bmj open · conclusions: ct scanning for all anticoagulated patients with head injury is not...

For peer review only

Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling of an observational

cohort

Journal: BMJ Open

Manuscript ID bmjopen-2016-013742

Article Type: Research

Date Submitted by the Author: 03-Aug-2016

Complete List of Authors: Kuczawski, Maxine; University of Sheffield School of Health and Related Research, School of Health and Health Related Research Stevenson, Matt; University of Sheffield School of Health and Related

Research, School of Health and Health Related Research Goodacre, Steve; University of Sheffield, Medical Care Research Unit Teare, M; University of Sheffield, School of Health and Related Research Ramlakhan, Shammi; Northern General Hospital, Emergency Department Morris, Francis; Northern General Hospital, Emergency Department mason, suzanne; university of sheffield, UK, school of health and related research

<b>Primary Subject Heading</b>:

Emergency medicine

Secondary Subject Heading: Health economics, Health policy, Radiology and imaging, Neurology

Keywords: Anticoagulation < HAEMATOLOGY, Head & neck imaging < RADIOLOGY & IMAGING, TRAUMA MANAGEMENT, Warfarin

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open on O

ctober 18, 2020 by guest. Protected by copyright.

http://bmjopen.bm

j.com/

BM

J Open: first published as 10.1136/bm

jopen-2016-013742 on 13 Decem

ber 2016. Dow

nloaded from

http://bmjopen.bmj.com/


Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling

of an observational cohort

Maxine Kuczawski, Matt Stevenson, Steve Goodacre, M Dawn Teare, Shammi Ramlakhan, Francis

Morris, Suzanne Mason

Maxine Kuczawski, School of Health and Related Research, University of Sheffield, Sheffield UK

Professor Matt Stevenson, School of Health and Related Research, University of Sheffield, Sheffield

UK

Professor Steve Goodacre, School of Health and Related Research, University of Sheffield, Sheffield

UK

MD Teare, School of Health and Related Research, University of Sheffield, Sheffield UK

Dr Shammi Ramlakhan, Emergency Department, Northern General Hospital, Sheffield UK

Dr Francis Morris, Emergency Department, Northern General Hospital, Sheffield UK

Professor Suzanne Mason, School of Health and Related Research, University of Sheffield, Sheffield

UK

Corresponding author: Professor Suzanne Mason

School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street,

Sheffield S1 4DA; [email protected]; 0114 222 0694

Word count: 2680 (excluding title page, abstract, references, tables and figures)

Page 1 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

on October 18, 2020 by guest. P

rotected by copyright.http://bm

jopen.bmj.com

/B

MJ O

pen: first published as 10.1136/bmjopen-2016-013742 on 13 D

ecember 2016. D

ownloaded from



ABSTRACT

Objectives: It is not currently clear whether all anticoagulated patients with a head injury should

receive CT scanning or only those with evidence of traumatic brain injury (e.g. loss of consciousness

or amnesia). We aimed to determine the cost-effectiveness of CT for all compared to selective CT

use for anticoagulated patients with a head injury.

Design: Decision-analysis modelling of data from a multi-centre observational study.

Setting: 33 Emergency Departments in England and Scotland.

Participants: 3566 adults (aged ≥16 years) who had suffered blunt head injury, were taking warfarin

and underwent selective CT scanning.

Main outcome measures: Estimated expected benefits in terms of quality-adjusted life years

(QALYs) were the entire cohort to receive a CT scan; estimated increased costs of CT and also the

potential cost implications associated with patient survival and improved health. These values were

used to estimate the cost per QALY of implementing a strategy of CT for all patients compared to

observed practice based on guidelines recommending selective CT use.

Results: Of the 1420/3534 patients (40%) who did not receive a CT scan, 7 (0.5%) suffered a

potentially avoidable head injury related adverse outcome. If CT scanning had been performed in all

patients, appropriate treatment could have gained 3.41 additional quality-adjusted life years (QALYs)

but would have incurred £193,149 additional treatment costs and £130,683 additional CT costs. The

incremental cost-effectiveness ratio of £94,895/QALY gained for unselective compared to selective

CT use is markedly above the threshold of £20-30,000/QALY used by the UK National Institute for

Care Excellence to determine cost-effectiveness.

Conclusions: CT scanning for all anticoagulated patients with head injury is not cost-effective

compared with selective use of CT scanning based on guidelines recommending scanning only for

those with evidence of traumatic brain injury.

Page 2 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Trial registration ClinicalTrials.gov NCT 02461498.

ARTICLE SUMMARY

Strengths and limitations of this study

• This is the largest study to model options for the clinical management of anticoagulated

patients taking warfarin with a head injury.

• The methods used to estimate health gain from treating additional cases detected by

universal CT scanning are transparent and reproducible, and were robust to the sensitivity

analyses undertaken.

• Some patients who suffered adverse outcome may not have been identified on follow-up

potentially being a limitation of the study, leading to underestimation of the potential

benefit of CT scan for all patients.

Page 3 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



BACKGROUND

It is estimated that at least 1% of the United Kingdom (UK) population are taking an anticoagulant,

such as warfarin, increasing to 8% in those aged 80 years and over[1, 2]. People taking an

anticoagulant who experience a head injury are at an increased risk of intracranial haemorrhage[3,4]

with rates of mortality reported between 45-70%.[3,5–7] Liberal use of CT scanning is therefore

required to identify intracranial haemorrhage in these patients. However, it is not clear whether all

anticoagulated patients with head injury should receive a CT scan or whether CT should be used

selectively and limited to those with evidence of traumatic brain injury, such as those with loss of

consciousness or amnesia.[8]

Management of head injury in the UK follows guidance from the National Institute for Health and

Care Excellence (NICE). NICE guidance issued in 2007[9] recommended that patients with

coagulopathy (including those currently treated with warfarin) should undergo CT scanning only if

they report amnesia or loss of consciousness following injury. Updated guidance issued in 2014[10]

recommended that all patients having warfarin treatment should undergo CT scanning regardless of

whether they reported amnesia or loss of consciousness (Figure 1). The new guidance should

increase the number of scans performed and intracranial injuries identified but it is not clear

whether the benefits of this approach justify the costs of additional CT scanning.

The AHEAD study was an observational cohort study of patients with head injury who were taking

warfarin and presented to a hospital emergency department (ED).[11] It was undertaken when NICE

2007 guidance was in operation but before NICE 2014 guidance was issued. We aimed to use data

from the AHEAD study and decision analysis modelling to determine the cost-effectiveness of CT for

all compared to observed practice based on guidelines recommending selective CT for those with

evidence of traumatic brain injury.

Page 4 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Figure 1: NICE guidance 2007 versus 2014

METHODS

The methods for the AHEAD study are described in detail elsewhere (Mason S, Kuczawski M, Teare

MD, et al. The AHEAD Study: An observational study of anticoagulated patients who suffer head

injury. UK; 2016. Unpublished). Briefly, 3566 adults who were taking warfarin and attended the ED

of 33 hospitals in England and Scotland between September 2011 and March 2013 following head

injury were recruited. Research staff in hospital sites recorded basic demographic information,

attendance details, injury mechanism, clinical examination findings and CT results. Patients were

then followed up to 10 weeks after presentation using hospital record review and postal

questionnaire.

We identified all patients with an adverse outcome who had not received a CT scan at their initial

hospital attendance. It is this group of patients who would be expected to receive clinical benefit

NICE Guidance CG56, 2007

• CT head scan patients with any of the

following risk factors within 1 hour:

o GCS<13

o GCS<15 at 2 hours

o Open or depressed skull fracture

o Sign of fracture at base of skull

o Post-traumatic seizure

o Focal neurological deficit

o >1 episode of vomiting

o Amnesia >30minutes before impact

• CT head scan patients that have experienced

Loss of consciousness or amnesia AND any

of the following risk factors:

Within 8 hours

o Aged 65 years or over

o Dangerous mechanism of injury

Within 1 hour

o Coagulopathy

NICE Guidance CG176, 2014

• CT head scan with any of the following risk

factors within 1 hour:

o GCS<13

o GCS<15 at 2 hours

o Open or depressed skull fracture

o Any sign of basal skull fracture

o Post-traumatic seizure

o Focal neurological deficit

o >1 episode of vomiting

• CT head scan patients that have

experienced Loss of consciousness or

amnesia AND any of the following risk

factors:

Within 8 hours

o Aged 65 years or over

o History of bleeding or clotting

disorders

o Dangerous mechanism of injury

o >30 minutes retrograde amnesia of

events

• CT head scan patients with no other

indications for CT head scan AND having

warfarin treatment, within 8 hours

Page 5 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



from a policy of CT scanning all patients. An adverse outcome was defined as: death; neurosurgery;

positive CT scan finding; or re-attendance to the hospital with a significant head injury-related

complication up to 10-weeks after the original attendance. These re-attendances were confirmed

following the review of hospital records and CT scan results, where undertaken.

Decision analysis modelling was used to estimate the quality adjusted life years (QALY) and cost

implications had those patients with an adverse outcome that were not CT scanned received a CT

scan on initial hospital attendance. Different assumptions were required for patients conditional on

whether they survived the adverse event. For patients who died, assumptions were required

regarding: the probability of survival if a CT scan had been performed; the Glasgow Outcome Scale

(GOS) state to which the patient would be categorised if they survived;[11] and the cost of

neurosurgery. For patients who survived, an assumption was required relating to the probability of

GOS increase if a CT scan had been performed. Regardless of survival outcome, assumptions were

required on: the life expectancy of a person with the same gender and age profile; the costs and

utility associated with each GOS state; and the cost of a CT scan. The assumptions used within the

model are detailed below. The results presented take an English and Scottish perspective and use

direct healthcare and personal social services costs.

Model Assumptions

For patients who did not survive the adverse event:

The probability of survival if a CT scan had been performed

Two clinicians provided estimates of the probability of survival had the patient received a CT scan. In

the main analysis an average value was used, although sensitivity analyses were undertaken

assuming that each clinician was correct.

The GOS state to which the patient would be categorised if they survived

Page 6 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



A single clinician provided an estimate of the GOS of the patient if they had survived. In a sensitivity

analysis the impact of the GOS state being one level higher (that is, more favourable to the patient)

was explored.

The costs of neurosurgery

The cost of neurosurgery was assumed to be that associated with the weighted average of NHS

Reference Cost Codes AA50A – AA57B, excluding codes relating to patients aged 18 years and under,

which was £3994.[12] It was assumed that all patients who died without having a CT scan would

undergo neurosurgery.

For patients who survived the adverse event:

The probability of GOS increase if a CT scan had been performed

Two clinicians provided estimates of the probability of an increase in the GOS level, (i.e. a better

patient outcome) if a CT scan had been performed. In the main analysis an average value was used,

although sensitivity analyses were undertaken assuming that each clinician was correct.

For all patients:

The life expectancy of the person

These data were taken from UK Life Tables[13] and it was assumed that these were not affected by

an adverse event that had been survived.

The costs and utility associated with each GOS state

The data for GOS states 2-4 were taken from Pandor et al[14] with costs inflated from 2008/2009

values to 2014/15 prices using hospital and community health services indices reported in Curtis and

Burns.[15] The resultant values are provided in Table 1. For GOS state 5 it was assumed that the UK

general population utility conditional on age and sex was appropriate which was taken from Ara and

Brazier.[16]

Page 7 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Table 1: Assumed costs and utility associated with each GOS state, and assumed cost of

neurosurgery.

GOS state One-off Cost (£) Annual Costs (£) Utility value Source

2 47,674 46,595 0.00 Pandor et al[14] with

costs inflated using

Curtis and Burns[15]

3 0 37,214 0.15

4 18,837 0 0.51

5 0 0 PopulaMon Value† Assumption

† The uMlity in GOS state 5 were estimated from Ara and Brazier[16] conditional on age and sex.

The cost of a CT scan

The cost of a CT scan was assumed to be that associated with NHS Reference Cost Code RD20A,

which was £92.

The mathematical model

The model calculated the expected difference in costs and QALYs of moving from observed practice

to a strategy of CT scanning all patients. The following formulae were used in calculating the cost

and quality adjusted life years (QALY) impacts associated with provided CT scans to patients with

adverse events who did not receive a CT scan. All values were discounted at 3.5% per annum in

accordance with NICE guidelines.[17] A lifetime horizon was assumed due to potential mortality

benefits of the CT all strategy.

For patients who did not survive:

Change in costs: Average probability of survival if CT scan performed x (Life Expectancy x Cost per

year in estimated GOS state + cost of neurosurgery)

Change in QALYs: Average probability of survival if CT scan performed x (Life Expectancy x utility per

year in estimated GOS state)

For patients who did survive

Page 8 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Change in costs: Average probability of GOS increase if CT scan performed x Life Expectancy x (Cost

per year in higher GOS state – Cost per year in lower GOS state)

Change in QALYs: Average probability of GOS increase if CT scan performed x (Life Expectancy x

utility per year in higher GOS state – utility per year in lower GOS state)

RESULTS

Follow-up data were available for 3534/3566 patients (99%) in the AHEAD cohort. Details of the

cohort are published elsewhere (Mason S, Kuczawski M, Teare MD, et al. The AHEAD Study:

Managing anticoagulated patients who suffer head injury. UK; 2016. Unpublished). Glasgow

Outcome Scale and diagnosis was available for 91.4% (n=3229) and 99.9% (n=3530) patients

respectively. Overall 2114/3534 patients (60%) received a CT scan. Of the 1420 patients without a CT

scan, 728 (51%) were admitted to hospital, 20 (1.4%) had subsequent head injury related hospital

attendances, and 74 (5.2%) died during follow-up. Cause of death was head injury related in four

(0.3%), unrelated in 52 (3.7%) and unknown in 19 (1.3%). Adverse outcomes were identified in

7/1420 (0.5%) patients who did not have CT scan: four deaths and three with a related further

hospital attendance and significant finding on CT scan at re-attendance.

The estimated changes in costs and QALYs per individual patient are provided in Table 2. The

summarised analyses including the increased costs of CT scans are provided in Table 3.

Page 9 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Table 2: Estimated outcomes for patients with adverse events who were not CT scanned if they had

been CT scanned on admission to hospital and modelled implications for costs and QALYs

Patient

Outcomes Modelling

Age Sex Admitted

Observed

CT head

scan

Reversal

therapy Neurosurgery

Further

hospital

attendance

HI

Death

Probability of

survival (%) Estimated

GOS if

survived

Change

in costs

Change in

QALYs Clinician

1

Clinician

2

1 81 M � � � � � � 75 75 3 £169,279 0.67

2 74 M � � � � � � 25 15 2 £13,528 0.00

3 90 M � � � � � � 0 0 2 £3,994 0.00

4 88 M � � � � � � 75 75 4 £18,122 1.45

Probability of GOS

increase (+1, %) Lower GOS

score Δ C Δ Q

Clinician

1

Clinician

2

5 76 M � � � � � � 25 50 4 -£7,064 0.86

6 77 F � � � � � � 25 0 4 -£2,355 0.27

7 82 M � � � � � � 25 0 4 -£2,355 0.17

Table 3: The comparison of CT all with observed practice.

Change in costs from

CT scanning (£)

Change in QALYs

from CT scanning

ICER (Cost per QALY

gained (£))

Changes in individual patient values 193,149 3.41

Additional CT scanning costs 130,683

Net Values 323,832 3.41 94,895

It is estimated that the cost per QALY gained through providing a CT scan is in excess of £90,000 per

QALY which is markedly greater than the £20,000 to £30,000 per QALY gained threshold reported by

NICE.[17] This conclusion did not alter within the sensitivity analyses performed. Using the estimates

from the individual expert clinicians which produced values of £90,659 and £99,547 per QALY gained

or if the cost of neurosurgery was not included for the patient who neither expert clinician believed

would have survived even with a CT scan (£93,725 per QALY gained). When it was assumed that all

patients survived at one GOS state better than estimated in the base case the cost per QALY gained

reduced to £36,864 (an additional £213,139 to obtain 5.78 QALYs) but still did not fall below NICE

thresholds.

Page 10 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



DISCUSSION

Follow-up of 1420 patients who did not have a CT scan in the AHEAD cohort identified seven cases

(four deaths, three delayed diagnoses) that might have been identified by CT scanning at initial

hospital attendance. Decision analytic modelling showed that appropriate treatment of these cases

could have gained 3.41 QALYs but would have incurred £193,149 additional treatment costs and

£130,683 additional costs for CT scanning. This produces an incremental cost of £94,895 per QALY

gained, which is greatly above the usual threshold of £20-30,000/QALY that NICE uses to determine

cost-effectiveness. Our analysis therefore suggests that CT for all anticoagulated patients with head

injury, as recommended in NICE 2014 guidance, is not cost-effective compared to the selective use

of CT scanning observed in practice when NICE 2007 guidance was in operation.

Our analysis has a number of strengths and weaknesses. It was based upon a large representative

cohort of patients who presented to a wide range of hospitals. The methods used to estimate health

gain from treating additional cases detected by universal CT scanning are transparent and

reproducible, and were robust to the sensitivity analyses undertaken. A potential limitation is that

some patients who suffered adverse outcome may not have been identified on follow-up leading to

underestimation of the potential benefit of CT scan for all patients. However, it is worth noting that

10.79 QALYs would be required to reach the NICE threshold of £30,000/QALY for cost-effectiveness,

so our conclusion regarding the lack of cost-effectiveness of unselective CT scanning would only be

undermined if follow-up had identified less than 1 in 3 patients with adverse events. This seems

extremely unlikely. Other limitations may have underestimated the additional costs of unselective

CT scanning, for example we did not include knock-on costs from additional CT scanning, such as

those generated by incidental findings.

Most international guidance, including the National Emergency X-Radiology Utilisation Study (NEXUS

II), CT in Head Injury Patients (CHIP), American College of Emergency Physicians (ACEP) head CT and

the European Federation of Neurological Societies (EFNS)[18-21] advocate that all patients taking

Page 11 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



warfarin should have an immediate CT scan irrespective of injury severity, GCS or neurological

symptoms. The UK guidelines (NICE) are based on the Canadian CT Head Rule(CCHR)[22] which

excluded patients taking warfarin and up until January 2014, stated that a CT scan should be

performed on patients taking warfarin if the patient presented with loss of consciousness or

amnesia. These guidelines have now been updated to recommend all anticoagulated patients

receive a CT scan but no new evidence appears to have been published to support this

recommended change in practice. Our analysis suggests that the 2014 revision to NICE guidance has

resulted in less cost-effective care.

Previous literature investigating the patient outcomes and costs associated with diagnosing and

treating head injured patients who are taking anticoagulants are limited and difficult to compare to

our analysis. Several recent studies have used decision analysis modelling to estimate the costs and

benefits of CT scanning in the general (i.e. non-anticoagulated) head injured population[23-25] and

have generally shown that using a clinical decision rule to select patients for CT scanning is more

cost-effective than unselective CT scanning. The only study identified that focused solely on

anticoagulated patients was undertaken by Li in 2012.[26] Li questioned how this cohort of patients

should be managed due to the nature of delayed complications associated with anticoagulant use,

whilst also considering the costs attached to CT imaging and admittance to hospital. The analyses

were based on data taken from other studies and included repeated CT scans (2) and 24-hour

admission per patient. The costs per year of a life saved in the US, Spain and Canada were estimated

as $1 million, $158,000 and $105,000 respectively.

CONCLUSION

CT scanning for all anticoagulated patients with head injury is not cost-effective compared with

selective use of CT scanning based on guidelines recommending scanning only for those with

evidence of traumatic brain injury. A move (or return to) selective use of CT scanning would

Page 12 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



substantially reduce health care costs with only a small increase in potentially avoidable adverse

outcomes.

Acknowledgements: We thank Rosemary Harper for her contribution as a patient representative

throughout the duration of the study; all the clinicians and research staff in the participating hospital

sites who identified patients in this study, without whose hard work this study would not have been

possible.

Contributors: All authors provided substantial contributions to the conception, design, acquisition of

the data, or analysis and interpretation of the study data. MK drafted the article and all authors

contributed to its revision for important intellectual content. All authors approved the final version.

SM is guarantor. All authors agree to be accountable for all aspects of the work ensuring that

questions related to accuracy or integrity of any party of the work are appropriately investigated and

resolved.

Transparency: SM affirms that this manuscript is an honest, accurate, and transparent account of

the study being reported; that no important aspects of the study have been omitted; and that any

discrepancies from the study as planned (and, if relevant, registered) have been explained.

Funding: This paper presents independent research commissioned by the National Institute for

Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme grant reference

number PB-PG-0808-17148. The views expressed are those of the author(s) and not necessarily

those of the NHS, the NIHR or the Department of Health.

Competing interests: All authors have completed the ICMJE uniform disclosure form at

www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted

work; no financial relationships with any organisations that might have an interest in the submitted

work in the previous three years; no other relationships or activities that could appear to have

influenced the submitted work.

Page 13 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Ethical approval: NRES Committee Yorkshire and The Humber – Sheffield: 11/H1308/13.

Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust – Ref.: STH15705.

Provenance and peer review: Not commissioned; externally peer reviewed.

Data Sharing Statement: No additional data are available.

Open Access: This is an Open Access article distributed in accordance with the terms of the Creative

Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build

upon this work, for commercial use, provided the original work is properly cited. See:

http://creativecommons.org/licenses/by/4.0/.

Page 14 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



REFERENCES

1 Kamali F, Pirmohamed M. The future prospects of pharmacogenetics in oral anticoagulation

therapy. Br J Clin Pharmacol 2006:746–51.

2 Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future

challenges. Pharmacogenomics J 2007;7(2):99–111.

3 Volans AP. The risks of minor head injury in the warfarinised patient. J Accid Emerg Med

1998;15(3):159–61.

4 Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and

hypotheses. Stroke 1995;26(8):1471–7.

5 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin.

Ann Intern Med 1994;120(11):897–902.

6 Ferrera PC, Bartfield JM. Outcomes of anticoagulated trauma patients. Am J Emerg Med

1999;17(2):154–6.

7 Mathiesen T, Benediktsdottir K, Johnsson H, et al. Intracranial traumatic and non-traumatic

haemorrhagic complications of warfarin treatment. Acta Neurol Scand 1995;91(3):208–14.

8 Leiblich a, Mason S. Emergency management of minor head injury in anticoagulated

patients. Emerg Med J 2011;28(2):115–8.

9 National Institute for Health and Care Excellence. Head injury: triage, assessment,

investigation and early management of head injury in infants, children and adults. (Clinical

Guideline 56.) London; 2007. http://www.nice.org.uk/CG56.

10 National Institute for Health and Care Excellence. Head injury: triage, assessment,

investigation and early management of head injury in infants, children and adults. (Clinical

Guideline 176.) London; 2014. http://www.nice.org.uk/CG176.

11 Wilson JTL, Pettigrew LEL, Teasdale GM. Structured interviews for the Glasgow Outcome

Scale and extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma

1998;15:573-585.

Page 15 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



12 Department of Health. National Schedule of Reference Costs 2014-15 for NHS trusts and

NHS foundation trusts. London; 2015 [Accessed January 2016]. Available from:

http://www.gov.uk/government/publications/nhs-reference-costs-2014-to-2015.

13 Office for National Statistics. National Life Tables, 2010-2012. London; 2014 [Accessed

January 2016]. Available from: http://www.ons.gov.uk/ons/publications/re-reference-

tables.html?edition=tcm%3A77-352834.

14 Pandor A, Goodacre S, Harnan S, et al. Diagnostic management strategies for adults and

children with minor head injury: a systematic review and an economic evaluation. Health

Technol Assess 2011;15(27):1–196.

15 Curtis L,Burns A. Unit Costs of Health and Social Care 2015. Personal Social Services Research

Unit, Canterbury, Kent; 2015 [Accessed January 2016]. Available from:

http://www.pssru.ac.uk/project-pages/unit-costs/2015/.

16 Ara R, Brazier JE. Populating an Economic Model with Health State Utility Values: Moving

toward Better Practice. Value Health 2010;13(5):509–18.

17 National Institute for Health and Care Excellence. Guide to the methods of technology

appraisals . London; 2013 [Accessed January 2016]. Available from:

http://www.nice.org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-of-

technology-appraisal-2013-pdf.

18 Mower WR, Hoffman JR, Herbert M, et al. Developing a clinical decision instrument to rule

out intracranial injuries in patients with minor head trauma: methodology of the NEXUS II

investigation. Ann Emerg Med 2002;40:505–14.

19 Smits M, Diederik W, Dippel W, et al. Predicting intracranial traumatic findings on computed

tomography in patients with minor head injury: the CHIP prediction rule. Ann Intern Med

2007;146:397-405.

20 Jagoda AS, Bazarian JJ, Bruns JJ Jr, et al. Clinical policy: neuroimaging and decisionmaking in

adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008;52:714-748.

Page 16 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



21 Vos PE, Battistin L, Girbamer G, et al. EFNS guideline on mild traumatic brain injury: report of

an EFNS task force. Eur J Neurol 2002;9:207-219.

22 Stiell IG, Wells GA, Vandemheen K, et al. The Canadian CT head rule for patients with minor

head injury. Lancet 2001;357:1391 –1396.

23 Melnick ER, Keegan J, Taylor RA. Redefining Overuse to Include Costs: A Decision Analysis for

Computed Tomography in Minor Head Injury. Jt Comm J Qual Patient Saf 2015;41(7):313-22.

24 Smits M, Dippel DW, Nederkoorn PJ, et al. Minor head injury: CT-based strategies for

management—a cost-effectiveness analysis. Radiology 2010 Feb;254(2):532-40.

25 Holmes MW, Goodacre S, Stevenson MD, et al. The cost-effectiveness of diagnostic

management strategies for adults with minor head injury. Injury 2012;43:1423-1431.

26 Li J. Admit all anticoagulated head-injured patients? A million dollars versus your dime. You

make the call. Ann of Emerg Med 2012;59(6):457-459.

Page 17 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



CHEERS checklist - Items to include when reporting economic evaluations of health interventions



Section/item Item

No Recommendation

Reported

on page

No/ line

No

Title and abstract

Title 1

Identify the study as an economic evaluation or use

more specific terms such as “cost-effectiveness

analysis”, and describe the interventions compared.

1

Abstract 2

Provide a structured summary of objectives,

perspective, setting, methods (including study design

and inputs), results (including base case and

uncertainty analyses), and conclusions.

2

Introduction

Background and objectives 3

Provide an explicit statement of the broader context

for the study. 4

Present the study question and its relevance for

health policy or practice decisions. 4

Methods

Target population and

subgroups 4

Describe characteristics of the base case population

and subgroups analysed, including why they were

chosen.

5

Setting and location 5 State relevant aspects of the system(s) in which the

decision(s) need(s) to be made. 5

Study perspective 6 Describe the perspective of the study and relate this

to the costs being evaluated. 6

Comparators 7 Describe the interventions or strategies being

compared and state why they were chosen. 4

Time horizon 8

State the time horizon(s) over which costs and

consequences are being evaluated and say why

appropriate.

8

Discount rate 9 Report the choice of discount rate(s) used for costs

and outcomes and say why appropriate. 8

Choice of health outcomes 10

Describe what outcomes were used as the

measure(s) of benefit in the evaluation and their

relevance for the type of analysis performed.

6,10

Measurement of effectiveness 11a

Single study-based estimates: Describe fully the

design features of the single effectiveness study and

why the single study was a sufficient source of

clinical effectiveness data.

4

Page 18 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



11b

Synthesis-based estimates: Describe fully the

methods used for identification of included studies

and synthesis of clinical effectiveness data.

N/A

Measurement and valuation of

preference based outcomes 12

If applicable, describe the population and methods

used to elicit preferences for outcomes. N/A

Estimating resources and costs

13a

Single study-based economic evaluation: Describe

approaches used to estimate resource use associated

with the alternative interventions. Describe primary

or secondary research methods for valuing each

resource item in terms of its unit cost. Describe any

adjustments made to approximate to opportunity

costs.

N/A

13b

Model-based economic evaluation: Describe

approaches and data sources used to estimate

resource use associated with model health states.

Describe primary or secondary research methods for

valuing each resource item in terms of its unit cost.

Describe any adjustments made to approximate to

opportunity costs.

7-8

Currency, price date, and

conversion 14

Report the dates of the estimated resource

quantities and unit costs. Describe methods for

adjusting estimated unit costs to the year of reported

costs if necessary. Describe methods for converting

costs into a common currency base and the exchange

rate.

7

Choice of model 15

Describe and give reasons for the specific type of

decision-analytical model used. Providing a figure to

show model structure is strongly recommended.

8

Assumptions 16 Describe all structural or other assumptions

underpinning the decision-analytical model. 5-8

Analytical methods 17

Describe all analytical methods supporting the

evaluation. This could include methods for dealing

with skewed, missing, or censored data;

extrapolation methods; methods for pooling data;

approaches to validate or make adjustments (such as

half cycle corrections) to a model; and methods for

handling population heterogeneity and uncertainty.

5-8

Results

Study parameters 18

Report the values, ranges, references, and, if used,

probability distributions for all parameters. Report

reasons or sources for distributions used to

represent uncertainty where appropriate. Providing a

table to show the input values is strongly

recommended.

6-8

Incremental costs and

outcomes 19

For each intervention, report mean values for the

main categories of estimated costs and outcomes of

interest, as well as mean differences between the

comparator groups. If applicable, report incremental

cost-effectiveness ratios.

10

Page 19 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Characterising uncertainty

20a


the effects of sampling uncertainty for the estimated

incremental cost and incremental effectiveness

parameters, together with the impact of

methodological assumptions (such as discount rate,

study perspective).

20b

Model-based economic evaluation: Describe the

effects on the results of uncertainty for all input

parameters, and uncertainty related to the structure

of the model and assumptions.

10

Characterising heterogeneity 21

If applicable, report differences in costs, outcomes,

or cost-effectiveness that can be explained by

variations between subgroups of patients with

different baseline characteristics or other observed

variability in effects that are not reducible by more

information.

N/A

Discussion

Study findings, limitations,

generalisability, and current

knowledge

22

Summarise key study findings and describe how they

support the conclusions reached. Discuss limitations

and the generalisability of the findings and how the

findings fit with current knowledge.

10-12

Other

Source of funding 23

Describe how the study was funded and the role of

the funder in the identification, design, conduct, and

reporting of the analysis. Describe other non-

monetary sources of support.

13

Conflicts of interest 24

Describe any potential for conflict of interest of study

contributors in accordance with journal policy. In the

absence of a journal policy, we recommend authors

comply with International Committee of Medical

Journal Editors recommendations.

13

Page 20 of 20


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling of an observational

cohort

Journal: BMJ Open

Manuscript ID bmjopen-2016-013742.R1

Article Type: Research

Date Submitted by the Author: 24-Oct-2016

Complete List of Authors: Kuczawski, Maxine; University of Sheffield School of Health and Related Research, School of Health and Health Related Research Stevenson, Matt; University of Sheffield School of Health and Related

Research, School of Health and Health Related Research Goodacre, Steve; University of Sheffield, Medical Care Research Unit Teare, M; University of Sheffield, School of Health and Related Research Ramlakhan, Shammi; Northern General Hospital, Emergency Department Morris, Francis; Northern General Hospital, Emergency Department mason, suzanne; university of sheffield, UK, school of health and related research

<b>Primary Subject Heading</b>:

Emergency medicine

Secondary Subject Heading: Health economics, Health policy, Radiology and imaging, Neurology

Keywords: Anticoagulation < HAEMATOLOGY, Head & neck imaging < RADIOLOGY & IMAGING, TRAUMA MANAGEMENT, Warfarin


BMJ Open on O

ctober 18, 2020 by guest. Protected by copyright.

http://bmjopen.bm

j.com/

BM

J Open: first published as 10.1136/bm

jopen-2016-013742 on 13 Decem

ber 2016. Dow

nloaded from



1

Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling 1

of an observational cohort 2

Maxine Kuczawski, Matt Stevenson, Steve Goodacre, M Dawn Teare, Shammi Ramlakhan, Francis 3

Morris, Suzanne Mason 4

Maxine Kuczawski, School of Health and Related Research, University of Sheffield, Sheffield UK 5

Professor Matt Stevenson, School of Health and Related Research, University of Sheffield, Sheffield 6

UK 7

Professor Steve Goodacre, School of Health and Related Research, University of Sheffield, Sheffield 8

UK 9

MD Teare, School of Health and Related Research, University of Sheffield, Sheffield UK 10

Dr Shammi Ramlakhan, Emergency Department, Northern General Hospital, Sheffield UK 11

Dr Francis Morris, Emergency Department, Northern General Hospital, Sheffield UK 12

Professor Suzanne Mason, School of Health and Related Research, University of Sheffield, Sheffield 13

UK 14

Corresponding author: Professor Suzanne Mason 15

School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, 16

Sheffield S1 4DA; [email protected]; 0114 222 0694 17

Word count: 2911 (excluding title page, abstract, references, tables and figures) 18

19

Page 1 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



2

ABSTRACT 1

Objectives: It is not currently clear whether all anticoagulated patients with a head injury should 2

receive CT scanning or only those with evidence of traumatic brain injury (e.g. loss of consciousness 3

or amnesia). We aimed to determine the cost-effectiveness of CT for all compared to selective CT 4

use for anticoagulated patients with a head injury. 5

Design: Decision-analysis modelling of data from a multi-centre observational study. 6

Setting: 33 Emergency Departments in England and Scotland. 7

Participants: 3566 adults (aged ≥16 years) who had suffered blunt head injury, were taking warfarin 8

and underwent selective CT scanning. 9

Main outcome measures: Estimated expected benefits in terms of quality-adjusted life years 10

(QALYs) were the entire cohort to receive a CT scan; estimated increased costs of CT and also the 11

potential cost implications associated with patient survival and improved health. These values were 12

used to estimate the cost per QALY of implementing a strategy of CT for all patients compared to 13

observed practice based on guidelines recommending selective CT use. 14

Results: Of the 1420/3534 patients (40%) who did not receive a CT scan, 7 (0.5%) suffered a 15

potentially avoidable head injury related adverse outcome. If CT scanning had been performed in all 16

patients, appropriate treatment could have gained 3.41 additional quality-adjusted life years (QALYs) 17

but would have incurred £193,149 additional treatment costs and £130,683 additional CT costs. The 18

incremental cost-effectiveness ratio of £94,895/QALY gained for unselective compared to selective 19

CT use is markedly above the threshold of £20-30,000/QALY used by the UK National Institute for 20

Care Excellence to determine cost-effectiveness. 21

Conclusions: CT scanning for all anticoagulated patients with head injury is not cost-effective 22

compared with selective use of CT scanning based on guidelines recommending scanning only for 23

those with evidence of traumatic brain injury. 24

Page 2 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



3

Trial registration ClinicalTrials.gov NCT 02461498. 1

ARTICLE SUMMARY 2

Strengths and limitations of this study 3

• This is the largest study to model options for the clinical management of anticoagulated 4

patients taking warfarin with a head injury. 5

• The methods used to estimate health gain from treating additional cases detected by 6

universal CT scanning are transparent and reproducible, and were robust to the sensitivity 7

analyses undertaken. 8

• Some patients who suffered adverse outcome may not have been identified on follow-up 9

potentially being a limitation of the study, leading to underestimation of the potential 10

benefit of CT scan for all patients. 11

12

Page 3 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



4

BACKGROUND 1

It is estimated that at least 1% of the United Kingdom (UK) population are taking an anticoagulant, 2

such as warfarin, increasing to 8% in those aged 80 years and over[1, 2]. People taking an 3

anticoagulant who experience a head injury are at an increased risk of intracranial haemorrhage[3,4] 4

with rates of mortality reported between 45-70%.[3,5–7] Liberal use of CT scanning is therefore 5

required to identify intracranial haemorrhage in these patients. However, it is not clear whether all 6

anticoagulated patients with head injury should receive a CT scan or whether CT should be used 7

selectively and limited to those with evidence of traumatic brain injury, such as those with loss of 8

consciousness or amnesia.[8] 9

Management of head injury in the UK follows guidance from the National Institute for Health and 10

Care Excellence (NICE). NICE guidance issued in 2007[9] recommended that patients with 11

coagulopathy (including those currently treated with warfarin) should undergo CT scanning only if 12

they report amnesia or loss of consciousness following injury. Updated guidance issued in 2014[10] 13

recommended that all patients having warfarin treatment should undergo CT scanning regardless of 14

whether they reported amnesia or loss of consciousness (Figure 1). The new guidance should 15

increase the number of scans performed and intracranial injuries identified but it is not clear 16

whether the benefits of this approach justify the costs of additional CT scanning. 17

The AHEAD study was an observational cohort study of patients with head injury who were taking 18

warfarin and presented to a hospital emergency department (ED).[11] It was undertaken when NICE 19

2007 guidance was in operation but before NICE 2014 guidance was issued. We aimed to use data 20

from the AHEAD study and decision analysis modelling to determine the cost-effectiveness of CT for 21

all compared to observed practice based on guidelines recommending selective CT for those with 22

evidence of traumatic brain injury. 23

24

25

Page 4 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



5

METHODS 1

The methods for the AHEAD study are described in detail elsewhere.[11] Briefly, 3566 adults who 2

were taking warfarin and attended the ED of 33 hospitals in England and Scotland between 3

September 2011 and March 2013 following head injury were recruited. Research staff in hospital 4

sites recorded basic demographic information, attendance details, injury mechanism, clinical 5

examination findings and CT results. Patients were then followed up to 10 weeks after presentation 6

using hospital record review and postal questionnaire. 7

We identified all patients with an adverse outcome who had not received a CT scan at their initial 8

hospital attendance. The patients that did receive a CT scan (under a selective CT scanning policy) 9

would receive the same treatment if a CT scan all policy was in place, therefore it is the former group 10

of patients who would be expected to receive clinical benefit from a policy of CT scanning all 11

patients. However, a threshold analysis was conducted to estimate the proportion of inpatient 12

attendances of less than 48 hours that would need to be avoided for the CT scan all policy to have a 13

cost per quality adjusted life year (QALY) below £30,000, assuming the cost of such an inpatient stay 14

to be that associated with a non-elective inpatient stay (£615)[12]. An adverse outcome was defined 15

as: death; neurosurgery; positive CT scan finding; or re-attendance to the hospital with a significant 16

head injury-related complication up to 10-weeks after the original attendance. These re-attendances 17

were confirmed following the review of hospital records and CT scan results, where undertaken. 18

Decision analysis modelling was used to estimate the incremental QALYs and costs had those 19

patients with an adverse outcome that were not CT scanned received a CT scan on initial hospital 20

attendance. Different assumptions were required for patients conditional on whether they survived 21

the adverse event. For patients who died, assumptions were required regarding: the probability of 22

survival if a CT scan had been performed; the Glasgow Outcome Scale (GOS) state to which the 23

patient would be categorised if they survived;[13] and the cost of neurosurgery. For patients who 24

survived, an assumption was required relating to the probability of GOS increase if a CT scan had 25

Page 5 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



6

been performed. Regardless of survival outcome, assumptions were required on: the life expectancy 1

of a person with the same gender and age profile; the costs and utility associated with each GOS 2

state; and the cost of a CT scan. The assumptions used within the model are detailed below. The 3

results presented take an English and Scottish perspective and use direct healthcare and personal 4

social services costs. 5

Model Assumptions 6

For patients who did not survive the adverse event: 7

The probability of survival if a CT scan had been performed 8

Two clinicians provided estimates of the probability of survival had the patient received a CT scan. In 9

the main analysis an average value was used, although sensitivity analyses were undertaken 10

assuming that each clinician was correct. 11

The GOS state to which the patient would be categorised if they survived 12

A single clinician provided an estimate of the GOS of the patient if they had survived. In a sensitivity 13

analysis the impact of the GOS state being one level higher (that is, more favourable to the patient) 14

was explored. 15

The costs of neurosurgery 16

The cost of neurosurgery was assumed to be that associated with the weighted average of NHS 17

Reference Cost Codes AA50A – AA57B, excluding codes relating to patients aged 18 years and under, 18

which was £3994.[14] It was assumed that all patients who died without having a CT scan would 19

undergo neurosurgery. 20

For patients who survived the adverse event: 21

The probability of GOS increase if a CT scan had been performed 22

Page 6 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



7

Two clinicians provided estimates of the probability of an increase in the GOS level, (i.e. a better 1

patient outcome) if a CT scan had been performed. In the main analysis an average value was used, 2

although sensitivity analyses were undertaken assuming that each clinician was correct. 3

For all patients: 4

The life expectancy of the person 5

These data were taken from UK Life Tables[15] and it was assumed that these were not affected by 6

an adverse event that had been survived. 7

The costs and utility associated with each GOS state 8

The data for GOS states 2-4 were taken from Pandor et al[16] with costs inflated from 2008/2009 9

values to 2014/15 prices using hospital and community health services indices reported in Curtis and 10

Burns.[12] The resultant values are provided in Table 1. For GOS state 5 it was assumed that the UK 11

general population utility conditional on age and sex was appropriate which was taken from Ara and 12

Brazier.[17] 13

Table 1: Assumed costs and utility associated with each GOS state, and assumed cost of 14

neurosurgery. 15

GOS state One-off Cost (£) Annual Costs (£) Utility value Source

2 47,674 46,595 0.00 Pandor et al[16] with

costs inflated using

Curtis and Burns[12]

3 0 37,214 0.15

4 18,837 0 0.51

5 0 0 PopulaKon Value† Assumption

† The uKlity in GOS state 5 were esKmated from Ara and Brazier[17] conditional on age and sex. 16

The cost of a CT scan 17

The cost of a CT scan was assumed to be that associated with NHS Reference Cost Code RD20A, 18

which was £92. 19

The mathematical model 20

Page 7 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



8

The model calculated the expected difference in costs and QALYs of moving from observed practice 1

to a strategy of CT scanning all patients. The following formulae were used in calculating the cost 2

and quality adjusted life years (QALY) impacts associated with provided CT scans to patients with 3

adverse events who did not receive a CT scan. All values were discounted at 3.5% per annum in 4

accordance with NICE guidelines.[18] A lifetime horizon was assumed due to potential mortality 5

benefits of the CT all strategy. 6

For patients who did not survive: 7

Change in costs: Average probability of survival if CT scan performed x (Life Expectancy x Cost per 8

year in estimated GOS state + cost of neurosurgery) 9

Change in QALYs: Average probability of survival if CT scan performed x (Life Expectancy x utility per 10

year in estimated GOS state) 11

For patients who did survive 12

Change in costs: Average probability of GOS increase if CT scan performed x Life Expectancy x (Cost 13

per year in higher GOS state – Cost per year in lower GOS state) 14

Change in QALYs: Average probability of GOS increase if CT scan performed x (Life Expectancy x 15

utility per year in higher GOS state – utility per year in lower GOS state) 16

RESULTS 17

Follow-up data were available for 3534/3566 patients (99%) in the AHEAD cohort. Details of the 18

cohort are published.[11] Glasgow Outcome Scale and diagnosis was available for 91.4% (n=3229) 19

and 99.9% (n=3530) patients respectively. Overall 2114/3534 patients (60%) received a CT scan. Of 20

the 1420 patients without a CT scan, 728 (51%) were admitted to hospital, 20 (1.4%) had subsequent 21

head injury related hospital attendances, and 74 (5.2%) died during follow-up. Cause of death was 22

head injury related in four (0.3%), unrelated in 52 (3.7%) and unknown in 19 (1.3%). Adverse 23

Page 8 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



9

outcomes were identified in 7/1420 (0.5%) patients who did not have CT scan: four deaths and three 1

with a related further hospital attendance and significant finding on CT scan at re-attendance. 2

The estimated changes in costs and QALYs per individual patient are provided in Table 2. The 3

summarised analyses including the increased costs of CT scans are provided in Table 3. 4

5

Page 9 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



10

Table 2: Estimated outcomes for patients with adverse events who were not CT scanned if they had 1

been CT scanned on admission to hospital and modelled implications for costs and QALYs. 2

Pa

tie

nt

Outcomes Modelling

Age Sex Admitted INR Observed CT

head scan

Reversal

therapy Neurosurgery

Further

hospital

attendance

HI

Death

Probability of

survival (%) Estimated

GOS if

survived

Change

in costs

Change

in QALYs Clinician

1

Clinician

2

1 81 M � NP � � � � � 75 75 3 £169,279 0.67

2 74 M � NP � � � � � 25 15 2 £13,528 0.00

3 90 M � 4.4 � � � � � 0 0 2 £3,994 0.00

4 88 M � NP � � � � � 75 75 4 £18,122 1.45

Probability of GOS

increase (+1, %) Lower GOS

score Δ C Δ Q

Clinician

1

Clinician

2

5 76 M � 2.0 � � � � � 25 50 4 -£7,064 0.86

6 77 F � 3.0 � � � � � 25 0 4 -£2,355 0.27

7 82 M � 3.5 � � � � � 25 0 4 -£2,355 0.17

NP= Not performed. 3

Table 3: The comparison of CT all with observed practice. 4

Change in costs from

CT scanning (£)

Change in QALYs

from CT scanning

ICER (Cost per QALY

gained (£))

Changes in individual patient values 193,149 3.41

Additional CT scanning costs 130,683

Net Values 323,832 3.41 94,895

It is estimated that the cost per QALY gained through providing a CT scan is in excess of £90,000 per 5

QALY which is markedly greater than the £20,000 to £30,000 per QALY gained threshold reported by 6

NICE.[18] This conclusion did not alter within the sensitivity analyses performed. Using the estimates 7

from the individual expert clinicians which produced values of £90,659 and £99,547 per QALY gained 8

or if the cost of neurosurgery was not included for the patient who neither expert clinician believed 9

would have survived even with a CT scan (£93,725 per QALY gained). When it was assumed that all 10

patients survived at one GOS state better than estimated in the base case the cost per QALY gained 11

reduced to £36,864 (an additional £213,139 to obtain 5.78 QALYs) but still did not fall below NICE 12

thresholds. 13

Page 10 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



11

It was estimated that over 67% of the 537 inpatient stays of less than 48 hours observed would need 1

to be avoided in order for the CT scan all policy to have a cost per QALY of less than £30,000. 2

DISCUSSION 3

Follow-up of 1420 patients who did not have a CT scan in the AHEAD cohort identified seven cases 4

(four deaths, three delayed diagnoses) that might have been identified by CT scanning at initial 5

hospital attendance. Decision analytic modelling showed that appropriate treatment of these cases 6

could have gained 3.41 QALYs but would have incurred £193,149 additional treatment costs and 7

£130,683 additional costs for CT scanning. This produces an incremental cost of £94,895 per QALY 8

gained, which is greatly above the usual threshold of £20-30,000/QALY that NICE uses to determine 9

cost-effectiveness. Our analysis therefore suggests that CT for all anticoagulated patients with head 10

injury, as recommended in NICE 2014 guidance, is not cost-effective compared to the selective use 11

of CT scanning observed in practice when NICE 2007 guidance was in operation. 12

Our analysis has a number of strengths and weaknesses. It was based upon a large representative 13

cohort of patients who presented to a wide range of hospitals. The methods used to estimate health 14

gain from treating additional cases detected by universal CT scanning are transparent and 15

reproducible, and were robust to the sensitivity analyses undertaken. A potential limitation is that 16

some patients who suffered adverse outcome may not have been identified on follow-up leading to 17

underestimation of the potential benefit of CT scan for all patients. However, it is worth noting that 18

10.79 QALYs would be required to reach the NICE threshold of £30,000/QALY for cost-effectiveness, 19

so our conclusion regarding the lack of cost-effectiveness of unselective CT scanning would only be 20

undermined if follow-up had identified less than 1 in 3 patients with adverse events. This seems 21

extremely unlikely. 22

It is not believed that the threshold level for avoiding inpatient admissions of less than 48 hours 23

would be plausible. Due to the age and comorbidities of this cohort of patients there will be many 24

Page 11 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



12

reasons for patients being admitted irrespective of whether a CT scan was performed. These reasons 1

may be head injury-related such as observation, but are also likely to include other reasons such as 2

intercurrent infections, injuries relating to attendance (other than the head injury) and for social 3

reasons. Additionally, one could also postulate that by detecting incidental findings the additional CT 4

scans could result in additional admissions. If so, the incremental costs of the CT all strategy would 5

increase and it would become less cost-effective. We have no data to determine whether additional 6

CT scans result in more or fewer admissions. 7

Most international guidance, including the National Emergency X-Radiology Utilisation Study (NEXUS 8

II), CT in Head Injury Patients (CHIP), American College of Emergency Physicians (ACEP) head CT and 9

the European Federation of Neurological Societies (EFNS)[19-22] advocate that all patients taking 10

warfarin should have an immediate CT scan irrespective of injury severity, GCS or neurological 11

symptoms. The UK guidelines (NICE) are based on the Canadian CT Head Rule(CCHR)[23] which 12

excluded patients taking warfarin and up until January 2014, stated that a CT scan should be 13

performed on patients taking warfarin if the patient presented with loss of consciousness or 14

amnesia. These guidelines have now been updated to recommend all anticoagulated patients 15

receive a CT scan but no new evidence appears to have been published to support this 16

recommended change in practice. Our analysis suggests that the 2014 revision to NICE guidance has 17

resulted in less cost-effective care. 18

Previous literature investigating the patient outcomes and costs associated with diagnosing and 19

treating head injured patients who are taking anticoagulants are limited and difficult to compare to 20

our analysis. Several recent studies have used decision analysis modelling to estimate the costs and 21

benefits of CT scanning in the general (i.e. non-anticoagulated) head injured population[24-26] and 22

have generally shown that using a clinical decision rule to select patients for CT scanning is more 23

cost-effective than unselective CT scanning. The only study identified that focused solely on 24

anticoagulated patients was undertaken by Li in 2012.[27] Li questioned how this cohort of patients 25

Page 12 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



13

should be managed due to the nature of delayed complications associated with anticoagulant use, 1

whilst also considering the costs attached to CT imaging and admittance to hospital. The analyses 2

were based on data taken from other studies and included repeated CT scans (2) and 24-hour 3

admission per patient. The costs per year of a life saved in the US, Spain and Canada were estimated 4

as $1 million, $158,000 and $105,000 respectively. 5

Future research is needed to validate our findings on the potential benefits, harms and costs of CT 6

scanning since the introduction of NICE 2014, in addition to further work on the criteria used for 7

deciding whether a CT scan is appropriate such as the use of serum protein biomarkers. 8

CONCLUSION 9

CT scanning for all anticoagulated patients with head injury is not cost-effective compared with 10

selective use of CT scanning based on guidelines recommending scanning only for those with 11

evidence of traumatic brain injury. A move (or return to) selective use of CT scanning would 12

substantially reduce health care costs with only a small increase in potentially avoidable adverse 13

outcomes. 14

Acknowledgements: We thank Rosemary Harper for her contribution as a patient representative 15

throughout the duration of the study; all the clinicians and research staff in the participating hospital 16

sites who identified patients in this study, without whose hard work this study would not have been 17

possible. 18

Contributors: All authors provided substantial contributions to the conception, design, acquisition of 19

the data, or analysis and interpretation of the study data. MK drafted the article and all authors 20

contributed to its revision for important intellectual content. All authors approved the final version. 21

SM is guarantor. All authors agree to be accountable for all aspects of the work ensuring that 22

questions related to accuracy or integrity of any party of the work are appropriately investigated and 23

resolved. 24

Page 13 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



14

Transparency: SM affirms that this manuscript is an honest, accurate, and transparent account of 1

the study being reported; that no important aspects of the study have been omitted; and that any 2

discrepancies from the study as planned (and, if relevant, registered) have been explained. 3

Funding: This paper presents independent research commissioned by the National Institute for 4

Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme grant reference 5

number PB-PG-0808-17148. The views expressed are those of the author(s) and not necessarily 6

those of the NHS, the NIHR or the Department of Health. 7

Competing interests: All authors have completed the ICMJE uniform disclosure form at 8

www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted 9

work; no financial relationships with any organisations that might have an interest in the submitted 10

work in the previous three years; no other relationships or activities that could appear to have 11

influenced the submitted work. 12

Ethical approval: NRES Committee Yorkshire and The Humber – Sheffield: 11/H1308/13. 13

Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust – Ref.: STH15705. 14

Provenance and peer review: Not commissioned; externally peer reviewed. 15

Data Sharing Statement: No additional data are available. 16

Open Access: This is an Open Access article distributed in accordance with the terms of the Creative 17

Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build 18

upon this work, for commercial use, provided the original work is properly cited. See: 19

http://creativecommons.org/licenses/by/4.0/. 20

REFERENCES 21

Page 14 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



15

1 Kamali F, Pirmohamed M. The future prospects of pharmacogenetics in oral anticoagulation 1

therapy. Br J Clin Pharmacol 2006:746–51. 2

2 Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future 3

challenges. Pharmacogenomics J 2007;7(2):99–111. 4

3 Volans AP. The risks of minor head injury in the warfarinised patient. J Accid Emerg Med 5

1998;15(3):159–61. 6

4 Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and 7

hypotheses. Stroke 1995;26(8):1471–7. 8

5 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. 9

Ann Intern Med 1994;120(11):897–902. 10

6 Ferrera PC, Bartfield JM. Outcomes of anticoagulated trauma patients. Am J Emerg Med 11

1999;17(2):154–6. 12

7 Mathiesen T, Benediktsdottir K, Johnsson H, et al. Intracranial traumatic and non-traumatic 13

haemorrhagic complications of warfarin treatment. Acta Neurol Scand 1995;91(3):208–14. 14

8 Leiblich a, Mason S. Emergency management of minor head injury in anticoagulated 15

patients. Emerg Med J 2011;28(2):115–8. 16

9 National Institute for Health and Care Excellence. Head injury: triage, assessment, 17

investigation and early management of head injury in infants, children and adults. (Clinical 18

Guideline 56.) London; 2007. http://www.nice.org.uk/CG56. 19

10 National Institute for Health and Care Excellence. Head injury: triage, assessment, 20

investigation and early management of head injury in infants, children and adults. (Clinical 21

Guideline 176.) London; 2014. http://www.nice.org.uk/CG176. 22

11 Mason S, Kuczawski M, Teare MD, et al. The AHEAD Study: An evaluation of the 23

management of anticoagulated patients who suffer head injury. UK; 2016. Unpublished. 24

Page 15 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



16

12 Curtis L, Burns A. Unit Costs of Health and Social Care 2015. Personal Social Services 1

Research Unit, Canterbury, Kent; 2015 [Accessed January 2016]. Available from: 2

http://www.pssru.ac.uk/project-pages/unit-costs/2015. 3

13 Wilson JTL, Pettigrew LEL, Teasdale GM. Structured interviews for the Glasgow Outcome 4

Scale and extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 5

1998;15:573-585. 6

14 Department of Health. National Schedule of Reference Costs 2014-15 for NHS trusts and 7

NHS foundation trusts. London; 2015 [Accessed January 2016]. Available from: 8

http://www.gov.uk/government/publications/nhs-reference-costs-2014-to-2015. 9

15 Office for National Statistics. National Life Tables, 2010-2012. London; 2014 [Accessed 10

January 2016]. Available from: http://www.ons.gov.uk/ons/publications/re-reference-11

tables.html?edition=tcm%3A77-352834. 12

16 Pandor A, Goodacre S, Harnan S, et al. Diagnostic management strategies for adults and 13

children with minor head injury: a systematic review and an economic evaluation. Health 14

Technol Assess 2011;15(27):1–196. 15

17 Ara R, Brazier JE. Populating an Economic Model with Health State Utility Values: Moving 16

toward Better Practice. Value Health 2010;13(5):509–18. 17

18 National Institute for Health and Care Excellence. Guide to the methods of technology 18

appraisals . London; 2013 [Accessed January 2016]. Available from: 19

http://www.nice.org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-of-20

technology-appraisal-2013-pdf. 21

19 Mower WR, Hoffman JR, Herbert M, et al. Developing a clinical decision instrument to rule 22

out intracranial injuries in patients with minor head trauma: methodology of the NEXUS II 23

investigation. Ann Emerg Med 2002;40:505–14. 24

Page 16 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



17

20 Smits M, Diederik W, Dippel W, et al. Predicting intracranial traumatic findings on computed 1

tomography in patients with minor head injury: the CHIP prediction rule. Ann Intern Med 2

2007;146:397-405. 3

21 Jagoda AS, Bazarian JJ, Bruns JJ Jr, et al. Clinical policy: neuroimaging and decisionmaking in 4

adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008;52:714-748. 5

22 Vos PE, Battistin L, Girbamer G, et al. EFNS guideline on mild traumatic brain injury: report of 6

an EFNS task force. Eur J Neurol 2002;9:207-219. 7

23 Stiell IG, Wells GA, Vandemheen K, et al. The Canadian CT head rule for patients with minor 8

head injury. Lancet 2001;357:1391 –1396. 9

24 Melnick ER, Keegan J, Taylor RA. Redefining Overuse to Include Costs: A Decision Analysis for 10

Computed Tomography in Minor Head Injury. Jt Comm J Qual Patient Saf 2015;41(7):313-22. 11

25 Smits M, Dippel DW, Nederkoorn PJ, et al. Minor head injury: CT-based strategies for 12

management—a cost-effectiveness analysis. Radiology 2010 Feb;254(2):532-40. 13

26 Holmes MW, Goodacre S, Stevenson MD, et al. The cost-effectiveness of diagnostic 14

management strategies for adults with minor head injury. Injury 2012;43:1423-1431. 15

27 Li J. Admit all anticoagulated head-injured patients? A million dollars versus your dime. You 16

make the call. Ann of Emerg Med 2012;59(6):457-459. 17

Page 17 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Figure 1: NICE guidance 2007 versus 2014

Figure 1

79x59mm (300 x 300 DPI)

Page 18 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



CHEERS checklist - Items to include when reporting economic evaluations of health interventions



Section/item Item

No Recommendation

Reported

on page

No/ line

No

Title and abstract

Title 1

Identify the study as an economic evaluation or use

more specific terms such as “cost-effectiveness

analysis”, and describe the interventions compared.

1

Abstract 2

Provide a structured summary of objectives,

perspective, setting, methods (including study design

and inputs), results (including base case and

uncertainty analyses), and conclusions.

2

Introduction

Background and objectives 3

Provide an explicit statement of the broader context

for the study. 4

Present the study question and its relevance for

health policy or practice decisions. 4

Methods

Target population and

subgroups 4

Describe characteristics of the base case population

and subgroups analysed, including why they were

chosen.

5

Setting and location 5 State relevant aspects of the system(s) in which the

decision(s) need(s) to be made. 5

Study perspective 6 Describe the perspective of the study and relate this

to the costs being evaluated. 6

Comparators 7 Describe the interventions or strategies being

compared and state why they were chosen. 4

Time horizon 8

State the time horizon(s) over which costs and

consequences are being evaluated and say why

appropriate.

8

Discount rate 9 Report the choice of discount rate(s) used for costs

and outcomes and say why appropriate. 8

Choice of health outcomes 10

Describe what outcomes were used as the

measure(s) of benefit in the evaluation and their

relevance for the type of analysis performed.

6,10

Measurement of effectiveness 11a

Single study-based estimates: Describe fully the

design features of the single effectiveness study and

why the single study was a sufficient source of

clinical effectiveness data.

4

Page 19 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



11b

Synthesis-based estimates: Describe fully the

methods used for identification of included studies

and synthesis of clinical effectiveness data.

N/A

Measurement and valuation of

preference based outcomes 12

If applicable, describe the population and methods

used to elicit preferences for outcomes. N/A

Estimating resources and costs

13a


approaches used to estimate resource use associated

with the alternative interventions. Describe primary

or secondary research methods for valuing each

resource item in terms of its unit cost. Describe any

adjustments made to approximate to opportunity

costs.

N/A

13b

Model-based economic evaluation: Describe

approaches and data sources used to estimate

resource use associated with model health states.

Describe primary or secondary research methods for

valuing each resource item in terms of its unit cost.

Describe any adjustments made to approximate to

opportunity costs.

7-8

Currency, price date, and

conversion 14

Report the dates of the estimated resource

quantities and unit costs. Describe methods for

adjusting estimated unit costs to the year of reported

costs if necessary. Describe methods for converting

costs into a common currency base and the exchange

rate.

7

Choice of model 15

Describe and give reasons for the specific type of

decision-analytical model used. Providing a figure to

show model structure is strongly recommended.

8

Assumptions 16 Describe all structural or other assumptions

underpinning the decision-analytical model. 5-8

Analytical methods 17

Describe all analytical methods supporting the

evaluation. This could include methods for dealing

with skewed, missing, or censored data;

extrapolation methods; methods for pooling data;

approaches to validate or make adjustments (such as

half cycle corrections) to a model; and methods for

handling population heterogeneity and uncertainty.

5-8

Results

Study parameters 18

Report the values, ranges, references, and, if used,

probability distributions for all parameters. Report

reasons or sources for distributions used to

represent uncertainty where appropriate. Providing a

table to show the input values is strongly

recommended.

6-8

Incremental costs and

outcomes 19

For each intervention, report mean values for the

main categories of estimated costs and outcomes of

interest, as well as mean differences between the

comparator groups. If applicable, report incremental

cost-effectiveness ratios.

10

Page 20 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from



Characterising uncertainty

20a


the effects of sampling uncertainty for the estimated

incremental cost and incremental effectiveness

parameters, together with the impact of

methodological assumptions (such as discount rate,

study perspective).

20b

Model-based economic evaluation: Describe the

effects on the results of uncertainty for all input

parameters, and uncertainty related to the structure

of the model and assumptions.

10

Characterising heterogeneity 21

If applicable, report differences in costs, outcomes,

or cost-effectiveness that can be explained by

variations between subgroups of patients with

different baseline characteristics or other observed

variability in effects that are not reducible by more

information.

N/A

Discussion

Study findings, limitations,

generalisability, and current

knowledge

22

Summarise key study findings and describe how they

support the conclusions reached. Discuss limitations

and the generalisability of the findings and how the

findings fit with current knowledge.

10-12

Other

Source of funding 23

Describe how the study was funded and the role of

the funder in the identification, design, conduct, and

reporting of the analysis. Describe other non-

monetary sources of support.

13

Conflicts of interest 24

Describe any potential for conflict of interest of study

contributors in accordance with journal policy. In the

absence of a journal policy, we recommend authors

comply with International Committee of Medical

Journal Editors recommendations.

13

Page 21 of 21


BMJ Open

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960



jopen.bmj.com

/B

MJ O


ecember 2016. D

ownloaded from


bmj open · conclusions: ct scanning for all anticoagulated patients with head injury is not...

Documents