, a cost of £1000 was attributed to this device. Forall equipment the one-off cost of purchase wasused and no assumptions were made about thelifetime of the equipment or how often it wasused.

For each trial an average cost per patient wascalculated based on staff time, equipment usedand number of patients randomised into thetrial. Subsequently, an average cost per therapy(i.e. RTT, CIMT and TM) was calculated basedon the average cost for each trial and thenumber of trials that contributed to that therapymodality. From this calculation the estimatedaverage cost per patient for the individualtherapies was £651 for RTT, £1773 for CIMTand £1870 for TM. Further estimates were thenmade of the average cost per patient forcombinations of therapy. To make the calculationfor combinations of therapy, an average cost forall trials in the relevant therapy modalities wasestimated. This resulted in an average cost perpatient of £1126 for RTT and CIMT combined,and £999 for RTT and TM combined. Theoverall average cost per person of RFTP (i.e.RTT, CIMT and TM combined) for the basemodel was estimated to be £1265.

Where outcome measures reflected all forms oftherapy (overall effect), the cost of theintervention was taken from the overall averagecost of RFTP. Where outcome measures reflectedtherapy focusing on the upper limb (arm functionand ADL), the cost of the intervention was takenfrom the average cost of RTT and CIMT. Whereoutcome measures reflected therapy focusing onthe lower limb (walking distance, functionalambulation and sit-to-stand), the cost of theintervention was taken from the average cost ofRTT and TM.

The modelGroups were identified, based on the BI at 3 yearsas described above. For each group the 3-year costwas estimated: the baseline cost in this analysis. Itwas then assumed that for an SMD of 0.2, therewould be a 1-point increase per patient on the BI,that the BI scores were evenly distributed withinthe groups and that the effect would bemaintained over 3 years. Using this assumption,the number of patients in each of the Barthelgroups was re-estimated. A new (3-year) cost wasthen calculated based on the new numbers in each

of the groups. The difference between the baselinecost and the new cost was considered to representthe impact of RFTP on cost. An average cost perpatient, reflecting the potential cost saving ofRFTP, was subsequently calculated, as £47,523/150= £316.82 (Appendix 8).

Adjustment for timing of costs and benefitsFor the base model the cost–utility of RFTP over3 years was assessed, and costs and effects werediscounted at an annual rate of 3.5%.

Allowances for uncertaintySeveral sensitivity analyses were performed toexplore the impact of varying certain parameterson the base model:

● RFTP efficacy● association between the SMD and the BI● association between the BI and the EQ-5D● cost of therapy● discount rates.

The relationship between the cost of RFTP per patient and the cost per QALY was alsoexplored.

ResultsFrom the systematic review, the overall effect sizefor RFTP was SMD 0.34 (95% CI 0.19 to 0.48).The following outcomes were based on studieswhere the combined sample size was more than250 patients, and revealed a significant effect ofRFTP.

● arm function: SMD 0.24 (95% CI 0.06 to 0.42)● ADL: SMD 0.30 (95% CI 0.09 to 0.52)● walking distance: SMD 0.45 (95% CI 0.20 to

0.70)● functional ambulation: SMD 0.28 (95% CI 0.05

to 0.51)● sit-to-stand: SMD 0.39 (95% CI 0.18 to 0.61).

The effect sizes for the five outcomes are based onRTT plus one of either CIMT or TM. For armfunction there was heterogeneity of effect betweenRTT, which was non significant (SMD 0.17, 95%CI –0.03 to 0.36) and CIMT, which was significant(SMD 0.77, 95% CI 0.26 to 1.29). However, theestimates of cost-effectiveness will use thecombined effect size.

Cost-effectiveness at 3 yearsIn the base-case analysis using the overall effectsize, the incremental cost-effectiveness ratio


47


(ICER) of RFTP was £10,870. Considering theefficacy and cost data for the outcome of armfunction, the cost per QALY gained was £15,185and when focusing on the efficacy and cost datafor ADLs the cost per QALY gained was £11,009.Based on efficacy and cost data for walkingdistance the cost per QALY gained was £4187, andfor functional ambulation and sit-to-stand the costper QALY gained was £10,187 and £5708,respectively. An intervention with an ICER of lessthan £20,000 is considered cost-effective138

(although interventions with an ICER of up to£30,000 may be considered cost-effective).Therefore, for all outcomes listed, the baseanalysis suggests that RFTP is cost-effective.Moreover, for walking distance and sit-to-stand,when the ICER was calculated using the lowerlimit of effectiveness from the 95% CI, both of theICER values were less than £20,000 (Appendix 9;Analysis 1).

Varying the association between theSMD and the BIIf a unit change of the SMD was related to asmaller change on the BI, the cost per QALYgained increases for all outcome measures. In thebase case the ratio of SMD to BI is 1:5. Even if thisratio is changed to 1:4, the ICER remains below£20,000 per QALY gained for all outcomes exceptfor arm function (£20,405). Sit-to-stand remainscost-effective at a ratio of 1:3 and walking distanceremains cost-effective at a ratio of 1:2 (Appendix 9; Analysis 2).

Varying the association between the BIand the EQ-5DIf a unit change on the BI is associated with asmaller change in the EQ-5D the ICER increasesfor all outcome measures. If a change in 1 pointon the BI is equivalent to only 0.04 of a QALY, alloutcomes continue to suggest that RFTP is costeffective (Appendix 9; Analysis 3).

Varying therapy costRFTP remains cost-effective on all outcomesexcept for arm function if the cost of therapy perhour is increased to £60. However, RFTP ismarginally cost-effective for arm function if thecost of therapy rises to £50 per hour (Appendix 9;Analysis 4).

Varying discount rate (cost)If the discount rate for costs is reduced from 3.5%to 0% then the ICER is reduced to £10,228 for theoverall outcome and, for example, £3545 forwalking distance and £14,543 for arm function. Ifthe discount rate for cost is increased from 3.5% to6%, RFTP is cost-effective on all outcomes(Appendix 9; Analysis 5).

Varying discount rate (outcome)If outcome is not discounted then the ICER isreduced to £9191 for the overall outcome and, forexample, £3186 for walking distance and £13,068for arm function. Even if the discount rate isincreased to 6%, RFTP is cost-effective on alloutcomes (Appendix 9; Analysis 6).

Economic analysis

48

0

5

10

15

20

25

30

35

435 740 1046 1352 1657 1963 2268 2574

Cost of RFTP (£)

Cos

t per

QA

LY g

aine

d (£

000s

)

FIGURE 30 Impact of varying the cost of RFTP on the cost per QALY gained

Association between cost of RFTP andcost per QALY gainedThe base costs were used to calculate how achange in the cost of RFTP per patient affects theICER per QALY gained. At an ICER of £20,000

per QALY gained the average cost of RFTP perpatient is £1963, which approximates to 49 hours’contact per patient, excluding equipment costs(Figure 30).


49


Summary of main resultsUpper limb function/sitting balanceIn total, 19 RFTP trials with 634 participantsmeasured arm or hand function. Eight were RTT trials with 467 participants. Of these, twotrials were whole therapy approaches,68,70

two trials were circuit-training approaches,50,52

three trials were functional task practice mixed in with other forms of upper limb exercise,53,69,71

and one trial was the intensive practicecomponent of constraint-induced movementtherapy, without the constraint.72 All of theseinterventions were delivered by a therapist, exceptfor one trial, which consisted of self-initiatedpractice in the home environment, using a bookletof exercises, after instruction by a therapist.69 Ofthe upper limb training trials, all but two52,72 werecarried out 0–6 months post-stroke. Five trials hada total training time of 20 hours or less,50,52,68,70,71

and three trials provided more than 20 hours’total training time.53,69,72 In two of the trialstraining time was additional.69,71 All eight trials with eight intervention–control pairs relevant to this review provided data suitable for pooling.

Eleven of the 19 trials measuring arm or handfunction were CIMT trials with 190 participants.Of these, five trials were of constraint-inducedtherapy,64,73,74,83,84 and six trials were of modifiedconstraint-induced therapy.61,62,79–81,139 All of theinterventions were delivered by a therapist, in one-to-one therapy. Three trials recruited within14 days post-stroke,81,82,84 four trials recruitedbetween 15 days and 6 months post-stroke,61,79,80,83 and four trials recruited after morethan 6 months post-stroke.64,73,74,139 All but twotrials81,82 had a total training time of over20 hours, with the majority providing between 30and 60 hours’ training. In four trials, training timewas additional to the amount of training timeprovided to the comparison group,74,79,80,82 whilein one trial it was unclear whether training timebetween experimental and comparison groups wasequivalent.73 Eight CIMT trials including 151participants in eight intervention–control pairsrelevant to this review provided data suitable forpooling. Pooled results show evidence of a smalleffect (SMD 0.24, 95% CI 0.06 to 0.42).

Seven RFTP trials with 357 participants measuredhand function. There was no statisticallysignificant pooled effect (SMD 0.19, 95% CI –0.03to 0.42).

Five trials (all RTT) with 256 participantsmeasured sitting balance/reach fromsitting.66,68,70,76,77 Of these, two trials were wholetherapy approaches,68,70 while the other threetrials specifically trained sitting balance or reachfrom sitting. All of the interventions were carriedout in the 0–6-month post-stroke period and weredelivered by a therapist in a hospital setting,except for one trial where the intervention wascarried out at home, with people more than 6months post-stroke.66 All of the interventions were20 hours’ training or less. There was no evidencefor impact on sitting balance/reach (SMD 0.23,95% CI –0.05 to 0.50).

Results at follow-up for all upper limb trials to6 months post-therapy were moderate andstatistically significant (SMD 0.55, 95% CI 0.06 to1.04). Evidence for a retention effect at more than6 months post-therapy was unclear (SMD –0.02 to95% CI –0.31 to 0.26), as it was noted that thetrials with 6–12-month follow-up also showed littleor no effect post-treatment.

Treatment effects for upper limb interventionswere not modified by amount/dosage of taskpractice or time since stroke, but were modified bytype of intervention, with RTT showing a smalleffect size just failing to reach significance (SMD0.17, 95% CI –0.03 to 0.36), and CIMT showing alarge, statistically significant effect (SMD 0.77,95% CI 0.26 to 1.29). However, tests for the effectof quality of allocation concealment and trial sizewere also significant, with all of the CIMT trials inboth the inadequate/unclear allocationconcealment subgroup and the small trialssubgroup. This suggests that the results for CIMTtrials could be influenced by quality issues andreporting bias.

Lower limb function/standing balanceSeventeen RFTP trials with 747 participantsmeasured some aspect of lower limb function orstanding balance/reach. Eleven were RTT trialswith 531 participants. Of these, one trial


51


Chapter 6

Discussion

specifically trained sit-to-stand movements,65 threetrials trained balance,66,76,77 two trials were wholetherapy approaches,68,70 three trials were circuit-training approaches,50,51,67 and two trials werelower limb task practice mixed in with other formsof mobility exercise.53,78 All interventions weredelivered by a therapist in a hospital orcommunity setting, except for one trial, which wasa home mobility programme, where theparticipant followed videotaped exercise withtherapist telephone contact and follow-up.78 Threeof the interventions were carried out more than6 months post-stroke.51,67,78 Two trials includedmore than 20 hours’ total practice time.53,78 All 11trials had data suitable for pooling. Six of the 17trials were TM trials with 229 participants. Ofthese, two trials were of unsupported TM87,88 andfour trials were of bodyweight supportedTM.63,85,86,89 All interventions were delivered by atherapist in a hospital setting. Two interventionswere carried out more than 6 months post-stroke.87,88 Only one of the trials included morethan 20 hours’ training time.88 Five trials with 199participants provided data suitable for pooling.

Results show large statistically significant effectsfor walking distance (WMD 50.05 m, 95% CI29.65 to 70.44 m; SMD 0.98, 95% CI 0.58 to1.39). In effect, participants in the experimentalgroups could walk on average 50 m further in6 minutes than the control groups. However, therewas some heterogeneity of treatment effects forwalking distance. There were also small statisticallysignificant effects for walking speed (SMD 0.28,95% CI 0.09 to 0.47) and functional ambulation(SMD 0.28, 95% CI 0.05 to 0.51). Trials of RTTshowed a small to moderate effect on sit-to-stand(standardised effect size 0.39, 95% CI 0.18 to0.61), but no evidence of effect on lower limbfunction measures (SMD 0.20, 95% CI –0.10 to0.50) or standing balance/reach (SMD 0.29, 95%CI, –0.06 to 0.63).

Retention effects on lower limbs were small tomoderate and statistically significant up to6 months post-therapy (SMD 0.37, 95% CI 0.05 to0.69), but there was no evidence of an effect atlater than 6 months (SMD –0.01, 95% CI –0.32 to0.29). This difference in retention effects wasborderline statistically significant (p = 0.09).However, few trials had long follow-up and thosethat did tended to show little or no effect post-treatment. Findings are also quite heterogeneous,which suggests that they are inconclusive.

Treatment effects were not modified by amount oftask practice, time since stroke or type of

intervention. Tests for the effect of quality ofallocation concealment were not statisticallysignificant. However, trials with high (>20%) lossto follow-up showed a significantly lower effect ofRFTP than did trials with lower (�20%) loss. Thisis an indication that any bias due to very highdropout is not in favour of RTT, although it wouldbe important in future trials to try to characterisedropouts and attempt to determine their effect onthe effectiveness of RFTP. There was someindication that treatment effects might bemodified by type of comparison group (p = 0.10),with usual care or alternative treatmentcomparisons showing a smaller treatment effectthan attention-control or no-treatmentcomparisons. This suggests that type ofcomparison group should be taken intoconsideration in future analyses.

Global motor functionTwo RTT trials68,70 and one TM trial with datasuitable for pooling88 recruiting 242 participantsin total measured global motor function. Datawere available for 76% (n = 183). There was apooled small to moderate, statistically significanteffect (SMD 0.38, 95% CI 0.09 to 0.68).

ADL functionFive RTT trials and one CIMT trial recruiting atotal of 422 participants used an ADL measure.Outcome data were available for 83% (n = 345).Overall results indicated a small effect size thatwas statistically significant (SMD 0.30, 95% CI0.09 to 0.52).

Adverse eventsTen out of the 31 trials included some report ofadverse events. Of these, seven reported noadverse events. One RTT trial reported a numberof falls occurring during the intervention orevaluation, none of which was serious,51 and oneCIMT trial reported that three participants hadsome discomfort in the unaffected limb, attributedto overuse during the constraint period.73 Theprotocol was subsequently modified. The only trialformally to measure adverse events did not showany significant difference in fall rates between theintervention and control groups.65

Overall completeness andapplicability of evidenceThe included trials were clinically diverse in termsof timing and focus, and there are gaps in theevidence base, particularly for people more than6 months post-stroke. Of the five trials that

Discussion

52

evaluated more than 20 hours’ therapy for upperlimbs in this participant group, only three hadusable data.72–74 Only one trial evaluated 20 hoursor less of upper limb therapy in people at least6 months post-stroke.52

There were only three trials that evaluated up to20 hours of lower limb therapy in people morethan 6 months post-stroke,51,67,87 and two trialsevaluating more than 20 hours of lower limbtherapy in this group.78,88

There have been more trials undertaken withpeople in the 0–6-month post-stroke period, buthere there are also gaps in the evidence base. Ofthe seven trials evaluating upper limb therapy ofmore than 20 hours’ duration, one had dataunsuitable for pooling. Of the remaining six, onewas quasi-experimental, and three had tenparticipants or fewer. While 11 trials haveevaluated 20 hours or less of lower limb therapy,only one trial has evaluated more than 20 hours oflower limb therapy in the 0–6-month post-strokeperiod.

Although it was not possible to classify studies intomore disabled or less disabled participantsubgroups, the tables of included studies(Appendixes 1–3) illustrate the wide range ofdisability levels of the participants in the includedtrials. However, many of the trials had inclusioncriteria specifying either minimum, or minimumand maximum levels of ability, motivation toparticipate and ability to understand instruction.The general evidence provided by the reviewtherefore appears to be widely applicable, perhapswith the exception of very severely disabled peoplewith little postural control or voluntary movement,those with very mild deficits and those with severecommunication difficulties who were excluded bytrialists. The exception to the above may be inCIMT studies, which identified criteria forminimum levels of finger and wrist extension.Treatment effects for CIMT may only beapplicable to a subgroup of participants with adegree of voluntary movement in the hand orarm. There is also the possibility that exclusioncriteria for maximum residual ability reducegeneralisability. The preliminary phase of a CIMTtrial reported that less than 5% of strokeadmissions qualified for randomisation.84

Trials were excluded where repetition appeared tobe primarily for strength or endurance training(e.g. cycling and gait training), or where the typeof training appeared divorced from the functionalaim (e.g. backward walking training, slot machines

and computer games). This may haveconsequences for the applicability of the evidence.The exclusion of trials of what could be defined as‘prefunctional’ types of movement will effectivelyhave excluded a group of people who cannot yetparticipate in functional movement. The sameconsequence applies to the exclusion of trials witha large element of passive and active assistedmovement.

In terms of generalisability to the UK, only RTT-type interventions have been evaluated in thissetting. One trial is a whole therapy approach,70

one trial evaluates balance training77 and onequasi-experimental trial evaluated self-deliveredexercise in the home environment.69 RTT has nottraditionally been a significant part of therapy afterstroke in the UK, which has been dominated bythe Bobath approach. This specifically minimisesrepetitive active movement, and relies ontherapist-guided restoration of ‘normal movement’patterns, rather than the functional but unnaturalones that could occur as a result of the morepragmatic approach within RFTP. Many studies inthis review were from outside the UK, or usedtherapy approaches that have been less popular,such as motor learning. While clinical experiencesuggests that modern UK stroke units have a moreeclectic therapy approach, it may take longer forthe results to change practice within the UK thanin countries that already use RFTP routinely.

There are no published trials of either CIMT orTM in a UK setting. While all of the interventionsare likely to be transferable in principle, theireffectiveness against other forms of care usual inthe UK and their acceptability in this healthcaresetting have not been tested. In particular, thefeasibility and acceptability of CIMT and circuit-training interventions delivered in communitysettings would need to be evaluated. The intensityof CIMT and the delivery of interventions afterthe normal rehabilitation period representadditional periods of treatment to those currentlyprovided.

The acceptability and safety of the different formsof RFTP to all types of participants are alsounclear. While there were few adverse effectsreported overall, the lack of formal reporting inmany trials means that this finding is inconclusive.Of the information provided about reasons fordropouts in the trials, the most frequent cause wasphysical illness, and only a very small proportionof those participating dropped out for physicalreasons that might have been related to theintervention. However, there was also a small


53


number of participants who were lost to follow-upfor reasons related to compliance or treatmentpreference. In the CIMT trials in particular,relatively long periods of constraint and intensiveperiods of practice with the affected limb have thepotential to impact on acceptability, althoughnone of the trials reported problems.

Information about recruitment was not oftenprovided, but of those that did provide information,a trial recruiting in hospital in the earlyrehabilitation period had relatively low numbers ofrefusal to participate (e.g. Kwakkel53 had four outof 101 people who did not give consent), while atrial recruiting in the community after rehabilitationhad high numbers of refusal of the intervention(e.g. Salbach51 had 73% refusal). It may be thatsome forms of intervention are less acceptable, orthat interventions only appeal to a subset of strokesurvivors, particularly if travel is involved.

No conclusions could be reached about the impactof numbers of repetitions as a measure of theintensity of practice, as this information was onlyprovided in one or two trials. The amount of taskpractice is therefore a measure of the duration (i.e.time spent).

By virtue of its focus on functional movement, thisreview does not consider the evidence forelectronic forms of delivery of repetitivemovement such as robotics or computer-mediatedpractice. The authors were also unable tocomment on the implications of different sites oftreatment, therapist-delivered versus self-deliveredinterventions or group versus individual delivery,as there were too few trials for comparison.However, the presence of two trials involving self-delivery in the home environment and four trialsinvolving group delivery of task-specific trainingsuggests that these modes of delivery are feasible,and further ongoing trials should provide moreinformation. The studies that collectedinformation showed generally high levels ofsatisfaction with the programme. Attendance levelsat community programmes were also very good,suggesting that training programmes were wellreceived by those who chose to participate.

Quality of evidenceFor lower limb trials, Salbach and colleagues51

estimate that a sample size of 60 would berequired to detect a group difference of 28 m inaverage change in the 6WMT (type I error = 0.05,type II error = 0.10, expected dropout rate of

10%) based on the results of a pilot study67 whichrecruited 91 patients. Five of the 17 trials of lowerlimb interventions had sample sizes above 60 (fourRTT, one TM). For upper limb trials, the sameresearch group estimated that a sample size of 60participants was required to detect a clinicallymeaningful difference for the BBT.52 Of the 19trials of upper limb interventions, five trials hadsample sizes greater than 60 (five RTT). No CIMTtrial had more than 25 participants.

Two-thirds of RTT trials had adequate allocationconcealment and most of the trials stated thatblinded independent assessors were used. Therapytime was non-equivalent in two trials. For TM, two out of five trials with data included in themeta-analysis described adequate allocationconcealment methods, blinding of outcomeassessors was attempted in three trials, and alltrials provided equivalent therapy time toexperimental and comparison groups. Only fourtrials (two RTT, one CIMT, one TM) had over 20%dropout. For CIMT, three trials provided dataunsuitable for pooling; and all of the CIMT trialshad unclear allocation concealment.

The overall quality of the included trials providesa degree of confidence in the pooled results forRTT and TM, although there were only five TMtrials with data suitable for pooling from 199participants. The results for CIMT have to beconsidered in the light of small size of the trials,together with the confounding effects of theselection of trials with non-equivalent therapy timein the experimental and control groups (i.e. no-treatment control groups). A number of CIMTtrials did include comparison groups who receivedtherapy with no constraint, but these wereintervention–control pairs that could not be usedfor this review as the comparison was alsorepetitive task practice. The use of no-treatmentcontrol comparison may lead to a differentconclusion from other reviews of CIMT. Three outof eight included CIMT trials compared theintervention against no therapy. This may explainthe large effect of the intervention on upper limbfunction, as the differential between these groupsmay be larger than would be expected bycomparing the intervention against usual care oranother intervention, such as bimanual training.

Non-reporting bias also has to be considered.Subgroup analysis for trial size and the funnel plotfor upper limb interventions suggested greatereffects for smaller trials, suggesting an absence ofsmall, negative trials. This might have led to smallor negative effect estimates not being included

Discussion

54

and, in particular, an ‘unbalancing’ due to the fourtrials with large effects.

Potential limitations in the reviewprocessThis review combined the results of trials of RTTwith results from trials of enhanced forms of RTT,namely TM and CIMT. Care must therefore betaken regarding attribution of pooled treatmenteffects solely to the task practice component. Forthis reason, both separate and pooled results areshown. This study also generally used fixed-effectanalyses, which some might criticise owing to thepresence of some clinical heterogeneity in thetreatments and trials combined. Many of the trialsoriginally reported data in median andinterquartile ranges. In addition, many of theoutcomes are measured on scales that are shortand bounded, where the use of means andstandard deviations can be misleading. However,the effect size for RFTP is greatest for walkingdistance, which is a truly quantitative measure. Itis also relatively consistent across other outcomes,including walking speed which is, like walkingdistance, a continuous measure with essentially nostrict upper bound. This would tend to indicatethat the use of means and standard deviations forshort, bounded, ordinal scales has notsubstantively affected the conclusions, at least forthe lower limb outcomes.

The major focus in this review was impact on task-specific function. In practice, a large number ofstudies was excluded on the basis that thereviewers did not judge the outcomes to befunctional or the intervention to be task specific.Studies were also included where the reviewers’interpretation of the intervention was thatrepetition of functional movement was a majormechanism of action, even when this was notexplicitly stated by the authors (e.g. de Sèze76).Whether balance training is truly ‘functional’ isalso a matter of interpretation, but its inclusionwas felt to be important so as not unintentionallyto exclude RFTP training for people with moresevere levels of disability, where the recovery ofbalance is a prerequisite of functional activity.

As CIMT and TM trials were sourced fromexisting reviews, trials with alternative or no-treatment comparisons were included. Two TMtrials included comparisons against alternativeforms of treatment, which is potentially likely tohave resulted in lower estimates of effect thancomparison against usual care; subgroup analysis

for type of comparison group was close tostatistical significance, with a lower effect estimatefor the usual care/alternative treatment than forthe attention-control/no-treatment comparisonsubgroup. Three CIMT trials included comparisonagainst a no-treatment group, with the potential toresult in greater estimates of effect thancomparison against usual care. However, analysisof the impact of comparison group provided noevidence of any difference between the effects inthe two subgroups.

Agreement or disagreement withprevious reviewsAll of the studies included in this review have acore component of repeated, task-specific practice,but they are also very diverse. The CIMT and TMcomponents of the review were subsets of existingreviews.20,23 While combining the results from sucha diverse group of studies has potential dangers,the summary finding of a pooled moderate impacton functional ability (SMD 0.34, 95% CI 0.19 to0.48) supports previous authors who havesuggested a focus on the efficacy of task-specifictreatments.14,34

Whether functional gain can be attributed to taskspecificity or repeated practice is unclear and anyattribution is highly speculative. This review didnot find a significant difference in treatment effectdependent on the amount of practice for lowerlimb interventions. Conversely, the greatest gainsfor lower limbs were seen in walking distance,while gains for walking speed were of a smallermagnitude, suggesting that an endurance trainingelement contained in repeated motor practicemakes some contribution to impact. In addition,this review could not take into account thepretherapy ability levels of the participants, and itmay also be that the mechanisms of repetition andtask specificity have different roles at differentstages of recovery. Repetition is the majormechanism of action of robotics, and a recentreview has shown impact at the level ofimpairment, but not for functional ability.36

For upper limb interventions, five out of eightCIMT studies with data suitable for poolingprovided more than 20 hours of therapy. Althoughthe overall difference between smaller and largeramounts of task practice was not statisticallysignificant, there was potential evidence of a trend(p = 0.18) towards larger effect sizes for more than20 hours’ practice (SMD 0.42, 95% CI 0.10 to0.75) versus 0–20 hours’ practice (SMD 0.22,


55


95% CI –0.12 to 0.57) for arm function. Thisfinding is consistent with other reviews that havesuggested that upper limb recovery may requireintensive intervention.16

Overall for RFTP, there were small to moderateeffects for ADLs and global motor function, and asmall effect on functional ambulation classification.Even though the amount of change for theseoutcomes is modest, the clinical benefits are likelyto be meaningful in relation to quality of life.136

In those studies that did show a benefit andprovided later assessments, improvements at theend of training were not evident at the later stage.It is unclear from this review whether this isrelated to characteristics of the participants, theintensity of training or the degree of improvementrequired before detectable change was noted.

Evidence from RFTP interventions does notconcur with the suggestion that earlier provisionof treatment results in greater functionalimprovement, as treatment effects were notmodified by time since stroke. Improvement infunction was possible even in the later stages ofrecovery.139 A recent review concluded that it wassurprising that CIMT should work in the chronicphase of stroke, but agreed that the trial andlaboratory evidence suggested that this was thecase. However, they concluded that teachingbimanual activities rather than constraint mightcreate the same outcome.140

The authors were unable to come to anyconclusions about the previously identifieddose–response relationship between amount oftherapy and improved outcome,15 but the resultsfrom subgroup analysis suggest this as a priorityfor further research.

Economic analysisThe base-case analysis suggested that RFTP iscost-effective. This analysis is based on a numberof assumptions about therapeutic inputs that hadto be made because of the paucity of economicdata associated with the individual trials.Furthermore, in calculating cost-effectiveness theauthors had to estimate the potential impact ofRFTP on pre-existing longitudinal data. To allowfor these assumptions their magnitude was variedin sensitivity analysis. The sensitivity analysestended to find that RFTP was cost-effectiveoverall, and in particular on the outcomemeasures of walking distance and sit-to-stand.

The existing data set used to estimate the impactof RFTP was appropriate to the study’s needsbecause it reflected the normal course of recoveryafter stroke in a cohort of patients that had beensystematically identified. The disadvantage ofusing this data set was that the analysis was basedaround predetermined data, which did notspecifically lend itself to assessing the impact ofRFTP. However, the existing data did allowreasonable assumptions to be made about howRFTP may have affected outcomes and costs, andmeant that the research team did not have to waitfor 3 years to collect data on resource use andoutcomes in a UK post-stroke population.

One of the costs from the existing data set thatcould have been included was the cost incurredthrough residence in institutions. These costs tendto be high and would most likely be important inpatients with more severe disability. Not includingthe cost of residence in institutions means that thecosts of these severe states are likely to have beenunderestimated. Evidence from this reviewsuggested that RFTP reduced disability. Therefore,by excluding the high severe state costs due toinstitutionalisation, the review is likely to haveunderestimated the potential savings andconsequently the cost-effectiveness of RFTP.

Translation of the potential effect of RFTP on thepatients in the data set made an assumption aboutthe relationship between the effect size and the BI.This assumption was based around the size of thestandard deviation in rehabilitation trials. Theassumption that the standard deviation was about5 is consistent with published data.53,68,141–143

Furthermore, in this systematic review the effect ofRFTP on ADLs resulted in an SMD of 0.30. Thiswould suggest that the assumption about therelationship between the SMD and the BI was, ifanything, a conservative one, therefore, it is likelythat the cost-effectiveness of RFTP has beenunderestimated.

A further assumption was then made about therelationship between the BI and the EQ-5D. Thisassumption allowed the calculation of ICER perQALY gained. The systematic review showed thatnone of the studies used the EQ-5D and only one65

used a measure of quality of life (not includinghealth status) as an outcome. It therefore seemedunreasonable to generate an effect size for qualityof life, based on one study. Consequently, thismakes it difficult to compare directly therelationship between RFTP and quality of life, andsuggests that future RFTP studies should use aquality of life measure as an outcome.

Discussion

56

To test the assumptions that were made about therelationships between the effect size, the BI andQALYs, sensitivity analyses were performed. Theseanalyses explored what would happen if theimpact of RFTP on outcome was less than in thebase model. For the assumptions made, the costper QALY gained was more sensitive to variationsbetween the effect size and the BI than tovariations between the BI and the EQ-5D. Overall,the cost per QALY gained for walking distance didnot rise much above £20,000, except for one ofthe assumptions made in the sensitivity analysis.This means that even when the assumptions arestacked against RFTP, this intervention stilldemonstrates cost-effectiveness.

The estimation of the cost of providing RFTP inthe trials was complicated for a number of reasons.Many of the trials were not conducted in the UK,so it was difficult to cost some items of equipment.The grade of staff performing the training was notoften reported; this was further compounded bythe trials not being UK based. In addition,because the individual trials had not specificallyrecorded resource-use data, no information wasavailable about the impact of RFTP on futuretherapy, support services or provision of mobilityaids. Moreover, there were no consistent dataabout adverse events, which would have thepotential to increase costs through patientsattending clinics or being admitted to hospital. Inone study87 some patients were transported tohospital at the expense of the researcher; for allother studies post discharge, patients made theirown way to clinics. It is likely that this cost wasincurred because the intervention was being usedin the context of a research study rather thannormal clinical practice. Furthermore, if RFTP wasintroduced as a rehabilitation therapy it is unlikelythat it would incur major direct costs for patienttransport. For this reason the cost of this transportwas not included as a source of cost for RFTP.Given the lack of associated economic data, thecosting of RFTP was a fair reflection of the directcosts incurred by this intervention.

The systematic review revealed the complex natureof RFTP in terms of what is being delivered as wellas when (after stroke), where and how it isdelivered. This provided a challenge formodelling the cost-effectiveness of thisintervention. It was therefore decided that ratherthan develop a complex model, the modellingshould be kept simple and transparent. As a resultof this decision the reviewers considered howRFTP might influence 3-year costs by looking at

the potential impact on the 3-year BI. It is self-evident that to have a 3-year BI a patient must bealive; this meant that the estimate did not takeinto account the possibility that a patient who hadRFTP died within the 3-year period, which mayhave impacted on the cost. A further analysis wassubsequently performed that examined how theimpact of RFTP on the 3-month BI would affectcost at 3 years, i.e. this analysis included peoplealive at 3 months, some of whom had died by3 years. It was found that the magnitude of thepotential cost saving was similar whether the 3-month or 3-year BI scores were used.

To make the modelling feasible a number of otherassumptions had to be made. The costing of usualcare went from discharge to 3 years post-stroke,which makes the assumption that the cost over3 years would be the same whenever RFTP wasstarted. Another related assumption was that theeffect of RFTP is constant over time. It isacknowledged that these assumptions are rathergeneral. However, given the complex nature of theintervention, described in the previous paragraph,and the lack of economic data about theintervention and its likely impact on cost, theauthors believe that these assumptions provided areasonable estimate.

In summary, the systematic review was able tocombine the results from different studies andprovide an overall effect size for RFTP. The lack ofeconomic data associated with the existing studiesmeant that an economic model had to bedeveloped to estimate the potential cost-effectiveness of RFTP. The modelling had theadvantage of using effect sizes from a largesample; the disadvantage was that it relied on pre-existing data. This meant that the modelling thatwas performed relied on a number of assumptionsabout costs and effectiveness. The assumptionsthat were made were generally weighted againstRFTP. Despite these assumptions, RFTPdemonstrated that it was cost-effective.

To combat the issues around measures of costs andeffectiveness, future trials need to be sufficientlypowered to detect the effectiveness of bothfunctional and economic outcomes. Furthermore,trials need to decide a priori what resources tocost; because the effects of RFTP are likely toextend beyond its impact on direct costs futuretrials should also consider indirect and possiblyintangible costs. Economic analysis would befacilitated further by including quality of life as anoutcome measure.


57


Implications for practiceThe results of this review provide sufficientevidence to validate the general principle thatRFTP for lower limbs can result in functional gain,when compared against other forms of usual careor attention-control. While functional gain overallis modest, impact does appear to be of a clinicallymeaningful magnitude. It is, however, unclear asto whether effects are sustained over 6 monthspost-therapy.

There is insufficient evidence to make anyrecommendations for upper limb interventions.Although effects of RFTP on arm function werestatistically significant, the variable quality of theevidence and the clinical heterogeneity of theinterventions mean that further research is neededbefore specific recommendations can be made.

Some caution is needed in interpreting the lack ofevidence for adverse effects, as few trialsspecifically monitored these as an outcome. Iftask-specific training is used in clinical practice,adverse effects should be monitored.

While the overall effectiveness of RFTP isrelatively modest, this sort of intervention appearsto be cost-effective, primarily because theintervention itself has a relatively small cost.

Recommendations for futureresearchThere is a large number of ongoing trials in thisarea. The first recommendation is that this review isupdated within 2 years. The updated review shouldalso consider any potential interaction effectsbetween type of training, amount of task practiceand stroke-related impairments. This reviewfocused initially on the evidence for the efficacy ofRFTP versus usual care or attention-controlcomparisons. Any future review should includecomparison of RFTP against alternative forms oftherapy, such as strength and stamina training.

Further well-designed, adequately powered trialsevaluating the impact of upper limb interventions,and in particular CIMT, are needed. One trial waspublished shortly after the closing date for this

review, and should provide more information onefficacy. Future CIMT trials should also target andmeasure hand function.

There were insufficient trials included in thisreview to evaluate the efficacy and cost-effectiveness of different intervention deliverymethods for RFTP, such as group training, deliveryby assistants or practice in the home environment.Further research should address practical and cost-effective ways of delivering such interventions. Inparticular, the acceptability of CIMT and of circuit-training-type interventions delivered in communitysettings would need to be evaluated.

The existence of retention effects up to 6 monthspost-therapy is a promising finding, and furtherresearch should be directed towards evaluatinglong-term functional gain by routine inclusion oflonger follow-up periods of 1 or possibly 2 years.Suitable methods to maintain functional gainshould also be investigated.

Future trials need to be designed to take accountof the following:

● This study was unable to investigate the impactof training on people with different levels of pre-intervention disability, because of the widerange of baseline measures used. Analyses of thistype would be facilitated by the inclusion in trialsof baseline data using a common measure suchas the BI, which can be related to populationnorms dependent on time since stroke.

● Monitoring and reporting of adverse effectsshould be explicitly included.

● When designing future trials of any type ofRFTP it is critical that the study is powered todetect not only a clinical effect, but also whetherit is cost-effective.

● Future studies need to identify clearly whichresources are likely to be affected by RFTP andensure that they are included in any economicanalysis. In addition, studies should include aquality of life measure as one of the outcomesto facilitate economic analysis.

● The benefit of RFTP may not be clear fromdirect costs alone; therefore, future studiesshould include indirect costs and give someconsideration to the inclusion of intangible costs.


59


Chapter 7

Conclusions

We wish to acknowledge the help and supportof Brenda Thomas and Hazel Fraser from

the Cochrane Stroke Group, for their help in thereview process. We would also like to thank all ofthe trial authors who kindly replied to ourrequests for information, and our translators: Jie Shen, Dr Qinghai Huang, Hua Zhang,Gediminas Juaga and Luyan Fang.

Contribution of authorsBeverley French (Senior Research Fellow,University of Central Lancashire) led thesystematic review, including coordinating thereview process, managing searching and main datainput and drafting the final report. MichaelLeathley (Postdoctoral Research Fellow, Universityof Central Lancashire) led the cost-effectivenesscomponent of the review, and contributed to dataextraction and appraisal for the review.Christopher Sutton (Senior Lecturer, University ofCentral Lancashire) provided statistical expertiseto the review and cost-effectiveness analysis.Joanna McAdam (Research Coordinator,University of Central Lancashire) managed the

TM component of the review, was responsible foradministration of the review process andcontributed to data extraction and appraisal andto drafting the final report. Lois Thomas (SeniorResearch Fellow, University of Central Lancashire)managed the CIMT component of the review andcontributed to data extraction and appraisal, andto drafting the final report. Anne Forster (Reader,Elderly Care, University of Leeds), PeterLanghorne (Professor of Stroke Care, University ofGlasgow) and Christopher Price (Clinical SeniorLecturer/Consultant Physician, NorthumbriaHealthcare NHS Trust) directed the review focusand quality, and undertook critical reading ofoutputs. Andrew Walker (Senior Lecturer inHealth Economics, University of Glasgow) directedthe focus and quality of the cost-effectivenesscomponent of the review. Caroline Watkins(Professor of Stroke and Older People’s Care,University of Central Lancashire) was leadinvestigator for the project, responsible formanaging the overall review process and quality ofoutputs.


61


Acknowledgements

1. Department of Health. National service frameworkfor older people. London: Department of Health;2001.

2. Adamson J, Beswick A, Ebrahim S. Is stroke themost common cause of disability? J StrokeCerebrovasc Dis 2004;13:171–7.

3. Wolfe CD. The impact of stroke. Br Med Bull2000;56:275–86.

4. Lawrence ES, Coshall C, Dundas R, Stewart J,Rudd AG, Howard R. Estimates of the prevalenceof acute stroke impairments and disability in amulti-ethnic population. Stroke 2001;32:1279–84.

5. Wade DT, Langton-Hewer R. Functional abilitiesafter stroke: measurement, natural history andprognosis. J Neurol Neurosurg Psychiatry 1987;50:177–82.

6. Wade DT, Langton-Hewer R, Wood VA, Skilbeck CE, Ismail HM. The hemiplegic armafter stroke: measurement and recovery. J NeurolNeurosurg Psychiatry 1983;46:521–4.

7. Heller A, Wade DT, Wood VA, Sunderland A,Hewer RL, Ward E. Arm function after stroke:measurement and recovery over the first threemonths. J Neurol Neurosurg Psychiatry 1987;50:714–19.

8. Sunderland A, Tinson D, Bradley L, Hewer RL.Arm function after stroke. An evaluation of gripstrength as a measure of recovery and a prognosticindicator. J Neurol Neurosurg Psychiatry1989;52:1267–72.

9. Nakayama H, Jorgensen HS, Raaschou HO,Olsen TS. Recovery of upper extremity function instroke patients: the Copenhagen study. Arch PhysMed Rehabil 1994;75:852–7.

10. Lord S, McPherson K, McNaughton H, Rochester L, Weatherall M. Communityambulation after stroke: how important andobtainable is it and what measures appearpredictive? Arch Phys Med Rehabil 2004;85:234–9.

11. Hendricks HT, van Limbeek J, Geurts AC, Zwarts MJ. Motor recovery after stroke: asystematic review of the literature. Arch Phys MedRehabil 2002;83:1629–37.

12. Intercollegiate Working Party for Stroke. NationalClinical Guidelines for Stroke. London: Royal Collegeof Physicians; 2004.

13. Youman P, Wilson K, Harraf F, Kalra L. The economic burden of stroke in the United

Kingdom. Pharmacoeconomics 2003;21(Suppl 1):43–50.

14. Van Peppen RPS, Kwakkel G, Wood-Dauphinee S,Hendriks HJM, van der Wees PJ, Dekker J. Theimpact of physical therapy on functional outcomesafter stroke: what’s the evidence? Clin Rehabil2004;18:833–62.

15. Kwakkel G, van Peppen R, Wagenaar RC,Dauphinee SW, Richards C, Ashburn A. Effects ofaugmented exercise therapy time after stroke – a meta-analysis. Stroke 2004;35:2529–36.

16. Van der Lee JH, Snels IA, Beckerman H,Lankhorst GJ, Wagenaar RC, Bouter LM. Exercise therapy for arm function in strokepatients: a systematic review of randomizedcontrolled trials. Clin Rehabil 2001;15:20–31.

17. Dobkin BH. Strategies for stroke rehabilitation.Lancet Neurol 2004;3:528–36.

18. Carr J, Shepherd R. A motor relearning programmefor stroke. Oxford: Butterworth Heinemann; 1987.

19. Wolf SL, Blanton S, Baer H, Breshears J, Butler AJ. Repetitive task practice: a critical reviewof constraint-induced movement therapy in stroke.Neurologist 2002;8:325–38.

20. Moseley AM, Stark A, Cameron ID, Pollock A.Treadmill training and body weight support forwalking after stroke. Cochrane Database Syst Rev2005 (Issue 4). Art. No. CD002840. DOI10.1002/14651858.

21. Hesse S. Rehabilitation of gait after stroke –evaluation, principles of therapy, novel treatmentapproaches, and assistive devices. Top GeriatrRehabil 2003;19:109–26.

22. Volpe BT, Krebs HI, Hogan N. Is robot-aidedsensorimotor training in stroke rehabilitation arealistic option? Curr Opin Neurol 2001;14:745–52.

23. Hakkenes S, Keating JL. Constraint-inducedmovement therapy following stroke: a systematicreview of randomised controlled trials. Aust JPhysiother 2005;51:221–31.

24. Barreca S, Wolf SL, Fasoli S, Bohannon R.Treatment interventions for the paretic limb ofstroke survivors: a critical review. NeurorehabilNeural Repair 2003;17:220–6.

25. Cifu DX, Stewart DG. Factors affecting functionaloutcome after stroke: a critical review ofrehabilitation interventions. Arch Phys Med Rehabil1999;80:S35–9.


63


References

26. Drukker M, de Bie RA, van Rossum E. The effectsof exercise training in institutionalised elderlypeople: a systematic review. Phys Ther Rev2001;6:273–85.

27. Duncan PW. Synthesis of intervention trials toimprove motor recovery following stroke. TopStroke Rehabil 1997;3:1–20.

28. Hiraoka K. Rehabilitation effort to improve upperextremity function in post-stroke patients: a meta-analysis. J Phys Ther Sci 2001;13:5–9.

29. Kwakkel G, Wagenaar RC, Koelman TW,Lankhorst GJ, Koetsier JC. Effects of intensity ofrehabilitation after stroke. Stroke 1997;28:1550–6.

30. Legg L, Drummond AE, Langhorne P.Occupational therapy for patients with problemsin activities of daily living after stroke. CochraneDatabase Syst Rev 2006 (Issue 4). Art. No.CD003585. DOI 10.1002/14651858.

31. Ma H, Trombly CA. A synthesis of the effects ofoccupational therapy for persons with stroke, Part II: Remediation of impairment. Am J OccupTher 2002;56:260–74.

32. Meek C, Pollock A, Potter J, Langhorne P.A systematic review of exercise trials post-stroke.Clin Rehabil 2003;17:6–13.

33. Ottenbacher KJ, Jannell S. The results of clinicaltrials in stroke rehabilitation research. Arch Neurol1993;50:37–44.

34. Pollock A, Baer G, Pomeroy V, Langhorne P.Physiotherapy treatment approaches for therecovery of postural control and lower limbfunction following stroke. Cochrane Database SystRev 2003 (Issue 2). Art. No. CD001920. DOI10.1002/14651858.

35. OST (Outpatient Service Trialists). Therapy basedrehabilitation services for stroke patients at home.Cochrane Database Syst Rev 2003 (Issue 1). Art. No.CD002925. DOI 10.1002/14651858.

36. Prange GB, Jannink MJA, Groothuis-Oudshoorn CGM, Hermens HJ,Ijzerman M. Systematic review of the effect ofrobot-aided therapy on recovery of thehemiparetic arm after stroke. J Rehabil Res Dev2006;43:171–84.

37. Saunders DH, Greig CA, Young A, Mead GE.Physical fitness training for stroke patients.Cochrane Database Syst Rev 2004 (Issue 1). Art. No.CD003316. DOI 10.1002/14651858.

38. Smidt N, de Vet HCW, Bouter LM, Dekker J.Effectiveness of exercise therapy: a best-evidencesummary of systematic reviews. Aust J Physiother2005;51:71–85.

39. Steultjens EMJ, Dekker J, Bouter LM, van de Nes JCM, Cup EHC, van den Ende CHM.Occupational therapy for stroke patients: a systematic review. Stroke 2003;34:676–87.

40. Steultjens EMJ, Dekker J, Bouter LM, Leemrijse CJ, van den Ende CHM. Evidence ofthe efficacy of occupational therapy in differentconditions: an overview of systematic reviews. Clin Rehabil 2005;19:247–54.

41. Stewart KC, Cauraugh JH, Summers JJ. Bilateralmovement training and stroke rehabilitation. J Neurol Sci 2006;244:89–95.

42. Teasell RW, Bhogal SK, Foley NC, Speechley MR.Gait retraining post stroke. Top Stroke Rehabil2003;10:34–65.

43. Trombly CA, Ma H. A synthesis of the effects ofoccupational therapy for persons with stroke, Part1: Restoration of roles, tasks, and activities. Am JOccup Ther 2002;56:250–9.

44. Van Dijk H, Hermens HJ. Distance training forthe restoration of motor function. J Telemed Telecare2004;10:63–71.

45. Walker MF, Leonardi-Bee J, Bath P, Langhorne P,Dewey M, Corr S. Individual patient data meta-analysis of randomized controlled trials ofcommunity occupational therapy for strokepatients. Stroke 2004;35:2226–32.

46. Bayona NA, Bitensky J, Salter K, Teasell R. The role of task specific training in rehabilitationtherapies. Top Stroke Rehabil 2005;12(3):58–65.

47. Carr J, Shepherd R. Neurological rehabilitation:optimizing motor performance. Edinburgh:Butterworth Heinemann; 1998.

48. Carr JH, Shepherd RB. Movement science:foundations of physical therapy in rehabilitation.Gaithersburg, MD: Aspen; 2000.

49. World Health Organisation Task Force on Strokeand Other Cerebrovascular Disorders.Recommendations on stroke prevention, diagnosis,and therapy: report of the WHO Task Force onStroke and Other Cerebrovascular Disorders. Stroke1989;20:1407–31.

50. Blennerhassett J, Dite W. Additional task-relatedpractice improves mobility and upper limbfunction early after stroke: a randomisedcontrolled trial. Aust J Physiother 2004;50:219–24.

51. Salbach NM, Mayo NE, Wood-Dauphinee S,Hanley JA, Richards CL, Côte R. A task-orientatedintervention enhances walking distance and speedin the first year post stroke: a randomizedcontrolled trial. Clin Rehabil 2004;18:509–19.

52. Higgins J, Salbach NM, Wood-Dauphinee S,Richards CL, Côté R, Mayo NE. The effect of atask oriented intervention on arm function inpeople with stroke: a randomized controlled trial.Clin Rehabil 2006;20:296–310.

53. Kwakkel G, Wagenaar RC, Twisk JWR, Langhorst GJ, Koetsier JC. Intensity of leg andarm training after primary middle-cerebral-arterystroke: a randomised trial. Lancet 1999;354:191–6.

References

64

54. Deeks JJ, Altman DG, Bradburn MJ. Statisticalmethods for examining heterogeneity andcombining results from several studies in meta-analysis. In Egger M, Davey Smith G, Altman DG,editors. Systematic review in health care: meta-analysisin context. London: BMJ Publishing; 2001.

55. Royal College of Physicians. National sentinel strokeaudit. London: Clinical Effectiveness andEvaluation Unit, Royal College of Physicians;2006.

56. Mehrholz J, Wagner K, Rutte K, Meisner D, Pohl M. Predictive validity and responsiveness ofthe functional ambulation category in hemipareticpatients after stroke. Arch Phys Med Rehabil 2007;88:1314–19.

57. Hsieh CL, Hsueh IP, Chiang FM, Lin PH. Inter-rater reliability and validity of the ActionResearch arm test in stroke patients. Age Ageing1998;27:107–13.

58. Hsueh IP, Hsieh CH. Responsiveness of two upperextremity function instruments for strokeinpatients receiving rehabilitation. Clin Rehabil2002;16:617–24.

59. Platz T, Pinowski C, van Wijck F, Kim IH,di Bella P, Johnson G. Reliability and validity ofarm function assessment with standardizedguidelines for the Fugl–Meyer Test, ActionResearch Arm Test and Box and Block Test: a multicentre study. Clin Rehabil 2005;19:404–11.

60. Wolf SL. The EXCITE Trial: attributes of the WolfMotor Function Test in patients with subacutestroke. Neurorehabil Neural Repair 2005;19:194–205.

61. Page SJ, Sisto S, Johnston MV, Levine P. Modifiedconstraint-induced therapy after subacute stroke: a preliminary study. Neurorehabil Neural Repair2002;16:290–5.

62. Page SJ, Sisto S, Levine P, McGrath RE. Efficacy ofmodified constraint-induced movement therapy inchronic stroke: a single-blinded randomizedcontrolled trial. Arch Phys Med Rehabil 2004;85:14–18.

63. Scheidtmann K, Brunner H, Muller F, Weinandy-Trapp M, Wulf D, Koenig E. Treadmilltraining in early poststroke patients – do timingand walking ability matter? [German]. Neurologieund Rehabilitation 1999;5:198–202.

64. Suputtitada A, Suwanwela NC, Tumvitee S.Effectiveness of constraint-induced movementtherapy in chronic stroke patients. J Med Assoc Thai2004;87:1482–90.

65. Barreca S, Sigouin CS, Lambert C, Ansley B.Effects of extra training on the ability of strokesurvivors to perform an independent sit-to stand:a randomized controlled trial. J Geriatr Phys Ther2004;27:59–64.

66. Dean CM, Shepherd RB. Task-related trainingimproves performance of seated reaching tasksafter stroke. Stroke 1997;28:722–8.

67. Dean CM, Richards CL, Malouin F. Task-relatedcircuit training improves performance oflocomotor tasks in chronic stroke: a randomized,controlled pilot trial. Arch Phys Med Rehabil2000;81:409–17.

68. Langhammer B, Stanghelle JK. Bobath or MotorRelearning Programme? A comparison of twodifferent approaches of physiotherapy in strokerehabilitation: a randomized controlled study. ClinRehabil 2000;14:361–9.

69. Turton A, Fraser C. The use of home therapyprogrammes for improving recovery of the upperlimb following stroke. Br J Occup Ther 1990;53:457–62.

70. Van Vliet PM, Lincoln NB, Foxall A. Comparisonof Bobath based and movement science basedtreatment for stroke: a randomised controlledtrial. J Neurol Neurosurg Psychiatry 2005;76:503–8.

71. Winstein CJ, Rose DK, Tan SM, Lewthwaite R,Chui HC, Azen SP. A randomized controlledcomparison of upper-extremity rehabilitationstrategies in acute stroke: a pilot study ofimmediate and long-term outcomes. Arch Phys MedRehabil 2004;85:620–8.

72. Yen JG, Wang RY, Chen HH, Hong CT.Effectiveness of modified constraint-inducedmovement therapy on upper limb function instroke subjects. Acta Neurol Taiwan 2005;14:16–20.

73. Taub E, Miller NE, Novack TA, Cook EW,Fleming WC, Nepomuceno CS, et al. Technique toimprove chronic motor deficit after stroke. ArchPhys Med Rehabil 1993;74:347–54.

74. Wittenberg GF, Chen R, Ishii K, Bushara KO,Eckloff S, Croarkin E, et al. Constraint-inducedtherapy in stroke: magnetic-stimulation motormaps and cerebral activation. Neurorehabil NeuralRepair 2003;17:48–57.

75. Wolf SL, Winstein CJ, Miller JP, Taub E,Uswatte G, Morris D, et al. Effect of constraint-induced movement therapy on upper extremityfunction 3 to 9 months after stroke: the EXCITErandomized clinical trial. JAMA 2006;296:2095–104.

76. de Sèze M, Wiart L, Bon-Saint-Côme A, Debelleix X, de Sèze M, Joseph P, et al.Rehabilitation of postural disturbances ofhemiplegic patients by using trunk controlretraining during exploratory exercises. Arch PhysMed Rehabil 2001;82:793–800.

77. Howe TE, Taylor I, Finn P, Jones H. Lateral weighttransference exercises following acute stroke: apreliminary study of clinical effectiveness. ClinRehabil 2005;19:45–53.


65


78. McClellan R, Ada L. A six week, resource-efficientmobility program after discharge fromrehabilitation improves standing in peopleaffected by stroke: placebo-controlled, randomisedtrial. Aust J Physiother 2004;50:163–7.

79. Atteya AA. Effects of modified constraint inducedtherapy on upper limb function in subacute strokepatients. Neurosciences 2004;9:24–9.

80. Page SJ, Sisto SA, Levine P, Johnston MV, Hughes M. Modified constraint induced therapy: a randomized feasibility and efficacy study. J Rehabil Res Dev 2001;38:583–90.

81. Dromerick AW, Edwards DF, Hahn M. Does theapplication of constraint-induced movementtherapy during acute rehabilitation reduce armimpairment after ischemic stroke? Stroke2000;31:2984–8.

82. Page SJ, Levine P, Leonard AC. Modifiedconstraint-induced therapy in acute stroke: a randomized controlled pilot study. NeurorehabilNeural Repair 2005;19:27–32.

83. Alberts JL, Butler AJ, Wolf SL. The effects ofconstraint-induced therapy on precision grip: a preliminary study. Neurorehabil Neural Repair2004;18:250–8.

84. Boake C, Noser EA, Ro T, Baraniuk S, Gaber M,Johnson R, et al. Constraint-induced movementtherapy during early stroke rehabilitation.Neurorehabil Neural Repair 2006;20:1–12.

85. Pohl M, Mehrholz J, Ritschel C, Ruckriem S.Speed-dependent treadmill training in ambulatoryhemiparetic stroke patients: a randomizedcontrolled trial. Stroke 2002;33:553–8.

86. da Cunha IT, Lim PA, Qureshy H, Henson H,Monga T, Protas EJ. Gait outcomes after acutestroke rehabilitation with supported treadmillambulation training: a randomized controlledpilot study. Arch Phys Med Rehabil 2002;83:1258–65.

87. Ada L, Dean CM, Hall JM, Bampton J,Crompton S. A treadmill and overground walkingprogram improves walking in persons residing inthe community after stroke: a placebo-controlled,randomized trial. Arch Phys Med Rehabil2003;84:1486–91.

88. Macko RF, Ivey FM, Forrester LW, Hanley D,Sorkin JD, Katzel LI, et al. Treadmill exerciserehabilitation improves ambulatory function andcardiovascular fitness in patients with chronicstroke: a randomized, controlled trial. Stroke2005;36:2206–11.

89. Eich HJ, Mach H, Werner C, Hesse S. Aerobictreadmill plus Bobath walking training improveswalking in subacute stroke: a randomizedcontrolled trial. Clin Rehabil 2004;18:640–51.

90. Allison R. Pilot randomised control trial to assessthe impact of additional supported standing

practice on functional ability post-stroke. NationalResearch Register N0620164288; 2005.

91. Askim T, Indredavik B. Does intensive task specifictraining improve balance after acute stroke?Clinical Trials.gov NCT00184431; 2005.

92. Harris N. Evaluation of a repetitive practicescheme to improve sit to stand performancefollowing stroke. National Research RegisterN0234135926; 2005.

93. English C, Warden-Flood A, Stiller K, Hillier S. Is task-related training an effective means ofproviding rehabilitation to acute stroke patients?In 1st APA Neurological Physiotherapy Conference,Sydney, Australia; 2005.

94. Sherrington C, Pamphlet P, Jacka J, Olivetti L,Nugent J, Hall J. A randomised controlled trial toevaluate task-related exercise classes for olderpeople with impaired mobility. e-Aust J Physiother2005;51:S431.

95. Miller K, Galae M, Kilbreath S, Phillips B. Earlyintensive task-specific sensory and motor trainingof the upper limb following acute stroke: a pilotstudy. In Proceedings of the 3rd World Congress ofPhysical Therapy, Venice, Italy; 2002.

96. Noser E. Constraint-induced movement therapyafter subacute stroke. Stroke Trials Register. URL: www.strokecenter.org; 2004.

97. Pomeroy V. Evaluation of whether functionalstrength training can enhance recovery of mobilityafter stroke. Clinical Trials.gov NCT00322192;2006.

98. Baer G. An investigation into the efficacy of ahome-based physiotherapy rehabilitationprogramme for late-stage stroke. A pilotrandomised controlled trial. National ResearchRegister N0417121685; 2002.

99. Bhakta B. Development of an intelligent roboticsystem to aid physical therapy in stroke. NHSTrusts Clinical Trials Register ISRCTNN23388474;2003.

100. Bratava DM, Richards L, Bever CT, Haselkorn J.Robotic assisted upper-limb neurorehabilitation instroke patients. Clinical Trials.gov NCT 00372411;2006.

101. Dewald J. Selective dynamic strength training toenhance upper limb coordination following stroke.National Rehabilitation Information CenterH133G030143; 2003.

102. DeLaurentis KJ. HARI: the hand/armrehabilitation interface for training the handfollowing stroke. National RehabilitationInformation Center H133S040140; 2004.

103. Hori M, Selbert K, Scremin AME, McCarty P,Moeder S, Van der Loos HFM. Assisted movementneuro-rehabilitation: VA multi-site clinical trial.Clinical Trials.gov NCT00223808; 2005.

References

66

104. Koeneman J. Air muscle device for ankle strokerehabilitation. CRISP 5R43HD047067-02; 2004.

105. Krebs HI. The effect of proximal and distaltraining on stroke recovery. CRISP5R01HD045343-02; 2004.

106. Otfinowski J, Jassiak-Tyrkalska B, Starowicz A,Regula K. Computer-based rehabilitation ofcognitive impairments and motor arm function ofpatients with hemiparesis after stroke [Polish].Neurologia i Neurochirurgia Polska 2006;40:112–18.

107. Tang PF. Balance recovery and training on fallprevention in stroke. Clinical Trials.govNCT00166907; 2005.

108. Edinger K, Herbold J, Mohr D, Vaidya S. Value ofa fitness programme after completion ofrehabilitation therapy poststroke. Arch Phys MedRehabil 2003;84:A10.

109. McClain J. An investigation into the effect of includinga goal orientated, independently practised, exerciseprogramme in early stroke rehabilitation. MSc thesis,Southampton University; 2003.

110. Muller K, Butefisch CM, Kleiser B, Korber B,Stephan J, Netz V. Recovery of hand function afterstroke by executed and mental repetitive training.Cerebrovasc Dis 2004;15(Suppl 5):115.

111. Manova N, Venova L. Rivermead (RMA) – test andtool for motor recovery after stroke. In Proceedingsof the 14th International Congress of the WorldConfederation for Physical Therapy, Barcelona; 2003.

112. Wang RY, Chen HI, Chen CY, Yang YR. Efficacy ofBobath versus orthopaedic approach onimpairment and function at different motorrecovery stages after stroke: a randomisedcontrolled study. Clin Rehabil 2005;19:155–64.

113. Yang YR, Wang RY, Lin KH, Chu MY, Chan RC.Task-oriented progressive resistance strengthtraining improves muscle strength and functionalperformance in individuals with stroke. ClinRehabil 2006;20:860–70.

114. Dromerick AW. Very early constraint-inducedmovement therapy: stroke. CRISP5R01NS041261-03; 2004.

115. Light KE. Examining parameters of constraint-induced therapy. CRISP 5R01HD045751-02;2005.

116. Huang YY, Wu CY, Aou SH, Lin KC, Chen CL.The modified constraint-induced movementtherapy improved reach-to-grasp movement inpatients with hemiparesis after stroke. Stroke2004;35:e313.

117. Bain BJ, McKenzie K, Brownlee MG, Brodie EE,Granat M, Parker D, et al. Constraint of thehemiparetic upper limb in stroke survivorsfollowing discharge from rehabilitation. ClinRehabil 2004;18:929–32.

118. Ada L. The efficacy of treadmill training inestablishing walking after stroke. ClinicalTrials.gov NCT00167531; 2002.

119. Brown DA. Strength Training Effectiveness Post-Stroke (STEPS). Clinical Trials.gov NCT00389012;2004.

120. Duncan PW. Locomotor experience applied poststroke (LEAPS) Trial. Clinical Trials.govNCT00108030; 2006.

121. Kilbreath SL. PBWST (partial body-weightsupported treadmill training) and muscle powertraining after sub-acute stroke. Clinical Trials.govNCT00108030; 2004.

122. Hidler JM. Walking therapy in hemiparetic strokepatients using robotic-assisted treadmill training.Clinical Trials.gov NCT00075283; 2002.

123. Sivenius J. Gait trainer versus traditionalphysiotherapy in acute stroke. Clinical Trials.govNCT00307762; 2003.

124. Zielke D. The effect of partial body weightsupported treadmill training on gait rehabilitationin early acute stroke patients: preliminary data.JNPT 2003;27:177.

125. Du J-B, Song W-Q, Wang M-B. The application ofpartial body weight support treadmill training inhemiplegia rehabilitation after stroke. [Chinese].Chin J Cerebrovasc Dis 2006;3:361–4.

126. Weng C-S, Bi S, Tian Z, Yu Z-Z, Xu J, Bi S-Q, et al.Application of structured speed-dependenttreadmill training in hemiplegic patients afterstroke [Chinese]. Chin J Clin Rehabil 2004;8:7617–19.

127. Zhu H-X, Dou Z-L, Li K, Lan Y, Hu X-Q. A preliminary investigation on the correlation ofpartial body weight support training withhemiplegic gait and ambulation function afterbrain injury [Chinese]. Chin J Clin Rehabil2004;8:5205–7.

128. Wolff D. Stroke rehabilitation outcomes withsupported treadmill ambulation training. ClinicalTrials.gov NCT00037895; 2001.

129. Kim BO, Lee JJ, Cho KH, Kim SH. Gait trainingrobot (gait trainer) in rehabilitation. In Proceedingsof the 1st International Congress of International Societyof Physical and Rehabilitation Medicine (ISPRM),7–13 July. Amsterdam: ISPRM; 2001.

130. Lennihan L, Wootten ME, Wainwright M,Tenteromano L, McMahon D, Cotier J. Treadmillwith partial body-weight support versusconventional gait training after stroke. Arch PhysMed Rehabil 2003;84:E5.

131. Stephenson J, Maitland M, Beckstead J. Bodyweight support treadmill training compared withPNF training in persons with chronic stroke. JNPT2004;28:186.


67


132. Van Vliet PM, Lincoln NB, Robinson E.Comparison of the content of two physiotherapyapproaches for stroke. Clin Rehabil 2001;15:398–414.

133. Salbach NM, Mayo NE, Robichaud-Ekstrand S,Hanley JA, Richards CL, Wood-Dauphinee S. Theeffect of a task-oriented walking intervention onimproving balance self-efficacy poststroke: arandomized, controlled trial. J Am Geriatr Soc2005;53:576–82.

134. Watkins CL, Leathley MJ, Jack CIA, Sharma AK.Stroke Interface Audit. Pre/post discharge audit of strokeservices and care in Liverpool and Sefton: deliverytimeliness and targeting – 36 month report. Preston:University of Central Lancashire; 2002.

135. Wade DT, Collin C. The Barthel ADL index: a standard measure of physical disability? Int Disabil Stud 1988;10:64–7.

136. Van Exel NJA, Scholte op Reimer WJM,Koopmanschap MA. Assessment of post-strokequality of life in cost-effectiveness studies: the usefulness of the Barthel Index and theEuroQol-5D. Qual Life Res 2004;13:427–33.

137. Curtis L, Netten A. Unit costs of health and socialcare. Canterbury: Personal Social Services ResearchUnit, University of Kent; 2006.

138. National Institute for Clinical Excellence. Guide tothe methods of technology appraisal. London: NICE;2004.

139. Page SJ, Gater DR, Bach YR. Reconsidering themotor recovery plateau in stroke rehabilitation.Arch Phys Med Rehabil 2004;85:1377–81.

140. Sunderland A, Tuke A. Neuroplasticity, learningand recovery after stroke: a critical evaluation ofconstraint-induced therapy. Neuropsychol Rehabil2005;15:81–96.

141. Ferrucci L, Bandinelli S, Guralnik JM, Lamponi RPT, Bertini C, Falchini M, et al.Recovery of functional status after stroke. A postrehabilitation follow-up study. Stroke1993;24:200–5.

142. Paolucci S, Antonucci G, Pratesi L, Traballesi M,Lubich S, Grasso MG. Functional outcome instroke inpatient rehabilitation: predicting no, lowand high response patients. Cerebrovasc Dis1998;8:228–34.

143. Langhammer B, Stanghelle JK. Bobath or MotorRelearning Programme? A follow-up one and fouryears post stroke. Clin Rehabil 2003;17:731–4.

144. Bobath B. Adult hemiplegia: evaluation and treatment.London: William Heinemann Medical Books;1990.

145. Bagley P, Hudson M, Forster A, Smith J, Young J.A randomized trial evaluation of the OswestryStanding Frame for patients after stroke. ClinRehabil 2005;4:354–64.

146. Brown DA, Burgar CG. Graded weight-bearingexercise for improved ambulation after stroke.URL: http://guide.stanford.edu/projects/2kprojects/stroke06.html; 2002.

147. Carey JR, Kimberley TJ, Lewis SM, Auerbach EJ,Dorsey L, Rundquist P. Analysis of fMRI andfinger tracking training in subjects with chronicstroke. Brain 2002;125:773–88.

148. Chan DYL, Chan CCH, Au DKS. Motor relearningprogramme for stroke patients: a randomizedcontrolled trial. Clin Rehabil 2006;20:191–200.

149. Chang JL, Sun B. Effect of motor relearningtraining on upper extremity function inhemiplegia patients. Modern Rehabilitation 2000;4:684–5.

150. Cirstea MC, Ptito A, Levin MF. Arm reachingimprovements with short-term practice depend onthe severity of the motor deficit in stroke. ExpBrain Res 2003;152:47–88.

151. Desrosiers J, Bourbonnais D, Corriveau H,Gosselin S, Bravo G. Effectiveness of unilateraland symmetrical bilateral task training for armduring the subacute phase after stroke: a randomized controlled trial. Clin Rehabil 2005;19:581–93.

152. Duncan P, Studenski S, Richards L, Gollub S,Lai SM, Reker D. Randomized clinical trial oftherapeutic exercise in subacute stroke. Stroke2003;34:2173–80.

153. Eng JJ, Chu KS, Kim CM, Dawson AS, Carswell A,Hepburn KE. A community-based group exerciseprogram for persons with chronic stroke. Med SciSports Exerc 2003;35:1271–8.

154. Feys HM, De Weerdt WJ, Selz BE, Cox Steck GA,Spichiger R, Vereeck LE, et al. Effect of atherapeutic intervention for the hemiplegic upperlimb in the acute phase after stroke. Stroke1998;29:785–92.

155. Gelber DA, Josefczyk PB, Herman D, Good DC,Verhulst SJ. Comparison of two therapyapproaches in the rehabilitation of the pure motorhemiparetic stroke patient. J Neurol Rehabil1995;9:191–6.

156. Hanlon RE. Motor learning following unilateralstroke. Arch Phys Med Rehabil 1996; 77:811–15.

157. Husemann B, Muller F, Krewer C, Lab A, Gille C,Heller S. Effects of locomotion training withassistance of a driven gait orthosis in hemipareticpatients after stroke [abstract]. Neurologie undRehabilitation 2004;10:187–217.

158. Inaba M, Edberg E, Montgomery J, Gillis MK.Effectiveness of functional training, active exercise,and resistive exercise for patients with hemiplegia.Phys Ther 1973;53:28–35.

159. Katz-Leurer M, Sender I, Keren O, Dvir Z. Theinfluence of early cycling training on balance in

References

68

stroke patients at the subacute stage: results of apreliminary trial. Clin Rehabil 2006;20:398–405.

160. Kayhan O, Guven Z, Erdilli S, Ozaras N,Renklitepe N. The effect of motor rehabilitation ofthe hand in stroke patients. Eur J Neurol 1996;3(Suppl 2):10.

161. Khanna PB. A randomised control study of theimmediate and long term benefits of conventionalstroke rehabilitation with task related grouptherapy in chronic stroke patients. URL:http://www.controlled-trials.com/2003; 2003.

162. Kilbreath SL, Heard R. Upper and lower limbfunction in stroke patients following task-specifictraining. In Proceedings of the Australasian Faculty ofRehabilitation Medicine 5th Annual ScientificConference, Melbourne, 1997.

163. Krutulyte G, Kimtys A, Krisciunas A. Theeffectiveness of physical therapy methods (Bobathand motor relearning program) in rehabilitationof stoke patients [Lithuanian]. Medicina (Kaunas)2003;39:889–95.

164. Li HF, Wang JH, Feng JC, Gao F. Application ofmotor relearning therapy in the earlyrehabilitation of stroke: a randomised controlledcomparison [Chinese]. Chin J Clin Rehabil2005;9(29):1–3.

165. Liao L, Luo W, Chen S. The effect of trunk controltraining on balance and lower limb function inpatients with hemiplegia [Chinese]. Chin J RehabilMed 2006;21:608–9.

166. Mudie MH, Winzeler-Mercay U, Radwan S, Lee L.Training symmetry of weight distribution afterstroke: a randomized controlled pilot studycomparing task-related reaching, Bobath andfeedback training approaches. Clin Rehabil2002;16:582–92.

167. Nelles G, Jentzen W, Jueptner M, Müller S, Diener HC. Arm training induced brain plasticityin stroke studied with serial positron emissiontomography. NeuroImage 2001;13:1146–54.

168. Pang MY, Harris JE, Eng JJ. A community-basedupper-extremity group exercise program improvesmotor function and performance of functionalactivities in chronic stroke: a randomizedcontrolled trial. Arch Phys Med Rehabil 2006;87:1–9.

169. Platz T, Winter T, Müller N, Pinkowski C,Eickhof C, Mauritz K. Arm ability training forstroke and traumatic brain injury patients withmild arm paresis: a single-blind, randomized,controlled trial. Arch Phys Med Rehabil 2001;82:961–8.

170. Pollock AS, Durard BR, Rowe PJ, Paul JP. The effect of independent practice of motor tasksby stroke patients: a pilot randomized controlledtrial. Clin Rehabil 2002;16:473–80.

171. Sunderland A, Tinson DJ, Bradley EL, Fletcher D,Langton HR, Wade DT. Enhanced physical

therapy improves recovery of arm function afterstroke. J Neurol Neurosurg Psychiatry 1992;55:530–5.

172. Theilman GT, Dean CM, Gentile AM.Rehabilitation of reaching after stroke: task-relatedtraining versus progressive resistive exercise. ArchPhys Med Rehabil 2004;85:1613–18.

173. Wellmon R, Newton RA. An examination ofchanges in gait and standing symmetry associatedwith the practice of a weight shifting task.Neurology Report 1997;21:52–3.

174. Xiao Z, Zhang L, Pang H. Application of motorrelearning programme for the recovery of upperlimb function in hemiplegic patients [Chinese].Chin J Phys Med Rehabil 2002;24:590–61.

175. Yang YR, Yen, JG, Wang RY, Yen LL, Lieu FK. Gait outcomes after additional backward walkingtraining in patients with stroke: a randomizedcontrolled trial. Clin Rehabil 2005;19:264–73.

176. Ploughman M, Corbett D. Can forced-use therapybe clinically applied after stroke? An exploratoryrandomized controlled trial. Arch Phys Med Rehabil2004;85:1417–23.

177. Ro T, Noser E, Boake C, Johnson R, Gaber M,Speroni A, et al. Functional reorganization andrecovery after constraint-induced movementtherapy in subacute stroke: case reports. Neurocase2006;12:50–60.

178. Sterr A, Elbert T, Berthold I, Kolbel S, Rockstroh B, Taub E. Longer versus shorter dailyconstraint-induced movement therapy of chronichemiparesis: an exploratory study. Arch Phys MedRehabil 2002;83:1374–7.

179. Van der Lee JH, Wagenaar RC, Lankhorst GJ,Vogelaar TW, Deville WL, Bouter LM. Forced useof the upper extremity in chronic stroke patients:results from a single-blind randomized clinicaltrial. Stroke 1999;30:2369–75.

180. Jaffe DL, Brown DA, Pierson-Carey CD,Buckley EL, Lew HL. Stepping over obstacles toimprove walking in individuals with poststrokehemiplegia. J Rehabil Res Dev 2004;41(3A):283–92.

181. Kosak MC, Reding MJ. Comparison of partialbody weight-supported treadmill gait trainingversus aggressive bracing assisted walking poststroke. Neurorehabil Neural Repair 2000;14:13–19.

182. Nilsson L, Carlsson J, Danielsson A, Fugl-Meyer A,Hellstrom K, Kristensen L, et al. Walking trainingof patients with hemiparesis at an early stage afterstroke: a comparison of walking training on atreadmill with body weight support and walkingtraining on the ground. Clin Rehabil 2001;15:515–27.

183. Laufer Y, Dickstein R, Chefez Y, Marcovitz E. The effect of treadmill training on the ambulationof stroke survivors in the early stages ofrehabilitation: a randomized study. J Rehabil ResDev 2001;38:69–78.


69


184. Liston R, Mickelborough J, Harris B, Hann AW,Tallis RC. Conventional physiotherapy andtreadmill re-training for higher-level gait disordersin cerebrovascular disease. Age Ageing2000;29:311–18.

185. Richards CL, Malouin F, Wood-Dauphinee S,Williams JI, Bourchard JP, Brunet D. Task-specificphysical therapy for optimisation of gait recoveryin acute stroke patients. Arch Phys Med Rehabil1993;74:612–20.

186. Richards CL, Malouin F, Bravo G, Dumas F, Wood-Dauphinee S. The role of technology intask-oriented training in persons with subacute

stroke: a randomised controlled trial. NeurorehabilNeural Repair 2004;18:199–211.

187. Visintin M, Barbeau H, Korner-Bitensky N, Mayo NE. A new approach to retrain gait in strokepatients through body weight support andtreadmill stimulation. Stroke 1998;29:1122–8.

188. Werner C, von FS, Treig T, Konrad M, Hesse S.Treadmill training with partial body weightsupport and an electromechanical gait trainer forrestoration of gait in subacute stroke patients: a randomized crossover study. Stroke 2002;33:2895–901.

References

70


71


Appendix 1

Included studies: repetitive task training

Appendix 1

72

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Barr

eca,

200

465Si

ngle

-cen

tre

RCT

Rand

omisa

tion

by c

oin

flip.

Dur

ing

first

4m

onth

s, e

ligib

lesu

bjec

ts w

ere

assig

ned

to a

con

vent

iona

lpr

actic

e gr

oup;

dur

ing

seco

nd 4

mon

ths,

elig

ible

sub

ject

s w

ere

assig

ned

to a

n ex

tra

prac

tice

grou

p, w

ithth

is se

quen

ce o

f blo

ckra

ndom

isatio

noc

curr

ing

thre

e tim

es in

tota

l

Can

ada

48 p

artic

ipan

ts: 2

5 in

terv

entio

n,

23 c

ontr

ol

Part

icip

ants

rec

ruite

d fr

om a

dmiss

ion

to a

reh

abili

tatio

n ce

ntre

with

in1

mon

th o

f str

oke

Incl

usio

n cr

iteria

: Bet

wee

n th

e ag

es o

f18

and

90,

med

ical

ly s

tabl

e, p

ostu

ral

cont

rol s

tage

3 o

r gr

eate

r on

the

Che

doke

McM

aste

r St

roke

Ass

essm

ent

(lyin

g to

sitt

ing

in b

edus

ing

stro

ng s

ide)

, but

not

sta

ge IV

(lyin

g to

sitt

ing

on s

ide

of b

ed, u

sing

stro

ng s

ide)

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 6

8 ye

ars

(ran

ge 5

6–78

)65

% m

ale

Stro

ke d

etai

ls: N

ot s

tate

d w

heth

erfir

st o

r re

curr

ent

stro

ke, 7

3%isc

haem

ic, 4

2% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: 3

0 da

ys, r

ange

18–5

0 da

ys

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l: La

ck o

f pos

tura

l con

trol

Sit-

to-s

tand

tra

inin

g:G

roup

cla

ss p

ract

ice

in a

ttai

ning

stan

ding

from

sitt

ing

from

a v

arie

tyof

diff

eren

t he

ight

s an

d su

rfac

es

Trai

ning

was

add

ition

al t

o us

ual

care

, whi

ch in

clud

ed d

aily

stre

ngth

enin

g ex

erci

se, r

epet

itive

trai

ning

, fun

ctio

nal t

rain

ing,

elec

tric

al s

timul

atio

n an

d ot

her

exer

cise

Sess

ions

wer

e 45

min

utes

, thr

eetim

es a

wee

k un

til c

ompe

tenc

e or

disc

harg

e (a

ppro

x. 6

wee

ks) =

13.5

hou

rs +

pra

ctic

e on

war

d.Ea

ch s

essio

n ai

med

to

invo

lve

thre

epr

actic

e se

ts o

f fiv

e sit

-to-

stan

dm

anoe

uvre

s pe

r cl

ass.

Ave

rage

tota

l rep

etiti

ons

durin

g tr

aini

ng =

450–

500.

Cla

sses

had

six

or

seve

npa

rtic

ipan

ts, s

uper

vise

d by

tw

ore

gist

ered

pra

ctic

al n

urse

s, w

ithex

tra

prac

tice

deliv

ered

by

nurs

estr

aine

d on

the

sit-

to-s

tand

pro

toco

lin

a w

ard

sett

ing

usin

g vi

deot

apes

,w

ritte

n in

stru

ctio

n an

d pr

actic

e

Com

paris

on g

roup

: Usu

al c

are

plus

recr

eatio

n th

erap

y

Out

com

es r

ecor

ded

atco

mpe

tenc

e or

disc

harg

e(a

ppro

x. 6

wee

ks)

Lim

b-sp

ecifi

c fu

nctio

n:N

umbe

r of

peo

ple

able

to

stan

d in

depe

nden

tly a

ndsa

fely

on

two

cons

ecut

ive

occa

sions

Oth

er: N

umbe

r of

falls

,he

alth

sta

tus

satis

fact

ion

(with

abi

lity

to s

tand

) and

satis

fact

ion

with

qua

lity

oflif

e (D

artm

outh

Prim

ary

Car

e C

oope

rativ

e C

hart

)

No

signi

fican

tdi

ffere

nces

in b

asel

ine

char

acte

ristic

s

No

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

Out

com

e as

sess

ors

blin

ded

to g

roup

allo

catio

n

No

inte

rven

tion

rela

ted

with

draw

als

cont

inue

d


73


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Blen

nerh

asse

tt,

2004

50Si

ngle

-cen

tre

RCT

Rand

omisa

tion

proc

edur

e no

tde

scrib

ed. C

once

aled

allo

catio

n to

gro

ups

usin

g in

depe

nden

tal

loca

tor

and

seal

edop

aque

env

elop

es

Aus

tral

ia30

par

ticip

ants

: 15

inte

rven

tion,

15

con

trol

Part

icip

ants

rec

ruite

d fr

om in

patie

ntad

miss

ions

to

a re

habi

litat

ion

cent

re,

2001

–200

3, w

ith a

prim

ary

diag

nosis

of s

trok

e, w

ithin

3 m

onth

s of

str

oke

Incl

usio

n cr

iteria

: Abl

e to

wal

k 10

m,

able

to

prov

ide

info

rmed

con

sent

Excl

usio

n cr

iteria

: Det

erio

ratin

gm

edic

al c

ondi

tion,

inde

pend

ent

com

mun

ity a

mbu

latio

n

Mea

n ag

e: M

obili

ty g

roup

53.

9 ye

ars

(SD

19.

8), u

pper

lim

b gr

oup

56.3

year

s (S

D10

.5)

56.6

% m

ale

Stro

ke d

etai

ls: F

irst

or r

ecur

rent

stro

ke: 7

3% is

chae

mic

, 47%

rig

hthe

mip

ares

is

Tim

e sin

ce s

trok

e: M

obili

ty g

roup

36da

ys (S

D 2

5.1)

, upp

er li

mb

grou

p50

day

s (S

D 4

9.2)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l: A

ble

to w

alk

10 m

, 6M

WT

182

m

(SD

85)

Mob

ility

inte

rven

tion:

Low

er li

mb

circ

uit

trai

ning

: fun

ctio

nal t

asks

suc

has

sit-

to-s

tand

, ste

p-up

s, o

bsta

cle

cour

se w

alki

ng, p

lus

stre

tchi

ng a

ndst

reng

then

ing

exer

cise

, and

som

een

dura

nce

trai

ning

on

stat

iona

rybi

kes/

trea

dmill

s

Upp

er e

xtre

mity

inte

rven

tion:

Func

tiona

l tas

ks t

o im

prov

e re

ach

and

gras

p, h

and–

eye

coor

dina

tion

activ

ities

, and

str

etch

ing

and

stre

ngth

enin

g ex

erci

ses

Both

gro

ups

wer

e du

ring

inpa

tient

reha

bilit

atio

n an

d ad

ditio

nal t

o us

ual

care

of 1

hou

r of

phy

sioth

erap

y,5

days

a w

eek,

bas

ed o

n M

ovem

ent

Scie

nce

App

roac

h

Sess

ions

wer

e 60

min

utes

, fiv

etim

es a

wee

k fo

r 4

wee

ks(2

0ho

urs

tota

l tra

inin

g tim

e). E

ach

circ

uit

incl

uded

ten

5-m

inut

ew

orks

tatio

ns

Sess

ions

wer

e de

liver

ed b

y a

phys

ical

the

rapi

st in

gro

ups

of u

p to

four

sub

ject

s

Com

paris

on g

roup

: Ble

nner

hass

ett,

2004

a: lo

wer

lim

b at

tent

ion

cont

rol,

Blen

nerh

asse

tt 2

004b

:up

per

limb

atte

ntio

n co

ntro

l

Out

com

es r

ecor

ded

atba

selin

e, w

hich

was

app

rox.

6 w

eeks

pos

t-st

roke

(ran

ge54

–74

days

), an

d at

4 w

eeks

and

6 m

onth

s af

ter

trai

ning

Upp

er li

mb

func

tion:

M

AS

uppe

r ar

m, M

AS

hand

,Je

bsen

Tay

lor

Test

of H

and

Func

tion

Low

er li

mb

func

tion:

6M

WT,

TU

G, S

tep

Test

No

signi

fican

tdi

ffere

nces

rep

orte

d at

base

line

3% lo

st t

o fo

llow

-up

aten

d of

tre

atm

ent

phas

e

Out

com

e as

sess

ors

blin

ded

to g

roup

allo

catio

n

No

likel

y in

terv

entio

n-re

late

d w

ithdr

awal

s

Ave

rage

att

enda

nce

was

app

rox.

80%

, with

no s

igni

fican

t di

ffere

nce

betw

een

the

grou

ps

cont

inue

d

Appendix 1

74

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

de S

èze,

200

176Si

ngle

-cen

tre,

pilo

t RC

T

Rand

omisa

tion

tabl

eus

ed. N

o de

tails

of

allo

catio

n co

ncea

lmen

tpr

oces

s

Fran

ce20

par

ticip

ants

: ten

exp

erim

enta

l, te

n co

ntro

l

Subj

ects

rec

ruite

d fr

om a

dmiss

ions

to

a n

euro

reha

bilit

atio

n un

it in

199

8

Incl

usio

n cr

iteria

: Hem

iple

gia

caus

edby

a s

ingl

e st

roke

occ

urrin

g at

leas

t1

mon

th p

revi

ously

. Sta

tic im

bala

nce

of t

he t

runk

res

ultin

g fr

om t

he s

trok

e

Excl

usio

n cr

iteria

: Mul

tiple

cer

ebra

lle

sions

, diso

rder

s of

the

loco

mot

orsy

stem

, a s

ever

e vi

sual

or

audi

tory

defic

it, a

sev

ere

defic

it of

exe

cutiv

efu

nctio

ns, o

r de

terio

ratio

n in

gen

eral

heal

th

Mea

n ag

e: E

xper

imen

tal g

roup

63.5

year

s (S

D 1

7), c

ontr

ol g

roup

67.7

year

s (S

D 1

5)55

% m

ale

Stro

ke d

etai

ls: F

irst

stro

ke: 3

5%isc

haem

ic, 2

5% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

36.8

days

(SD

25)

, con

trol

gro

up27

.7da

ys (S

D 1

5)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l: La

ck o

f pos

tura

l bal

ance

Expe

rimen

tal i

nter

vent

ion:

Pos

tura

ltr

aini

ng u

sing

the

Bon

Sain

t C

ôme

devi

ce, a

cus

tom

-mou

lded

ort

hosis

that

hol

ds a

poi

ntin

g de

vice

, use

dby

the

sub

ject

to

poin

t to

tar

gets

on a

ver

tical

pan

el, w

hich

em

it lig

htan

d so

und

whe

n ac

tivat

ed. T

hesu

bjec

t pe

rfor

ms

exer

cise

s of

loca

ting

and

poin

ting

by c

ontr

ollin

gtr

unk

mov

emen

t

Inte

rven

tion

was

dur

ing

reha

bilit

atio

n an

d ad

ditio

nal t

o us

ual

care

Usu

al c

are

cons

isted

of a

Bob

ath-

insp

ired

appr

oach

and

func

tiona

lth

erap

y fo

r 1

hour

per

day

, plu

s a

sess

ion

of o

ccup

atio

nal t

hera

py5

days

a w

eek

Sess

ions

wer

e 60

min

utes

(unc

lear

whe

ther

5 o

r 7

days

per

wee

k), f

or4

wee

ks =

20–

28 h

ours

Sess

ions

wer

e de

liver

ed in

divi

dual

ly,by

a p

hysic

al t

hera

pist

Com

paris

on g

roup

: Con

vent

iona

lre

habi

litat

ion

for

2 ho

urs

per

day

Out

com

es r

ecor

ded

atba

selin

e, p

ost-

inte

rven

tion

(4 w

eeks

) and

at

2 m

onth

s

Lim

b-sp

ecifi

c fu

nctio

n: S

ittin

gEq

uilib

rium

Inde

x, U

prig

htEq

uilib

rium

Inde

x, F

AC

Mot

or p

erfo

rman

ce: T

runk

Con

trol

Tes

t, M

otric

ityIn

dex,

Ash

wor

th S

cale

ADL:

FIM

At

base

line,

pos

tura

lde

ficit

and

unila

tera

lne

glec

t te

nded

to

bem

ore

seve

re in

the

devi

ce g

roup

, alth

ough

not

signi

fican

t. Tr

unk

Con

trol

Tes

t: de

vice

grou

p 36

.6 (S

D 3

2.3)

,co

ntro

l gro

up 5

0.4

(SD

31.9

), U

prig

htEq

uilib

rium

Inde

xD

evic

e gr

oup

0.8

(SD

0.9)

, con

trol

gro

up1.

2 (S

D 1

.0).

0% lo

st t

o fo

llow

-up

aten

d of

tre

atm

ent

phas

e

Out

com

e as

sess

ors

blin

d to

tre

atm

ent

grou

p

No

inte

rven

tion

rela

ted

reas

ons

for

with

draw

al

All

subj

ects

com

plet

edtr

aini

ng

cont

inue

d


75


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Dea

n, 1

99766

Sing

le-c

entr

e RC

T

Rand

omisa

tion

was

bloc

ked.

Sub

ject

sal

loca

ted

by d

raw

ing

aca

rd fr

om a

box

of t

enex

perim

enta

l and

ten

cont

rol c

ards

Aus

tral

ia20

par

ticip

ants

: ten

exp

erim

enta

l, te

nco

ntro

l.

Subj

ects

wer

e re

crui

ted

from

str

oke

club

s ar

ound

Syd

ney,

Aus

tral

ia

Incl

usio

n cr

iteria

: Dia

gnos

is of

str

oke

resu

lting

in h

emip

legi

a at

leas

t12

mon

ths

prev

ious

ly, d

ischa

rged

from

all

reha

bilit

atio

n se

rvic

es, a

bilit

yto

und

erst

and

inst

ruct

ions

and

giv

ein

form

ed c

onse

nt, n

o or

thop

aedi

cpr

oble

m t

hat

wou

ld in

terf

ere

with

seat

ed r

each

ing,

abi

lity

to s

itun

supp

orte

d fo

r 20

min

utes

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 6

6.9

year

s (S

D 8

.2)

70%

mal

e

Stro

ke d

etai

ls: N

ot s

tate

d w

heth

erfir

st o

r re

curr

ent

stro

ke. 4

2% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

6.7

year

s (S

D5.

8), c

ontr

ol g

roup

5.

9 ye

ars

(SD

2.9)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:6M

WT:

mea

n 20

7 m

(SD

128

)

Expe

rimen

tal i

nter

vent

ion:

Tra

inin

gde

signe

d to

impr

ove

sittin

g ba

lanc

ean

d in

volv

ing

emph

asis

onap

prop

riate

load

ing

of t

he a

ffect

edle

g w

hile

pra

ctisi

ng r

each

ing

task

sus

ing

the

unaf

fect

ed h

and

to g

rasp

obje

cts

loca

ted

beyo

nd a

rm’s

leng

th

Inte

rven

tion

was

afte

r di

scha

rge

from

all

reha

bilit

atio

n pr

ogra

mm

es

Sess

ions

wer

e 30

min

utes

, 5 d

ays

per

wee

k fo

r 2

wee

ks =

5 h

ours

Sess

ions

wer

e de

liver

ed b

y a

phys

ical

the

rapi

st in

the

per

son’

sow

n ho

me

Com

paris

on g

roup

: Upp

er e

xtre

mity

atte

ntio

n co

ntro

l: pe

rfor

man

ce o

fco

gniti

ve m

anip

ulat

ive

task

s w

hile

seat

ed a

t a

tabl

e

Out

com

es r

ecor

ded

atba

selin

e an

d at

2 w

eeks

(pos

t-tr

eatm

ent)

Lim

b-sp

ecifi

c fu

nctio

n:

Reac

hing

dist

ance

, rea

chin

gsp

eed,

wal

king

spe

ed(6

MW

T)

No

signi

fican

tdi

ffere

nces

rep

orte

d at

base

line

5% lo

ss t

o fo

llow

-up

at e

nd o

f tre

atm

ent

phas

e

Out

com

e as

sess

ors

blin

d to

tre

atm

ent

grou

p

No

inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al

cont

inue

d

Appendix 1

76

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Dea

n, 2

00067

Pilo

t RC

T

Subj

ects

gro

uped

into

mat

ched

pai

rs b

ased

on

wal

king

spe

ed, t

hen

rand

omise

d by

dra

win

gca

rds

from

a b

ox.

Car

ds d

raw

n by

ape

rson

inde

pend

ent

from

the

stu

dy

Can

ada

12 p

artic

ipan

ts: s

ix m

obili

tyin

terv

entio

n, s

ix u

pper

lim

b at

tent

ion

cont

rol g

roup

Subj

ects

rec

ruite

d fr

om a

reha

bilit

atio

n re

sear

ch g

roup

data

base

Incl

usio

n cr

iteria

: Firs

t st

roke

, at

leas

t3

mon

ths

post

-str

oke,

disc

harg

edfr

om a

ll re

habi

litat

ion

serv

ices

, abl

eto

att

end

a re

habi

litat

ion

cent

re t

hree

times

a w

eek

for

4 w

eeks

, abl

e to

wal

k 10

m

Excl

usio

n cr

iteria

: Any

med

ical

cond

ition

tha

t w

ould

pre

vent

part

icip

atio

n

Mea

n ag

e: E

xper

imen

tal g

roup

66.2

year

s (7

.7),

cont

rol g

roup

62.3

year

s (6

.6)

58%

mal

e

Stro

ke d

etai

ls: N

ot s

tate

d w

heth

erfir

st o

r re

curr

ent

stro

ke. 5

8% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: M

obili

ty g

roup

2.3

year

s (S

D 0

.7),

uppe

r lim

bat

tent

ion-

cont

rol g

roup

1.3

yea

rs(S

D0.

9)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:6M

WT

mea

n 23

5 m

(SD

139

)

Mob

ility

inte

rven

tion:

Low

er li

mb

circ

uit

trai

ning

of t

en w

orks

tatio

nsin

clud

ing

sittin

g re

ach,

sit-

to-s

tand

,st

eppi

ng, h

eel l

ifts,

sta

ndin

gba

lanc

e, le

g st

reng

then

ing,

tre

adm

illw

alki

ng, o

bsta

cle

wal

king

, slo

pe a

ndst

air

wal

king

, plu

s pa

rtic

ipat

ion

inw

alki

ng r

aces

and

rel

ays

Inte

rven

tion

was

afte

r di

scha

rge

from

all

reha

bilit

atio

n pr

ogra

mm

es

Sess

ions

wer

e 60

min

utes

, thr

eetim

es a

wee

k fo

r 4

wee

ks =

12ho

urs

Sess

ions

wer

e de

liver

ed t

o a

grou

pof

six

sub

ject

s by

tw

o ph

ysic

alth

erap

ists,

in a

reh

abili

tatio

n ce

ntre

sett

ing

Upp

er e

xtre

mity

inte

rven

tion:

Circ

uit

prog

ram

me

desig

ned

to im

prov

efu

nctio

n of

the

affe

cted

upp

er li

mb

Out

com

es r

ecor

ded

atba

selin

e, a

t 4

wee

ks(p

ost-

trea

tmen

t) a

nd2

mon

ths

afte

rco

mpl

etio

n of

tra

inin

g

Lim

b-sp

ecifi

c fu

nctio

n:6M

WT,

10M

WS

(with

and

with

out

assis

tive

devi

ce),

Step

Tes

t, T

UG

Oth

er: S

atisf

actio

n w

ithpr

ogra

mm

e

No

signi

fican

t di

ffere

nce

in w

alki

ng v

eloc

ity a

tba

selin

e fo

r to

tal g

roup

,bu

t af

ter

with

draw

als,

mea

sure

s of

wal

king

spee

d an

d di

stan

cefa

vour

ed t

he c

ontr

olgr

oup.

6M

WT:

mob

ility

grou

p 20

7.9

m (S

D 1

19),

uppe

r lim

b gr

oup

259.

6m

(SD

154

.6);

wal

king

spe

ed w

ithas

sistiv

e de

vice

: mob

ility

grou

p 70

.7cm

/s(S

D41

.8),

uppe

r lim

bgr

oup

86.1

cm/s

(SD

52.6

)

25%

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

Out

com

e as

sess

ors

blin

ded

to g

roup

allo

catio

n, b

ut m

ay h

ave

been

inad

vert

ently

unm

aske

d. 6

MW

Tun

dert

aken

by

one

of t

hein

vest

igat

ors

Inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al:

two

subj

ects

with

drew

befo

re t

rain

ing

(one

owin

g to

tra

nspo

rt c

osts

)

Nin

e pa

rtic

ipan

tsat

tend

ed a

t le

ast

nine

out

of 1

2 se

ssio

ns

cont

inue

d


77


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Hig

gins

, 200

652Se

e Sa

lbac

h, 2

00451

How

e, 2

00577

Two-

cent

re, p

ilot

RCT

Gro

up a

lloca

tion

via

rand

omise

d pe

rmut

edbl

ocks

, with

the

pro

ject

man

ager

hol

ding

det

ails

of a

ssig

nmen

t un

tilal

loca

tion

by a

the

rapi

st

UK

35 p

artic

ipan

ts: 1

8 ex

perim

enta

l, 17

con

trol

Subj

ects

rec

ruite

d fr

om a

dmiss

ions

to

an

acut

e st

roke

uni

t be

twee

n 20

01 a

nd 2

002

Incl

usio

n cr

iteria

: Age

d 18

and

ove

r,ac

ute

vasc

ular

str

oke

pres

entin

g w

ithhe

mip

legi

a, m

edic

ally

sta

ble,

abl

e to

coop

erat

e, p

revi

ously

inde

pend

ently

mob

ile, a

nd in

depe

nden

t in

AD

Ls

Excl

usio

n cr

iteria

: Hist

ory

ofco

nditi

ons

or m

edic

atio

n af

fect

ing

bala

nce,

dem

entia

, im

paire

dco

nsci

ousn

ess

leve

ls, c

onco

mita

ntm

edic

al il

lnes

s or

mus

culo

skel

etal

cond

ition

, ser

ious

per

cept

ual

prob

lem

s

Mea

n ag

e: E

xper

imen

tal g

roup

:71

.5ye

ars

(SD

10.9

), co

ntro

l gro

up70

.7ye

ars

(SD

7.6

)51

% m

ale

Stro

ke d

etai

ls: U

nkno

wn

whe

ther

recu

rren

t st

roke

incl

uded

, 47%

rig

hthe

mip

ares

is

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

26.5

day

s (S

D 1

5.7)

, con

trol

gro

up23

.1 d

ays

(SD

17.

5)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:Ri

verm

ead

Mob

ility

Inde

x 24

Expe

rimen

tal g

roup

: Usu

al c

are

plus

exer

cise

s ai

med

at

impr

ovin

g la

tera

lw

eigh

t tr

ansf

eren

ce in

sitt

ing

and

stan

ding

. Thi

s in

clud

ed r

epet

ition

of

self-

initi

ated

goa

l-orie

ntat

edac

tiviti

es in

var

ious

pos

ture

s.

16 t

asks

in t

otal

, with

ten

repe

titio

ns o

f eac

h ex

erci

se

Sess

ions

wer

e 30

min

utes

, thr

eetim

es a

wee

k, fo

r 4

wee

ks =

6ho

urs

Sess

ions

wer

e de

liver

ed b

y tr

aine

dph

ysio

ther

apy

assis

tant

s

Com

paris

on g

roup

: Usu

al c

are:

no

deta

ils g

iven

Out

com

es r

ecor

ded

atba

selin

e, p

ost-

trea

tmen

t(4

wee

ks) a

nd a

t8

wee

ks p

ost-

base

line

Lim

b-sp

ecifi

c fu

nctio

n:Si

t-to

-sta

nd, s

tand

-to-

sit(t

ime

in s

econ

ds),

late

ral

reac

h te

st (t

ime

tore

turn

to

quie

t sit

ting)

No

signi

fican

t di

ffere

nces

repo

rted

at

base

line

6% lo

st t

o fo

llow

-up

aten

d of

tre

atm

ent

phas

e

Out

com

e as

sess

ors

blin

dto

tre

atm

ent

grou

p

No

inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al

Subj

ects

com

plet

ed 1

0.6

sess

ions

on

aver

age cont

inue

d

Appendix 1

78

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Kw

akke

l, 19

9953

Mul

ticen

tre

RCT

Rest

ricte

dra

ndom

isatio

n(p

erm

uted

blo

cks

ofni

ne) w

as a

pplie

d, u

sing

rand

om n

umbe

r ta

bles

for

each

of t

hree

part

icip

atin

g ho

spita

ls.A

lloca

tion

was

conc

eale

d by

use

of

seal

ed e

nvel

opes

12%

lost

to

follo

w-u

pat

end

of t

reat

men

tph

ase

Net

herla

nds

101

part

icip

ants

: 31

leg

trai

ning

grou

p, 3

3 ar

m t

rain

ing

grou

p,

37 c

ontr

ol

Part

icip

ants

rec

ruite

d fr

om s

even

hosp

itals

in T

he N

ethe

rland

s,19

94–1

997

Incl

usio

n cr

iteria

: Prim

ary

first

eve

rst

roke

in t

he t

errit

ory

of t

he m

iddl

ece

rebr

al a

rter

y, c

onfir

med

by

CT

or

MRI

, age

d 30

–80,

impa

ired

mot

orfu

nctio

n of

the

arm

and

leg,

inab

ility

to w

alk

at fi

rst

asse

ssm

ent

Excl

usio

n cr

iteria

: Com

plic

atin

gm

edic

al h

istor

y or

sev

ere

defic

its in

com

mun

icat

ion,

mem

ory

orun

ders

tand

ing

Mea

n ag

e: A

rm t

rain

ing

grou

p69

year

s (S

D 9

.8),

leg

trai

ning

gro

up64

.5ye

ars

(SD

9.7

), co

ntro

l gro

up64

.1ye

ars

(SD

15)

43%

mal

e

Stro

ke d

etai

ls: F

irst

ever

str

oke

(TA

CI

61%

, PA

CI 3

3%, L

AC

I 6%

), 41

%rig

ht h

emip

ares

is

Tim

e sin

ce s

trok

e: A

rm t

rain

ing

grou

p7.

2 da

ys (S

D 2

.8),

leg

trai

ning

gro

up7.

0 da

ys (S

D 2

.5),

cont

rol g

roup

7.5

days

(SD

2.9

)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:BI

of 9

or

low

er

Leg

trai

ning

gro

up: S

ittin

g, s

tand

ing

and

wei

ght-

bear

ing

exer

cise

,em

phas

is on

ach

ievi

ng s

tabi

lity

and

impr

ovin

g ga

it ve

loci

ty. T

read

mill

trai

ning

was

use

d if

avai

labl

e

Arm

tra

inin

g gr

oup:

Fun

ctio

nal

exer

cise

to

faci

litat

e fo

rced

arm

and

hand

act

ivity

suc

h as

lean

ing,

punc

hing

a b

all,

gras

ping

, rea

chin

g,dr

essin

g, h

air-

com

bing

and

mov

ing

obje

cts

Both

gro

ups:

If t

reat

men

t at

disa

bilit

y le

vel n

ot p

ossib

le,

stre

ngth

enin

g ex

erci

ses

wer

e us

ed

Inte

rven

tion

was

add

ition

al t

o ba

sicre

habi

litat

ion

of 1

5 m

inut

es e

ach

arm

and

leg

reha

bilit

atio

n an

d1.

5ho

urs

per

wee

k of

AD

L tr

aini

ngby

an

occu

patio

nal t

hera

pist

Sess

ions

wer

e 30

min

utes

, 5 d

ays

aw

eek

for

20 w

eeks

= 4

5 ho

urs.

Sess

ions

wer

e de

liver

ed in

divi

dual

lyby

a p

hysio

ther

apist

Com

paris

on g

roup

s: C

ontr

ol g

roup

:im

mob

ilisa

tion

of t

he p

aret

ic a

rman

d le

g by

mea

ns o

f an

infla

tabl

epr

essu

re s

plin

t

Out

com

es r

ecor

ded

atba

selin

e, w

eekl

ybe

twee

n w

eeks

1 a

nd10

, and

eve

ry 2

wee

ksbe

twee

n w

eeks

11

and

26. P

ost-

inte

rven

tion

mea

sure

s w

ere

at w

eek

20. F

inal

mea

sure

men

tsw

ere

at 2

6 w

eeks

.Re

sults

are

pre

sent

edfo

r ba

selin

e, w

eeks

6,

12, 2

0 an

d 26

Low

er li

mb

func

tion:

FAC

, wal

king

spe

ed(c

omfo

rtab

le a

ndm

axim

um)

Upp

er li

mb

func

tion:

ARA

T

Glo

bal A

DL:

BI

Hea

lth s

tatu

s/qu

ality

of

life:

NH

P

No

signi

fican

t di

ffere

nces

repo

rted

at

base

line

Ass

esso

rs w

ere

blin

d to

grou

p al

loca

tion.

Trea

tmen

t as

signm

ent

was

uni

nten

tiona

llydi

sclo

sed

for

ten

subj

ects

(one

leg

trai

ning

, fou

rar

m t

rain

ing,

five

con

trol

grou

p)

No

likel

y in

terv

entio

n-re

late

d re

ason

s fo

rw

ithdr

awal

, alth

ough

tw

opa

tient

s re

fuse

d th

e sp

lint

cont

rol t

reat

men

t

Com

plia

nce

with

del

iver

yof

inte

nded

am

ount

s of

trai

ning

was

mon

itore

dan

d ac

hiev

ed

cont

inue

d

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es


79


Lang

ham

mer

, 200

068St

ratif

ied,

sin

gle-

cent

reRC

T

Subj

ects

ran

dom

ised

and

stra

tifie

d ac

cord

ing

to g

ende

r an

dhe

misp

here

site

. No

deta

ils o

f ran

dom

isatio

n

Nor

way

61 p

artic

ipan

ts: 3

3 ex

perim

enta

l, 28

con

trol

Subj

ects

rec

ruite

d fr

om p

atie

nts

atte

ndin

g ho

spita

l in

Nor

way

,19

96–1

997

Incl

usio

n cr

iteria

: Firs

t ev

er s

trok

ew

ith h

emip

ares

is ve

rifie

d cl

inic

ally

and

by C

T

Excl

usio

n cr

iteria

: Mor

e th

an o

nest

roke

inci

dent

, sub

arac

hnoi

dbl

eedi

ng, t

umou

rs o

f the

bra

in,

othe

r se

vere

med

ical

con

ditio

ns in

com

bina

tion

with

str

oke,

5 o

r m

ore

poin

ts o

n ea

ch o

f the

sco

res

on t

heM

AS

Mea

n ag

e:78

yea

rs (S

D 9

) (ra

nge

49–7

5)59

% m

ale

Stro

ke d

etai

ls: F

irst

stro

ke, 5

6% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: B

asel

ine

mea

sure

sta

ken

with

in 3

days

of a

dmiss

ion

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:BI

mea

n 51

Expe

rimen

tal g

roup

: Mot

orRe

lear

ning

Pro

gram

me

as p

er C

arr

and

Shep

herd

, 198

7.18

Func

tiona

lta

sk t

rain

ing

in o

rdin

ary

sett

ings

,w

ith o

rdin

ary

task

s, u

sing

the

prin

cipl

es o

f max

imal

rep

etiti

on,

task

and

set

ting

varia

tion

Expe

rimen

tal i

nter

vent

ion

was

inst

ead

of u

sual

car

e

Sess

ions

wer

e 40

min

utes

min

imum

per

sess

ion,

5 d

ays

a w

eek

for

aslo

ng a

s ho

spita

lised

, and

con

tinui

ngin

to t

he c

omm

unity

, alth

ough

rece

ipt

of p

hysio

ther

apy

inco

mm

unity

set

tings

was

var

iabl

e

Sess

ions

wer

e de

liver

ed b

y ho

spita

lan

d ou

tpat

ient

phy

sioth

erap

ists.

Afte

r di

scha

rge,

som

e su

bjec

tsre

ceiv

ed t

hera

py in

the

ir ow

nho

mes

, at

reha

bilit

atio

n ce

ntre

s or

priv

ate

outp

atie

nt d

epar

tmen

ts,

depe

nden

t on

nee

d

Com

paris

on g

roup

: Bob

ath

prog

ram

me,

as

per

Boba

th, 1

99014

4

Out

com

es r

ecor

ded

atba

selin

e, a

nd a

t 2

wee

ks,

3 m

onth

s, 1

yea

r an

d4

year

s po

st-s

trok

e

Lim

b-sp

ecifi

c fu

nctio

n:M

AS,

SM

ES –

sub

scal

efo

r tr

unk/

bala

nce/

gait,

Berg

Bal

ance

Sca

le(1

year

onl

y)

Mot

or p

erfo

rman

ce:

SMES

– s

ubsc

ales

for

leg

func

tion

and

arm

func

tion

Glo

bal f

unct

ion:

BI,

NH

P.

Oth

er m

easu

res:

Len

gth

of s

tay,

use

of

whe

elch

air,

disc

harg

ede

stin

atio

n

Con

trol

gro

up s

light

lym

ore

depe

nden

t at

ent

ry(b

asel

ine)

, but

no

signi

fican

t di

ffere

nce

inM

AS,

SM

ES o

r BI

Dat

a av

aila

ble

for

87%

at

3 m

onth

s

Blin

ding

sta

ted,

but

no

desc

riptio

n gi

ven

No

inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al

Doe

s no

t st

ate

mon

itorin

g of

tim

e sp

ent

in t

hera

py

cont

inue

d

Appendix 1

80

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

McC

lella

n, 2

00478

Dou

ble-

blin

d RC

T

Rand

omisa

tion

bynu

mbe

red,

sea

led,

opaq

ue e

nvel

opes

Aus

tral

ia26

par

ticip

ants

: 15

expe

rimen

tal,

11 c

ontr

ol

Subj

ects

rec

ruite

d on

disc

harg

e fr

omph

ysio

ther

apy

serv

ices

in s

ix h

ospi

tals

in o

ne r

egio

n

Incl

usio

n cr

iteria

: Str

oke

with

in t

hepa

st 1

8 m

onth

s, 4

5 ye

ars

and

olde

r,liv

ing

in t

he c

omm

unity

, sco

re >

0an

d <

6 on

MA

S, s

core

<6

on

item

7 o

r 8

of t

he M

AS

Excl

usio

n cr

iteria

: Una

ble

to c

onse

nt,

unco

ntro

lled

card

iac

sym

ptom

s or

othe

r m

edic

al c

ondi

tions

tha

t lim

ited

exer

cise

, or

with

a p

acem

aker

Mea

n ag

e: E

xper

imen

tal g

roup

69ye

ars

(SD

13)

, con

trol

gro

up72

year

s (S

D 9

)50

% m

ale

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or r

ecur

rent

str

oke,

50%

rig

hthe

mip

ares

is

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

med

ian

6.5

mon

ths

(IQR

5.5)

, con

trol

grou

p m

edia

n 4.

5 m

onth

s (IQ

R 3)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:A

ll su

bjec

ts c

ould

wal

k, b

ut w

ithdi

fficu

lty

Expe

rimen

tal g

roup

: Hom

e-ba

sed

exer

cise

pro

gram

me

aim

ed a

tim

prov

ing

mob

ility

in s

tand

ing

bala

nce

and

wal

king

, bas

ed o

n a

list

of 2

3 ac

tiviti

es a

rran

ged

hier

arch

ical

ly o

n th

eir

chal

leng

e to

bala

nce.

The

hom

e pr

ogra

mm

eus

ed v

ideo

sel

f-m

odel

ling

prep

ared

on a

bas

elin

e vi

sit t

o th

e cl

inic

to

pres

crib

e th

e ex

erci

se p

rogr

amm

e,te

leph

one

mon

itorin

g to

enc

oura

geco

mpl

ianc

e, a

nd t

wo

clin

ic v

isits

for

prog

ram

me

revi

ew

Sess

ions

wer

e pr

escr

ibed

60m

inut

es p

er d

ay o

ver

6 w

eeks

= 4

2 ho

urs.

Sub

ject

s w

ere

requ

ired

to k

eep

a re

cord

of

prac

tice

Com

paris

on g

roup

: Hom

e-ba

sed

exer

cise

pro

gram

me

for

impr

ovin

gup

per

limb

func

tion,

sta

rtin

g fr

omba

sic m

ovem

ent

thro

ugh

tofu

nctio

nal a

ctiv

ity, u

sing

the

sam

ese

lf-in

stru

ctio

nal v

ideo

, sel

f and

tele

phon

e m

onito

ring

and

clin

icvi

sits

as t

he e

xper

imen

tal g

roup

Out

com

es r

ecor

ded

atba

selin

e, p

ost-

trea

tmen

t(6

wee

ks) a

nd a

t14

wee

ks

Lim

b-sp

ecifi

c fu

nctio

n:Fu

nctio

nal R

each

Tes

t(c

m),

MA

S w

alki

ng

No

base

line

com

paris

ons

repo

rted

19%

lost

to

follo

w-u

p by

end

of t

reat

men

t ph

ase

Ass

esso

rs a

nd s

ubje

cts

blin

d to

gro

up a

lloca

tion

No

likel

y in

terv

entio

n-re

late

d re

ason

s fo

rw

ithdr

awal

Subj

ects

sel

f-re

port

ed75

% c

ompl

ianc

e w

ithpr

escr

ibed

exe

rcise

s

cont

inue

d


81


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Salb

ach,

200

4;51

Hig

gins

, 200

652St

ratif

ied,

mul

ticen

tre

RCT

Part

icip

ants

str

atifi

edin

to t

hree

gro

ups

base

don

com

fort

able

wal

king

spee

d. S

eque

nce

ofra

ndom

ass

ignm

ents

com

pute

r ge

nera

ted

inra

ndom

ly o

rder

edbl

ocks

of 2

and

4 fo

rea

ch s

trat

um. A

lloca

tion

mai

ntai

ned

in s

eale

d,op

aque

env

elop

es,

prep

ared

bef

ore

recr

uitm

ent

by p

erso

nsno

t in

volv

ed in

the

stud

y, a

nd u

nvei

led

afte

r ba

selin

eas

sess

men

t an

dst

ratif

icat

ion

Can

ada

91 p

artic

ipan

ts: 4

4 m

obili

ty, 4

7 ar

mtr

aini

ng g

roup

Subj

ects

wer

e re

crui

ted

from

nin

eho

spita

ls an

d tw

o re

habi

litat

ion

cent

res

in M

ontr

eal o

r Q

uebe

c

Incl

usio

n cr

iteria

: Firs

t or

rec

urre

ntst

roke

, und

er 1

yea

r po

st-s

trok

e at

recr

uitm

ent,

able

to

wal

k 10

m b

utw

ith r

esid

ual w

alki

ng d

efic

it fr

omm

ost

rece

nt s

trok

e, m

enta

lco

mpe

tenc

y an

d ab

ility

to

com

preh

end

inst

ruct

ions

, disc

harg

edfr

om p

hysic

al r

ehab

ilita

tion

and

resid

ent

in t

he c

omm

unity

Excl

usio

n cr

iteria

: Res

iden

t in

perm

anen

t ca

re fa

cilit

y, c

o-m

orbi

dity

prec

ludi

ng p

artic

ipat

ion

Mea

n ag

e: 7

2 ye

ars,

(ran

ge 3

8–91

)61

.5%

mal

e

Stro

ke d

etai

ls: F

irst

or r

ecur

rent

stro

ke, 8

3% is

chae

mic

, 56%

rig

hthe

mip

ares

is, 4

3% le

ft he

mip

ares

is,1%

bila

tera

l

Tim

e sin

ce s

trok

e: m

ean

228

days

(S

D 7

8)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:6M

WT

mea

n 20

7m

(SD

128

)

Mob

ility

inte

rven

tion:

Ten

wal

king

-re

late

d ta

sks

desig

ned

tost

reng

then

the

low

er e

xtre

miti

esan

d en

hanc

e w

alki

ng b

alan

ce,

spee

d an

d di

stan

ce in

a p

rogr

essiv

em

anne

r

Upp

er e

xtre

mity

inte

rven

tion:

Func

tiona

l tas

ks s

uch

asm

anip

ulat

ing

card

s, u

sing

ake

yboa

rd a

nd w

ritin

g w

hile

sea

ted

Inte

rven

tion

was

afte

r di

scha

rge

from

phy

sical

reh

abili

tatio

n

Sess

ions

wer

e 60

min

utes

, thr

eetim

es a

wee

k fo

r 6

wee

ks =

18ho

urs

Sess

ions

wer

e de

liver

ed in

divi

dual

lyby

a p

hysic

al o

r oc

cupa

tiona

lth

erap

ist in

a h

ospi

tal o

utpa

tient

or

reha

bilit

atio

n se

ttin

g

Com

paris

on g

roup

: Sal

bach

, 200

4:51

uppe

r ex

trem

ity t

rain

ing,

Hig

gins

,20

06:52

low

er e

xtre

mity

tra

inin

g

Out

com

es r

ecor

ded

atba

selin

e an

d at

6 w

eeks

Lim

b-sp

ecifi

c fu

nctio

n:6M

WT,

5-m

wal

k at

com

fort

able

and

max

imum

spe

ed, T

UG

,Be

rg B

alan

ce S

cale

,A

ctiv

ities

Spe

cific

Bala

nce

Con

fiden

ceSc

ale

Glo

bal A

DL:

BI

No

repo

rt o

f sig

nific

ant

diffe

renc

es a

t ba

selin

e

Inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al:

one

unw

illin

g to

tra

vel,

one

expe

rienc

ed t

heon

set

of g

roin

pai

n; t

wo

wan

ted

the

othe

rin

terv

entio

n

Full

inte

ntio

n-to

-tre

atan

alys

is us

ed, w

ith

post

-inte

rven

tion

valu

esfo

r su

bjec

ts im

pute

d

Ass

esso

rs w

ere

blin

d to

grou

p al

loca

tion.

Unb

lindi

ng o

ccur

red

for

18/4

2 in

the

mob

ility

grou

p an

d 16

/43

of t

heup

per

extr

emity

tra

inin

ggr

oup,

but

did

not

bia

sth

e es

timat

ed e

ffect

as

eval

uate

d by

mul

tiple

linea

r re

gres

sion

mod

el

86%

of m

obili

ty g

roup

subj

ects

att

ende

d 17

or

mor

e se

ssio

ns o

ut o

f 18.

72%

of u

pper

ext

rem

ityat

tend

ed 1

7 or

mor

ese

ssio

ns

344

peop

le w

ere

eval

uate

d fo

r pa

rtic

ipat

ion

but

73%

ref

used

bec

ause

they

cou

ld n

ot t

oler

ate

the

trav

el r

equi

red

for

atte

ndan

ce

cont

inue

d

Appendix 1

82

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Turt

on, 1

99069

Sing

le-c

entr

e, q

uasi-

rand

omise

d tr

ial

Subj

ects

wer

e as

signe

din

alte

rnat

e ru

ns o

f fiv

e

UK

22 p

artic

ipan

ts: 1

2 ex

perim

enta

l, te

nin

the

con

trol

Subj

ects

rec

ruite

d fr

om s

trok

epa

tient

s di

scha

rged

from

inpa

tient

care

at

one

hosp

ital,

1986

–198

7

Incl

usio

n cr

iteria

: Som

e im

pairm

ent

offu

nctio

n of

the

affe

cted

upp

er li

mb

(i.e.

less

tha

n 95

% p

erfo

rman

ce o

n a

peg

tran

sfer

tas

k), a

ble

to u

nder

stan

din

stru

ctio

ns, l

ives

with

in 2

5 m

iles

(15.

5 km

) of h

ospi

tal

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: E

xper

imen

tal g

roup

59ye

ars

(SD

11.

97),

cont

rol g

roup

58ye

ars

(SD

6.8

6)55

% m

ale

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or r

ecur

rent

str

oke,

56%

rig

hthe

mip

ares

is

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

24 w

eeks

(SD

25.

8), c

ontr

ol g

roup

16 w

eeks

(SD

6.1

)

Prei

nter

vent

ion

disa

bilit

y le

vel:

12.5

/20

on S

outh

ern

Mot

or A

sses

smen

t Sc

ale

Expe

rimen

tal g

roup

: Usu

alou

tpat

ient

car

e pl

us h

ome-

base

dex

erci

se p

rogr

amm

e fo

r th

e up

per

limb,

bas

ed o

n m

otor

rel

earn

ing

prin

cipl

es. E

xerc

ises

incl

uded

mov

emen

t an

d ta

sk-r

elat

ed r

each

,gr

asp

and

grip

. Sub

ject

s w

ere

visit

ed b

y an

occ

upat

iona

l the

rapi

stat

hom

e, a

nd g

iven

exe

rcise

s an

dre

petit

ions

. Exe

rcise

s w

ere

deta

iled

in a

boo

klet

. Sub

ject

s w

ere

visit

ed e

very

2–4

wee

ks fo

r re

view

.C

arer

s w

ere

invo

lved

if a

ble

and

will

ing

Subj

ects

wer

e as

signe

d tw

o to

thre

e pr

actic

e se

ssio

ns p

er d

ay(a

ppro

x. 1

hou

r), 7

day

s a

wee

k fo

r8–

11 w

eeks

= 6

3 ho

urs

appr

ox.

Sess

ions

wer

e se

lf-m

anag

ed b

y th

esu

bjec

t an

d th

eir

care

rs a

t ho

me,

with

tw

o to

thr

ee h

ome

visit

s by

an

occu

patio

nal t

hera

pist

for

prog

ram

me

revi

ew

Com

paris

on g

roup

: Usu

al o

utpa

tient

care

(som

e ha

d th

erap

y, b

ut o

ther

sdi

d no

t)

Out

com

es r

ecor

ded

atba

selin

e an

d po

st-

trea

tmen

t (8

–11

wee

ks)

Lim

b-sp

ecifi

c m

otor

perfo

rman

ce: S

ittin

g pa

rtof

the

upp

er li

mb

activ

ity a

sses

smen

t –

Sout

hern

Mot

or G

roup

Ass

essm

ent,

10H

PT

Base

line

diffe

renc

es:

Diff

eren

ce in

tim

e sin

cest

roke

: exp

erim

enta

lgr

oup

mea

n of

24

wee

ks,

and

usua

l car

e m

ean

of16

wee

ks. 1

0HPT

perf

orm

ance

:ex

perim

enta

l gro

up m

ore

disa

bled

, hom

e th

erap

ygr

oup

had

mor

e ca

rers

livin

g at

hom

e

No

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

Out

com

e as

sess

or n

otbl

inde

d to

tre

atm

ent

grou

p

No

inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al

Self-

repo

rted

rat

es o

fco

mpl

ianc

e: m

ean

68%

(SD

25)

. Thr

ee o

ut o

f 12

sub

ject

s ra

ted

less

than

50%

cont

inue

d


83


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Van

Vlie

t, 20

0570

Sing

le-c

entr

e RC

T

Rand

omisa

tion

was

by

com

pute

r-ge

nera

ted

rand

om s

eque

nce

prov

ided

by

anin

depe

nden

t pe

rson

.Bl

ocke

d ra

ndom

isatio

nw

as u

sed.

Allo

catio

nsw

ere

prov

ided

inen

velo

pes

and

open

edaf

ter

initi

al a

sses

smen

t

UK

120

part

icip

ants

: 60

expe

rimen

tal,

60 c

ontr

ol

Subj

ects

wer

e re

crui

ted

from

peo

ple

adm

itted

to

a st

roke

reh

abili

tatio

nw

ard

over

a p

erio

d of

21

mon

ths

Incl

usio

n cr

iteria

: Dia

gnos

is of

str

oke,

refe

rral

to

phys

ioth

erap

y

Excl

usio

n cr

iteria

: Mor

e th

an 2

wee

kspo

st-s

trok

e, u

ncon

scio

us o

nad

miss

ion,

una

ble

to t

oile

tin

depe

nden

tly p

rior

to s

trok

e, li

ving

mor

e th

an 2

5km

from

hos

pita

l,un

able

to

tole

rate

mor

e th

an30

min

utes

of p

hysic

al t

asks

req

uire

din

initi

al a

sses

smen

t

Mea

n ag

e: E

xper

imen

tal g

roup

75ye

ars

(SD

9.1

), co

ntro

l gro

up73

.3ye

ars

(SD

10.

4)50

% m

ale

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or r

ecur

rent

str

oke.

51%

rig

hthe

mip

ares

is, 4

6% le

ft he

mip

ares

is,3%

bila

tera

l

Tim

e sin

ce s

trok

e: W

ithin

14

days

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:Ri

verm

ead

Mot

or A

sses

smen

t gr

oss

func

tion

subs

cale

: med

ian

(IQR)

expe

rimen

tal g

roup

2 (1

–6),

cont

rol

grou

p 1

(1–4

)

Mov

emen

t sc

ienc

e th

erap

y: B

ased

on

the

prin

cipl

e th

at s

kill

inpe

rfor

man

ce is

a d

irect

func

tion

ofth

e am

ount

of p

ract

ice.

Pro

gram

me

invo

lved

use

of e

very

day

obje

cts

for

func

tiona

l tra

inin

g, a

nd p

ract

ice

outs

ide

deliv

ered

ses

sions

Inte

rven

tion

was

inst

ead

of u

sual

care

Subj

ects

rec

eive

d a

med

ian

23m

inut

es o

f tre

atm

ent

by a

phys

ioth

erap

ist p

er w

eek

day

(IQR

13–3

2m

). M

edia

n to

tal n

umbe

r of

min

utes

of t

reat

men

t w

as 3

65 (I

QR

140–

1160

), eq

uatin

g to

app

rox.

6ho

urs’

tot

al t

rain

ing

time

Trea

tmen

t w

as d

eliv

ered

by

phys

ioth

erap

ists,

occ

upat

iona

lth

erap

ists

and

phys

ioth

erap

yas

sista

nts,

in h

ospi

tal,

and

as a

nou

tpat

ient

afte

r di

scha

rge.

Trea

tmen

t w

as d

eliv

ered

for

as lo

ngas

nee

ded

Com

paris

on g

roup

: Bob

ath-

base

dth

erap

y

Out

com

es r

ecor

ded

atba

selin

e, 4

wee

ks,

3m

onth

s an

d 6

mon

ths

Lim

b-sp

ecifi

c fu

nctio

n:RM

A S

cale

, MA

S,6M

WS,

10H

PT

Glo

bal f

unct

ion:

BI,

Exte

nded

Act

iviti

es o

fD

aily

Liv

ing

At

base

line,

con

trol

gro

upha

d hi

gher

med

ian

scor

esfo

r Ri

verm

ead

gros

sfu

nctio

n, a

nd le

g an

dtr

unk

subs

cale

s, a

nd fo

rsu

pine

to

side

lyin

g,su

pine

to

sittin

g, b

alan

ced

sittin

g, a

nd s

it-to

-sta

ndse

ctio

ns o

f the

MA

S.Ex

perim

enta

l gro

up h

adhi

gher

med

ian

scor

es fo

rth

e up

per

arm

sec

tion

ofth

e M

AS

Dat

a av

aila

ble

for

71%

at

3 m

onth

s

Out

com

e as

sess

ors

blin

dto

tre

atm

ent

allo

catio

n.Bl

indi

ng a

sses

sed

assu

cces

sful

Inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al:

seve

n su

bjec

ts r

efus

edou

tcom

e m

easu

rem

ent

at3

mon

ths,

5 in

the

expe

rimen

tal g

roup

and

two

in t

he c

ontr

ol g

roup

,bu

t re

ason

s ar

e no

tkn

own

cont

inue

d

Appendix 1

84

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Win

stei

n, 2

00471

(onl

y FT

P an

d us

ual-

care

con

trol

gro

upda

ta in

clud

ed)

Stra

tifie

d, s

ingl

e-ce

ntre

pilo

t RC

T

Subj

ects

wer

era

ndom

ised

to g

roup

sw

ithin

sev

erity

str

ata,

usin

g O

rpin

gton

Prog

nost

ic S

cale

(1.6

–4.1

= m

ore

seve

re, 4

.2–6

.8 =

less

seve

re),

usin

g a

bloc

king

fact

or n

otid

entif

ied

to s

tudy

pers

onne

l. Se

aled

enve

lope

s de

liver

ed b

yin

depe

nden

t pe

rson

,an

d op

ened

on

enro

lmen

t of

nex

tel

igib

le s

ubje

ct

USA

64 p

artic

ipan

ts: 2

2 fu

nctio

nal t

ask

prac

tice

(FT

P), 2

1 st

reng

th t

rain

ing,

21 u

sual

car

e (U

K)

Subj

ects

wer

e re

crui

ted

from

new

adm

issio

ns t

o a

neur

oreh

abili

tatio

nse

rvic

es c

entr

e

Incl

usio

n cr

iteria

: Age

d 29

–76,

firs

ttim

e st

roke

. Str

oke

onse

t 2–

35 d

ays

befo

re s

tudy

ent

ry, F

IM s

core

of

40–8

0, w

iden

ed t

o in

clud

e a

broa

der

rang

e ea

rly in

rec

ruitm

ent

phas

e

Excl

usio

n cr

iteria

: Con

ditio

ns t

hat

inte

rfer

ed w

ith a

rm m

ovem

ents

,ca

rdia

c di

seas

e lim

iting

func

tion,

bra

inin

jury

, sev

ere

apha

sia, n

egle

ct,

agita

tion

or d

epre

ssio

n th

at c

ould

limit

part

icip

atio

n

Mea

n ag

e: E

xper

imen

tal g

roup

<35

year

s =

2, 3

5–75

year

s =

18,

cont

rol g

roup

<35

year

s =

0,

35–7

5ye

ars

= 1

9, >

75ye

ars

= 1

52.5

% m

ale

(FT

P +

UC

gro

ups)

Stro

ke d

etai

ls: F

irst

stro

ke, 8

5%isc

haem

ic s

trok

e, 6

2% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

15.5

day

s (S

D 6

), co

ntro

l gro

up15

.4da

ys (S

D 5

.5)

Prei

nter

vent

ion

disa

bilit

y le

vel:

Orp

ingt

on S

core

1.6

–4.1

Func

tiona

l tas

k pr

actic

e gr

oup:

Usu

alca

re p

lus

task

-spe

cific

func

tiona

ltr

aini

ng b

ased

on

the

prin

cipl

es o

fm

otor

rel

earn

ing,

focu

sing

onsy

stem

atic

and

rep

etiti

ve p

ract

ice

of t

asks

. Tas

ks w

ere

rand

omly

orde

red,

and

pro

gres

sed

indi

fficu

lty

Sess

ions

wer

e 1

hour

per

day

,5

days

per

wee

k, fo

r 4

wee

ks =

20ho

urs

addi

tiona

l to

usua

l car

e

Sess

ions

wer

e de

liver

ed b

y a

phys

ical

the

rapi

st in

hos

pita

l, an

d in

an o

utpa

tient

set

ting

whe

ndi

scha

rged

Com

paris

on g

roup

: Usu

al c

are,

deliv

ered

prim

arily

by

occu

patio

nal

ther

apist

s, w

hich

cou

ld in

clud

em

uscl

e fa

cilit

atio

n ex

erci

ses

emph

asisi

ng t

hene

urod

evel

opm

enta

l tre

atm

ent

appr

oach

, neu

rom

uscu

lar

elec

tric

alst

imul

atio

n, s

tret

chin

g ex

erci

ses

and

AD

Ls

Out

com

es r

ecor

ded

atba

selin

e, p

ost-

trea

tmen

t(4

–6 w

eeks

) and

9m

onth

s af

ter

stro

ke

Lim

b-sp

ecifi

c fu

nctio

n:FT

HU

E

Mot

or p

erfo

rman

ce: F

M

ADL:

FIM

No

signi

fican

t di

ffere

nces

repo

rted

at

base

line

7% lo

ss t

o fo

llow

-up

aten

d of

tre

atm

ent

phas

e

Out

com

e as

sess

ors

not

blin

ded

to g

roup

allo

catio

n

Inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al:

one

part

icip

ant

in t

heex

perim

enta

l gro

up lo

stin

tere

st

Com

plia

nce

repo

rted

as

near

per

fect

, exc

ept

for

one

pers

on in

the

expe

rimen

tal g

roup

who

,af

ter

disc

harg

e, a

ndbe

caus

e of

tra

vel

dist

ance

, com

plet

ed o

nly

15 o

f the

20

hour

s’tr

aini

ng

cont

inue

d


85


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Yen,

200

572Si

ngle

-cen

tre

RCT

No

deta

ils o

fra

ndom

isatio

n m

etho

d

Taiw

an30

par

ticip

ants

: 13

expe

rimen

tal,

17co

ntro

l

Subj

ects

rec

ruite

d fr

om a

dep

artm

ent

of n

euro

logy

Incl

usio

n cr

iteria

: Sin

gle

stro

kere

sulti

ng in

hem

ipar

esis,

min

imum

of

20 d

egre

es o

f act

ive

wris

t ex

tens

ion

and

10 d

egre

es o

f act

ive

finge

rex

tens

ion,

age

d 18

–80,

no

seve

reap

hasia

or

cogn

itive

impa

irmen

t

Excl

usio

n cr

iteria

: Oth

er d

iseas

es t

hat

wou

ld c

onfo

und

the

stud

y su

ch a

sPa

rkin

son’

s di

seas

e, s

houl

der

subl

uxat

ion,

rec

urre

nt s

trok

e du

ring

the

trai

ning

per

iod

Mea

n ag

e68

year

s (r

ange

47–

80)

46%

mal

e

Stro

ke d

etai

ls: F

irst

stro

ke, 6

0% r

ight

hem

ipar

esis

Tim

e sin

ce s

trok

e: E

xper

imen

tal g

roup

8.4

mon

ths

(SD

8),

cont

rol g

roup

6.2

mon

ths

(SD

7.9

)

Prei

nter

vent

ion

func

tiona

l abi

lity

leve

l:ba

selin

e m

ean

3.28

sec

onds

per

item

on t

he W

MFT

Expe

rimen

tal i

nter

vent

ion:

Pra

ctic

eof

15–

20 t

asks

sel

ecte

d fr

om a

batt

ery

of 5

0 ta

sks,

with

tas

ksh

apin

g, c

onsis

ting

of v

erba

lfe

edba

ck fo

r sm

all i

mpr

ovem

ents

,ta

sk s

elec

tion

base

d on

nee

ds o

fin

divi

dual

, and

per

form

ance

assis

tanc

e in

the

initi

al s

tage

s if

unab

le t

o pe

rfor

m in

depe

nden

tly

Inte

rven

tion

was

inst

ead

of u

sual

care

Sess

ions

wer

e 6

hour

s pe

r da

y. It

isun

clea

r w

heth

er t

here

wer

e fiv

e or

seve

n se

ssio

ns p

er w

eek.

Trea

tmen

t du

ratio

n w

as 2

wee

ks =

60–8

4 ho

urs

Sess

ions

wer

e de

liver

ed b

y a

phys

ical

the

rapi

st. I

t is

uncl

ear

whe

ther

ses

sions

wer

e gr

oup

base

dor

indi

vidu

al

Com

paris

on g

roup

: Reg

ular

prog

ram

me

of p

hysic

al t

hera

pyin

clud

ing

gait

trai

ning

, fac

ilita

tion,

bala

nce

trai

ning

or

occu

patio

nal

ther

apy.

It is

unc

lear

how

muc

htim

e th

e co

ntro

l gro

up s

pent

inth

erap

y

Out

com

es r

ecor

ded

atba

selin

e an

d po

st-

trea

tmen

t (2

wee

ks)

Lim

b-sp

ecifi

c fu

nctio

n:M

ean

time

take

n to

com

plet

e in

divi

dual

item

s on

the

WM

FT.

Resu

lts fo

r ite

ms

8–15

are

only

pre

sent

edfo

r su

bjec

ts a

ble

toco

mpl

ete

them

with

in2

min

utes

No

base

line

diffe

renc

esre

port

ed

No

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

Blin

ding

sta

ted,

but

no

desc

riptio

n gi

ven

No

inte

rven

tion-

rela

ted

reas

ons

for

with

draw

al

No

repo

rt o

f att

enda

nce

CT,

com

pute

d to

mog

raph

y; F

M, F

ugl–

Mey

er; F

TP,

func

tiona

l tas

k pr

actic

e; L

AC

I, la

cuna

r in

farc

tion;

MI,

myo

card

ial i

nfar

ctio

n; N

HP,

Not

tingh

am H

ealth

Pro

file;

PA

CI,

part

ial a

nter

ior

circ

ulat

ion

infa

rctio

n; T

AC

I, to

tal a

nter

ior

circ

ulat

ion

infa

rctio

n; U

C, u

sual

car

e.


87


Appendix 2

Included studies: constraint-induced movement therapy

Appendix 2

88

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Alb

erts

, 200

483RC

T

Rand

omisa

tion

proc

edur

e no

tde

scrib

ed

USA

Ten

part

icip

ants

: fiv

e in

terv

entio

n,fiv

e co

ntro

l

Part

icip

ants

rec

ruite

d fr

om s

ubac

ute

stro

ke p

atie

nts

(3–9

mon

ths

post

-st

roke

) who

wer

e pa

rtic

ipat

ing

inEX

CIT

E tr

ial

Incl

usio

n cr

iteria

:Onl

y on

e st

roke

, at

leas

t 20

deg

rees

act

ive

wris

tex

tens

ion,

10-

degr

ee a

ctiv

e fin

ger

exte

nsio

n, m

inim

um p

assiv

e ra

nge

ofm

otio

n of

90

degr

ees

for

shou

lder

flexi

on a

nd a

bduc

tion,

sco

re o

f at

leas

t 24

on

MM

SE a

nd n

ot r

ecei

ving

any

othe

r th

erap

y at

tim

e of

stu

dy

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 6

4.1

year

s (r

ange

41–

84)

50%

mal

e

Stro

ke d

etai

ls: F

irst

stro

ke o

nly,

20%

right

hem

ipar

esis,

% is

chae

mic

stro

ke n

ot s

tate

d

Mea

n tim

e sin

ce s

trok

e: 6

mon

ths,

(ran

ge 3

–9)

Mea

n FM

sco

re p

re-in

terv

entio

n:O

vera

ll 39

.9 (S

D 1

2.5)

, int

erve

ntio

n34

.4 (S

D 7

.6),

cont

rol 4

5.4

(SD

14.

0)

Expe

rimen

tal g

roup

: con

stra

int-

indu

ced

mov

emen

t th

erap

y in

whi

ch le

ss a

ffect

ed h

and

was

pla

ced

in a

mitt

en. M

itten

wor

n fo

rap

prox

. 90%

of w

akin

g ho

urs

Con

stra

int-

indu

ced

mov

emen

tth

erap

y tr

aini

ng s

essio

ns a

tten

ded

5da

ys p

er w

eek

for

up t

o 6

hour

spe

r da

y fo

r 2

cons

ecut

ive

wee

ks.

Shap

ing,

or

adap

tive

task

pra

ctic

ean

d re

petit

ive

task

pra

ctic

ete

chni

ques

use

d du

ring

trai

ning

sess

ions

. All

trai

ning

was

one

-on-

one

with

reh

abili

tatio

n sp

ecia

list

Com

paris

on g

roup

: Del

ayed

gro

upsc

hedu

led

to r

ecei

ve c

onst

rain

t-in

duce

d m

ovem

ent

ther

apy

1 ye

arla

ter.

Dur

ing

inte

rven

tion

perio

ddi

d no

t pa

rtic

ipat

e in

form

alre

habi

litat

ion

prog

ram

mes

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n.

Lim

b-sp

ecifi

c fu

nctio

n:W

MFT

Mot

or im

pairm

ent:

FM (a

rm a

nd h

and

sect

ion)

Allo

catio

n co

ncea

lmen

tst

ated

, but

met

hod

uncl

ear

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

cont

inue

d


89


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Att

eya,

200

479RC

T

Rand

omisa

tion

proc

edur

e no

tde

scrib

ed

Saud

i Ara

bia

Six

part

icip

ants

: tw

o in

terv

entio

n,tw

o tr

aditi

onal

the

rapy

, tw

o co

ntro

l

Incl

usio

n cr

iteria

: Str

oke

4w

eeks

to

6m

onth

s ag

o, a

ge 1

8–75

, disc

harg

edfr

om r

ehab

ilita

tion,

10-

degr

ee a

ctiv

eex

tens

ion

in fi

nger

s, m

otiv

ated

,w

illin

g to

follo

w in

terv

entio

ngu

idel

ines

Excl

usio

n cr

iteria

: Sig

nific

ant

cogn

itive

impa

irmen

t ha

emor

rhag

ic o

r bi

late

ral

lesio

ns, l

esio

ns in

the

prim

ary

sens

ory

or m

otor

cor

tical

are

as, s

igni

fican

tsp

astic

ity, s

igni

fican

t pa

in in

the

affe

cted

upp

er li

mb,

invo

lvem

ent

inan

y ot

her

expe

rimen

tal r

ehab

ilita

tion

or d

rug

stud

ies

Mea

n ag

e: 5

4.3

year

s (r

ange

45–

67)

50%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 50%

rig

hthe

mip

ares

is, %

isch

aem

ic s

trok

e no

tst

ated

Mea

n tim

e sin

ce s

trok

e: 4

.7 m

onth

s(r

ange

2.3

–5.8

)

Mea

n am

ount

of u

se o

f affe

cted

arm

at

base

line

(mea

sure

d by

MAL

):co

nstr

aint

-indu

ced

mov

emen

tth

erap

y gr

oup

2, t

radi

tiona

l the

rapy

grou

p 1,

con

trol

gro

up 3

(5 is

hig

hest

ratin

g)

Expe

rimen

tal i

nter

vent

ion:

cons

trai

nt-in

duce

d m

ovem

ent

ther

apy

with

res

trai

nt o

f low

er a

rman

d ha

nd e

very

wee

kday

for

5ho

urs

usin

g a

cott

on B

obat

h sli

ng.

Patie

nts

part

icip

ated

in 3

0 m

inut

esof

phy

sical

the

rapy

and

30

min

utes

of o

ccup

atio

nal t

hera

py o

n an

outp

atie

nt b

asis

thre

e tim

es p

erw

eek

for

10 w

eeks

. Int

erve

ntio

nsin

clud

ed ‘s

hapi

ng’,

oper

ant

cond

ition

ing

met

hod

in w

hich

abe

havi

oura

l obj

ectiv

e is

appr

oach

edin

sm

all s

teps

of p

rogr

essiv

ely

incr

easin

g di

fficu

lty

Patie

nts

disc

harg

ed fr

omre

habi

litat

ion

Sett

ing:

Out

patie

nt c

linic

Com

paris

on g

roup

: tra

ditio

nal

ther

apy:

as

abov

e, b

ut w

ithou

tre

stra

int

Con

trol

gro

up r

ecei

ved

no t

hera

pydu

ring

10-w

eek

perio

d

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT,

WM

FT, M

AL

Mot

or im

pairm

ent:

FM

Allo

catio

n co

ncea

lmen

tun

clea

r

No

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

cont

inue

d

Appendix 2

90

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Boak

e, 2

00684

RCT

Met

hod

ofra

ndom

isatio

n no

tst

ated

USA

23 p

artic

ipan

ts: t

en in

terv

entio

n,

13 c

ontr

ol

Incl

usio

n cr

iteria

: Isc

haem

ic o

rha

emor

rhag

ic s

trok

e w

ithin

14

days

of e

nter

ing

tria

l, sc

ore

1–3

on it

em 5

(arm

mot

or) o

f the

NIH

SS, 1

0de

gree

s of

act

ive

mov

emen

t in

thum

b an

d tw

o fin

gers

of t

he a

ffect

edha

nd, t

otal

NIH

SS s

core

�14

if r

ight

-sid

ed a

nd �

19 if

left-

sided

str

oke,

abili

ty t

o pr

ovid

e in

form

ed c

onse

nt,

no p

revi

ous

stro

ke, n

o ne

glec

t or

spee

ch c

ompr

ehen

sion

that

wou

ldpr

even

t pa

rtic

ipat

ion

in s

tudy

Excl

usio

n cr

iteria

: NIH

SS a

rm m

otor

scor

e cr

iterio

n ex

clud

ed p

atie

nts

with

no

arm

mov

emen

t at

all,

or

node

tect

able

sho

ulde

r w

eakn

ess

Mea

n ag

e: 6

0.7

year

s, (r

ange

not

stat

ed)

65%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 48%

rig

hthe

mip

ares

is, 7

8% is

chae

mic

str

oke

Mea

n tim

e sin

ce s

trok

e: w

ithin

14da

ys

Mea

n N

IHSS

tot

al s

core

at

base

line:

CIM

T g

roup

4.9

(SD

1.8

), tr

aditi

onal

grou

p 5.

3 (S

D 3

.4)

Expe

rimen

tal i

nter

vent

ion:

CIM

T fo

rup

to

3 ho

urs

per

day,

for

14–1

5da

ys a

t a

freq

uenc

y of

6 d

ays

per

wee

k, e

xclu

ding

Sun

days

.In

terv

entio

ns in

clud

ed p

erfo

rmin

gta

sks

with

the

affe

cted

upp

erex

trem

ity in

clud

ing

reac

hing

,gr

aspi

ng, l

iftin

g an

d pl

acin

g. T

ask

diffi

culty

pro

gres

sivel

y in

crea

sed

usin

g be

havi

oura

l tec

hniq

ues

ofsh

apin

g an

d su

cces

sive

appr

oxim

atio

n. P

artic

ipan

ts w

ore

mitt

en o

n un

affe

cted

han

d fo

r 90

%of

wak

ing

hour

s

Inte

rven

tion

deliv

ered

by

licen

sed

ther

apist

s an

d th

erap

y as

sista

nts

incl

udin

g oc

cupa

tiona

l and

phy

sical

ther

apist

s

Gro

up s

ize

not

stat

ed

Sett

ing:

inpa

tient

reh

abili

tatio

n un

itan

d ou

tpat

ient

reh

abili

tatio

n cl

inic

Out

com

es r

ecor

ded

post

-tre

atm

ent

and

3–4

mon

ths

afte

r st

roke

Lim

b-sp

ecifi

c fu

nctio

n:G

roov

ed P

egbo

ard

Test

,M

AL

Mot

or im

pairm

ent:

FM

Stat

es r

ando

m a

lloca

tion,

but

no d

escr

iptio

n of

proc

edur

e gi

ven

Blin

ded

outc

ome

asse

ssor

s

cont

inue

d


91


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Dro

mer

ick,

200

081Pi

lot

RCT

Tabl

e of

ran

dom

num

bers

USA

23 p

artic

ipan

ts: 1

1 in

terv

entio

n, n

ine

cont

rol

Patie

nts

recr

uite

d fr

om in

patie

ntfa

cilit

y

Incl

usio

n cr

iteria

: Adm

issio

n to

inpa

tient

reh

abili

tatio

n w

ithin

14

days

of is

chae

mic

str

oke,

per

siste

nthe

mip

ares

is le

adin

g to

impa

ired

uppe

r ex

trem

ity fu

nctio

n as

indi

cate

dby

sco

re o

f 1–2

on

NIH

SS, e

vide

nce

of p

rese

rved

cog

nitiv

e fu

nctio

n as

indi

cate

d by

0–1

on

the

cons

ciou

snes

s, c

omm

unic

atio

n an

dne

glec

t ite

ms

of t

he N

IHSS

, pre

senc

eof

pro

tect

ive

resp

onse

, no

uppe

rex

trem

ity in

jury

or

cond

ition

s th

atlim

ited

use

befo

re s

trok

e

Excl

usio

n cr

iterio

n: H

aem

orrh

agic

stro

ke

Mea

n ag

e: 6

6.0

year

s (r

ange

47–

83)

55%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 69.

6% r

ight

hem

ipar

esis,

100

% is

chae

mic

str

oke

Mea

n tim

e sin

ce s

trok

e: N

ot s

tate

d,bu

t al

l par

ticip

ants

with

in 1

4 da

ys o

fst

roke

NIH

SS s

core

at

base

line:

Inte

rven

tion

10.2

±9.

4, c

ontr

ol 7

.5 ±

2.8

Expe

rimen

tal i

nter

vent

ion:

CIM

Tin

volv

ing

wea

ring

padd

ed m

itten

for

at le

ast

6 ho

urs

per

day

durin

g14

-day

tre

atm

ent

perio

d, w

ith20

hour

s’ t

rain

ing.

Inte

rven

tions

incl

uded

occ

upat

iona

l the

rapy

trea

tmen

t fo

cuse

d on

AD

Ls, u

pper

extr

emity

tra

inin

g an

d C

IMT

circ

uit

trai

ning

Trea

tmen

t su

perv

ised

byoc

cupa

tiona

l the

rapi

st in

bot

hgr

oups

Gro

up s

ize

not

stat

ed

Sett

ing:

Inpa

tient

Com

paris

on g

roup

: Sta

ndar

doc

cupa

tiona

l the

rapy

tre

atm

ent

incl

udin

g co

mpe

nsat

ory

tech

niqu

esfo

r A

DLs

, upp

er e

xtre

mity

stre

ngth

, ran

ge o

f mot

ion

and

posit

ioni

ng

Part

icip

ants

rec

eive

d eq

uiva

lent

time

and

inte

nsity

of t

reat

men

tdi

rect

ly s

uper

vise

d by

occ

upat

iona

lth

erap

ist

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT

Glo

bal A

DL:

BI,

FIM

Att

empt

at

conc

ealm

ent,

but

real

cha

nce

ofdi

sclo

sure

of a

ssig

nmen

tbe

fore

form

al e

ntry

Blin

ded

outc

ome

asse

ssm

ent

Loss

to

follo

w-u

p: 1

3%(n

=3)

cont

inue

d

Appendix 2

92

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Page

, 200

180RC

T

Rand

omisa

tion

proc

edur

e no

tde

scrib

ed

USA

Six

part

icip

ants

: tw

o in

terv

entio

n,tw

o tr

aditi

onal

reh

abili

tatio

n, t

wo

cont

rol

Incl

usio

n cr

iteria

: Str

oke

expe

rienc

edbe

twee

n 4

wee

ks a

nd 6

mon

ths

befo

re s

tudy

enr

olm

ent,

scor

e of

70

or h

ighe

r on

Mod

ified

MM

SE, n

oha

emor

rhag

ic o

r bi

late

ral l

esio

ns o

rle

sions

in t

he p

rimar

y se

nsor

y or

mot

or c

ortic

al a

reas

, age

18–

95, n

oex

cess

ive

spas

ticity

, no

exce

ssiv

e pa

inin

the

affe

cted

upp

er li

mb,

com

plet

ely

disc

harg

ed fr

om a

ll fo

rms

of p

hysic

al r

ehab

ilita

tion,

not

part

icip

atin

g in

any

exp

erim

enta

lre

habi

litat

ion

or d

rug

stud

ies

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 5

5.8

year

s (r

ange

44–

77)

50%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 66.

7% r

ight

hem

ipar

esis,

% is

chae

mic

str

oke

not

stat

ed

Mea

n tim

e sin

ce s

trok

e: 4

.6 m

onth

s(r

ange

2–5

.5)

Mea

n FM

sco

res

pre-

inte

rven

tion:

Inte

rven

tion

40 (S

D 7

), tr

aditi

onal

reha

bilit

atio

n 56

.5 (S

D 3

.5),

cont

rol

58.5

(SD

3.5

)

Expe

rimen

tal i

nter

vent

ion:

mC

IMT

com

prisi

ng 3

0 m

inut

es o

f phy

sical

ther

apy

and

30 m

inut

es o

foc

cupa

tiona

l the

rapy

thr

ee t

imes

per

wee

k fo

r 10

wee

ks. 8

0% o

fea

ch p

hysic

al a

nd o

ccup

atio

nth

erap

y se

ssio

n fo

cuse

d on

neur

omus

cula

r fa

cilit

atio

nte

chni

ques

, with

em

phas

is on

AD

Lta

sks

whe

neve

r po

ssib

le, a

nd 2

0%fo

cuse

d on

com

pens

ator

yte

chni

ques

usin

g th

e un

affe

cted

side

(i.e.

rea

chin

g an

d pe

rfor

min

gta

sks

with

una

ffect

ed a

rm).

Low

erar

ms

and

hand

s re

stra

ined

for

5ho

urs

initi

ally

usin

g co

tton

Bob

ath

sling

Gro

up s

ize

not

stat

ed

Sett

ing:

Out

patie

nt

Com

paris

on g

roup

: Tra

ditio

nal

reha

bilit

atio

n gr

oup

rece

ived

the

abov

e w

ith n

o re

stra

int.

Con

trol

grou

p re

ceiv

ed n

o th

erap

y du

ring

the

sam

e 10

-wee

k pe

riod

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT,

WM

FT, M

AL

Mot

or im

pairm

ent:

FM

Stat

es r

ando

m a

lloca

tion

but

no d

escr

iptio

n of

proc

edur

e gi

ven

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p

cont

inue

d


93


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Page

, 200

261RC

T

Rand

omisa

tion

proc

edur

e no

tde

scrib

ed

USA

14 p

artic

ipan

ts: f

our

inte

rven

tion,

five

trad

ition

al r

ehab

ilita

tion,

five

con

trol

Incl

usio

n cr

iteria

: Str

oke

betw

een

4w

eeks

and

6 m

onth

s be

fore

stu

dyen

rolm

ent,

10-d

egre

e fin

ger

exte

nsio

n, a

nd 2

0 de

gree

s at

the

wris

t, sc

ore

of 7

0 or

hig

her

onM

odifi

ed M

MSE

, no

haem

orrh

agic

or

bila

tera

l les

ions

or

lesio

ns in

the

prim

ary

sens

ory

or m

otor

cor

tical

area

s, a

ge 1

8–95

, no

exce

ssiv

esp

astic

ity, n

o ex

cess

ive

pain

in m

ore

affe

cted

upp

er li

mb,

disc

harg

ed fr

omal

l for

ms

of r

ehab

ilita

tion,

not

part

icip

atin

g in

any

exp

erim

enta

lre

habi

litat

ion

or d

rug

stud

ies

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 6

4.8

year

s (r

ange

45–

83)

64%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 42.

9% r

ight

hem

ipar

esis,

% is

chae

mic

str

oke

not

stat

ed

Mea

n tim

e sin

ce s

trok

e: 4

.4 m

onth

s(r

ange

4–6

)

Mea

n FM

sco

re a

t ba

selin

e: m

CIM

T31

.0, t

radi

tiona

l reh

abili

tatio

n 51

.4,

cont

rol 3

7.0

Expe

rimen

tal i

nter

vent

ion:

mC

IMT

cons

istin

g of

par

ticip

atio

n in

30

min

utes

of p

hysio

ther

apy

and

30 m

inut

es o

f occ

upat

iona

l the

rapy

thre

e tim

es p

er w

eek

for

10w

eeks

. Int

erve

ntio

n in

clud

ed P

Tco

ncen

trat

ion

on a

ffect

ed u

pper

limb

stre

tchi

ng, d

ynam

icst

and/

bala

nce

activ

ities

and

gai

ttr

aini

ng. ‘

Shap

ing’

tec

hniq

ues

appl

ied.

Les

s af

fect

ed li

mb

rest

rain

ed e

very

wee

kday

for

5-ho

ur p

erio

d

Gro

up s

ize

not

stat

ed

Sett

ing:

Sub

acut

e ou

tpat

ient

clin

ic

Com

paris

on g

roup

s:

(1) T

radi

tiona

l reh

abili

tatio

npa

rtic

ipan

ts r

ecei

ved

the

sam

eam

ount

of o

ccup

atio

nal a

ndph

ysic

al t

hera

py s

essio

ns; t

reat

edac

cord

ing

to n

euro

mus

cula

rfa

cilit

atio

n pr

inci

ples

with

som

eco

mpe

nsat

ory

tech

niqu

es t

augh

t(2

) Con

trol

par

ticip

ants

did

not

part

icip

ate

in a

ny in

terv

entio

ns fo

rth

e 10

-wee

k pe

riod

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT,

MA

L

Mot

or im

pairm

ent:

FM

Stat

es r

ando

m a

lloca

tion,

but

no d

escr

iptio

n of

proc

edur

e gi

ven

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p

cont

inue

d

Appendix 2

94

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Page

, 200

462RC

T

Com

pute

r-ge

nera

ted

rand

om n

umbe

rs t

able

USA

17 p

artic

ipan

ts: s

even

inte

rven

tion,

four

tra

ditio

nal r

ehab

ilita

tion,

six

cont

rol

Incl

usio

n cr

iteria

: Abi

lity

to e

xten

d at

leas

t 10

deg

rees

at

the

met

acar

poph

alan

geal

and

inte

rpha

lang

eal j

oint

s an

d 20

degr

ees

at t

he w

rist,

stro

ke m

ore

than

1 y

ear

befo

re s

tudy

, sco

re o

f70

or

high

er o

n M

odifi

ed M

MSE

, no

haem

orrh

agic

lesio

ns, a

ge 1

8–95

, no

exce

ssiv

e sp

astic

ity, n

o ex

cess

ive

pain

in m

ore

affe

cted

upp

er li

mb,

disc

harg

ed fr

om a

ll fo

rms

ofre

habi

litat

ion,

not

par

ticip

atin

g in

any

expe

rimen

tal r

ehab

ilita

tion

ordr

ug s

tudi

es

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 5

9.2

year

s (r

ange

37–

76)

82%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 58.

8% r

ight

-he

mip

ares

is, %

isch

aem

ic s

trok

eno

t st

ated

Mea

n tim

e sin

ce s

trok

e: 3

2.3

mon

ths

(ran

ge 1

4–74

)

Mea

n FM

sco

re a

t ba

selin

e: m

CIM

T31

.3, t

radi

tiona

l reh

abili

tatio

n 29

.3,

cont

rol 3

1.8

Expe

rimen

tal i

nter

vent

ion:

mC

IMT

cons

istin

g of

par

ticip

atio

n in

30

min

utes

of p

hysio

ther

apy

and

30 m

inut

es o

f occ

upat

iona

lth

erap

y th

ree

times

per

wee

k fo

r10

wee

ks. I

nter

vent

ion

incl

uded

phys

ical

the

rapy

con

cent

ratio

non

low

er li

mb

activ

ities

(e.g

.dy

nam

ic s

tand

and

bal

ance

activ

ities

, gai

t tr

aini

ng) w

ith s

ome

time

spen

t on

upp

er li

mb

stre

tchi

ng t

o fa

cilit

ate

AD

Ls. L

ess

affe

cted

lim

b re

stra

ined

eve

ryw

eekd

ay fo

r a

5-ho

ur p

erio

d

Gro

up s

ize

not

stat

ed

Sett

ing:

Out

patie

nt c

linic

Com

paris

on g

roup

s:(1

) Tra

ditio

nal r

ehab

ilita

tion

part

icip

ants

rec

eive

d th

e sa

me

amou

nt o

f occ

upat

iona

l and

phys

ical

the

rapy

ses

sions

, tre

ated

acco

rdin

g to

neu

rom

uscu

lar

faci

litat

ion

prin

cipl

es w

ith s

ome

com

pens

ator

y te

chni

ques

tau

ght

(2) C

ontr

ol p

artic

ipan

ts d

id n

otpa

rtic

ipat

e in

any

inte

rven

tions

for

the

10-w

eek

perio

d

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT,

MA

L

Mot

or im

pairm

ent:

FM

Att

empt

at

conc

ealm

ent,

but

real

cha

nce

ofdi

sclo

sure

of a

ssig

nmen

tbe

fore

form

al e

ntry

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p

cont

inue

d


95


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Page

, 200

582RC

T

Rand

om n

umbe

rs t

able

USA

Ten

part

icip

ants

: fiv

e in

terv

entio

ngr

oup,

five

tra

ditio

nal r

ehab

ilita

tion

Incl

usio

n cr

iteria

: 10-

degr

ee fi

nger

exte

nsio

n, a

nd 2

0 de

gree

s at

the

wris

t, isc

haem

ic s

trok

e fe

wer

tha

n14

day

s be

fore

stu

dy e

nrol

men

t,sc

ore

of 7

0 or

hig

her

on M

odifi

edM

MSE

, age

18–

95, n

o ex

cess

ive

spas

ticity

, no

exce

ssiv

e pa

in in

mor

eaf

fect

ed u

pper

lim

b, m

ore

affe

cted

limb

non-

use

(am

ount

of u

se s

core

of <

2.5

on M

AL)

, disc

harg

ed fr

omal

l for

ms

of r

ehab

ilita

tion,

not

part

icip

atin

g in

any

exp

erim

enta

lre

habi

litat

ion

or d

rug

stud

ies

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 6

0.4

year

s (r

ange

46–

72)

80%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 80%

rig

hthe

mip

ares

is, 1

00%

isch

aem

ic s

trok

e

Mea

n tim

e sin

ce s

trok

e: 4

.4 d

ays

(ran

ge 2

–9)

Mea

n FM

sco

re a

t ba

selin

e: m

CIM

T33

.6, t

radi

tiona

l reh

abili

tatio

n 34

.8

Expe

rimen

tal i

nter

vent

ion:

mC

IMT

cons

istin

g of

par

ticip

atio

n in

30m

inut

es o

f phy

sioth

erap

y an

d30

min

utes

of o

ccup

atio

nal

ther

apy

thre

e tim

es p

er w

eek

for

10w

eeks

, all

adm

inist

ered

by

the

sam

e th

erap

ist. I

nter

vent

ion

incl

uded

con

cent

ratio

n on

mor

eaf

fect

ed li

mb

use

in t

hree

AD

Lsch

osen

by

part

icip

ant

and

ther

apist

(app

rox.

25

min

utes

); 5

min

utes

of t

hera

py s

pent

on

affe

cted

lim

b ra

nge

of m

otio

n.‘S

hapi

ng’ t

echn

ique

s us

ed w

ithth

ree

AD

Ls. L

ess

affe

cted

lim

bre

stra

ined

eve

ry w

eekd

ay fo

r a

5-ho

ur p

erio

d

Gro

up s

ize

not

stat

ed

Sett

ing:

Reh

abili

tatio

n ho

spita

l

Com

paris

on g

roup

: Tra

ditio

nal

reha

bilit

atio

n gr

oup

rece

ived

stan

dard

the

rapy

for

30 m

inut

es3

days

a w

eek

for

10 w

eeks

.Se

ssio

ns in

clud

ed s

tret

chin

g of

the

affe

cted

lim

b, w

eigh

t be

arin

g w

ithth

e af

fect

ed li

mb

and

man

ual

dext

erity

exe

rcise

s

Out

com

es r

ecor

ded

pre-

and

po

st-in

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT,

MA

L

Mot

or im

pairm

ent:

FM

Att

empt

at

conc

ealm

ent,

but

real

cha

nce

ofdi

sclo

sure

of a

ssig

nmen

tbe

fore

form

al e

ntry

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p

cont

inue

d

Appendix 2

96

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Supu

ttita

da, 2

00464

RCT

‘Tab

le o

f ran

dom

isatio

n’

Tha

iland

69 p

artic

ipan

ts: 3

3 in

terv

entio

n,

36 c

ontr

ol

Incl

usio

n cr

iteria

: Age

18–

80 y

ears

,hi

stor

y of

a s

ingl

e st

roke

, dur

atio

n of

stro

ke b

efor

e st

art

of s

tudy

bet

wee

n1

and

10 y

ears

, min

imum

of

20de

gree

s ac

tive

wris

t ex

tens

ion

and

10 d

egre

es o

f fin

ger

exte

nsio

n,A

RAT

sco

re <

51, a

ble

to w

alk

indo

ors

with

out

a st

ick

indi

catin

g no

maj

or b

alan

ce p

robl

ems,

no

seve

reap

hasia

, no

sens

ory

diso

rder

, no

seve

re c

ogni

tive

impa

irmen

ts

Excl

usio

n cr

iteria

: Non

e st

ated

Mea

n ag

e: 5

9.4

year

s (r

ange

not

stat

ed)

68%

mal

e

Stro

ke d

etai

ls: F

irst

stro

ke o

nly,

92.8

% r

ight

hem

ipar

esis,

66.

7%isc

haem

ic s

trok

e

Mea

n tim

e sin

ce s

trok

e: N

ot p

ossib

leto

cal

cula

te, b

ut m

ostly

(81.

2%)

with

in 1

–3 y

ears

Tota

l ARA

T at

bas

elin

e: In

terv

entio

nm

edia

n 41

.0 (r

ange

26–

51),

cont

rol

med

ian

43.5

(ran

ge 1

0–51

)

Expe

rimen

tal i

nter

vent

ion:

Part

icip

ants

rec

eive

d tr

eatm

ent

for

2 co

nsec

utiv

e w

eeks

, 5 d

ays

aw

eek

for

6 ho

urs

a da

y. H

ealth

yha

nd c

over

ed b

y a

glov

e

Part

icip

ants

tre

ated

in g

roup

s of

thre

e or

four

Sett

ing:

Out

patie

nt c

linic

Com

paris

on g

roup

: Par

ticip

ants

trea

ted

acco

rdin

g to

neur

odev

elop

men

tal t

hera

pym

etho

d. A

ll ac

tiviti

es p

erfo

rmed

bim

anua

lly

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

Lim

b-sp

ecifi

c fu

nctio

n:A

RAT

Att

empt

at

conc

ealm

ent,

but

real

cha

nce

ofdi

sclo

sure

of a

ssig

nmen

tbe

fore

form

al e

ntry

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p

cont

inue

d


97


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Taub

, 199

373RC

T

Rand

omisa

tion

proc

edur

e no

tde

scrib

ed

USA

Nin

e pa

rtic

ipan

ts: f

our

inte

rven

tion,

five

cont

rol

Incl

usio

n cr

iteria

(ex

pres

sed

asex

clus

ion

crite

ria b

y au

thor

s): S

trok

eex

perie

nced

mor

e th

an 1

yea

r ag

o,10

-deg

ree

finge

r ex

tens

ion

and

20de

gree

s at

the

wris

t, no

bal

ance

prob

lem

s, in

abili

ty t

o m

ake

exte

nsiv

e us

e of

invo

lved

upp

erex

trem

ity s

o th

at s

igni

fican

t fu

rthe

rim

prov

emen

t co

uld

not

beex

pect

ed, n

o se

rious

cog

nitiv

ede

ficits

, no

exce

ssiv

e sp

astic

ity, n

ose

rious

unc

ontr

olle

d m

edic

alpr

oble

ms,

less

tha

n 75

yea

rs o

f age

,no

left

arm

dom

inan

ce o

r le

fthe

mip

legi

a

Age:

inte

rven

tion

med

ian

65ye

ars,

com

paris

on m

edia

n 63

year

s22

% m

ale

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or s

ubse

quen

t st

roke

, 100

% r

ight

hem

ipar

esis,

% is

chae

mic

str

oke

not

stat

ed

Mea

n tim

e sin

ce s

trok

e: N

ot s

tate

d(r

ange

1.2

–18

year

s)

Mea

n fu

nctio

nal a

bilit

y on

Em

ory

test

at b

asel

ine:

Inte

rven

tion

3.2

(est

imat

ed),

cont

rol 3

.3 (e

stim

ated

)

Expe

rimen

tal i

nter

vent

ion:

Una

ffect

ed a

rm s

ecur

ed in

res

ting

hand

spl

int

and

sling

; res

trai

ntde

vice

wor

n fo

r 14

day

s fo

r w

ell

over

90%

of w

akin

g ho

urs.

One

each

wee

kday

, pat

ient

s sp

ent

7ho

urs

at r

ehab

ilita

tion

cent

re a

ndw

ere

give

n a

varie

ty o

f tas

ks, e

.g.

thro

win

g a

ball,

pla

ying

dom

inoe

s,pu

shin

g a

broo

m

No

deta

ils g

iven

of i

nter

vent

ion

prov

ider

s

Gro

up s

ize

not

stat

ed

Sett

ing:

Reh

abili

tatio

n ce

ntre

Com

paris

on g

roup

: Att

entio

nco

ntro

l: pr

oced

ures

des

igne

d to

focu

s at

tent

ion

on t

he in

volv

edex

trem

ity, b

ut in

volv

ed li

mb

not

give

n an

y ex

perie

nce

of o

r tr

aini

ngfo

r ac

tive

mov

emen

t

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

Lim

b-sp

ecifi

c fu

nctio

n:Em

ory

Mot

or F

unct

ion

Test

, Arm

Mot

or A

ctiv

ityTe

st, M

AL

Stat

es r

ando

m a

lloca

tion,

but

no d

escr

iptio

n of

proc

edur

e gi

ven

No

men

tion

of b

linde

dou

tcom

e as

sess

men

t

No

loss

to

follo

w-u

p

cont

inue

d

Appendix 2

98

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Witt

enbe

rg, 2

00374

RCT

Rand

om n

umbe

rs t

able

.Ra

ndom

isatio

npe

rfor

med

in p

airs

, if

poss

ible

, or

inin

divi

dual

s, b

ut n

ever

mor

e th

an t

wo

subj

ects

rece

ivin

g in

terv

entio

n.Bo

th m

embe

rs o

f pai

ras

signe

d to

sam

e ar

mto

avo

id s

ubje

cts

obse

rvin

g th

erap

y in

othe

r ar

m

USA

16 p

artic

ipan

ts: n

ine

inte

rven

tion,

seve

n co

ntro

l

Incl

usio

n cr

iteria

: Sin

gle,

sub

cort

ical

infa

rctio

n m

ore

than

12

mon

ths

befo

re e

ntry

to

the

stud

y, s

igni

fican

tfu

nctio

nal i

mpa

irmen

t of

the

affe

cted

side

(indi

cate

d by

a s

core

of <

2.7

onth

e M

AL)

, vol

unta

ry e

xten

sion

of a

tle

ast

10 d

egre

es o

f the

affe

cted

finge

rs a

nd 2

0 de

gree

s of

the

wris

t

Excl

usio

n cr

iteria

: Pat

ient

s w

ithou

tvo

lunt

ary

exte

nsio

n of

at

leas

t10

degr

ees

of t

he a

ffect

ed fi

nger

s or

20 d

egre

es o

f the

wris

t

Mea

n ag

e: 6

4 ye

ars

(ran

ge 4

1–81

)81

% m

ale

Stro

ke d

etai

ls: F

irst

stro

ke o

nly,

%rig

ht h

emip

ares

is no

t st

ated

, 12.

5%ha

d in

farc

ts a

ffect

ing

non-

dom

inan

tsid

e, %

isch

aem

ic s

trok

e no

t st

ated

Mea

n tim

e sin

ce s

trok

e: 3

3 m

onth

s(r

ange

12–

86)

WM

FT a

t ba

selin

e: in

terv

entio

n 6.

7(S

D 2

.0),

cont

rol 5

.5 (S

D 2

.6)

Expe

rimen

tal i

nter

vent

ion:

Res

trai

ntof

the

upp

er e

xtre

mity

dur

ing

wak

ing

hour

s an

d ta

sk-o

rient

ated

ther

apy

of t

he a

ffect

ed u

pper

extr

emity

on

10 c

ontin

uous

inpa

tient

day

s fo

r 6

hour

s a

day

(4ho

urs

a da

y on

wee

kend

s).

The

rapy

invo

lved

pro

gres

sivel

yim

prov

ing

mot

or t

ask

perf

orm

ance

by a

suc

cess

ive

appr

oxim

atio

npr

oced

ure

durin

g co

mbi

ned

phys

ical

, occ

upat

iona

l and

recr

eatio

nal t

hera

pyN

o de

tails

giv

en o

f int

erve

ntio

npr

ovid

ers

Gro

up s

ize

not

stat

ed

Sett

ing:

Clin

ical

cen

tre

Com

paris

on g

roup

: Des

igne

d to

be

less

inte

nse

(3 h

ours

a d

ay o

nw

eekd

ays

and

no t

reat

men

t on

wee

kend

s), b

ut a

lso a

imed

to

impr

ove

task

per

form

ance

with

the

unaf

fect

ed s

ide

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

and

at 6

mon

ths

post

-inte

rven

tion

Lim

b-sp

ecifi

c fu

nctio

n:W

MFT

, MA

L

Mot

or im

pairm

ent:

Ass

essm

ent

of M

otor

and

Proc

ess

Skill

s

Att

empt

at

conc

ealm

ent,

but

real

cha

nce

ofdi

sclo

sure

of a

ssig

nmen

tbe

fore

form

al e

ntry

Blin

ded

outc

ome

asse

ssm

ent

No

loss

to

follo

w-u

p

MM

SE, M

ini-M

enta

l Sta

te E

xam

inat

ion;

NIH

SS, N

atio

nal I

nstit

utes

of H

ealth

Str

oke

Scal

e.


99


Appendix 3

Included studies: treadmill training

Appendix 3

100

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Ada

, 200

387Ra

ndom

ised,

pla

cebo

-co

ntro

lled

clin

ical

tria

l

Part

icip

ants

ran

ked

inde

scen

ding

ord

erac

cord

ing

to w

alki

ngsp

eed

and

orga

nise

din

to c

onse

cutiv

e pa

irs.

Part

icip

ants

ran

dom

lyal

loca

ted

by c

oin

toss

Aus

tral

ia29

par

ticip

ants

: 14

inte

rven

tion,

15co

ntro

l

Volu

ntee

r sa

mpl

e re

crui

ted

via

adve

rtise

men

t an

d st

roke

clu

bs

Incl

usio

n cr

iteria

: >6

mon

ths

post

-st

roke

, <5

year

s po

st-s

trok

e, fi

rst

stro

ke, p

rese

nted

with

hem

ipar

esis,

aged

50–

85, c

an w

alk

10 m

inde

pend

ently

with

a s

peed

of

<1.

2 m

/s

Excl

usio

n cr

iteria

: Car

diov

ascu

lar

prob

lem

s th

at w

ould

pre

clud

epa

rtic

ipat

ion

in t

rain

ing,

sev

ere

cogn

itive

def

icits

suc

h th

atpa

rtic

ipan

ts c

ould

not

follo

win

stru

ctio

ns

Mea

n ag

e: 6

6 ye

ars

(SD

11)

70%

mal

e

Stro

ke d

etai

ls: F

irst

stro

ke

Tim

e sin

ce s

trok

e: E

xper

imen

tal

28m

onth

s (S

D 1

7),

cont

rol 2

6m

onth

s (S

D 2

0)

Prei

nter

vent

ion

func

tiona

l abi

lity:

Mea

n w

alki

ng s

peed

(m/s

)ex

perim

enta

l 0.6

2 (S

D 0

.24)

, co

ntro

l 0.5

3 (S

D 0

.30)

Expe

rimen

tal i

nter

vent

ion:

Tre

adm

illw

alki

ng (w

ithou

t bo

dyw

eigh

tsu

ppor

t) a

nd o

verg

roun

d w

hole

-ta

sk p

ract

ice

of w

alki

ng o

f var

ious

type

s. T

he p

ropo

rtio

n of

tre

adm

illw

alki

ng d

ecre

ased

by

10%

eac

hw

eek

from

80%

in w

eek

1 to

50%

in w

eek

4

Part

icip

ants

wer

e tr

eate

d as

outp

atie

nts

in a

com

mun

ity s

ettin

gfo

r th

ree

30-m

inut

e se

ssio

ns p

erw

eek

for

4 w

eeks

= 6

hou

rs.

Two

subj

ects

tra

ined

con

curr

ently

,w

ith t

rain

ing

prov

ided

by

aph

ysio

ther

apist

Com

paris

on g

roup

: Hom

e ex

erci

sepr

ogra

mm

e co

nsist

ing

of e

xerc

ises

to le

ngth

en/s

tren

gthe

n lo

wer

lim

bm

uscl

es, t

rain

bal

ance

and

coor

dina

tion.

Par

ticip

ants

wer

eal

so e

ncou

rage

d to

wal

k ev

ery

day.

The

aim

was

to

prov

ide

a sh

ampr

ogra

mm

e to

con

trol

for

the

effe

ct o

f pla

cebo

. Par

ticip

ants

wer

e in

stru

cted

to

carr

y ou

t th

epr

ogra

mm

e th

ree

times

a w

eek

for

4w

eeks

. Pa

rtic

ipan

ts w

ere

tele

phon

ed o

nce

a w

eek

and

exer

cise

s w

ere

prog

ress

edac

cord

ingl

y

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

and

at 3

mon

ths

afte

rth

e ce

ssat

ion

ofin

terv

entio

n

Lim

b-sp

ecifi

c fu

nctio

n:10

MW

S, 6

MW

T

Mot

or im

pairm

ent:

Step

leng

th o

f bot

h th

eaf

fect

ed a

nd u

naffe

cted

leg,

cad

ence

, ste

p w

idth

over

10

m

Allo

catio

n co

ncea

lmen

tad

equa

te

No

signi

fican

t di

ffere

nces

in b

asel

ine

char

acte

ristic

s

Blin

ded

outc

ome

asse

ssm

ent

Loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase:

7%

No

inte

rven

tion-

rela

ted

with

draw

als

Att

enda

nce:

Tra

nspo

rtw

as p

rovi

ded

if ne

cess

ary.

On

aver

age,

sub

ject

s in

the

expe

rimen

tal g

roup

atte

nded

11

out

of 1

2se

ssio

ns

cont

inue

d


101


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Da

Cuh

na, 2

00286

RCT

pilo

t st

udy

Part

icip

ants

wer

era

ndom

ised

to g

roup

sus

ing

rand

om n

umbe

rsto

pre

assig

n pa

rtic

ipan

tsba

sed

on r

ecru

itmen

tor

der

USA

15 p

artic

ipan

ts: s

even

inte

rven

tion,

eigh

t co

ntro

l

Part

icip

ants

rec

ruite

d fr

om in

patie

ntre

habi

litat

ion

Incl

usio

n cr

iteria

: With

in 6

wee

ks o

fst

roke

, gai

t sp

eed

of 0

.6m

/s o

r le

ssan

d sc

ore

0–2

on t

he F

unct

iona

lA

mbu

latio

n ca

tego

ry, s

uffic

ient

cogn

ition

to

part

icip

ate,

abl

e to

stan

d an

d to

tak

e at

leas

t on

e st

epw

ith a

ssist

ance

, sta

ble

med

ical

cond

ition

Excl

usio

n cr

iteria

: Co-

mor

bidi

ty o

rdi

sabi

lity

that

wou

ld p

recl

ude

gait

trai

ning

, car

diac

illn

ess,

unc

ontr

olle

dhe

alth

con

ditio

n fo

r w

hich

exe

rcise

is co

ntra

indi

cate

d, e

.g. d

iabe

tes,

hype

rten

sion,

low

er e

xtre

mity

join

tdi

seas

e, b

odyw

eigh

t ov

er 1

10 k

g,co

gniti

ve im

pairm

ent,

hist

ory

ofbi

late

ral c

ereb

rova

scul

ar a

ccid

ent

Mea

n ag

e: 5

7.80

yea

rs (S

D 5

.50)

inte

rven

tion,

58.

90 (S

D 1

2.90

)co

ntro

l (no

t in

clud

ing

drop

outs

)10

0% m

ale

Stro

ke d

etai

ls: 9

2% is

chae

mic

str

oke

Tim

e sin

ce s

trok

e: E

xper

imen

tal

15.7

days

(SD

7.7

), co

ntro

l 19

days

(SD

12.

7)

Prev

entio

n fu

nctio

nal a

bilit

y: M

ean

wal

king

spe

ed (m

/s):

inte

rven

tion

0.36

(SD

0.2

5), c

ontr

ol 0

.12

(SD

0.1

5) (n

ot in

clud

ing

drop

-out

s)

Expe

rimen

tal i

nter

vent

ion:

Part

icip

ants

rec

eive

d re

gula

rre

habi

litat

ion

but

with

out

the

usua

lga

it tr

aini

ng. I

n pl

ace

of u

sual

gai

ttr

aini

ng w

as t

read

mill

tra

inin

g w

ithbo

dyw

eigh

t su

ppor

t. Pa

rtic

ipan

tsw

alke

d on

a t

read

mill

with

sup

port

usin

g a

harn

ess

of u

p to

30%

body

wei

ght.

Supp

ort

was

prog

ress

ivel

y de

crea

sed

aspa

rtic

ipan

ts a

cqui

red

grea

ter

self-

supp

ort

Part

icip

ants

wer

e tr

eate

d as

inpa

tient

s fo

r fiv

e 20

-min

ute

sess

ions

per

wee

k fo

r 3

wee

ks =

5 ho

urs.

Tra

inin

g w

as d

eliv

ered

indi

vidu

ally

by

a ph

ysio

ther

apist

Com

paris

on g

roup

: Reg

ular

reha

bilit

atio

n: d

aily

ses

sions

of

phys

ioth

erap

y, k

ines

ioth

erap

y an

doc

cupa

tiona

l the

rapy

ove

r 3

hour

s.Ph

ysio

ther

apy

focu

sed

onst

reng

then

ing,

func

tion

and

mob

ility

act

iviti

es in

clud

ing

gait

trai

ning

. Occ

upat

iona

l the

rapy

rela

ted

to A

DLs

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

Lim

b-sp

ecifi

c fu

nctio

n:FA

C, f

ast

wal

king

spe

edov

er 5

m, 5

MW

T

Mot

or im

pairm

ent:

Gai

ten

ergy

exp

endi

ture

, gai

ten

ergy

cos

t

Allo

catio

n co

ncea

lmen

tun

clea

r

No

signi

fican

t di

ffere

nces

in b

asel

ine

char

acte

ristic

s

Blin

ding

of o

utco

me

asse

ssor

s no

t st

ated

Inte

rven

tion-

rela

ted

with

draw

als:

one

sub

ject

drop

ped

from

the

stu

dybe

caus

e he

did

not

com

plet

e at

leas

t ni

nese

ssio

ns

Loss

to

follo

w-u

p at

end

of

trea

tmen

t ph

ase:

13%

No

deta

ils g

iven

of

atte

ndan

ce

cont

inue

d

Appendix 3

102

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Eich

, 200

489RC

T

Rand

omisa

tion

byin

depe

nden

t pe

rson

usin

g se

aled

env

elop

es

Ger

man

y50

par

ticip

ants

: 25

inte

rven

tion,

25co

ntro

l

Part

icip

ants

rec

ruite

d fr

om in

patie

ntre

habi

litat

ion

unit

Incl

usio

n cr

iteria

: Age

ran

ge fr

om50

–75

year

s, fi

rst-

time

supr

aten

toria

lst

roke

, les

s th

an 6

wee

ks p

ost-

stro

ke, a

ble

to w

alk

a m

inim

umdi

stan

ce o

f 12

m w

ith e

ither

inte

rmitt

ent

help

or

stan

dby

whi

lew

alki

ng, B

I ran

ging

from

50–

80,

part

icip

atio

n in

a 1

2-w

eek

com

preh

ensiv

e re

habi

litat

ion

prog

ram

me,

car

diov

ascu

larly

sta

ble,

no o

ther

neu

rolo

gica

l or

orth

opae

dic

dise

ase

impa

iring

wal

king

, abl

e to

unde

rsta

nd t

he p

urpo

se a

nd c

onte

ntof

the

stu

dy

Mea

n ag

e: 6

2.4

year

s (S

D 4

.8)

inte

rven

tion,

64.

0 ye

ars

(SD

6.0

)co

ntro

l66

% m

ale

Stro

ke d

etai

ls: F

irst

stro

ke. 1

00%

ischa

emic

str

oke

Tim

e sin

ce s

trok

e: E

xper

imen

tal

6.1

wee

ks (S

D 2

.2),

cont

rol 6

.32

wee

ks (S

D 6

)

Prei

nter

vent

ion

func

tiona

l abi

lity:

Mea

n w

alki

ng s

peed

(m/s

):in

terv

entio

n 0.

40 (S

D 0

.17)

, co

ntro

l 0.4

4 (S

D 0

.22)

Expe

rimen

tal i

nter

vent

ion:

Aer

obic

trea

dmill

tra

inin

g w

ith b

odyw

eigh

tei

ther

not

sup

port

ed o

r su

ppor

ted

to a

max

imum

of 1

5% u

sing

aha

rnes

s. I

nter

vent

ion

also

incl

uded

oth

er in

divi

dual

phy

sical

ther

apy.

Tre

adm

ill t

rain

ing

was

grad

ed t

o a

defin

ed t

rain

ing

hear

tra

te. I

f nec

essa

ry, o

ne o

r tw

oth

erap

ists

prov

ided

hel

p w

ithse

ttin

g th

e pa

retic

lim

b, a

ssist

ing

wei

ght

shift

ing

and

hip

exte

nsio

n

Trea

ted

as in

patie

nts

for

five

60-m

inut

e se

ssio

ns c

onsis

ting

of30

min

utes

’ tre

adm

ill t

rain

ing

and

30m

inut

es’ i

ndiv

idua

l phy

sical

ther

apy

per

wee

k fo

r 6

wee

ks

Com

paris

on g

roup

: Bob

ath-

orie

ntat

ed in

divi

dual

phy

sioth

erap

yex

clus

ivel

y co

ncen

trat

ed o

nw

alki

ng r

ehab

ilita

tion.

Incl

uded

tone

-inhi

bitin

g an

d ga

itpr

epar

ator

y m

anoe

uvre

s an

dw

alki

ng p

ract

ice

on t

he fl

oor

and

stai

rs

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

and

at 1

2 w

eeks

afte

rth

e ce

ssat

ion

of t

hetr

eatm

ent

Lim

b-sp

ecifi

c fu

nctio

n:10

MW

S, 6

MW

T g

ross

mot

or fu

nctio

n in

clud

ing

wal

king

abi

lity

usin

g th

eRM

A s

core

, wal

king

qual

ity a

sses

sed

with

acu

stom

ised

scor

e,ad

apte

d fr

om t

he L

osRa

ncho

s Lo

s A

mig

os G

ait

Ana

lysis

Han

dboo

k

Allo

catio

n co

ncea

lmen

tad

equa

te

No

signi

fican

t di

ffere

nces

in b

asel

ine

char

acte

ristic

s

Out

com

e ob

serv

ers

may

not

have

bee

n to

tally

blin

d in

the

giv

en c

linic

alse

ttin

g

No

loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase

No

inte

rven

tion-

rela

ted

with

draw

als

No

adve

rse

even

ts cont

inue

d


103


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Mac

ko, 2

00588

RCT

Part

icip

ants

wer

era

ndom

ised

to g

roup

sus

ing

a co

mpu

ter-

base

dsy

stem

tha

t w

asst

ratif

ied

by d

efic

itse

verit

y an

d ag

e

USA

61 p

artic

ipan

ts: 3

2 in

terv

entio

n,

29 c

ontr

ol

Part

icip

ants

rec

ruite

d fr

om c

hron

icst

roke

par

ticip

ants

with

hem

ipar

etic

gait

(>6

mon

ths)

Incl

usio

n cr

iteria

: Chr

onic

hem

ipar

etic

str

oke

(mor

e th

an6

mon

ths)

, age

d 45

yea

rs o

r m

ore,

resid

ual m

ild t

o m

oder

ate

hem

iple

gic

gait

defic

its, a

chie

vem

ent

of a

dequ

ate

exer

cise

inte

nsity

with

out

signs

of m

yoca

rdia

lisc

haem

ia o

r ot

her

cont

rain

dica

tions

to t

rain

ing

Excl

usio

n cr

iteria

: Hea

rt fa

ilure

,un

stab

le a

ngin

a, p

erip

hera

l art

eria

loc

clus

ive

dise

ase,

aph

asia

, dem

entia

,un

trea

ted

maj

or d

epre

ssio

n an

dot

her

med

ical

con

ditio

ns p

recl

udin

gpa

rtic

ipat

ion

in e

xerc

ise

Mea

n ag

e: 6

3 ye

ars

(SD

10)

inte

rven

tion,

64

year

s (S

D 8

) con

trol

71%

mal

e

Stro

ke d

etai

ls: U

ncle

ar w

heth

er fi

rst

or r

ecur

rent

str

oke

Tim

e sin

ce s

trok

e: E

xper

imen

tal

grou

p 35

mon

ths

(SD

29)

, con

trol

39 m

onth

s (S

D 5

9)

Prei

nter

vent

ion

func

tiona

l abi

lity:

Mea

n w

alki

ng s

peed

(m/s

):in

terv

entio

n 0.

82 (S

D 0

.08)

, co

ntro

l 0.9

(SD

0.1

0)

Expe

rimen

tal i

nter

vent

ion:

Tre

adm

illtr

aini

ng a

t ta

rget

aer

obic

inte

nsity

of 6

0–70

% h

eart

-rat

e re

serv

e.Tr

aini

ng s

tart

ed a

t lo

w in

tens

ity(4

0–50

%) f

or 1

0–20

min

utes

and

incr

ease

d ev

ery

2 w

eeks

as

tole

rate

d. T

ask-

orie

ntat

ed t

rain

ing

adm

inist

ered

acc

ordi

ng t

o a

prog

ress

ive

aero

bic

exer

cise

form

ula.

No

body

wei

ght

supp

ort

was

pro

vide

d

Trea

ted

as o

utpa

tient

s fo

r th

ree

40-m

inut

e se

ssio

ns p

er w

eek

for

6m

onth

s

Trai

ning

was

del

iver

ed b

y ex

erci

seph

ysio

logi

sts

unde

r th

e su

perv

ision

of a

phy

sicia

n

Com

paris

on g

roup

: Mat

ched

dura

tion

expo

sure

to

staf

fim

plem

entin

g co

mm

onco

mpo

nent

s of

con

vent

iona

lth

erap

y. P

artic

ipan

ts c

ompl

eted

supe

rvise

d st

retc

hing

mov

emen

tsan

d 5

min

utes

of l

ow-in

tens

itytr

eadm

ill w

alki

ng a

t 30

–40%

hear

t-ra

te r

eser

ve w

ithou

tbo

dyw

eigh

t su

ppor

t

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

Lim

b-sp

ecifi

c fu

nctio

n:W

alki

ng s

peed

ove

r30

feet

(9.1

m),

6MW

T,Ri

verm

ead

Mob

ility

Inde

x

Impa

irmen

t: W

alki

ngIm

pairm

ent

Que

stio

nnai

re. E

cono

my

of g

ait

Vo2

peak

Allo

catio

n co

ncea

lmen

tun

clea

r

No

signi

fican

t di

ffere

nces

in b

asel

ine

char

acte

ristic

s

Blin

ding

of o

utco

me

asse

ssor

s to

gro

upal

loca

tion

for

ambu

lato

rym

easu

res

and

func

tiona

lm

obili

ty. T

read

mill

exer

cise

tes

ting

not

blin

ded

Loss

to

follo

w-u

p at

end

of t

reat

men

t ph

ase:

27%

Inte

rven

tion-

rela

ted

with

draw

als:

thr

ee o

ut o

f25

sub

ject

s w

ere

lost

from

bot

h th

eex

perim

enta

l and

con

trol

grou

ps fo

r co

mpl

ianc

ere

ason

s

No

adve

rse

even

ts s

tate

d

cont

inue

d

Appendix 3

104

Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Pohl

, 200

285

(Det

ails

on g

roup

ssu

pple

men

ted

from

Mos

eley

, 200

520)

RCT

Part

icip

ants

ran

dom

ised

to g

roup

s by

blo

ckra

ndom

isatio

n st

ratif

ied

by w

alki

ng s

peed

ove

r10

m w

ithou

t as

sista

nce

Ger

man

y69

par

ticip

ants

: 25

grou

p 1,

22

gro

up 2

, 22

cont

rol (

from

Mos

eley

, 200

520)

Part

icip

ants

rec

ruite

d fr

om in

patie

ntre

habi

litat

ion

Incl

usio

n cr

iteria

: Hem

ipar

esis

caus

edby

isch

aem

ic s

trok

e or

intr

acer

ebra

lha

emor

rhag

e, im

paire

d ga

it, d

urat

ion

of h

emip

ares

is >

4 w

eeks

, no

orsli

ght

spas

ticity

, abl

e to

wal

k w

ithou

tpe

rson

al a

ssist

ance

, tim

e re

quire

d to

wal

k 10

m >

5 se

cond

s an

d<

60se

cond

s

Excl

usio

n cr

iteria

: Pre

viou

s tr

eadm

illtr

aini

ng, c

lass

C/D

exe

rcise

risk

(Am

eric

an C

olle

ge o

f Spo

rts

Med

icin

e cr

iteria

), co

gniti

ve d

efic

its,

mov

emen

t di

sord

ers,

ort

hopa

edic

and

othe

r ga

it in

fluen

cing

dise

ase

Mea

n ag

e: G

roup

1: 5

8.2

year

s(S

D10

.5),

grou

p 2:

57.

1 ye

ars

(SD

13.

9), g

roup

3: 6

1.6

year

s (S

D 1

0.6)

71.6

% m

ale

Stro

ke d

etai

ls: 7

0% is

chae

mic

str

oke

Tim

e sin

ce s

trok

e: E

xper

imen

tal

16.8

wee

ks (S

D 2

0.5)

, co

ntro

l 16.

1w

eeks

(SD

18.

5)

Prei

nter

vent

ion

func

tiona

l abi

lity:

Mea

n w

alki

ng s

peed

(m/s

): gr

oup

10.

61 (S

D 0

.32)

, gro

up 2

0.6

6 (S

D 0

.39)

, gro

up 3

0.6

6 (S

D 0

.42)

Expe

rimen

tal i

nter

vent

ion:

Tria

lin

clud

ed t

wo

inte

rven

tion–

cont

rol

pairs

: spe

ed-d

epen

dent

, and

limite

d pr

ogre

ssiv

e tr

eadm

illtr

aini

ng. T

he li

mite

d pr

ogre

ssiv

ein

terv

entio

n–co

ntro

l com

paris

onw

as u

sed

Inte

rven

tion

grou

p 2

cons

isted

of

limite

d pr

ogre

ssiv

e tr

eadm

illtr

aini

ng. P

artic

ipan

ts w

alke

d on

atr

eadm

ill w

ith t

he t

rain

ing

spee

din

crea

sed

by n

o m

ore

than

5%

of

the

max

imum

initi

al w

alki

ng s

peed

each

wee

k. P

hysic

al t

hera

pist

sdi

rect

ly a

ssist

ed p

artic

ipan

ts in

the

wal

king

cyc

le. B

odyw

eigh

t su

ppor

tal

low

ed o

nly

in t

he fi

rst

thre

etr

aini

ng s

essio

ns

Trea

ted

as in

patie

nts

for

thre

e 30

-min

ute

sess

ions

per

wee

k fo

r4

wee

ks. I

nter

vent

ion

was

addi

tiona

l to

conv

entio

nal

phys

ioth

erap

y re

ceiv

ed b

y al

lgr

oups

Com

paris

on g

roup

: Con

vent

iona

lga

it tr

aini

ng: p

hysio

ther

apeu

tic g

ait

ther

apy

base

d on

neur

ophy

siolo

gica

l tec

hniq

ues.

T

hree

45-

min

ute

sess

ions

per

wee

k fo

r 4

wee

ks. A

dditi

onal

to

conv

entio

nal p

hysio

ther

apy

rece

ived

Out

com

es r

ecor

ded

pre-

and

post

-inte

rven

tion

Lim

b-sp

ecifi

c fu

nctio

n:Fa

stes

t co

mfo

rtab

lew

alki

ng s

peed

ove

r 10

mus

ing

gait

aids

if r

equi

red,

FAC

Mot

or im

pairm

ent:

Cad

ence

, str

ide

leng

th

Allo

catio

n co

ncea

lmen

tun

clea

r

No

signi

fican

t di

ffere

nces

in b

asel

ine

char

acte

ristic

s

Blin

ded

outc

ome

asse

ssm

ent

Loss

to

follo

w-u

p at

end

of t

reat

men

t pe

riod:

10%

No

inte

rven

tion-

rela

ted

with

draw

als

No

adve

rse

even

tsre

port

ed

cont

inue

d


105


Aut

hor

and

year

Stud

y de

tails

Cou

ntry

and

par

tici

pant

sIn

terv

enti

onO

utco

mes

Not

es

Sche

idtm

ann,

199

963

(Des

crip

tion

take

nfr

om t

rans

latio

n an

dsu

pple

men

ted

byde

tails

giv

en in

Mos

eley

, 200

520)

Cro

ss-o

ver

grou

pde

sign

Part

icip

ants

ran

dom

ised

to g

roup

s (m

etho

d of

rand

omisa

tion

and

conc

ealm

ent

not

stat

ed)

Ger

man

y15

par

ticip

ants

allo

cate

d to

expe

rimen

tal t

hen

cont

rol g

roup

,an

d 15

par

ticip

ants

allo

cate

d to

cont

rol t

hen

expe

rimen

tal g

roup

Incl

usio

n cr

iteria

: Hem

ipar

esis,

str

oke

(infa

rct

or h

aem

orrh

age)

, at

leas

t4

wee

ks p

ost-

stro

ke, n

ot a

ble

tow

alk,

abl

e to

sta

nd fo

r 20

sec

onds

Excl

usio

n cr

iteria

: Car

diov

ascu

lar

prob

lem

s or

infe

ctio

ns w

ith a

decr

ease

in g

ener

al h

ealth

Age:

57.

7 (S

D 1

1)52

% m

ale

Stro

ke d

etai

ls: 6

9% is

chae

mic

str

oke

Tim

e sin

ce s

trok

e: 5

8.2

days

(S

D 2

8.6)

Prei

nter

vent

ion

abili

ty le

vel:

Abl

e to

stan

d fo

r up

to

20 s

econ

ds

Expe

rimen

tal i

nter

vent

ion:

Tre

adm

illtr

aini

ng c

ombi

ned

with

phys

ioth

erap

y w

ith b

odyw

eigh

tsu

ppor

t. Pa

rtic

ipan

ts w

alke

d on

atr

eadm

ill w

ith p

artia

l bod

ywei

ght

supp

ort

prov

ided

by

a ha

rnes

s fo

r30

min

utes

and

com

plet

ed30

min

utes

of u

sual

phy

sioth

erap

ype

r da

y

Trea

ted

as in

-par

ticip

ants

for

five

1-ho

ur s

essio

ns p

er w

eek

for

3w

eeks

Com

paris

on g

roup

: Par

ticip

ants

com

plet

ed t

wo

30-m

inut

e se

ssio

nsof

phy

sioth

erap

y pe

r da

y

Out

com

es a

sses

sed

atba

selin

e, a

t cr

oss-

over

(3w

eeks

) and

afte

rtr

eatm

ent

phas

e (a

t6

wee

ks)

Lim

b-sp

ecifi

c fu

nctio

n:RM

A S

cale

, wal

king

spee

d ov

er 1

0 m

(ite

m 6

of t

he R

MA

),co

mfo

rtab

le o

rm

axim

um

Pers

onal

ass

istan

ce,

supe

rvisi

on a

nd g

ait

aid

use

wer

e no

t re

port

ed

Mot

or im

pairm

ent:

Self-

deve

lope

d ga

it sc

ale

base

d on

clin

ical

asse

ssm

ent

Allo

catio

n co

ncea

lmen

tun

clea

r

Blin

ding

of o

utco

me

asse

ssor

s to

gro

upal

loca

tion

not

repo

rted

No

drop

outs

at

end

offir

st t

reat

men

t ph

ase

No

inte

rven

tion-

rela

ted

with

draw

als

Adv

erse

eve

nts

not

stat

ed


107


Appendix 4

Characteristics of excluded studies

Study Comment

RTTBagley, 2005145 xBrown, 2002146 xCarey, 2002147 xChan, 2006148 xChang, 2000149 xCirstea, 2003150 xDesrosiers, 2005151 xDuncan, 2003152 xEng, 2003153 xFeys, 1998154 xGelber, 1995155 xHanlon, 1996156 x No baseline measures for functionHusemann, 2004157 xInaba, 1973158 xKatz-Leurer, 2006159 xKayhan, 1996160 x Unable to contact authorKhanna, 2003161 x Study did not startKilbreath, 1997162 x Study information not availableKrutulyte, 2004163 x Unable to determine whether randomisedLi, 2005164 xLiao, 2006165 xMudie, 2002166 xNelles, 2001167 x Not designed to evaluate interventionPang, 2006168 xPlatz, 2001169 x No subgroup dataPollock, 2002170 xSunderland, 1992171 xTheilman, 2004172 xWellmon, 1997173 xXiao, 2002174 xYang, 2005175 x

CIMTPloughman, 2004176 xRo, 2006177 x Subgroup of Boake, 200684

Sterr, 2002178 x Not RCTVan der Lee, 1999179 x

continued

Not

func

tion

al, o

r no

func

tion

alou

tcom

e

Mix

ed in

terv

enti

on, o

r m

ain

focu

son

exe

rcis

e ra

ther

tha

n fu

ncti

on

Not

rep

etit

ion,

or

unab

le t

ode

term

ine

amou

nt o

f pra

ctic

e

Pass

ive

mov

emen

t

Com

pare

d ag

ains

t an

othe

rre

peti

tive

func

tion

al in

terv

enti

on

Met

hod

or r

epor

ting

rea

sons

Appendix 4

108

Study Comment

TMJaffe, 2004180 xKosak, 2000181 xNilsson, 2001182 xLaufer, 2001183 xListon, 2000184 xRichards, 1993185 xRichards, 2004186 xVisintin, 1998187 x Bodyweight support comparisonWerner, 2002188 x

Not

func

tion

al, o

r no

func

tion

alou

tcom

e

Mix

ed in

terv

enti

on, o

r m

ain

focu

son

exe

rcis

e ra

ther

tha

n fu

ncti

on

Not

rep

etit

ion,

or

unab

le t

ode

term

ine

amou

nt o

f pra

ctic

e

Pass

ive

mov

emen

t

Com

pare

d ag

ains

t an

othe

rre

peti

tive

func

tion

al in

terv

enti

on

Met

hod

or r

epor

ting

rea

sons


109


Appendix 5

Characteristics of ongoing studies

Appendix 5

110

Stud

yTr

ial n

ame

Part

icip

ants

Inte

rven

tion

sO

utco

mes

Star

ting

dat

eN

otes

RT

TA

lliso

n, 2

00590

Pilo

t ra

ndom

ised

cont

rol t

rial t

o as

sess

0–

3 m

onth

s St

andi

ng p

ract

ice

plus

RM

A, T

runk

Con

trol

20

01Tr

ial c

ompl

ete

and

the

impa

ct o

f add

ition

al s

uppo

rted

po

st-s

trok

eus

ual c

are

Test

, Ber

g Ba

lanc

e Sc

ale

bein

g su

bmitt

ed fo

r st

andi

ng p

ract

ice

on fu

nctio

nal a

bilit

y pu

blic

atio

npo

st-s

trok

e

Ask

im, 2

00591

Doe

s in

tens

ive

task

spe

cific

tra

inin

g 0–

3 m

onth

s Ba

lanc

e tr

aini

ng p

lus

Bala

nce,

sit-

to-s

tand

, 20

05Tr

ial d

ue t

o co

mpl

ete

impr

ove

bala

nce

afte

r ac

ute

stro

ke?

post

-str

oke

usua

l car

ew

alki

ng s

peed

, AD

L, fa

lls,

2012

low

er li

mb

func

tion

Engl

ish, 2

00593

Is t

ask-

rela

ted

circ

uit

trai

ning

an

0–3

mon

ths

Task

-rel

ated

circ

uit

Bala

nce,

MA

S, g

ait

spee

d 20

03Tr

ial c

ompl

ete

and

effe

ctiv

e m

eans

of p

rovi

ding

po

st-s

trok

etr

aini

ngan

d en

dura

nce,

NH

P, be

ing

subm

itted

for

reha

bilit

atio

n to

acu

te s

trok

e pa

tient

s?pa

tient

sat

isfac

tion

publ

icat

ion

Har

ris, 2

00692

Eval

uatio

n of

a r

epet

itive

pra

ctic

e 0–

3 m

onth

s Re

petit

ive

sit-t

o-st

and

Sit-

to-s

tand

2005

Tria

l due

to

com

plet

e sc

hem

e to

impr

ove

sit-t

o-st

and

post

-str

oke

trai

ning

2006

perf

orm

ance

follo

win

g st

roke

Lang

ham

mer

, St

roke

: red

uctio

n of

phy

sical

Po

st-a

cute

M

otor

rel

earn

ing

Phys

ical

end

uran

ce,

2003

Tria

l clo

sed

inta

ke

2005

(per

sona

l pe

rfor

man

ce p

ost-

stro

ke: i

nact

ivity

or

reha

bilit

atio

nst

reng

th, b

alan

ceau

tum

n 20

05co

mm

unic

atio

n)se

cond

ary

com

plic

atio

ns?

Mill

er, 2

00295

Early

inte

nsiv

e ta

sk-s

peci

fic s

enso

ry a

nd

0–3

mon

ths

Task

-spe

cific

tra

inin

g of

M

AS,

Che

doke

McM

aste

r 20

02Ph

D d

ue t

o co

mpl

ete

mot

or t

rain

ing

of t

he u

pper

lim

b af

ter

post

-str

oke

the

uppe

r lim

b,

Impa

irmen

t In

vent

ory,

in

200

7ac

ute

stro

ke: a

pilo

t st

udy

emph

asisi

ng u

nim

anua

l Si

ckne

ss Im

pact

Pro

file,

an

d bi

man

ual f

unct

iona

l ha

nd d

exte

rity

activ

ities

Sher

ringt

on,

A r

ando

mise

d co

ntro

lled

tria

l to

173

olde

r C

ircui

t de

signe

d to

Ba

lanc

e, g

ait,

sit-t

o-st

and,

20

05Pu

blic

atio

n su

bmitt

ed.

2005

94ev

alua

te t

ask-

rela

ted

exer

cise

cla

sses

pe

ople

, 90

with

pr

ovid

e re

petit

ive,

w

alki

ng e

ndur

ance

Subg

roup

dat

a fo

r ol

der

peop

le w

ith im

paire

d m

obili

tyne

urol

ogic

al

func

tiona

l, av

aila

ble

2008

prob

lem

sta

sk-r

elat

ed e

xerc

ise

CIM

TN

oser

, 200

496C

onst

rain

t-in

duce

d m

ovem

ent

ther

apy

4–10

day

s C

IMT

Arm

and

han

d fu

nctio

n20

00Tr

ial d

ue t

o co

mpl

ete

afte

r su

bacu

te s

trok

epo

st-s

trok

eJu

ne 2

007


111


Appendix 6

Criteria for subgroup analyses

Appendix 6

112

Stud

yTa

sk p

ract

ice

Tim

e si

nce

Inte

rven

tion

A

lloca

tion

C

ompa

riso

n T

hera

py

Tria

l siz

eg

amou

nta

stro

keb

deliv

eryc

conc

ealm

entd

grou

peti

mef

RT

TBl

enne

rhas

sett

, 200

4501

32

AA

CEQ

2D

ean,

199

7661

31

BA

CEQ

1D

ean,

200

0671

32

AA

CEQ

1de

Sèz

e, 2

00176

12

1B

UC

EQ2

How

e, 2

00577

12

1A

UC

EQ2

Kw

akke

l, 19

9953

21

1A

AC

EQ2

Lang

ham

mer

, 200

0681

11

BU

CEQ

2M

cCle

llan,

200

4782

33

AA

CEQ

2Sa

lbac

h, 2

00451

13

2A

AC

EQ2

Turt

on, 1

99069

22

3B

UC

AD

D1

Van

Vlie

t, 20

0570

11

1A

UC

EQ2

Win

stei

n, 2

00471

11

1A

UC

AD

D2

Yen,

200

5722

31

BU

CEQ

2

TM

Ada

, 200

3871

31

AA

CEQ

2da

Cuh

na, 2

00286

12

1B

UC

EQ1

Eich

, 200

4891

21

AA

LTEQ

2M

acko

, 200

5882

31

BA

LTEQ

2Po

hl, 2

00285

12

1B

UC

EQ2

CIM

TA

lber

ts, 2

00483

22

1B

NT

AD

D1

Att

eya,

200

4792

21

BN

TA

DD

1Bo

ake,

200

6842

11

BU

CEQ

1D

rom

eric

k, 2

00081

11

1B

UC

EQ1

Page

, 200

1802

21

BN

TA

DD

1Pa

ge, 2

00582

11

1B

UC

AD

D1

Taub

, 199

3732

31

BA

CEQ

1W

itten

berg

, 200

3742

31

BA

CA

DD

1

a 1

= �

20 h

ours

, 2 =

>20

hou

rs.

b 1

= 1

–14

days

, 2 =

15

days

to

6 m

onth

s, 3

= >

6 m

onth

s.c 1

= in

divi

dual

the

rapy

, 2 =

gro

up, 3

= s

elf –

hom

e.d

A =

ade

quat

e, B

=in

adeq

uate

/unc

lear

.e

AC

= a

tten

tion

cont

rol,

UC

= u

sual

car

e, A

LT =

alte

rnat

ive

trea

tmen

t, N

T =

no

trea

tmen

t.f EQ

= e

qual

tim

e, A

DD

= a

dditi

onal

tim

e.g 1

= <

25 p

artic

ipan

ts, 2

= �

25 p

artic

ipan

ts.


113


Appendix 7

Summary of baseline characteristics of patients from the cohort in the patient data set who

survived to 3 years

Age (years) median (IQR) 69.5 (64 to 77)

Gender female, n (%) 58 (39)Lesion type, n (%)

IC 108 (72)Primary intracerebral haemorrhage 17 (11)Haemorrhagic transformation of IC 4 (3)No scan 21 (14)

Side, n (%)Left 52 (35)Right 64 (42)No bilateral signs 34 (23)

IC, ischaemic infarction.


115


Appendix 8

Numbers of patients and costs in the baseline and new groups

Baseline groups New groups

Barthel category Average cost n Total cost na Total cost Difference

�10 £4,398 28 £123,154 25.5 £111,95811–14 £6,874 34 £233,727 28.0 £192,79315–17 £4,914 33 £162,169 30.5 £149,88318 or 19 £2,153 25 £53,819 23.5 £50,58920 £1,610 30 £48,291 42.5 £68,412Total 150 £621,159 150 £573,636 £47,523Average £4,141 £3,824 £317

a Approximate.


117


Appendix 9

Cost-effectiveness at 3 years per QALY gained for RFTP on outcome measures that

were significant in the systematic review

Analysisa Outcome Overallb Arm ADLc Walking Functional Sit-to-functionc distanced ambulationd standd

1 SMD £10,870 £15,185 £11,009 £4,187 £10,187 £5,708SMD lower limit CI £23,947 £77,821 £49,983 £16,539 £83,239 £19,010SMD upper limit CI £6,039 £6,237 £3,942 £658 £3,025 £1,596

2 SMD: BI; 0.2:1.0 £10,870 £15,185 £11,009 £4,187 £10,187 £5,708SMD: BI; 0.2:0.8 £15,011 £20,405 £15,185 £6,658 £14,157 £8,558SMD: BI; 0.2:0.6 £21,913 £29,104 £22,144 £10,775 £20,774 £13,309SMD: BI; 0.2:0.4 £35,716 £46,503 £36,064 £19,010 £34,008 £22,810SMD: BI; 0.2:0.2 £77,126 £98,700 £77,821 £43,713 £73,711 £51,315

3 BI: EQ-5D; 1:0.05 £10,870 £15,185 £11,009 £4,187 £10,187 £5,708BI: EQ-5D; 1:0.04 £13,587 £18,981 £13,761 £5,234 £12,734 £7,135BI: EQ-5D; 1:0.03 £18,116 £25,308 £18,348 £6,979 £16,978 £9,513BI: EQ-5D; 1:0.02 £27,175 £37,962 £27,523 £10,469 £25,467 £14,269BI: EQ-5D; 1:0.01 £54,349 £75,924 £55,045 £20,937 £50,935 £28,538

4 £35 per hour £9,143 £12,712 £9,031 £3,283 £8,734 £4,664£40 per hour £10,870 £15,185 £11,009 £4,187 £10,187 £5,708£45 per hour £12,597 £17,657 £12,987 £5,092 £11,640 £6,751£50 per hour £14,323 £20,129 £14,965 £5,996 £13,093 £7,794£55 per hour £16,050 £22,602 £16,943 £6,900 £14,546 £8,837£60 per hour £17,777 £25,074 £18,921 £7,804 £15,999 £9,880

5 Discount = 0% £10,228 £14,543 £10,367 £3,545 £9,545 £5,065Discount = 3.5% £10,870 £15,185 £11,009 £4,187 £10,187 £5,708Discount = 6.0% £11,301 £15,616 £11,440 £4,619 £10,618 £6,139

6 Discount = 0% £9,191 £13,068 £9,316 £3,186 £8,577 £4,552Discount = 3.5% £10,870 £15,185 £11,009 £4,187 £10,187 £5,708Discount = 6.0% £12,227 £16,895 £12,377 £4,997 £11,488 £6,642

a 1, Base case; 2, varying the association between the SMD and the BI (shaded cells are base case); 3, varying the associationbetween the BI and the EQ-5D (shaded cells are base case); 4, varying the cost per hour of client contact with therapist(shaded cells are base case); 5, varying the discount rate on cost (shaded cells are base case); 6, varying the discount rateon outcome (shaded cells are base case).

b Cost per QALY gained, where the cost of the intervention is £1265 (based on the average cost of RTT, CIMT and TM).c Cost per QALY gained, where the cost of the intervention is £1126 (based on the average cost of RTT and CIMT).d Cost per QALY gained, where the cost of the intervention is £999 (based on the average cost of RTT and TM).

Volume 1, 1997

No. 1Home parenteral nutrition: a systematicreview.

By Richards DM, Deeks JJ, SheldonTA, Shaffer JL.

No. 2Diagnosis, management and screeningof early localised prostate cancer.

A review by Selley S, Donovan J,Faulkner A, Coast J, Gillatt D.

No. 3The diagnosis, management, treatmentand costs of prostate cancer in Englandand Wales.

A review by Chamberlain J, Melia J,Moss S, Brown J.

No. 4Screening for fragile X syndrome.

A review by Murray J, Cuckle H,Taylor G, Hewison J.

No. 5A review of near patient testing inprimary care.

By Hobbs FDR, Delaney BC,Fitzmaurice DA, Wilson S, Hyde CJ,Thorpe GH, et al.

No. 6Systematic review of outpatient servicesfor chronic pain control.

By McQuay HJ, Moore RA, EcclestonC, Morley S, de C Williams AC.

No. 7Neonatal screening for inborn errors ofmetabolism: cost, yield and outcome.

A review by Pollitt RJ, Green A,McCabe CJ, Booth A, Cooper NJ,Leonard JV, et al.

No. 8Preschool vision screening.

A review by Snowdon SK, Stewart-Brown SL.

No. 9Implications of socio-cultural contextsfor the ethics of clinical trials.

A review by Ashcroft RE, ChadwickDW, Clark SRL, Edwards RHT, Frith L,Hutton JL.

No. 10A critical review of the role of neonatalhearing screening in the detection ofcongenital hearing impairment.

By Davis A, Bamford J, Wilson I,Ramkalawan T, Forshaw M, Wright S.

No. 11Newborn screening for inborn errors ofmetabolism: a systematic review.

By Seymour CA, Thomason MJ,Chalmers RA, Addison GM, Bain MD,Cockburn F, et al.

No. 12Routine preoperative testing: a systematic review of the evidence.

By Munro J, Booth A, Nicholl J.

No. 13Systematic review of the effectiveness of laxatives in the elderly.

By Petticrew M, Watt I, Sheldon T.

No. 14When and how to assess fast-changingtechnologies: a comparative study ofmedical applications of four generictechnologies.

A review by Mowatt G, Bower DJ,Brebner JA, Cairns JA, Grant AM,McKee L.

Volume 2, 1998

No. 1Antenatal screening for Down’ssyndrome.

A review by Wald NJ, Kennard A,Hackshaw A, McGuire A.

No. 2Screening for ovarian cancer: a systematic review.

By Bell R, Petticrew M, Luengo S,Sheldon TA.

No. 3Consensus development methods, andtheir use in clinical guidelinedevelopment.

A review by Murphy MK, Black NA,Lamping DL, McKee CM, SandersonCFB, Askham J, et al.

No. 4A cost–utility analysis of interferon beta for multiple sclerosis.

By Parkin D, McNamee P, Jacoby A,Miller P, Thomas S, Bates D.

No. 5Effectiveness and efficiency of methodsof dialysis therapy for end-stage renaldisease: systematic reviews.

By MacLeod A, Grant A, Donaldson C, Khan I, Campbell M,Daly C, et al.

No. 6Effectiveness of hip prostheses inprimary total hip replacement: a criticalreview of evidence and an economicmodel.

By Faulkner A, Kennedy LG, Baxter K, Donovan J, Wilkinson M,Bevan G.

No. 7Antimicrobial prophylaxis in colorectalsurgery: a systematic review ofrandomised controlled trials.

By Song F, Glenny AM.

No. 8Bone marrow and peripheral bloodstem cell transplantation for malignancy.

A review by Johnson PWM, Simnett SJ,Sweetenham JW, Morgan GJ, Stewart LA.

No. 9Screening for speech and languagedelay: a systematic review of theliterature.

By Law J, Boyle J, Harris F, HarknessA, Nye C.

No. 10Resource allocation for chronic stableangina: a systematic review ofeffectiveness, costs and cost-effectiveness of alternativeinterventions.

By Sculpher MJ, Petticrew M, Kelland JL, Elliott RA, Holdright DR,Buxton MJ.

No. 11Detection, adherence and control ofhypertension for the prevention ofstroke: a systematic review.

By Ebrahim S.

No. 12Postoperative analgesia and vomiting,with special reference to day-casesurgery: a systematic review.

By McQuay HJ, Moore RA.

No. 13Choosing between randomised andnonrandomised studies: a systematicreview.

By Britton A, McKee M, Black N,McPherson K, Sanderson C, Bain C.

No. 14Evaluating patient-based outcomemeasures for use in clinical trials.

A review by Fitzpatrick R, Davey C,Buxton MJ, Jones DR.


119


Health Technology Assessment reports published to date

No. 15Ethical issues in the design and conductof randomised controlled trials.

A review by Edwards SJL, Lilford RJ,Braunholtz DA, Jackson JC, Hewison J,Thornton J.

No. 16Qualitative research methods in healthtechnology assessment: a review of theliterature.

By Murphy E, Dingwall R, GreatbatchD, Parker S, Watson P.

No. 17The costs and benefits of paramedicskills in pre-hospital trauma care.

By Nicholl J, Hughes S, Dixon S,Turner J, Yates D.

No. 18Systematic review of endoscopicultrasound in gastro-oesophagealcancer.

By Harris KM, Kelly S, Berry E,Hutton J, Roderick P, Cullingworth J, et al.

No. 19Systematic reviews of trials and otherstudies.

By Sutton AJ, Abrams KR, Jones DR,Sheldon TA, Song F.

No. 20Primary total hip replacement surgery: a systematic review of outcomes andmodelling of cost-effectivenessassociated with different prostheses.

A review by Fitzpatrick R, Shortall E,Sculpher M, Murray D, Morris R, LodgeM, et al.

Volume 3, 1999

No. 1Informed decision making: an annotatedbibliography and systematic review.

By Bekker H, Thornton JG, Airey CM, Connelly JB, Hewison J,Robinson MB, et al.

No. 2Handling uncertainty when performingeconomic evaluation of healthcareinterventions.

A review by Briggs AH, Gray AM.

No. 3The role of expectancies in the placeboeffect and their use in the delivery ofhealth care: a systematic review.

By Crow R, Gage H, Hampson S,Hart J, Kimber A, Thomas H.

No. 4A randomised controlled trial ofdifferent approaches to universalantenatal HIV testing: uptake andacceptability. Annex: Antenatal HIVtesting – assessment of a routinevoluntary approach.

By Simpson WM, Johnstone FD, BoydFM, Goldberg DJ, Hart GJ, GormleySM, et al.

No. 5Methods for evaluating area-wide andorganisation-based interventions inhealth and health care: a systematicreview.

By Ukoumunne OC, Gulliford MC,Chinn S, Sterne JAC, Burney PGJ.

No. 6Assessing the costs of healthcaretechnologies in clinical trials.

A review by Johnston K, Buxton MJ,Jones DR, Fitzpatrick R.

No. 7Cooperatives and their primary careemergency centres: organisation andimpact.

By Hallam L, Henthorne K.

No. 8Screening for cystic fibrosis.

A review by Murray J, Cuckle H,Taylor G, Littlewood J, Hewison J.

No. 9A review of the use of health statusmeasures in economic evaluation.

By Brazier J, Deverill M, Green C,Harper R, Booth A.

No. 10Methods for the analysis of quality-of-life and survival data in healthtechnology assessment.

A review by Billingham LJ, AbramsKR, Jones DR.

No. 11Antenatal and neonatalhaemoglobinopathy screening in theUK: review and economic analysis.

By Zeuner D, Ades AE, Karnon J,Brown J, Dezateux C, Anionwu EN.

No. 12Assessing the quality of reports ofrandomised trials: implications for theconduct of meta-analyses.

A review by Moher D, Cook DJ, JadadAR, Tugwell P, Moher M, Jones A, et al.

No. 13‘Early warning systems’ for identifyingnew healthcare technologies.

By Robert G, Stevens A, Gabbay J.

No. 14A systematic review of the role of humanpapillomavirus testing within a cervicalscreening programme.

By Cuzick J, Sasieni P, Davies P,Adams J, Normand C, Frater A, et al.

No. 15Near patient testing in diabetes clinics:appraising the costs and outcomes.

By Grieve R, Beech R, Vincent J,Mazurkiewicz J.

No. 16Positron emission tomography:establishing priorities for healthtechnology assessment.

A review by Robert G, Milne R.

No. 17 (Pt 1)The debridement of chronic wounds: a systematic review.

By Bradley M, Cullum N, Sheldon T.

No. 17 (Pt 2)Systematic reviews of wound caremanagement: (2) Dressings and topicalagents used in the healing of chronicwounds.

By Bradley M, Cullum N, Nelson EA,Petticrew M, Sheldon T, Torgerson D.

No. 18A systematic literature review of spiraland electron beam computedtomography: with particular reference toclinical applications in hepatic lesions,pulmonary embolus and coronary arterydisease.

By Berry E, Kelly S, Hutton J, Harris KM, Roderick P, Boyce JC, et al.

No. 19What role for statins? A review andeconomic model.

By Ebrahim S, Davey Smith G,McCabe C, Payne N, Pickin M, SheldonTA, et al.

No. 20Factors that limit the quality, numberand progress of randomised controlledtrials.

A review by Prescott RJ, Counsell CE,Gillespie WJ, Grant AM, Russell IT,Kiauka S, et al.

No. 21Antimicrobial prophylaxis in total hipreplacement: a systematic review.

By Glenny AM, Song F.

No. 22Health promoting schools and healthpromotion in schools: two systematicreviews.

By Lister-Sharp D, Chapman S,Stewart-Brown S, Sowden A.

No. 23Economic evaluation of a primary care-based education programme for patientswith osteoarthritis of the knee.

A review by Lord J, Victor C,Littlejohns P, Ross FM, Axford JS.

Volume 4, 2000

No. 1The estimation of marginal timepreference in a UK-wide sample(TEMPUS) project.

A review by Cairns JA, van der PolMM.

No. 2Geriatric rehabilitation followingfractures in older people: a systematicreview.

By Cameron I, Crotty M, Currie C,Finnegan T, Gillespie L, Gillespie W, et al.


120

No. 3Screening for sickle cell disease andthalassaemia: a systematic review withsupplementary research.

By Davies SC, Cronin E, Gill M,Greengross P, Hickman M, Normand C.

No. 4Community provision of hearing aidsand related audiology services.

A review by Reeves DJ, Alborz A,Hickson FS, Bamford JM.

No. 5False-negative results in screeningprogrammes: systematic review ofimpact and implications.

By Petticrew MP, Sowden AJ, Lister-Sharp D, Wright K.

No. 6Costs and benefits of communitypostnatal support workers: arandomised controlled trial.

By Morrell CJ, Spiby H, Stewart P,Walters S, Morgan A.

No. 7Implantable contraceptives (subdermalimplants and hormonally impregnatedintrauterine systems) versus other formsof reversible contraceptives: twosystematic reviews to assess relativeeffectiveness, acceptability, tolerabilityand cost-effectiveness.

By French RS, Cowan FM, MansourDJA, Morris S, Procter T, Hughes D, et al.

No. 8An introduction to statistical methodsfor health technology assessment.

A review by White SJ, Ashby D, Brown PJ.

No. 9Disease-modifying drugs for multiplesclerosis: a rapid and systematic review.

By Clegg A, Bryant J, Milne R.

No. 10Publication and related biases.

A review by Song F, Eastwood AJ,Gilbody S, Duley L, Sutton AJ.

No. 11Cost and outcome implications of theorganisation of vascular services.

By Michaels J, Brazier J, PalfreymanS, Shackley P, Slack R.

No. 12Monitoring blood glucose control indiabetes mellitus: a systematic review.

By Coster S, Gulliford MC, Seed PT,Powrie JK, Swaminathan R.

No. 13The effectiveness of domiciliary healthvisiting: a systematic review ofinternational studies and a selective review of the Britishliterature.

By Elkan R, Kendrick D, Hewitt M,Robinson JJA, Tolley K, Blair M, et al.

No. 14The determinants of screening uptakeand interventions for increasing uptake:a systematic review.

By Jepson R, Clegg A, Forbes C,Lewis R, Sowden A, Kleijnen J.

No. 15The effectiveness and cost-effectivenessof prophylactic removal of wisdomteeth.

A rapid review by Song F, O’Meara S,Wilson P, Golder S, Kleijnen J.

No. 16Ultrasound screening in pregnancy: asystematic review of the clinicaleffectiveness, cost-effectiveness andwomen’s views.

By Bricker L, Garcia J, Henderson J,Mugford M, Neilson J, Roberts T, et al.

No. 17A rapid and systematic review of theeffectiveness and cost-effectiveness ofthe taxanes used in the treatment ofadvanced breast and ovarian cancer.

By Lister-Sharp D, McDonagh MS,Khan KS, Kleijnen J.

No. 18Liquid-based cytology in cervicalscreening: a rapid and systematic review.

By Payne N, Chilcott J, McGoogan E.

No. 19Randomised controlled trial of non-directive counselling,cognitive–behaviour therapy and usualgeneral practitioner care in themanagement of depression as well asmixed anxiety and depression inprimary care.

By King M, Sibbald B, Ward E, BowerP, Lloyd M, Gabbay M, et al.

No. 20Routine referral for radiography ofpatients presenting with low back pain:is patients’ outcome influenced by GPs’referral for plain radiography?

By Kerry S, Hilton S, Patel S, DundasD, Rink E, Lord J.

No. 21Systematic reviews of wound caremanagement: (3) antimicrobial agentsfor chronic wounds; (4) diabetic footulceration.

By O’Meara S, Cullum N, Majid M,Sheldon T.

No. 22Using routine data to complement andenhance the results of randomisedcontrolled trials.

By Lewsey JD, Leyland AH, Murray GD, Boddy FA.

No. 23Coronary artery stents in the treatmentof ischaemic heart disease: a rapid andsystematic review.

By Meads C, Cummins C, Jolly K,Stevens A, Burls A, Hyde C.

No. 24Outcome measures for adult criticalcare: a systematic review.

By Hayes JA, Black NA, Jenkinson C, Young JD, Rowan KM,Daly K, et al.

No. 25A systematic review to evaluate theeffectiveness of interventions to promote the initiation of breastfeeding.

By Fairbank L, O’Meara S, RenfrewMJ, Woolridge M, Sowden AJ, Lister-Sharp D.

No. 26Implantable cardioverter defibrillators:arrhythmias. A rapid and systematicreview.

By Parkes J, Bryant J, Milne R.

No. 27Treatments for fatigue in multiplesclerosis: a rapid and systematic review.

By Brañas P, Jordan R, Fry-Smith A,Burls A, Hyde C.

No. 28Early asthma prophylaxis, naturalhistory, skeletal development andeconomy (EASE): a pilot randomisedcontrolled trial.

By Baxter-Jones ADG, Helms PJ,Russell G, Grant A, Ross S, Cairns JA, et al.

No. 29Screening for hypercholesterolaemiaversus case finding for familialhypercholesterolaemia: a systematicreview and cost-effectiveness analysis.

By Marks D, Wonderling D,Thorogood M, Lambert H, HumphriesSE, Neil HAW.

No. 30A rapid and systematic review of theclinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIaantagonists in the medical managementof unstable angina.

By McDonagh MS, Bachmann LM,Golder S, Kleijnen J, ter Riet G.

No. 31A randomised controlled trial ofprehospital intravenous fluidreplacement therapy in serious trauma.

By Turner J, Nicholl J, Webber L,Cox H, Dixon S, Yates D.

No. 32Intrathecal pumps for giving opioids inchronic pain: a systematic review.

By Williams JE, Louw G, Towlerton G.

No. 33Combination therapy (interferon alfaand ribavirin) in the treatment ofchronic hepatitis C: a rapid andsystematic review.

By Shepherd J, Waugh N, Hewitson P.


121


No. 34A systematic review of comparisons ofeffect sizes derived from randomisedand non-randomised studies.

By MacLehose RR, Reeves BC,Harvey IM, Sheldon TA, Russell IT,Black AMS.

No. 35Intravascular ultrasound-guidedinterventions in coronary artery disease:a systematic literature review, withdecision-analytic modelling, of outcomesand cost-effectiveness.

By Berry E, Kelly S, Hutton J,Lindsay HSJ, Blaxill JM, Evans JA, et al.

No. 36A randomised controlled trial toevaluate the effectiveness and cost-effectiveness of counselling patients withchronic depression.

By Simpson S, Corney R, Fitzgerald P,Beecham J.

No. 37Systematic review of treatments foratopic eczema.

By Hoare C, Li Wan Po A, Williams H.

No. 38Bayesian methods in health technologyassessment: a review.

By Spiegelhalter DJ, Myles JP, Jones DR, Abrams KR.

No. 39The management of dyspepsia: asystematic review.

By Delaney B, Moayyedi P, Deeks J,Innes M, Soo S, Barton P, et al.

No. 40A systematic review of treatments forsevere psoriasis.

By Griffiths CEM, Clark CM, ChalmersRJG, Li Wan Po A, Williams HC.

Volume 5, 2001

No. 1Clinical and cost-effectiveness ofdonepezil, rivastigmine andgalantamine for Alzheimer’s disease: arapid and systematic review.

By Clegg A, Bryant J, Nicholson T,McIntyre L, De Broe S, Gerard K, et al.

No. 2The clinical effectiveness and cost-effectiveness of riluzole for motorneurone disease: a rapid and systematicreview.

By Stewart A, Sandercock J, Bryan S,Hyde C, Barton PM, Fry-Smith A, et al.

No. 3Equity and the economic evaluation ofhealthcare.

By Sassi F, Archard L, Le Grand J.

No. 4Quality-of-life measures in chronicdiseases of childhood.

By Eiser C, Morse R.

No. 5Eliciting public preferences forhealthcare: a systematic review oftechniques.

By Ryan M, Scott DA, Reeves C, BateA, van Teijlingen ER, Russell EM, et al.

No. 6General health status measures forpeople with cognitive impairment:learning disability and acquired braininjury.

By Riemsma RP, Forbes CA, Glanville JM, Eastwood AJ, Kleijnen J.

No. 7An assessment of screening strategies forfragile X syndrome in the UK.

By Pembrey ME, Barnicoat AJ,Carmichael B, Bobrow M, Turner G.

No. 8Issues in methodological research:perspectives from researchers andcommissioners.

By Lilford RJ, Richardson A, StevensA, Fitzpatrick R, Edwards S, Rock F, et al.

No. 9Systematic reviews of wound caremanagement: (5) beds; (6) compression;(7) laser therapy, therapeuticultrasound, electrotherapy andelectromagnetic therapy.

By Cullum N, Nelson EA, FlemmingK, Sheldon T.

No. 10Effects of educational and psychosocialinterventions for adolescents withdiabetes mellitus: a systematic review.

By Hampson SE, Skinner TC, Hart J,Storey L, Gage H, Foxcroft D, et al.

No. 11Effectiveness of autologous chondrocytetransplantation for hyaline cartilagedefects in knees: a rapid and systematicreview.

By Jobanputra P, Parry D, Fry-SmithA, Burls A.

No. 12Statistical assessment of the learningcurves of health technologies.

By Ramsay CR, Grant AM, Wallace SA, Garthwaite PH, Monk AF,Russell IT.

No. 13The effectiveness and cost-effectivenessof temozolomide for the treatment ofrecurrent malignant glioma: a rapid andsystematic review.

By Dinnes J, Cave C, Huang S, Major K, Milne R.

No. 14A rapid and systematic review of theclinical effectiveness and cost-effectiveness of debriding agents intreating surgical wounds healing bysecondary intention.

By Lewis R, Whiting P, ter Riet G,O’Meara S, Glanville J.

No. 15Home treatment for mental healthproblems: a systematic review.

By Burns T, Knapp M, Catty J, Healey A, Henderson J, Watt H, et al.

No. 16How to develop cost-consciousguidelines.

By Eccles M, Mason J.

No. 17The role of specialist nurses in multiplesclerosis: a rapid and systematic review.

By De Broe S, Christopher F, Waugh N.

No. 18A rapid and systematic review of theclinical effectiveness and cost-effectiveness of orlistat in themanagement of obesity.

By O’Meara S, Riemsma R, Shirran L, Mather L, ter Riet G.

No. 19The clinical effectiveness and cost-effectiveness of pioglitazone for type 2diabetes mellitus: a rapid and systematicreview.

By Chilcott J, Wight J, Lloyd JonesM, Tappenden P.

No. 20Extended scope of nursing practice: amulticentre randomised controlled trialof appropriately trained nurses andpreregistration house officers in pre-operative assessment in elective generalsurgery.

By Kinley H, Czoski-Murray C,George S, McCabe C, Primrose J, Reilly C, et al.

No. 21Systematic reviews of the effectiveness ofday care for people with severe mentaldisorders: (1) Acute day hospital versusadmission; (2) Vocational rehabilitation;(3) Day hospital versus outpatient care.

By Marshall M, Crowther R, Almaraz-Serrano A, Creed F, Sledge W, Kluiter H, et al.

No. 22The measurement and monitoring ofsurgical adverse events.

By Bruce J, Russell EM, Mollison J,Krukowski ZH.

No. 23Action research: a systematic review andguidance for assessment.

By Waterman H, Tillen D, Dickson R,de Koning K.

No. 24A rapid and systematic review of theclinical effectiveness and cost-effectiveness of gemcitabine for thetreatment of pancreatic cancer.

By Ward S, Morris E, Bansback N,Calvert N, Crellin A, Forman D, et al.


122

No. 25A rapid and systematic review of theevidence for the clinical effectivenessand cost-effectiveness of irinotecan,oxaliplatin and raltitrexed for thetreatment of advanced colorectal cancer.

By Lloyd Jones M, Hummel S,Bansback N, Orr B, Seymour M.

No. 26Comparison of the effectiveness ofinhaler devices in asthma and chronicobstructive airways disease: a systematicreview of the literature.

By Brocklebank D, Ram F, Wright J,Barry P, Cates C, Davies L, et al.

No. 27The cost-effectiveness of magneticresonance imaging for investigation ofthe knee joint.

By Bryan S, Weatherburn G, BungayH, Hatrick C, Salas C, Parry D, et al.

No. 28A rapid and systematic review of theclinical effectiveness and cost-effectiveness of topotecan for ovariancancer.

By Forbes C, Shirran L, Bagnall A-M,Duffy S, ter Riet G.

No. 29Superseded by a report published in alater volume.

No. 30The role of radiography in primary carepatients with low back pain of at least 6weeks duration: a randomised(unblinded) controlled trial.

By Kendrick D, Fielding K, Bentley E,Miller P, Kerslake R, Pringle M.

No. 31Design and use of questionnaires: areview of best practice applicable tosurveys of health service staff andpatients.

By McColl E, Jacoby A, Thomas L,Soutter J, Bamford C, Steen N, et al.

No. 32A rapid and systematic review of theclinical effectiveness and cost-effectiveness of paclitaxel, docetaxel,gemcitabine and vinorelbine in non-small-cell lung cancer.

By Clegg A, Scott DA, Sidhu M,Hewitson P, Waugh N.

No. 33Subgroup analyses in randomisedcontrolled trials: quantifying the risks offalse-positives and false-negatives.

By Brookes ST, Whitley E, Peters TJ, Mulheran PA, Egger M,Davey Smith G.

No. 34Depot antipsychotic medication in thetreatment of patients with schizophrenia:(1) Meta-review; (2) Patient and nurseattitudes.

By David AS, Adams C.

No. 35A systematic review of controlled trialsof the effectiveness and cost-effectiveness of brief psychologicaltreatments for depression.

By Churchill R, Hunot V, Corney R,Knapp M, McGuire H, Tylee A, et al.

No. 36Cost analysis of child healthsurveillance.

By Sanderson D, Wright D, Acton C,Duree D.

Volume 6, 2002

No. 1A study of the methods used to selectreview criteria for clinical audit.

By Hearnshaw H, Harker R, CheaterF, Baker R, Grimshaw G.

No. 2Fludarabine as second-line therapy forB cell chronic lymphocytic leukaemia: a technology assessment.

By Hyde C, Wake B, Bryan S, BartonP, Fry-Smith A, Davenport C, et al.

No. 3Rituximab as third-line treatment forrefractory or recurrent Stage III or IVfollicular non-Hodgkin’s lymphoma: asystematic review and economicevaluation.

By Wake B, Hyde C, Bryan S, BartonP, Song F, Fry-Smith A, et al.

No. 4A systematic review of dischargearrangements for older people.

By Parker SG, Peet SM, McPherson A,Cannaby AM, Baker R, Wilson A, et al.

No. 5The clinical effectiveness and cost-effectiveness of inhaler devices used inthe routine management of chronicasthma in older children: a systematicreview and economic evaluation.

By Peters J, Stevenson M, Beverley C,Lim J, Smith S.

No. 6The clinical effectiveness and cost-effectiveness of sibutramine in themanagement of obesity: a technologyassessment.

By O’Meara S, Riemsma R, ShirranL, Mather L, ter Riet G.

No. 7The cost-effectiveness of magneticresonance angiography for carotidartery stenosis and peripheral vasculardisease: a systematic review.

By Berry E, Kelly S, Westwood ME,Davies LM, Gough MJ, Bamford JM,et al.

No. 8Promoting physical activity in SouthAsian Muslim women through ‘exerciseon prescription’.

By Carroll B, Ali N, Azam N.

No. 9Zanamivir for the treatment of influenzain adults: a systematic review andeconomic evaluation.

By Burls A, Clark W, Stewart T,Preston C, Bryan S, Jefferson T, et al.

No. 10A review of the natural history andepidemiology of multiple sclerosis:implications for resource allocation andhealth economic models.

By Richards RG, Sampson FC, Beard SM, Tappenden P.

No. 11Screening for gestational diabetes: asystematic review and economicevaluation.

By Scott DA, Loveman E, McIntyre L,Waugh N.

No. 12The clinical effectiveness and cost-effectiveness of surgery for people withmorbid obesity: a systematic review andeconomic evaluation.

By Clegg AJ, Colquitt J, Sidhu MK,Royle P, Loveman E, Walker A.

No. 13The clinical effectiveness of trastuzumabfor breast cancer: a systematic review.

By Lewis R, Bagnall A-M, Forbes C,Shirran E, Duffy S, Kleijnen J, et al.

No. 14The clinical effectiveness and cost-effectiveness of vinorelbine for breastcancer: a systematic review andeconomic evaluation.

By Lewis R, Bagnall A-M, King S,Woolacott N, Forbes C, Shirran L, et al.

No. 15A systematic review of the effectivenessand cost-effectiveness of metal-on-metalhip resurfacing arthroplasty fortreatment of hip disease.

By Vale L, Wyness L, McCormack K,McKenzie L, Brazzelli M, Stearns SC.

No. 16The clinical effectiveness and cost-effectiveness of bupropion and nicotinereplacement therapy for smokingcessation: a systematic review andeconomic evaluation.

By Woolacott NF, Jones L, Forbes CA,Mather LC, Sowden AJ, Song FJ, et al.

No. 17A systematic review of effectiveness andeconomic evaluation of new drugtreatments for juvenile idiopathicarthritis: etanercept.

By Cummins C, Connock M, Fry-Smith A, Burls A.

No. 18Clinical effectiveness and cost-effectiveness of growth hormone inchildren: a systematic review andeconomic evaluation.

By Bryant J, Cave C, Mihaylova B,Chase D, McIntyre L, Gerard K, et al.


123


No. 19Clinical effectiveness and cost-effectiveness of growth hormone inadults in relation to impact on quality oflife: a systematic review and economicevaluation.

By Bryant J, Loveman E, Chase D,Mihaylova B, Cave C, Gerard K, et al.

No. 20Clinical medication review by apharmacist of patients on repeatprescriptions in general practice: arandomised controlled trial.

By Zermansky AG, Petty DR, RaynorDK, Lowe CJ, Freementle N, Vail A.

No. 21The effectiveness of infliximab andetanercept for the treatment ofrheumatoid arthritis: a systematic reviewand economic evaluation.

By Jobanputra P, Barton P, Bryan S,Burls A.

No. 22A systematic review and economicevaluation of computerised cognitivebehaviour therapy for depression andanxiety.

By Kaltenthaler E, Shackley P, StevensK, Beverley C, Parry G, Chilcott J.

No. 23A systematic review and economicevaluation of pegylated liposomaldoxorubicin hydrochloride for ovariancancer.

By Forbes C, Wilby J, Richardson G,Sculpher M, Mather L, Reimsma R.

No. 24A systematic review of the effectivenessof interventions based on a stages-of-change approach to promote individualbehaviour change.

By Riemsma RP, Pattenden J, Bridle C,Sowden AJ, Mather L, Watt IS, et al.

No. 25A systematic review update of theclinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIaantagonists.

By Robinson M, Ginnelly L, SculpherM, Jones L, Riemsma R, Palmer S, et al.

No. 26A systematic review of the effectiveness,cost-effectiveness and barriers toimplementation of thrombolytic andneuroprotective therapy for acuteischaemic stroke in the NHS.

By Sandercock P, Berge E, Dennis M,Forbes J, Hand P, Kwan J, et al.

No. 27A randomised controlled crossover trial of nurse practitioner versus doctor-led outpatient care in abronchiectasis clinic.

By Caine N, Sharples LD,Hollingworth W, French J, Keogan M,Exley A, et al.

No. 28Clinical effectiveness and cost –consequences of selective serotoninreuptake inhibitors in the treatment ofsex offenders.

By Adi Y, Ashcroft D, Browne K,Beech A, Fry-Smith A, Hyde C.

No. 29Treatment of established osteoporosis: a systematic review and cost–utilityanalysis.

By Kanis JA, Brazier JE, Stevenson M,Calvert NW, Lloyd Jones M.

No. 30Which anaesthetic agents are cost-effective in day surgery? Literaturereview, national survey of practice andrandomised controlled trial.

By Elliott RA Payne K, Moore JK,Davies LM, Harper NJN, St Leger AS,et al.

No. 31Screening for hepatitis C amonginjecting drug users and ingenitourinary medicine clinics:systematic reviews of effectiveness,modelling study and national survey ofcurrent practice.

By Stein K, Dalziel K, Walker A,McIntyre L, Jenkins B, Horne J, et al.

No. 32The measurement of satisfaction withhealthcare: implications for practicefrom a systematic review of theliterature.

By Crow R, Gage H, Hampson S,Hart J, Kimber A, Storey L, et al.

No. 33The effectiveness and cost-effectivenessof imatinib in chronic myeloidleukaemia: a systematic review.

By Garside R, Round A, Dalziel K,Stein K, Royle R.

No. 34A comparative study of hypertonicsaline, daily and alternate-day rhDNase in children with cystic fibrosis.

By Suri R, Wallis C, Bush A,Thompson S, Normand C, Flather M, et al.

No. 35A systematic review of the costs andeffectiveness of different models ofpaediatric home care.

By Parker G, Bhakta P, Lovett CA,Paisley S, Olsen R, Turner D, et al.

Volume 7, 2003

No. 1How important are comprehensiveliterature searches and the assessment oftrial quality in systematic reviews?Empirical study.

By Egger M, Jüni P, Bartlett C,Holenstein F, Sterne J.

No. 2Systematic review of the effectivenessand cost-effectiveness, and economicevaluation, of home versus hospital orsatellite unit haemodialysis for peoplewith end-stage renal failure.

By Mowatt G, Vale L, Perez J, WynessL, Fraser C, MacLeod A, et al.

No. 3Systematic review and economicevaluation of the effectiveness ofinfliximab for the treatment of Crohn’sdisease.

By Clark W, Raftery J, Barton P, Song F, Fry-Smith A, Burls A.

No. 4A review of the clinical effectiveness andcost-effectiveness of routine anti-Dprophylaxis for pregnant women whoare rhesus negative.

By Chilcott J, Lloyd Jones M, WightJ, Forman K, Wray J, Beverley C, et al.

No. 5Systematic review and evaluation of theuse of tumour markers in paediatriconcology: Ewing’s sarcoma andneuroblastoma.

By Riley RD, Burchill SA, Abrams KR,Heney D, Lambert PC, Jones DR, et al.

No. 6The cost-effectiveness of screening forHelicobacter pylori to reduce mortalityand morbidity from gastric cancer andpeptic ulcer disease: a discrete-eventsimulation model.

By Roderick P, Davies R, Raftery J,Crabbe D, Pearce R, Bhandari P, et al.

No. 7The clinical effectiveness and cost-effectiveness of routine dental checks: asystematic review and economicevaluation.

By Davenport C, Elley K, Salas C,Taylor-Weetman CL, Fry-Smith A, Bryan S, et al.

No. 8A multicentre randomised controlledtrial assessing the costs and benefits ofusing structured information andanalysis of women’s preferences in themanagement of menorrhagia.

By Kennedy ADM, Sculpher MJ,Coulter A, Dwyer N, Rees M, Horsley S, et al.

No. 9Clinical effectiveness and cost–utility ofphotodynamic therapy for wet age-relatedmacular degeneration: a systematic reviewand economic evaluation.

By Meads C, Salas C, Roberts T,Moore D, Fry-Smith A, Hyde C.

No. 10Evaluation of molecular tests forprenatal diagnosis of chromosomeabnormalities.

By Grimshaw GM, Szczepura A,Hultén M, MacDonald F, Nevin NC,Sutton F, et al.


124

No. 11First and second trimester antenatalscreening for Down’s syndrome: theresults of the Serum, Urine andUltrasound Screening Study (SURUSS).

By Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L,Mackinson AM.

No. 12The effectiveness and cost-effectivenessof ultrasound locating devices forcentral venous access: a systematicreview and economic evaluation.

By Calvert N, Hind D, McWilliamsRG, Thomas SM, Beverley C, Davidson A.

No. 13A systematic review of atypicalantipsychotics in schizophrenia.

By Bagnall A-M, Jones L, Lewis R,Ginnelly L, Glanville J, Torgerson D, et al.

No. 14Prostate Testing for Cancer andTreatment (ProtecT) feasibility study.

By Donovan J, Hamdy F, Neal D,Peters T, Oliver S, Brindle L, et al.

No. 15Early thrombolysis for the treatment of acute myocardial infarction: asystematic review and economicevaluation.

By Boland A, Dundar Y, Bagust A,Haycox A, Hill R, Mujica Mota R,et al.

No. 16Screening for fragile X syndrome: a literature review and modelling.

By Song FJ, Barton P, Sleightholme V,Yao GL, Fry-Smith A.

No. 17Systematic review of endoscopic sinussurgery for nasal polyps.

By Dalziel K, Stein K, Round A,Garside R, Royle P.

No. 18Towards efficient guidelines: how tomonitor guideline use in primary care.

By Hutchinson A, McIntosh A, Cox S,Gilbert C.

No. 19Effectiveness and cost-effectiveness ofacute hospital-based spinal cord injuriesservices: systematic review.

By Bagnall A-M, Jones L, Richardson G, Duffy S, Riemsma R.

No. 20Prioritisation of health technologyassessment. The PATHS model:methods and case studies.

By Townsend J, Buxton M, Harper G.

No. 21Systematic review of the clinicaleffectiveness and cost-effectiveness of tension-free vaginal tape fortreatment of urinary stress incontinence.

By Cody J, Wyness L, Wallace S,Glazener C, Kilonzo M, Stearns S,et al.

No. 22The clinical and cost-effectiveness ofpatient education models for diabetes: a systematic review and economicevaluation.

By Loveman E, Cave C, Green C,Royle P, Dunn N, Waugh N.

No. 23The role of modelling in prioritisingand planning clinical trials.

By Chilcott J, Brennan A, Booth A,Karnon J, Tappenden P.

No. 24Cost–benefit evaluation of routineinfluenza immunisation in people 65–74years of age.

By Allsup S, Gosney M, Haycox A,Regan M.

No. 25The clinical and cost-effectiveness ofpulsatile machine perfusion versus coldstorage of kidneys for transplantationretrieved from heart-beating and non-heart-beating donors.

By Wight J, Chilcott J, Holmes M,Brewer N.

No. 26Can randomised trials rely on existingelectronic data? A feasibility study toexplore the value of routine data inhealth technology assessment.

By Williams JG, Cheung WY, Cohen DR, Hutchings HA, Longo MF, Russell IT.

No. 27Evaluating non-randomised interventionstudies.

By Deeks JJ, Dinnes J, D’Amico R,Sowden AJ, Sakarovitch C, Song F, et al.

No. 28A randomised controlled trial to assessthe impact of a package comprising apatient-orientated, evidence-based self-help guidebook and patient-centredconsultations on disease managementand satisfaction in inflammatory boweldisease.

By Kennedy A, Nelson E, Reeves D,Richardson G, Roberts C, Robinson A,et al.

No. 29The effectiveness of diagnostic tests forthe assessment of shoulder pain due tosoft tissue disorders: a systematic review.

By Dinnes J, Loveman E, McIntyre L,Waugh N.

No. 30The value of digital imaging in diabeticretinopathy.

By Sharp PF, Olson J, Strachan F,Hipwell J, Ludbrook A, O’Donnell M, et al.

No. 31Lowering blood pressure to preventmyocardial infarction and stroke: a new preventive strategy.

By Law M, Wald N, Morris J.

No. 32Clinical and cost-effectiveness ofcapecitabine and tegafur with uracil forthe treatment of metastatic colorectalcancer: systematic review and economicevaluation.

By Ward S, Kaltenthaler E, Cowan J,Brewer N.

No. 33Clinical and cost-effectiveness of new and emerging technologies for earlylocalised prostate cancer: a systematicreview.

By Hummel S, Paisley S, Morgan A,Currie E, Brewer N.

No. 34Literature searching for clinical andcost-effectiveness studies used in healthtechnology assessment reports carriedout for the National Institute forClinical Excellence appraisal system.

By Royle P, Waugh N.

No. 35Systematic review and economicdecision modelling for the preventionand treatment of influenza A and B.

By Turner D, Wailoo A, Nicholson K,Cooper N, Sutton A, Abrams K.

No. 36A randomised controlled trial toevaluate the clinical and cost-effectiveness of Hickman line insertions in adult cancer patients bynurses.

By Boland A, Haycox A, Bagust A,Fitzsimmons L.

No. 37Redesigning postnatal care: arandomised controlled trial of protocol-based midwifery-led carefocused on individual women’s physical and psychological health needs.

By MacArthur C, Winter HR, Bick DE, Lilford RJ, Lancashire RJ,Knowles H, et al.

No. 38Estimating implied rates of discount inhealthcare decision-making.

By West RR, McNabb R, Thompson AGH, Sheldon TA, Grimley Evans J.


125


No. 39Systematic review of isolation policies inthe hospital management of methicillin-resistant Staphylococcus aureus: a review ofthe literature with epidemiological andeconomic modelling.

By Cooper BS, Stone SP, Kibbler CC,Cookson BD, Roberts JA, Medley GF, et al.

No. 40Treatments for spasticity and pain inmultiple sclerosis: a systematic review.

By Beard S, Hunn A, Wight J.

No. 41The inclusion of reports of randomisedtrials published in languages other thanEnglish in systematic reviews.

By Moher D, Pham B, Lawson ML,Klassen TP.

No. 42The impact of screening on futurehealth-promoting behaviours and healthbeliefs: a systematic review.

By Bankhead CR, Brett J, Bukach C,Webster P, Stewart-Brown S, Munafo M,et al.

Volume 8, 2004

No. 1What is the best imaging strategy foracute stroke?

By Wardlaw JM, Keir SL, Seymour J,Lewis S, Sandercock PAG, Dennis MS, et al.

No. 2Systematic review and modelling of theinvestigation of acute and chronic chestpain presenting in primary care.

By Mant J, McManus RJ, Oakes RAL,Delaney BC, Barton PM, Deeks JJ, et al.

No. 3The effectiveness and cost-effectivenessof microwave and thermal balloonendometrial ablation for heavymenstrual bleeding: a systematic reviewand economic modelling.

By Garside R, Stein K, Wyatt K,Round A, Price A.

No. 4A systematic review of the role ofbisphosphonates in metastatic disease.

By Ross JR, Saunders Y, Edmonds PM,Patel S, Wonderling D, Normand C, et al.

No. 5Systematic review of the clinicaleffectiveness and cost-effectiveness ofcapecitabine (Xeloda®) for locallyadvanced and/or metastatic breast cancer.

By Jones L, Hawkins N, Westwood M,Wright K, Richardson G, Riemsma R.

No. 6Effectiveness and efficiency of guidelinedissemination and implementationstrategies.

By Grimshaw JM, Thomas RE,MacLennan G, Fraser C, Ramsay CR,Vale L, et al.

No. 7Clinical effectiveness and costs of theSugarbaker procedure for the treatmentof pseudomyxoma peritonei.

By Bryant J, Clegg AJ, Sidhu MK,Brodin H, Royle P, Davidson P.

No. 8Psychological treatment for insomnia inthe regulation of long-term hypnoticdrug use.

By Morgan K, Dixon S, Mathers N,Thompson J, Tomeny M.

No. 9Improving the evaluation of therapeuticinterventions in multiple sclerosis:development of a patient-based measureof outcome.

By Hobart JC, Riazi A, Lamping DL,Fitzpatrick R, Thompson AJ.

No. 10A systematic review and economicevaluation of magnetic resonancecholangiopancreatography comparedwith diagnostic endoscopic retrogradecholangiopancreatography.

By Kaltenthaler E, Bravo Vergel Y,Chilcott J, Thomas S, Blakeborough T,Walters SJ, et al.

No. 11The use of modelling to evaluate newdrugs for patients with a chroniccondition: the case of antibodies againsttumour necrosis factor in rheumatoidarthritis.

By Barton P, Jobanputra P, Wilson J,Bryan S, Burls A.

No. 12Clinical effectiveness and cost-effectiveness of neonatal screening forinborn errors of metabolism usingtandem mass spectrometry: a systematicreview.

By Pandor A, Eastham J, Beverley C,Chilcott J, Paisley S.

No. 13Clinical effectiveness and cost-effectiveness of pioglitazone androsiglitazone in the treatment of type 2 diabetes: a systematic review and economic evaluation.

By Czoski-Murray C, Warren E,Chilcott J, Beverley C, Psyllaki MA,Cowan J.

No. 14Routine examination of the newborn:the EMREN study. Evaluation of anextension of the midwife role including a randomised controlled trial of appropriately trained midwivesand paediatric senior house officers.

By Townsend J, Wolke D, Hayes J,Davé S, Rogers C, Bloomfield L, et al.

No. 15Involving consumers in research anddevelopment agenda setting for theNHS: developing an evidence-basedapproach.

By Oliver S, Clarke-Jones L, Rees R, Milne R, Buchanan P, Gabbay J, et al.

No. 16A multi-centre randomised controlledtrial of minimally invasive directcoronary bypass grafting versuspercutaneous transluminal coronaryangioplasty with stenting for proximalstenosis of the left anterior descendingcoronary artery.

By Reeves BC, Angelini GD, BryanAJ, Taylor FC, Cripps T, Spyt TJ, et al.

No. 17Does early magnetic resonance imaginginfluence management or improveoutcome in patients referred tosecondary care with low back pain? A pragmatic randomised controlledtrial.

By Gilbert FJ, Grant AM, GillanMGC, Vale L, Scott NW, Campbell MK,et al.

No. 18The clinical and cost-effectiveness ofanakinra for the treatment ofrheumatoid arthritis in adults: asystematic review and economic analysis.

By Clark W, Jobanputra P, Barton P,Burls A.

No. 19A rapid and systematic review andeconomic evaluation of the clinical andcost-effectiveness of newer drugs fortreatment of mania associated withbipolar affective disorder.

By Bridle C, Palmer S, Bagnall A-M,Darba J, Duffy S, Sculpher M, et al.

No. 20Liquid-based cytology in cervicalscreening: an updated rapid andsystematic review and economic analysis.

By Karnon J, Peters J, Platt J, Chilcott J, McGoogan E, Brewer N.

No. 21Systematic review of the long-termeffects and economic consequences oftreatments for obesity and implicationsfor health improvement.

By Avenell A, Broom J, Brown TJ,Poobalan A, Aucott L, Stearns SC, et al.

No. 22Autoantibody testing in children withnewly diagnosed type 1 diabetesmellitus.

By Dretzke J, Cummins C,Sandercock J, Fry-Smith A, Barrett T,Burls A.


126

No. 23Clinical effectiveness and cost-effectiveness of prehospital intravenousfluids in trauma patients.

By Dretzke J, Sandercock J, Bayliss S,Burls A.

No. 24Newer hypnotic drugs for the short-term management of insomnia: asystematic review and economicevaluation.

By Dündar Y, Boland A, Strobl J,Dodd S, Haycox A, Bagust A, et al.

No. 25Development and validation of methodsfor assessing the quality of diagnosticaccuracy studies.

By Whiting P, Rutjes AWS, Dinnes J,Reitsma JB, Bossuyt PMM, Kleijnen J.

No. 26EVALUATE hysterectomy trial: amulticentre randomised trial comparingabdominal, vaginal and laparoscopicmethods of hysterectomy.

By Garry R, Fountain J, Brown J,Manca A, Mason S, Sculpher M, et al.

No. 27Methods for expected value ofinformation analysis in complex healtheconomic models: developments on thehealth economics of interferon-� andglatiramer acetate for multiple sclerosis.

By Tappenden P, Chilcott JB,Eggington S, Oakley J, McCabe C.

No. 28Effectiveness and cost-effectiveness ofimatinib for first-line treatment ofchronic myeloid leukaemia in chronicphase: a systematic review and economicanalysis.

By Dalziel K, Round A, Stein K,Garside R, Price A.

No. 29VenUS I: a randomised controlled trialof two types of bandage for treatingvenous leg ulcers.

By Iglesias C, Nelson EA, Cullum NA,Torgerson DJ on behalf of the VenUSTeam.

No. 30Systematic review of the effectivenessand cost-effectiveness, and economicevaluation, of myocardial perfusionscintigraphy for the diagnosis andmanagement of angina and myocardialinfarction.

By Mowatt G, Vale L, Brazzelli M,Hernandez R, Murray A, Scott N, et al.

No. 31A pilot study on the use of decisiontheory and value of information analysisas part of the NHS Health TechnologyAssessment programme.

By Claxton Kon K, Ginnelly L, SculpherM, Philips Z, Palmer S.

No. 32The Social Support and Family HealthStudy: a randomised controlled trial andeconomic evaluation of two alternativeforms of postnatal support for mothersliving in disadvantaged inner-city areas.

By Wiggins M, Oakley A, Roberts I,Turner H, Rajan L, Austerberry H, et al.

No. 33Psychosocial aspects of genetic screeningof pregnant women and newborns: a systematic review.

By Green JM, Hewison J, Bekker HL,Bryant, Cuckle HS.

No. 34Evaluation of abnormal uterinebleeding: comparison of threeoutpatient procedures within cohortsdefined by age and menopausal status.

By Critchley HOD, Warner P, Lee AJ, Brechin S, Guise J, Graham B.

No. 35Coronary artery stents: a rapid systematicreview and economic evaluation.

By Hill R, Bagust A, Bakhai A,Dickson R, Dündar Y, Haycox A, et al.

No. 36Review of guidelines for good practicein decision-analytic modelling in healthtechnology assessment.

By Philips Z, Ginnelly L, Sculpher M,Claxton K, Golder S, Riemsma R, et al.

No. 37Rituximab (MabThera®) for aggressivenon-Hodgkin’s lymphoma: systematicreview and economic evaluation.

By Knight C, Hind D, Brewer N,Abbott V.

No. 38Clinical effectiveness and cost-effectiveness of clopidogrel andmodified-release dipyridamole in thesecondary prevention of occlusivevascular events: a systematic review andeconomic evaluation.

By Jones L, Griffin S, Palmer S, MainC, Orton V, Sculpher M, et al.

No. 39Pegylated interferon �-2a and -2b incombination with ribavirin in thetreatment of chronic hepatitis C: asystematic review and economicevaluation.

By Shepherd J, Brodin H, Cave C,Waugh N, Price A, Gabbay J.

No. 40Clopidogrel used in combination withaspirin compared with aspirin alone inthe treatment of non-ST-segment-elevation acute coronary syndromes: asystematic review and economicevaluation.

By Main C, Palmer S, Griffin S, Jones L, Orton V, Sculpher M, et al.

No. 41Provision, uptake and cost of cardiacrehabilitation programmes: improvingservices to under-represented groups.

By Beswick AD, Rees K, Griebsch I,Taylor FC, Burke M, West RR, et al.

No. 42Involving South Asian patients inclinical trials.

By Hussain-Gambles M, Leese B,Atkin K, Brown J, Mason S, Tovey P.

No. 43Clinical and cost-effectiveness ofcontinuous subcutaneous insulininfusion for diabetes.

By Colquitt JL, Green C, Sidhu MK,Hartwell D, Waugh N.

No. 44Identification and assessment ofongoing trials in health technologyassessment reviews.

By Song FJ, Fry-Smith A, DavenportC, Bayliss S, Adi Y, Wilson JS, et al.

No. 45Systematic review and economicevaluation of a long-acting insulinanalogue, insulin glargine

By Warren E, Weatherley-Jones E,Chilcott J, Beverley C.

No. 46Supplementation of a home-basedexercise programme with a class-basedprogramme for people with osteoarthritisof the knees: a randomised controlledtrial and health economic analysis.

By McCarthy CJ, Mills PM, Pullen R, Richardson G, Hawkins N,Roberts CR, et al.

No. 47Clinical and cost-effectiveness of once-daily versus more frequent use of samepotency topical corticosteroids for atopiceczema: a systematic review andeconomic evaluation.

By Green C, Colquitt JL, Kirby J,Davidson P, Payne E.

No. 48Acupuncture of chronic headachedisorders in primary care: randomisedcontrolled trial and economic analysis.

By Vickers AJ, Rees RW, Zollman CE,McCarney R, Smith CM, Ellis N, et al.

No. 49Generalisability in economic evaluationstudies in healthcare: a review and casestudies.

By Sculpher MJ, Pang FS, Manca A,Drummond MF, Golder S, Urdahl H, et al.

No. 50Virtual outreach: a randomisedcontrolled trial and economic evaluationof joint teleconferenced medicalconsultations.

By Wallace P, Barber J, Clayton W,Currell R, Fleming K, Garner P, et al.


127


Volume 9, 2005

No. 1Randomised controlled multipletreatment comparison to provide a cost-effectiveness rationale for theselection of antimicrobial therapy inacne.

By Ozolins M, Eady EA, Avery A,Cunliffe WJ, O’Neill C, Simpson NB, et al.

No. 2Do the findings of case series studiesvary significantly according tomethodological characteristics?

By Dalziel K, Round A, Stein K,Garside R, Castelnuovo E, Payne L.

No. 3Improving the referral process forfamilial breast cancer geneticcounselling: findings of threerandomised controlled trials of twointerventions.

By Wilson BJ, Torrance N, Mollison J,Wordsworth S, Gray JR, Haites NE, et al.

No. 4Randomised evaluation of alternativeelectrosurgical modalities to treatbladder outflow obstruction in men withbenign prostatic hyperplasia.

By Fowler C, McAllister W, Plail R,Karim O, Yang Q.

No. 5A pragmatic randomised controlled trialof the cost-effectiveness of palliativetherapies for patients with inoperableoesophageal cancer.

By Shenfine J, McNamee P, Steen N,Bond J, Griffin SM.

No. 6Impact of computer-aided detectionprompts on the sensitivity and specificityof screening mammography.

By Taylor P, Champness J, Given-Wilson R, Johnston K, Potts H.

No. 7Issues in data monitoring and interimanalysis of trials.

By Grant AM, Altman DG, BabikerAB, Campbell MK, Clemens FJ,Darbyshire JH, et al.

No. 8Lay public’s understanding of equipoiseand randomisation in randomisedcontrolled trials.

By Robinson EJ, Kerr CEP, StevensAJ, Lilford RJ, Braunholtz DA, EdwardsSJ, et al.

No. 9Clinical and cost-effectiveness ofelectroconvulsive therapy for depressiveillness, schizophrenia, catatonia andmania: systematic reviews and economicmodelling studies.

By Greenhalgh J, Knight C, Hind D,Beverley C, Walters S.

No. 10Measurement of health-related qualityof life for people with dementia:development of a new instrument(DEMQOL) and an evaluation ofcurrent methodology.

By Smith SC, Lamping DL, Banerjee S, Harwood R, Foley B, Smith P, et al.

No. 11Clinical effectiveness and cost-effectiveness of drotrecogin alfa(activated) (Xigris®) for the treatment ofsevere sepsis in adults: a systematicreview and economic evaluation.

By Green C, Dinnes J, Takeda A,Shepherd J, Hartwell D, Cave C, et al.

No. 12A methodological review of howheterogeneity has been examined insystematic reviews of diagnostic testaccuracy.

By Dinnes J, Deeks J, Kirby J,Roderick P.

No. 13Cervical screening programmes: canautomation help? Evidence fromsystematic reviews, an economic analysisand a simulation modelling exerciseapplied to the UK.

By Willis BH, Barton P, Pearmain P,Bryan S, Hyde C.

No. 14Laparoscopic surgery for inguinalhernia repair: systematic review ofeffectiveness and economic evaluation.

By McCormack K, Wake B, Perez J,Fraser C, Cook J, McIntosh E, et al.

No. 15Clinical effectiveness, tolerability andcost-effectiveness of newer drugs forepilepsy in adults: a systematic reviewand economic evaluation.

By Wilby J, Kainth A, Hawkins N,Epstein D, McIntosh H, McDaid C, et al.

No. 16A randomised controlled trial tocompare the cost-effectiveness oftricyclic antidepressants, selectiveserotonin reuptake inhibitors andlofepramine.

By Peveler R, Kendrick T, Buxton M,Longworth L, Baldwin D, Moore M, et al.

No. 17Clinical effectiveness and cost-effectiveness of immediate angioplastyfor acute myocardial infarction:systematic review and economicevaluation.

By Hartwell D, Colquitt J, LovemanE, Clegg AJ, Brodin H, Waugh N, et al.

No. 18A randomised controlled comparison ofalternative strategies in stroke care.

By Kalra L, Evans A, Perez I, Knapp M, Swift C, Donaldson N.

No. 19The investigation and analysis of criticalincidents and adverse events inhealthcare.

By Woloshynowych M, Rogers S,Taylor-Adams S, Vincent C.

No. 20Potential use of routine databases inhealth technology assessment.

By Raftery J, Roderick P, Stevens A.

No. 21Clinical and cost-effectiveness of newerimmunosuppressive regimens in renaltransplantation: a systematic review andmodelling study.

By Woodroffe R, Yao GL, Meads C,Bayliss S, Ready A, Raftery J, et al.

No. 22A systematic review and economicevaluation of alendronate, etidronate,risedronate, raloxifene and teriparatidefor the prevention and treatment ofpostmenopausal osteoporosis.

By Stevenson M, Lloyd Jones M, De Nigris E, Brewer N, Davis S, Oakley J.

No. 23A systematic review to examine theimpact of psycho-educationalinterventions on health outcomes andcosts in adults and children with difficultasthma.

By Smith JR, Mugford M, Holland R,Candy B, Noble MJ, Harrison BDW, et al.

No. 24An evaluation of the costs, effectivenessand quality of renal replacementtherapy provision in renal satellite unitsin England and Wales.

By Roderick P, Nicholson T, ArmitageA, Mehta R, Mullee M, Gerard K, et al.

No. 25Imatinib for the treatment of patientswith unresectable and/or metastaticgastrointestinal stromal tumours:systematic review and economicevaluation.

By Wilson J, Connock M, Song F, YaoG, Fry-Smith A, Raftery J, et al.

No. 26Indirect comparisons of competinginterventions.

By Glenny AM, Altman DG, Song F,Sakarovitch C, Deeks JJ, D’Amico R, et al.

No. 27Cost-effectiveness of alternativestrategies for the initial medicalmanagement of non-ST elevation acutecoronary syndrome: systematic reviewand decision-analytical modelling.

By Robinson M, Palmer S, SculpherM, Philips Z, Ginnelly L, Bowens A, et al.


128

No. 28Outcomes of electrically stimulatedgracilis neosphincter surgery.

By Tillin T, Chambers M, Feldman R.

No. 29The effectiveness and cost-effectivenessof pimecrolimus and tacrolimus foratopic eczema: a systematic review andeconomic evaluation.

By Garside R, Stein K, Castelnuovo E,Pitt M, Ashcroft D, Dimmock P, et al.

No. 30Systematic review on urine albumintesting for early detection of diabeticcomplications.

By Newman DJ, Mattock MB, DawnayABS, Kerry S, McGuire A, Yaqoob M, et al.

No. 31Randomised controlled trial of the cost-effectiveness of water-based therapy forlower limb osteoarthritis.

By Cochrane T, Davey RC, Matthes Edwards SM.

No. 32Longer term clinical and economicbenefits of offering acupuncture care topatients with chronic low back pain.

By Thomas KJ, MacPherson H,Ratcliffe J, Thorpe L, Brazier J,Campbell M, et al.

No. 33Cost-effectiveness and safety of epiduralsteroids in the management of sciatica.

By Price C, Arden N, Coglan L,Rogers P.

No. 34The British Rheumatoid Outcome StudyGroup (BROSG) randomised controlledtrial to compare the effectiveness andcost-effectiveness of aggressive versussymptomatic therapy in establishedrheumatoid arthritis.

By Symmons D, Tricker K, Roberts C,Davies L, Dawes P, Scott DL.

No. 35Conceptual framework and systematicreview of the effects of participants’ andprofessionals’ preferences in randomisedcontrolled trials.

By King M, Nazareth I, Lampe F,Bower P, Chandler M, Morou M, et al.

No. 36The clinical and cost-effectiveness ofimplantable cardioverter defibrillators: a systematic review.

By Bryant J, Brodin H, Loveman E,Payne E, Clegg A.

No. 37A trial of problem-solving by communitymental health nurses for anxiety,depression and life difficulties amonggeneral practice patients. The CPN-GPstudy.

By Kendrick T, Simons L, Mynors-Wallis L, Gray A, Lathlean J,Pickering R, et al.

No. 38The causes and effects of socio-demographic exclusions from clinicaltrials.

By Bartlett C, Doyal L, Ebrahim S,Davey P, Bachmann M, Egger M, et al.

No. 39Is hydrotherapy cost-effective? Arandomised controlled trial of combinedhydrotherapy programmes comparedwith physiotherapy land techniques inchildren with juvenile idiopathicarthritis.

By Epps H, Ginnelly L, Utley M,Southwood T, Gallivan S, Sculpher M, et al.

No. 40A randomised controlled trial and cost-effectiveness study of systematicscreening (targeted and total populationscreening) versus routine practice forthe detection of atrial fibrillation inpeople aged 65 and over. The SAFEstudy.

By Hobbs FDR, Fitzmaurice DA,Mant J, Murray E, Jowett S, Bryan S, et al.

No. 41Displaced intracapsular hip fractures in fit, older people: a randomisedcomparison of reduction and fixation,bipolar hemiarthroplasty and total hiparthroplasty.

By Keating JF, Grant A, Masson M,Scott NW, Forbes JF.

No. 42Long-term outcome of cognitivebehaviour therapy clinical trials incentral Scotland.

By Durham RC, Chambers JA, Power KG, Sharp DM, Macdonald RR,Major KA, et al.

No. 43The effectiveness and cost-effectivenessof dual-chamber pacemakers comparedwith single-chamber pacemakers forbradycardia due to atrioventricularblock or sick sinus syndrome: systematic review and economicevaluation.

By Castelnuovo E, Stein K, Pitt M,Garside R, Payne E.

No. 44Newborn screening for congenital heartdefects: a systematic review and cost-effectiveness analysis.

By Knowles R, Griebsch I, DezateuxC, Brown J, Bull C, Wren C.

No. 45The clinical and cost-effectiveness of leftventricular assist devices for end-stageheart failure: a systematic review andeconomic evaluation.

By Clegg AJ, Scott DA, Loveman E,Colquitt J, Hutchinson J, Royle P, et al.

No. 46The effectiveness of the HeidelbergRetina Tomograph and laser diagnosticglaucoma scanning system (GDx) indetecting and monitoring glaucoma.

By Kwartz AJ, Henson DB, Harper RA, Spencer AF, McLeod D.

No. 47Clinical and cost-effectiveness ofautologous chondrocyte implantationfor cartilage defects in knee joints:systematic review and economicevaluation.

By Clar C, Cummins E, McIntyre L,Thomas S, Lamb J, Bain L, et al.

No. 48Systematic review of effectiveness ofdifferent treatments for childhoodretinoblastoma.

By McDaid C, Hartley S, Bagnall A-M, Ritchie G, Light K,Riemsma R.

No. 49Towards evidence-based guidelines for the prevention of venousthromboembolism: systematic reviews of mechanical methods, oralanticoagulation, dextran and regionalanaesthesia as thromboprophylaxis.

By Roderick P, Ferris G, Wilson K,Halls H, Jackson D, Collins R,et al.

No. 50The effectiveness and cost-effectivenessof parent training/educationprogrammes for the treatment ofconduct disorder, including oppositionaldefiant disorder, in children.

By Dretzke J, Frew E, Davenport C,Barlow J, Stewart-Brown S, Sandercock J, et al.

Volume 10, 2006

No. 1The clinical and cost-effectiveness ofdonepezil, rivastigmine, galantamineand memantine for Alzheimer’s disease.

By Loveman E, Green C, Kirby J,Takeda A, Picot J, Payne E, et al.

No. 2FOOD: a multicentre randomised trialevaluating feeding policies in patientsadmitted to hospital with a recentstroke.

By Dennis M, Lewis S, Cranswick G,Forbes J.

No. 3The clinical effectiveness and cost-effectiveness of computed tomographyscreening for lung cancer: systematicreviews.

By Black C, Bagust A, Boland A,Walker S, McLeod C, De Verteuil R, et al.


129


No. 4A systematic review of the effectivenessand cost-effectiveness of neuroimagingassessments used to visualise the seizure focus in people with refractoryepilepsy being considered for surgery.

By Whiting P, Gupta R, Burch J,Mujica Mota RE, Wright K, Marson A, et al.

No. 5Comparison of conference abstracts and presentations with full-text articles in the health technologyassessments of rapidly evolvingtechnologies.

By Dundar Y, Dodd S, Dickson R,Walley T, Haycox A, Williamson PR.

No. 6Systematic review and evaluation ofmethods of assessing urinaryincontinence.

By Martin JL, Williams KS, AbramsKR, Turner DA, Sutton AJ, Chapple C,et al.

No. 7The clinical effectiveness and cost-effectiveness of newer drugs for childrenwith epilepsy. A systematic review.

By Connock M, Frew E, Evans B-W, Bryan S, Cummins C, Fry-Smith A, et al.

No. 8Surveillance of Barrett’s oesophagus:exploring the uncertainty throughsystematic review, expert workshop andeconomic modelling.

By Garside R, Pitt M, Somerville M,Stein K, Price A, Gilbert N.

No. 9Topotecan, pegylated liposomaldoxorubicin hydrochloride andpaclitaxel for second-line or subsequenttreatment of advanced ovarian cancer: asystematic review and economicevaluation.

By Main C, Bojke L, Griffin S,Norman G, Barbieri M, Mather L, et al.

No. 10Evaluation of molecular techniques in prediction and diagnosis ofcytomegalovirus disease inimmunocompromised patients.

By Szczepura A, Westmoreland D,Vinogradova Y, Fox J, Clark M.

No. 11Screening for thrombophilia in high-risksituations: systematic review and cost-effectiveness analysis. The Thrombosis:Risk and Economic Assessment ofThrombophilia Screening (TREATS)study.

By Wu O, Robertson L, Twaddle S,Lowe GDO, Clark P, Greaves M, et al.

No. 12A series of systematic reviews to informa decision analysis for sampling andtreating infected diabetic foot ulcers.

By Nelson EA, O’Meara S, Craig D,Iglesias C, Golder S, Dalton J, et al.

No. 13Randomised clinical trial, observationalstudy and assessment of cost-effectiveness of the treatment of varicoseveins (REACTIV trial).

By Michaels JA, Campbell WB,Brazier JE, MacIntyre JB, PalfreymanSJ, Ratcliffe J, et al.

No. 14The cost-effectiveness of screening fororal cancer in primary care.

By Speight PM, Palmer S, Moles DR,Downer MC, Smith DH, Henriksson Met al.

No. 15Measurement of the clinical and cost-effectiveness of non-invasive diagnostictesting strategies for deep veinthrombosis.

By Goodacre S, Sampson F, StevensonM, Wailoo A, Sutton A, Thomas S, et al.

No. 16Systematic review of the effectivenessand cost-effectiveness of HealOzone®

for the treatment of occlusal pit/fissurecaries and root caries.

By Brazzelli M, McKenzie L, FieldingS, Fraser C, Clarkson J, Kilonzo M, et al.

No. 17Randomised controlled trials ofconventional antipsychotic versus newatypical drugs, and new atypical drugsversus clozapine, in people withschizophrenia responding poorly to, or intolerant of, current drugtreatment.

By Lewis SW, Davies L, Jones PB,Barnes TRE, Murray RM, Kerwin R, et al.

No. 18Diagnostic tests and algorithms used inthe investigation of haematuria:systematic reviews and economicevaluation.

By Rodgers M, Nixon J, Hempel S,Aho T, Kelly J, Neal D, et al.

No. 19Cognitive behavioural therapy inaddition to antispasmodic therapy forirritable bowel syndrome in primarycare: randomised controlled trial.

By Kennedy TM, Chalder T, McCrone P, Darnley S, Knapp M, Jones RH, et al.

No. 20A systematic review of the clinicaleffectiveness and cost-effectiveness ofenzyme replacement therapies forFabry’s disease andmucopolysaccharidosis type 1.

By Connock M, Juarez-Garcia A, FrewE, Mans A, Dretzke J, Fry-Smith A, et al.

No. 21Health benefits of antiviral therapy formild chronic hepatitis C: randomisedcontrolled trial and economicevaluation.

By Wright M, Grieve R, Roberts J,Main J, Thomas HC on behalf of theUK Mild Hepatitis C Trial Investigators.

No. 22Pressure relieving support surfaces: arandomised evaluation.

By Nixon J, Nelson EA, Cranny G,Iglesias CP, Hawkins K, Cullum NA, et al.

No. 23A systematic review and economicmodel of the effectiveness and cost-effectiveness of methylphenidate,dexamfetamine and atomoxetine for thetreatment of attention deficithyperactivity disorder in children andadolescents.

By King S, Griffin S, Hodges Z,Weatherly H, Asseburg C, Richardson G,et al.

No. 24The clinical effectiveness and cost-effectiveness of enzyme replacementtherapy for Gaucher’s disease: a systematic review.

By Connock M, Burls A, Frew E, Fry-Smith A, Juarez-Garcia A, McCabe C, et al.

No. 25Effectiveness and cost-effectiveness ofsalicylic acid and cryotherapy forcutaneous warts. An economic decisionmodel.

By Thomas KS, Keogh-Brown MR,Chalmers JR, Fordham RJ, Holland RC,Armstrong SJ, et al.

No. 26A systematic literature review of theeffectiveness of non-pharmacologicalinterventions to prevent wandering indementia and evaluation of the ethicalimplications and acceptability of theiruse.

By Robinson L, Hutchings D, CornerL, Beyer F, Dickinson H, Vanoli A, et al.

No. 27A review of the evidence on the effectsand costs of implantable cardioverterdefibrillator therapy in different patientgroups, and modelling of cost-effectiveness and cost–utility for thesegroups in a UK context.

By Buxton M, Caine N, Chase D,Connelly D, Grace A, Jackson C, et al.


130

No. 28Adefovir dipivoxil and pegylatedinterferon alfa-2a for the treatment ofchronic hepatitis B: a systematic reviewand economic evaluation.

By Shepherd J, Jones J, Takeda A,Davidson P, Price A.

No. 29An evaluation of the clinical and cost-effectiveness of pulmonary arterycatheters in patient management inintensive care: a systematic review and arandomised controlled trial.

By Harvey S, Stevens K, Harrison D,Young D, Brampton W, McCabe C, et al.

No. 30Accurate, practical and cost-effectiveassessment of carotid stenosis in the UK.

By Wardlaw JM, Chappell FM,Stevenson M, De Nigris E, Thomas S,Gillard J, et al.

No. 31Etanercept and infliximab for thetreatment of psoriatic arthritis: a systematic review and economicevaluation.

By Woolacott N, Bravo Vergel Y,Hawkins N, Kainth A, Khadjesari Z,Misso K, et al.

No. 32The cost-effectiveness of testing forhepatitis C in former injecting drugusers.

By Castelnuovo E, Thompson-Coon J,Pitt M, Cramp M, Siebert U, Price A, et al.

No. 33Computerised cognitive behaviourtherapy for depression and anxietyupdate: a systematic review andeconomic evaluation.

By Kaltenthaler E, Brazier J, De Nigris E, Tumur I, Ferriter M,Beverley C, et al.

No. 34Cost-effectiveness of using prognosticinformation to select women with breast cancer for adjuvant systemic therapy.

By Williams C, Brunskill S, Altman D,Briggs A, Campbell H, Clarke M, et al.

No. 35Psychological therapies includingdialectical behaviour therapy forborderline personality disorder: a systematic review and preliminaryeconomic evaluation.

By Brazier J, Tumur I, Holmes M,Ferriter M, Parry G, Dent-Brown K, et al.

No. 36Clinical effectiveness and cost-effectiveness of tests for the diagnosisand investigation of urinary tractinfection in children: a systematic reviewand economic model.

By Whiting P, Westwood M, Bojke L,Palmer S, Richardson G, Cooper J, et al.

No. 37Cognitive behavioural therapy inchronic fatigue syndrome: a randomisedcontrolled trial of an outpatient groupprogramme.

By O’Dowd H, Gladwell P, Rogers CA,Hollinghurst S, Gregory A.

No. 38A comparison of the cost-effectiveness offive strategies for the prevention of non-steroidal anti-inflammatory drug-inducedgastrointestinal toxicity: a systematicreview with economic modelling.

By Brown TJ, Hooper L, Elliott RA,Payne K, Webb R, Roberts C, et al.

No. 39The effectiveness and cost-effectivenessof computed tomography screening forcoronary artery disease: systematicreview.

By Waugh N, Black C, Walker S,McIntyre L, Cummins E, Hillis G.

No. 40What are the clinical outcome and cost-effectiveness of endoscopy undertakenby nurses when compared with doctors?A Multi-Institution Nurse EndoscopyTrial (MINuET).

By Williams J, Russell I, Durai D,Cheung W-Y, Farrin A, Bloor K, et al.

No. 41The clinical and cost-effectiveness ofoxaliplatin and capecitabine for theadjuvant treatment of colon cancer:systematic review and economicevaluation.

By Pandor A, Eggington S, Paisley S,Tappenden P, Sutcliffe P.

No. 42A systematic review of the effectivenessof adalimumab, etanercept andinfliximab for the treatment ofrheumatoid arthritis in adults and aneconomic evaluation of their cost-effectiveness.

By Chen Y-F, Jobanputra P, Barton P,Jowett S, Bryan S, Clark W, et al.

No. 43Telemedicine in dermatology: a randomised controlled trial.

By Bowns IR, Collins K, Walters SJ,McDonagh AJG.

No. 44Cost-effectiveness of cell salvage andalternative methods of minimisingperioperative allogeneic bloodtransfusion: a systematic review andeconomic model.

By Davies L, Brown TJ, Haynes S,Payne K, Elliott RA, McCollum C.

No. 45Clinical effectiveness and cost-effectiveness of laparoscopic surgery forcolorectal cancer: systematic reviews andeconomic evaluation.

By Murray A, Lourenco T, de Verteuil R, Hernandez R, Fraser C,McKinley A, et al.

No. 46Etanercept and efalizumab for thetreatment of psoriasis: a systematicreview.

By Woolacott N, Hawkins N, Mason A, Kainth A, Khadjesari Z, Bravo Vergel Y, et al.

No. 47Systematic reviews of clinical decisiontools for acute abdominal pain.

By Liu JLY, Wyatt JC, Deeks JJ,Clamp S, Keen J, Verde P, et al.

No. 48Evaluation of the ventricular assistdevice programme in the UK.

By Sharples L, Buxton M, Caine N,Cafferty F, Demiris N, Dyer M, et al.

No. 49A systematic review and economicmodel of the clinical and cost-effectiveness of immunosuppressivetherapy for renal transplantation inchildren.

By Yao G, Albon E, Adi Y, Milford D,Bayliss S, Ready A, et al.

No. 50Amniocentesis results: investigation ofanxiety. The ARIA trial.

By Hewison J, Nixon J, Fountain J,Cocks K, Jones C, Mason G, et al.

Volume 11, 2007

No. 1Pemetrexed disodium for the treatmentof malignant pleural mesothelioma: a systematic review and economicevaluation.

By Dundar Y, Bagust A, Dickson R,Dodd S, Green J, Haycox A, et al.

No. 2A systematic review and economicmodel of the clinical effectiveness andcost-effectiveness of docetaxel incombination with prednisone orprednisolone for the treatment ofhormone-refractory metastatic prostatecancer.

By Collins R, Fenwick E, Trowman R,Perard R, Norman G, Light K, et al.

No. 3A systematic review of rapid diagnostictests for the detection of tuberculosisinfection.

By Dinnes J, Deeks J, Kunst H,Gibson A, Cummins E, Waugh N, et al.

No. 4The clinical effectiveness and cost-effectiveness of strontium ranelate forthe prevention of osteoporotic fragility fractures in postmenopausalwomen.

By Stevenson M, Davis S, Lloyd-Jones M, Beverley C.


131


No. 5A systematic review of quantitative andqualitative research on the role andeffectiveness of written informationavailable to patients about individualmedicines.

By Raynor DK, Blenkinsopp A,Knapp P, Grime J, Nicolson DJ, Pollock K, et al.

No. 6Oral naltrexone as a treatment forrelapse prevention in formerly opioid-dependent drug users: a systematic review and economicevaluation.

By Adi Y, Juarez-Garcia A, Wang D,Jowett S, Frew E, Day E, et al.

No. 7Glucocorticoid-induced osteoporosis: a systematic review and cost–utility analysis.

By Kanis JA, Stevenson M, McCloskey EV, Davis S, Lloyd-Jones M.

No. 8Epidemiological, social, diagnostic andeconomic evaluation of populationscreening for genital chlamydial infection.

By Low N, McCarthy A, Macleod J,Salisbury C, Campbell R, Roberts TE, et al.

No. 9Methadone and buprenorphine for themanagement of opioid dependence: a systematic review and economicevaluation.

By Connock M, Juarez-Garcia A,Jowett S, Frew E, Liu Z, Taylor RJ, et al.

No. 10Exercise Evaluation Randomised Trial(EXERT): a randomised trial comparingGP referral for leisure centre-basedexercise, community-based walking andadvice only.

By Isaacs AJ, Critchley JA, See Tai S, Buckingham K, Westley D,Harridge SDR, et al.

No. 11Interferon alfa (pegylated and non-pegylated) and ribavirin for thetreatment of mild chronic hepatitis C: a systematic review and economicevaluation.

By Shepherd J, Jones J, Hartwell D,Davidson P, Price A, Waugh N.

No. 12Systematic review and economicevaluation of bevacizumab andcetuximab for the treatment ofmetastatic colorectal cancer.

By Tappenden P, Jones R, Paisley S,Carroll C.

No. 13A systematic review and economicevaluation of epoetin alfa, epoetin betaand darbepoetin alfa in anaemiaassociated with cancer, especially thatattributable to cancer treatment.

By Wilson J, Yao GL, Raftery J,Bohlius J, Brunskill S, Sandercock J, et al.

No. 14A systematic review and economicevaluation of statins for the preventionof coronary events.

By Ward S, Lloyd Jones M, Pandor A,Holmes M, Ara R, Ryan A, et al.

No. 15A systematic review of the effectivenessand cost-effectiveness of differentmodels of community-based respite care for frail older people and theircarers.

By Mason A, Weatherly H, SpilsburyK, Arksey H, Golder S, Adamson J, et al.

No. 16Additional therapy for young childrenwith spastic cerebral palsy: a randomised controlled trial.

By Weindling AM, Cunningham CC,Glenn SM, Edwards RT, Reeves DJ.

No. 17Screening for type 2 diabetes: literaturereview and economic modelling.

By Waugh N, Scotland G, McNamee P, Gillett M, Brennan A,Goyder E, et al.

No. 18The effectiveness and cost-effectivenessof cinacalcet for secondaryhyperparathyroidism in end-stage renal disease patients on dialysis: asystematic review and economicevaluation.

By Garside R, Pitt M, Anderson R,Mealing S, Roome C, Snaith A, et al.

No. 19The clinical effectiveness and cost-effectiveness of gemcitabine formetastatic breast cancer: a systematicreview and economic evaluation.

By Takeda AL, Jones J, Loveman E,Tan SC, Clegg AJ.

No. 20A systematic review of duplexultrasound, magnetic resonanceangiography and computed tomographyangiography for the diagnosis and assessment of symptomatic, lowerlimb peripheral arterial disease.

By Collins R, Cranny G, Burch J,Aguiar-Ibáñez R, Craig D, Wright K, et al.

No. 21The clinical effectiveness and cost-effectiveness of treatments for childrenwith idiopathic steroid-resistantnephrotic syndrome: a systematic review.

By Colquitt JL, Kirby J, Green C,Cooper K, Trompeter RS.

No. 22A systematic review of the routinemonitoring of growth in children ofprimary school age to identify growth-related conditions.

By Fayter D, Nixon J, Hartley S,Rithalia A, Butler G, Rudolf M, et al.

No. 23Systematic review of the effectiveness ofpreventing and treating Staphylococcusaureus carriage in reducing peritonealcatheter-related infections.

By McCormack K, Rabindranath K,Kilonzo M, Vale L, Fraser C, McIntyre L,et al.

No. 24The clinical effectiveness and cost ofrepetitive transcranial magneticstimulation versus electroconvulsivetherapy in severe depression: a multicentre pragmatic randomisedcontrolled trial and economic analysis.

By McLoughlin DM, Mogg A, Eranti S, Pluck G, Purvis R, Edwards D,et al.

No. 25A randomised controlled trial andeconomic evaluation of direct versusindirect and individual versus groupmodes of speech and language therapyfor children with primary languageimpairment.

By Boyle J, McCartney E, Forbes J,O’Hare A.

No. 26Hormonal therapies for early breastcancer: systematic review and economicevaluation.

By Hind D, Ward S, De Nigris E,Simpson E, Carroll C, Wyld L.

No. 27Cardioprotection against the toxic effects of anthracyclines given tochildren with cancer: a systematic review.

By Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A.

No. 28Adalimumab, etanercept and infliximabfor the treatment of ankylosingspondylitis: a systematic review andeconomic evaluation.

By McLeod C, Bagust A, Boland A,Dagenais P, Dickson R, Dundar Y, et al.


132

No. 29Prenatal screening and treatmentstrategies to prevent group Bstreptococcal and other bacterialinfections in early infancy: cost-effectiveness and expected value ofinformation analyses.

By Colbourn T, Asseburg C, Bojke L,Philips Z, Claxton K, Ades AE, et al.

No. 30Clinical effectiveness and cost-effectiveness of bone morphogeneticproteins in the non-healing of fracturesand spinal fusion: a systematic review.

By Garrison KR, Donell S, Ryder J,Shemilt I, Mugford M, Harvey I, et al.

No. 31A randomised controlled trial ofpostoperative radiotherapy followingbreast-conserving surgery in aminimum-risk older population. ThePRIME trial.

By Prescott RJ, Kunkler IH, WilliamsLJ, King CC, Jack W, van der Pol M, et al.

No. 32Current practice, accuracy, effectivenessand cost-effectiveness of the schoolentry hearing screen.

By Bamford J, Fortnum H, Bristow K,Smith J, Vamvakas G, Davies L, et al.

No. 33The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation.

By Black C, Cummins E, Royle P,Philip S, Waugh N.

No. 34Surveillance of cirrhosis forhepatocellular carcinoma: systematicreview and economic analysis.

By Thompson Coon J, Rogers G,Hewson P, Wright D, Anderson R,Cramp M, et al.

No. 35The Birmingham Rehabilitation UptakeMaximisation Study (BRUM). Home-based compared with hospital-basedcardiac rehabilitation in a multi-ethnicpopulation: cost-effectiveness andpatient adherence.

By Jolly K, Taylor R, Lip GYH,Greenfield S, Raftery J, Mant J, et al.

No. 36A systematic review of the clinical,public health and cost-effectiveness of rapid diagnostic tests for thedetection and identification of bacterial intestinal pathogens in faeces and food.

By Abubakar I, Irvine L, Aldus CF, Wyatt GM, Fordham R, Schelenz S, et al.

No. 37A randomised controlled trialexamining the longer-term outcomes ofstandard versus new antiepileptic drugs. The SANAD trial.

By Marson AG, Appleton R, Baker GA,Chadwick DW, Doughty J, Eaton B, et al.

No. 38Clinical effectiveness and cost-effectiveness of different models of managing long-term oralanticoagulation therapy: a systematicreview and economic modelling.

By Connock M, Stevens C, Fry-Smith A,Jowett S, Fitzmaurice D, Moore D, et al.

No. 39A systematic review and economicmodel of the clinical effectiveness andcost-effectiveness of interventions forpreventing relapse in people withbipolar disorder.

By Soares-Weiser K, Bravo Vergel Y,Beynon S, Dunn G, Barbieri M, Duffy S,et al.

No. 40Taxanes for the adjuvant treatment ofearly breast cancer: systematic reviewand economic evaluation.

By Ward S, Simpson E, Davis S, Hind D, Rees A, Wilkinson A.

No. 41The clinical effectiveness and cost-effectiveness of screening for open angleglaucoma: a systematic review andeconomic evaluation.

By Burr JM, Mowatt G, Hernández R,Siddiqui MAR, Cook J, Lourenco T, et al.

No. 42Acceptability, benefit and costs of earlyscreening for hearing disability: a studyof potential screening tests and models.

By Davis A, Smith P, Ferguson M,Stephens D, Gianopoulos I.

No. 43Contamination in trials of educationalinterventions.

By Keogh-Brown MR, BachmannMO, Shepstone L, Hewitt C, Howe A,Ramsay CR, et al.

No. 44Overview of the clinical effectiveness ofpositron emission tomography imagingin selected cancers.

By Facey K, Bradbury I, Laking G,Payne E.

No. 45The effectiveness and cost-effectiveness ofcarmustine implants and temozolomidefor the treatment of newly diagnosedhigh-grade glioma: a systematic reviewand economic evaluation.

By Garside R, Pitt M, Anderson R,Rogers G, Dyer M, Mealing S, et al.

No. 46Drug-eluting stents: a systematic reviewand economic evaluation.

By Hill RA, Boland A, Dickson R, Dündar Y, Haycox A, McLeod C, et al.

No. 47The clinical effectiveness and cost-effectiveness of cardiac resynchronisation(biventricular pacing) for heart failure:systematic review and economic model.

By Fox M, Mealing S, Anderson R,Dean J, Stein K, Price A, et al.

No. 48Recruitment to randomised trials:strategies for trial enrolment andparticipation study. The STEPS study.

By Campbell MK, Snowdon C,Francis D, Elbourne D, McDonald AM,Knight R, et al.

No. 49Cost-effectiveness of functional cardiac testing in the diagnosis andmanagement of coronary artery disease: a randomised controlled trial. The CECaT trial.

By Sharples L, Hughes V, Crean A,Dyer M, Buxton M, Goldsmith K, et al.

No. 50Evaluation of diagnostic tests whenthere is no gold standard. A review ofmethods.

By Rutjes AWS, Reitsma JB,Coomarasamy A, Khan KS, Bossuyt PMM.

No. 51Systematic reviews of the clinicaleffectiveness and cost-effectiveness ofproton pump inhibitors in acute uppergastrointestinal bleeding.

By Leontiadis GI, Sreedharan A,Dorward S, Barton P, Delaney B,Howden CW, et al.

No. 52A review and critique of modelling inprioritising and designing screeningprogrammes.

By Karnon J, Goyder E, Tappenden P,McPhie S, Towers I, Brazier J, et al.

No. 53An assessment of the impact of the NHS Health Technology AssessmentProgramme.

By Hanney S, Buxton M, Green C,Coulson D, Raftery J.

Volume 12, 2008

No. 1A systematic review and economicmodel of switching from non-glycopeptide to glycopeptide antibioticprophylaxis for surgery.

By Cranny G, Elliott R, Weatherly H,Chambers D, Hawkins N, Myers L, et al.


133


No. 2‘Cut down to quit’ with nicotinereplacement therapies in smokingcessation: a systematic review ofeffectiveness and economic analysis.

By Wang D, Connock M, Barton P,Fry-Smith A, Aveyard P, Moore D.

No. 3A systematic review of the effectivenessof strategies for reducing fracture risk inchildren with juvenile idiopathicarthritis with additional data on long-term risk of fracture and cost of diseasemanagement.

By Thornton J, Ashcroft D, O’Neill T, Elliott R, Adams J, Roberts C,et al.

No. 4Does befriending by trained lay workersimprove psychological well-being andquality of life for carers of people with dementia, and at what cost? A randomised controlled trial.

By Charlesworth G, Shepstone L,Wilson E, Thalanany M, Mugford M,Poland F.

No. 5A multi-centre retrospective cohort studycomparing the efficacy, safety and cost-effectiveness of hysterectomy anduterine artery embolisation for thetreatment of symptomatic uterinefibroids. The HOPEFUL study.

By Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al.

No. 6Methods of prediction and preventionof pre-eclampsia: systematic reviews ofaccuracy and effectiveness literature witheconomic modelling.

By Meads CA, Cnossen JS, Meher S,Juarez-Garcia A, ter Riet G, Duley L, et al.

No. 7The use of economic evaluations inNHS decision-making: a review andempirical investigation.

By Williams I, McIver S, Moore D,Bryan S.

No. 8Stapled haemorrhoidectomy(haemorrhoidopexy) for the treatmentof haemorrhoids: a systematic reviewand economic evaluation.

By Burch J, Epstein D, Baba-Akbari A,Weatherly H, Fox D, Golder S, et al.

No. 9The clinical effectiveness of diabeteseducation models for Type 2 diabetes: a systematic review.

By Loveman E, Frampton GK, Clegg AJ.

No. 10Payment to healthcare professionals forpatient recruitment to trials: systematicreview and qualitative study.

By Raftery J, Bryant J, Powell J, Kerr C, Hawker S.

No. 11Cyclooxygenase-2 selective non-steroidalanti-inflammatory drugs (etodolac,meloxicam, celecoxib, rofecoxib,etoricoxib, valdecoxib and lumiracoxib)for osteoarthritis and rheumatoidarthritis: a systematic review andeconomic evaluation.

By Chen Y-F, Jobanputra P, Barton P,Bryan S, Fry-Smith A, Harris G, et al.

No. 12The clinical effectiveness and cost-effectiveness of central venous catheterstreated with anti-infective agents inpreventing bloodstream infections: a systematic review and economicevaluation.

By Hockenhull JC, Dwan K, BolandA, Smith G, Bagust A, Dündar Y, et al.

No. 13Stepped treatment of older adults onlaxatives. The STOOL trial.

By Mihaylov S, Stark C, McColl E,Steen N, Vanoli A, Rubin G, et al.

No. 14A randomised controlled trial ofcognitive behaviour therapy inadolescents with major depressiontreated by selective serotonin reuptakeinhibitors. The ADAPT trial.

By Goodyer IM, Dubicka B, Wilkinson P, Kelvin R, Roberts C, Byford S, et al.

No. 15The use of irinotecan, oxaliplatin andraltitrexed for the treatment ofadvanced colorectal cancer: systematicreview and economic evaluation.

By Hind D, Tappenden P, Tumur I,Eggington E, Sutcliffe P, Ryan A.

No. 16Ranibizumab and pegaptanib for thetreatment of age-related maculardegeneration: a systematic review andeconomic evaluation.

By Colquitt JL, Jones J, Tan SC,Takeda A, Clegg AJ, Price A.

No. 17Systematic review of the clinicaleffectiveness and cost-effectiveness of64-slice or higher computedtomography angiography as analternative to invasive coronaryangiography in the investigation ofcoronary artery disease.

By Mowatt G, Cummins E, Waugh N,Walker S, Cook J, Jia X, et al.

No. 18Structural neuroimaging in psychosis: a systematic review and economicevaluation.

By Albon E, Tsourapas A, Frew E,Davenport C, Oyebode F, Bayliss S, et al.

No. 19Systematic review and economic analysisof the comparative effectiveness ofdifferent inhaled corticosteroids andtheir usage with long-acting beta2agonists for the treatment of chronicasthma in adults and children aged 12 years and over.

By Shepherd J, Rogers G, Anderson R,Main C, Thompson-Coon J, Hartwell D,et al.

No. 20Systematic review and economic analysisof the comparative effectiveness ofdifferent inhaled corticosteroids andtheir usage with long-acting beta2agonists for the treatment of chronicasthma in children under the age of 12 years.

By Main C, Shepherd J, Anderson R,Rogers G, Thompson-Coon J, Liu Z, et al.

No. 21Ezetimibe for the treatment ofhypercholesterolaemia: a systematicreview and economic evaluation.

By Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al.

No. 22Topical or oral ibuprofen for chronicknee pain in older people. The TOIBstudy.

By Underwood M, Ashby D, Carnes D,Castelnuovo E, Cross P, Harding G, et al.

No. 23A prospective randomised comparisonof minor surgery in primary andsecondary care. The MiSTIC trial.

By George S, Pockney P, Primrose J,Smith H, Little P, Kinley H, et al.

No. 24A review and critical appraisal ofmeasures of therapist–patientinteractions in mental health settings.

By Cahill J, Barkham M, Hardy G,Gilbody S, Richards D, Bower P, et al.

No. 25The clinical effectiveness and cost-effectiveness of screening programmesfor amblyopia and strabismus inchildren up to the age of 4–5 years: a systematic review and economicevaluation.

By Carlton J, Karnon J, Czoski-Murray C, Smith KJ, Marr J.


134

No. 26A systematic review of the clinicaleffectiveness and cost-effectiveness andeconomic modelling of minimal incisiontotal hip replacement approaches in the management of arthritic disease ofthe hip.

By de Verteuil R, Imamura M, Zhu S,Glazener C, Fraser C, Munro N, et al.

No. 27A preliminary model-based assessmentof the cost–utility of a screeningprogramme for early age-relatedmacular degeneration.

By Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U,Davis S, et al.

No. 28Intravenous magnesium sulphate andsotalol for prevention of atrialfibrillation after coronary artery bypasssurgery: a systematic review andeconomic evaluation.

By Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D,Price A.

No. 29Absorbent products for urinary/faecalincontinence: a comparative evaluationof key product categories.

By Fader M, Cottenden A, Getliffe K,Gage H, Clarke-O’Neill S, Jamieson K,et al.

No. 30A systematic review of repetitivefunctional task practice with modellingof resource use, costs and effectiveness.

By French B, Leathley M, Sutton C,McAdam J, Thomas L, Forster A, et al.


135



137

Health Technology AssessmentProgramme

Prioritisation Strategy GroupMembers

Chair,Professor Tom Walley, Director, NHS HTA Programme,Department of Pharmacology &Therapeutics,University of Liverpool

Professor Bruce Campbell,Consultant Vascular & GeneralSurgeon, Royal Devon & ExeterHospital

Professor Robin E Ferner,Consultant Physician andDirector, West Midlands Centrefor Adverse Drug Reactions,City Hospital NHS Trust,Birmingham

Dr Edmund Jessop, MedicalAdviser, National Specialist,Commissioning Advisory Group(NSCAG), Department ofHealth, London

Professor Jon Nicholl, Director,Medical Care Research Unit,University of Sheffield, School of Health and Related Research

Dr Ron Zimmern, Director,Public Health Genetics Unit,Strangeways ResearchLaboratories, Cambridge

Director, Professor Tom Walley, Director, NHS HTA Programme,Department of Pharmacology &Therapeutics,University of Liverpool

Deputy Director, Professor Jon Nicholl,Director, Medical Care ResearchUnit, University of Sheffield,School of Health and RelatedResearch

HTA Commissioning BoardMembers

Programme Director, Professor Tom Walley, Director, NHS HTA Programme,Department of Pharmacology &Therapeutics,University of Liverpool

Chair,Professor Jon Nicholl,Director, Medical Care ResearchUnit, University of Sheffield,School of Health and RelatedResearch

Deputy Chair, Dr Andrew Farmer, University Lecturer in GeneralPractice, Department of Primary Health Care, University of Oxford

Dr Jeffrey Aronson,Reader in ClinicalPharmacology, Department ofClinical Pharmacology,Radcliffe Infirmary, Oxford

Professor Deborah Ashby,Professor of Medical Statistics,Department of Environmentaland Preventative Medicine,Queen Mary University ofLondon

Professor Ann Bowling,Professor of Health ServicesResearch, Primary Care andPopulation Studies,University College London

Professor John Cairns, Professor of Health Economics,Public Health Policy, London School of Hygiene and Tropical Medicine, London

Professor Nicky Cullum,Director of Centre for EvidenceBased Nursing, Department ofHealth Sciences, University ofYork

Professor Jon Deeks, Professor of Health Statistics,University of Birmingham

Professor Jenny Donovan,Professor of Social Medicine,Department of Social Medicine,University of Bristol

Professor Freddie Hamdy,Professor of Urology, University of Sheffield

Professor Allan House, Professor of Liaison Psychiatry,University of Leeds

Professor Sallie Lamb, Director,Warwick Clinical Trials Unit,University of Warwick

Professor Stuart Logan,Director of Health & SocialCare Research, The PeninsulaMedical School, Universities ofExeter & Plymouth

Professor Miranda Mugford,Professor of Health Economics,University of East Anglia

Dr Linda Patterson, Consultant Physician,Department of Medicine,Burnley General Hospital

Professor Ian Roberts, Professor of Epidemiology &Public Health, InterventionResearch Unit, London Schoolof Hygiene and TropicalMedicine

Professor Mark Sculpher,Professor of Health Economics,Centre for Health Economics,Institute for Research in theSocial Services, University of York

Professor Kate Thomas,Professor of Complementaryand Alternative Medicine,University of Leeds

Professor David John Torgerson,Director of York Trial Unit,Department of Health Sciences,University of York

Professor Hywel Williams,Professor of Dermato-Epidemiology,University of Nottingham

Current and past membership details of all HTA ‘committees’ are available from the HTA website (www.hta.ac.uk)


Health Technology Assessment Programme

138

Diagnostic Technologies & Screening PanelMembers

Chair,Dr Ron Zimmern, Director ofthe Public Health Genetics Unit,Strangeways ResearchLaboratories, Cambridge

Ms Norma Armston,Freelance Consumer Advocate,Bolton

Professor Max Bachmann,Professor of Health CareInterfaces, Department ofHealth Policy and Practice,University of East Anglia

Professor Rudy BilousProfessor of Clinical Medicine &Consultant Physician,The Academic Centre,South Tees Hospitals NHS Trust

Ms Dea Birkett, Service UserRepresentative, London

Dr Paul Cockcroft, ConsultantMedical Microbiologist andClinical Director of Pathology,Department of ClinicalMicrobiology, St Mary'sHospital, Portsmouth

Professor Adrian K Dixon,Professor of Radiology,University Department ofRadiology, University ofCambridge Clinical School

Dr David Elliman, Consultant inCommunity Child Health,Islington PCT & Great OrmondStreet Hospital, London

Professor Glyn Elwyn, Research Chair, Centre forHealth Sciences Research,Cardiff University, Departmentof General Practice, Cardiff

Professor Paul Glasziou,Director, Centre for Evidence-Based Practice,University of Oxford

Dr Jennifer J Kurinczuk,Consultant ClinicalEpidemiologist, NationalPerinatal Epidemiology Unit,Oxford

Dr Susanne M Ludgate, Clinical Director, Medicines &Healthcare Products RegulatoryAgency, London

Mr Stephen Pilling, Director,Centre for Outcomes, Research & Effectiveness, Joint Director, NationalCollaborating Centre for MentalHealth, University CollegeLondon

Mrs Una Rennard, Service User Representative,Oxford

Dr Phil Shackley, SeniorLecturer in Health Economics,Academic Vascular Unit,University of Sheffield

Dr Margaret Somerville,Director of Public HealthLearning, Peninsula MedicalSchool, University of Plymouth

Dr Graham Taylor, ScientificDirector & Senior Lecturer,Regional DNA Laboratory, TheLeeds Teaching Hospitals

Professor Lindsay WilsonTurnbull, Scientific Director,Centre for MR Investigations &YCR Professor of Radiology,University of Hull

Professor Martin J Whittle,Clinical Co-director, NationalCo-ordinating Centre forWomen’s and Childhealth

Dr Dennis Wright, Consultant Biochemist &Clinical Director, The North West LondonHospitals NHS Trust, Middlesex

Pharmaceuticals PanelMembers

Chair,Professor Robin Ferner,Consultant Physician andDirector, West Midlands Centrefor Adverse Drug Reactions, City Hospital NHS Trust,Birmingham

Ms Anne Baileff, ConsultantNurse in First Contact Care,Southampton City Primary CareTrust, University ofSouthampton

Professor Imti Choonara,Professor in Child Health,Academic Division of ChildHealth, University ofNottingham

Professor John Geddes,Professor of EpidemiologicalPsychiatry, University of Oxford

Mrs Barbara Greggains, Non-Executive Director,Greggains Management Ltd

Dr Bill Gutteridge, MedicalAdviser, National SpecialistCommissioning Advisory Group(NSCAG), London

Mrs Sharon Hart, Consultant PharmaceuticalAdviser, Reading

Dr Jonathan Karnon, SeniorResearch Fellow, HealthEconomics and DecisionScience, University of Sheffield

Dr Yoon Loke, Senior Lecturerin Clinical Pharmacology,University of East Anglia

Ms Barbara Meredith,Lay Member, Epsom

Dr Andrew Prentice, SeniorLecturer and ConsultantObstetrician & Gynaecologist,Department of Obstetrics &Gynaecology, University ofCambridge

Dr Frances Rotblat, CPMPDelegate, Medicines &Healthcare Products RegulatoryAgency, London

Dr Martin Shelly, General Practitioner, Leeds

Mrs Katrina Simister, AssistantDirector New Medicines,National Prescribing Centre,Liverpool

Dr Richard Tiner, MedicalDirector, Medical Department,Association of the BritishPharmaceutical Industry,London



139

Therapeutic Procedures PanelMembers

Chair, Professor Bruce Campbell,Consultant Vascular andGeneral Surgeon, Departmentof Surgery, Royal Devon &Exeter Hospital

Dr Mahmood Adil, DeputyRegional Director of PublicHealth, Department of Health,Manchester

Dr Aileen Clarke,Consultant in Public Health,Public Health Resource Unit,Oxford

Professor Matthew Cooke,Professor of EmergencyMedicine, Warwick EmergencyCare and Rehabilitation,University of Warwick

Mr Mark Emberton, SeniorLecturer in OncologicalUrology, Institute of Urology,University College Hospital

Professor Paul Gregg,Professor of OrthopaedicSurgical Science, Department ofGeneral Practice and PrimaryCare, South Tees Hospital NHSTrust, Middlesbrough

Ms Maryann L Hardy, Lecturer, Division ofRadiography, University ofBradford

Dr Simon de Lusignan,Senior Lecturer, Primary CareInformatics, Department ofCommunity Health Sciences,St George’s Hospital MedicalSchool, London

Dr Peter Martin, ConsultantNeurologist, Addenbrooke’sHospital, Cambridge

Professor Neil McIntosh,Edward Clark Professor of ChildLife & Health, Department ofChild Life & Health, Universityof Edinburgh

Professor Jim Neilson,Professor of Obstetrics andGynaecology, Department ofObstetrics and Gynaecology,University of Liverpool

Dr John C Pounsford,Consultant Physician,Directorate of Medical Services,North Bristol NHS Trust

Dr Karen Roberts, NurseConsultant, Queen ElizabethHospital, Gateshead

Dr Vimal Sharma, ConsultantPsychiatrist/Hon. Senior Lecturer, Mental HealthResource Centre, Cheshire andWirral Partnership NHS Trust,Wallasey

Professor Scott Weich, Professor of Psychiatry, Division of Health in theCommunity, University ofWarwick

Disease Prevention PanelMembers

Chair, Dr Edmund Jessop, MedicalAdviser, National SpecialistCommissioning Advisory Group(NSCAG), London

Mrs Sheila Clark, ChiefExecutive, St James’s Hospital,Portsmouth

Mr Richard Copeland, Lead Pharmacist: ClinicalEconomy/Interface, Wansbeck General Hospital,Northumberland

Dr Elizabeth Fellow-Smith,Medical Director, West London Mental HealthTrust, Middlesex

Mr Ian Flack, Director PPIForum Support, Council ofEthnic Minority VoluntarySector Organisations, Stratford

Dr John Jackson, General Practitioner, Newcastle upon Tyne

Mrs Veronica James, ChiefOfficer, Horsham District AgeConcern, Horsham

Professor Mike Kelly, Director, Centre for PublicHealth Excellence, National Institute for Healthand Clinical Excellence, London

Professor Yi Mien Koh, Director of Public Health andMedical Director, London NHS (North West LondonStrategic Health Authority),London

Ms Jeanett Martin, Director of Clinical Leadership& Quality, Lewisham PCT,London

Dr Chris McCall, GeneralPractitioner, Dorset

Dr David Pencheon, Director,Eastern Region Public HealthObservatory, Cambridge

Dr Ken Stein, Senior ClinicalLecturer in Public Health,Director, Peninsula TechnologyAssessment Group, University of Exeter, Exeter

Dr Carol Tannahill, Director,Glasgow Centre for PopulationHealth, Glasgow

Professor Margaret Thorogood,Professor of Epidemiology,University of Warwick, Coventry

Dr Ewan Wilkinson, Consultant in Public Health,Royal Liverpool UniversityHospital, Liverpool


Health Technology Assessment Programme

140Current and past membership details of all HTA ‘committees’ are available from the HTA website (www.hta.ac.uk)

Expert Advisory NetworkMembers

Professor Douglas Altman,Professor of Statistics inMedicine, Centre for Statisticsin Medicine, University ofOxford

Professor John Bond,Director, Centre for HealthServices Research, University ofNewcastle upon Tyne, School ofPopulation & Health Sciences,Newcastle upon Tyne

Professor Andrew Bradbury,Professor of Vascular Surgery,Solihull Hospital, Birmingham

Mr Shaun Brogan, Chief Executive, RidgewayPrimary Care Group, Aylesbury

Mrs Stella Burnside OBE,Chief Executive, Regulation and ImprovementAuthority, Belfast

Ms Tracy Bury, Project Manager, WorldConfederation for PhysicalTherapy, London

Professor Iain T Cameron,Professor of Obstetrics andGynaecology and Head of theSchool of Medicine,University of Southampton

Dr Christine Clark,Medical Writer & ConsultantPharmacist, Rossendale

Professor Collette Clifford,Professor of Nursing & Head ofResearch, School of HealthSciences, University ofBirmingham, Edgbaston,Birmingham

Professor Barry Cookson,Director, Laboratory ofHealthcare Associated Infection,Health Protection Agency,London

Dr Carl Counsell, ClinicalSenior Lecturer in Neurology,Department of Medicine &Therapeutics, University ofAberdeen

Professor Howard Cuckle,Professor of ReproductiveEpidemiology, Department ofPaediatrics, Obstetrics &Gynaecology, University ofLeeds

Dr Katherine Darton, Information Unit, MIND – The Mental Health Charity,London

Professor Carol Dezateux, Professor of PaediatricEpidemiology, London

Dr Keith Dodd, ConsultantPaediatrician, Derby

Mr John Dunning,Consultant CardiothoracicSurgeon, CardiothoracicSurgical Unit, PapworthHospital NHS Trust, Cambridge

Mr Jonothan Earnshaw,Consultant Vascular Surgeon,Gloucestershire Royal Hospital,Gloucester

Professor Martin Eccles, Professor of ClinicalEffectiveness, Centre for HealthServices Research, University ofNewcastle upon Tyne

Professor Pam Enderby,Professor of CommunityRehabilitation, Institute ofGeneral Practice and PrimaryCare, University of Sheffield

Professor Gene Feder, Professorof Primary Care Research &Development, Centre for HealthSciences, Barts & The LondonQueen Mary’s School ofMedicine & Dentistry, London

Mr Leonard R Fenwick, Chief Executive, Newcastleupon Tyne Hospitals NHS Trust

Mrs Gillian Fletcher, Antenatal Teacher & Tutor andPresident, National ChildbirthTrust, Henfield

Professor Jayne Franklyn,Professor of Medicine,Department of Medicine,University of Birmingham,Queen Elizabeth Hospital,Edgbaston, Birmingham

Dr Neville Goodman, Consultant Anaesthetist,Southmead Hospital, Bristol

Professor Robert E Hawkins, CRC Professor and Director ofMedical Oncology, Christie CRCResearch Centre, ChristieHospital NHS Trust, Manchester

Professor Allen Hutchinson, Director of Public Health &Deputy Dean of ScHARR,Department of Public Health,University of Sheffield

Professor Peter Jones, Professorof Psychiatry, University ofCambridge, Cambridge

Professor Stan Kaye, CancerResearch UK Professor ofMedical Oncology, Section ofMedicine, Royal MarsdenHospital & Institute of CancerResearch, Surrey

Dr Duncan Keeley,General Practitioner (Dr Burch& Ptnrs), The Health Centre,Thame

Dr Donna Lamping,Research Degrees ProgrammeDirector & Reader in Psychology,Health Services Research Unit,London School of Hygiene andTropical Medicine, London

Mr George Levvy,Chief Executive, Motor Neurone Disease Association,Northampton

Professor James Lindesay,Professor of Psychiatry for theElderly, University of Leicester,Leicester General Hospital

Professor Julian Little,Professor of Human GenomeEpidemiology, Department ofEpidemiology & CommunityMedicine, University of Ottawa

Professor Rajan Madhok, Consultant in Public Health,South Manchester Primary Care Trust, Manchester

Professor Alexander Markham, Director, Molecular MedicineUnit, St James’s UniversityHospital, Leeds

Professor Alistaire McGuire,Professor of Health Economics,London School of Economics

Dr Peter Moore, Freelance Science Writer, Ashtead

Dr Andrew Mortimore, PublicHealth Director, SouthamptonCity Primary Care Trust,Southampton

Dr Sue Moss, Associate Director,Cancer Screening EvaluationUnit, Institute of CancerResearch, Sutton

Mrs Julietta Patnick, Director, NHS Cancer ScreeningProgrammes, Sheffield

Professor Robert Peveler,Professor of Liaison Psychiatry,Royal South Hants Hospital,Southampton

Professor Chris Price, Visiting Professor in ClinicalBiochemistry, University ofOxford

Professor William Rosenberg,Professor of Hepatology andConsultant Physician, Universityof Southampton, Southampton

Professor Peter Sandercock,Professor of Medical Neurology,Department of ClinicalNeurosciences, University ofEdinburgh

Dr Susan Schonfield, Consultantin Public Health, HillingdonPCT, Middlesex

Dr Eamonn Sheridan,Consultant in Clinical Genetics,Genetics Department,St James’s University Hospital,Leeds

Professor Sarah Stewart-Brown, Professor of Public Health,University of Warwick, Division of Health in theCommunity Warwick MedicalSchool, LWMS, Coventry

Professor Ala Szczepura, Professor of Health ServiceResearch, Centre for HealthServices Studies, University ofWarwick

Dr Ross Taylor, Senior Lecturer, Department ofGeneral Practice and PrimaryCare, University of Aberdeen

Mrs Joan Webster, Consumer member, HTA –Expert Advisory Network

How to obtain copies of this and other HTA Programme reports.An electronic version of this publication, in Adobe Acrobat format, is available for downloading free ofcharge for personal use from the HTA website (http://www.hta.ac.uk). A fully searchable CD-ROM isalso available (see below).

Printed copies of HTA monographs cost £20 each (post and packing free in the UK) to both public andprivate sector purchasers from our Despatch Agents.

Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is£2 per monograph and for the rest of the world £3 per monograph.

You can order HTA monographs from our Despatch Agents:

– fax (with credit card or official purchase order) – post (with credit card or official purchase order or cheque)– phone during office hours (credit card only).

Additionally the HTA website allows you either to pay securely by credit card or to print out yourorder and then post or fax it.

Contact details are as follows:HTA Despatch Email: [email protected]/o Direct Mail Works Ltd Tel: 02392 492 0004 Oakwood Business Centre Fax: 02392 478 555Downley, HAVANT PO9 2NP, UK Fax from outside the UK: +44 2392 478 555

NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30–40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current orforthcoming volume.

Payment methods

Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltdand drawn on a bank with a UK address.

Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard,Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email.

Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK.We cannot at present accept purchase orders from commercial companies or from outside the UK.

How do I get a copy of HTA on CD?

Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (seecontact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.

The website also provides information about the HTA Programme and lists the membership of the variouscommittees.

HTA

A preliminary model-based assessmentof the cost–utility of a screening programme for early age-related macular degeneration

J Karnon, C Czoski-Murray, K Smith, C Brand, U Chakravarthy, S Davis, N Bansback, C Beverley, A Bird, S Harding, I Chisholm and YC Yang


HTAHealth Technology AssessmentNHS R&D HTA Programmewww.hta.ac.uk

The National Coordinating Centre for Health Technology Assessment,Alpha House, Enterprise RoadSouthampton Science ParkChilworthSouthampton SO16 7NS, UK.Fax: +44 (0) 23 8059 5639 Email: [email protected]://www.hta.ac.uk ISSN 1366-5278

FeedbackThe HTA Programme and the authors would like to know

your views about this report.

The Correspondence Page on the HTA website(http://www.hta.ac.uk) is a convenient way to publish

your comments. If you prefer, you can send your comments to the address below, telling us whether you would like

us to transfer them to the website.

We look forward to hearing from you.

June 2008

Health Technology Assessm

ent 2008;Vol. 12: No. 27

Cost–utility of a screening program

me for early age-related m

acular degeneration

nhs r&d hta programme hta · 2012-10-07 · the assumptions made for the model were used to...

Documents