revman for registrars paul glue, psychological medicine
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RevMan for Registrars Paul Glue, Psychological Medicine. What is EBM? Different approaches/tools Systematic reviews Introduction to Review Manager Practical example Relapse prevention drug trials in anxiety disorders Perform a RevMan analysis on a set of papers Calculate NNT. - PowerPoint PPT PresentationTRANSCRIPT
RevMan for RegistrarsRevMan for RegistrarsPaul Glue, Psychological MedicinePaul Glue, Psychological Medicine
What is EBM?What is EBM? Different approaches/toolsDifferent approaches/tools
Systematic reviewsSystematic reviewsIntroduction to Review ManagerIntroduction to Review Manager
Practical examplePractical exampleRelapse prevention drug trials in anxiety disordersRelapse prevention drug trials in anxiety disorders
Perform a RevMan analysis on a set of Perform a RevMan analysis on a set of paperspapers
Calculate NNTCalculate NNT
What is EBM?What is EBM?
An approach to systematically apply the best An approach to systematically apply the best available available scientific evidencescientific evidence to assist with to assist with medical decision makingmedical decision making. .
Also assesses the Also assesses the quality of evidencequality of evidence of the of the risks and benefits of treatments/interventionsrisks and benefits of treatments/interventions
Cannot be applied to all medical decision-Cannot be applied to all medical decision-making (e.g. quality of life) making (e.g. quality of life)
Scope can be broad (e.g. EB Guidelines) or Scope can be broad (e.g. EB Guidelines) or narrow (EB individual decision making) narrow (EB individual decision making)
TechniquesTechniques
Systematic reviewsSystematic reviews of published research studies to of published research studies to evaluate treatments/interventions. evaluate treatments/interventions.
e.g.Cochrane Collaboration – organization defining methods, e.g.Cochrane Collaboration – organization defining methods, repository for completed systematic reviews. repository for completed systematic reviews.
Requires authors to provide a Requires authors to provide a detaileddetailed and and repeatable repeatable plan of plan of literature searchliterature search and and evidence evaluations.evidence evaluations.
Explicit assessment of clinical trial qualityExplicit assessment of clinical trial quality Trial design considerations: e.g. clearly-defined eligibility criteria, Trial design considerations: e.g. clearly-defined eligibility criteria,
validated endpoints, minimal missing data.validated endpoints, minimal missing data. Generalizability considerations: e.g. data from narrowly-defined Generalizability considerations: e.g. data from narrowly-defined
patient populations may not be generalizable to clinical practice.patient populations may not be generalizable to clinical practice. Followup: Was there adequate time for defined outcomes to Followup: Was there adequate time for defined outcomes to
occur? occur? Statistical power: Was the study size adequate to detect a Statistical power: Was the study size adequate to detect a
difference between treatment arms?difference between treatment arms?
TechniquesTechniquesSystems to Systems to stratify evidence by qualitystratify evidence by quality e.g. e.g. US Preventive Services Task ForceUS Preventive Services Task Force Level I: Evidence obtained from at least one properly designed Level I: Evidence obtained from at least one properly designed
randomized controlled trial. randomized controlled trial. Level II-1: … from well-designed controlled trials without Level II-1: … from well-designed controlled trials without
randomization. randomization. Level II-2: … from well-designed cohort or case-control analytic Level II-2: … from well-designed cohort or case-control analytic
studies, preferably from more than one centre or research group. studies, preferably from more than one centre or research group. Level II-3: … from multiple time series with or without the Level II-3: … from multiple time series with or without the
intervention. intervention. Level III: Opinions of respected authorities, based on clinical Level III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert committees.experience, descriptive studies, or reports of expert committees.
Statistical measuresStatistical measures Meta-analytic methodsMeta-analytic methods ROC curvesROC curves NNTNNT
Randomized Controlled TrialsRandomized Controlled Trials
Gold standard for EBMGold standard for EBMRandomizedRandomized – subjects are allocated to – subjects are allocated to treatment arms randomly (usually by a treatment arms randomly (usually by a computer generated random code)computer generated random code)Double blindDouble blind – treatment allocation is – treatment allocation is hidden from Dr and patienthidden from Dr and patientControlControl arm – new treatment compared arm – new treatment compared with (e.g.) active control, placebo (inactive) with (e.g.) active control, placebo (inactive) controlcontrol
Questions to be studied todayQuestions to be studied today
How effective are antidepressants at preventing How effective are antidepressants at preventing relapse in anxiety disorders?relapse in anxiety disorders? All major anxiety disorders respond to All major anxiety disorders respond to
antidepressantsantidepressants Clinical guidances recommend that after response, Clinical guidances recommend that after response,
treatment should continue for treatment should continue for >>6 months to prevent 6 months to prevent re-emergence of original disorderre-emergence of original disorder
However this has not been studied systematicallyHowever this has not been studied systematically
Is the effect of antidepressants on relapse prevention Is the effect of antidepressants on relapse prevention the same for all anxiety disorders? the same for all anxiety disorders?
Antidepressant relapse prevention designs Antidepressant relapse prevention designs
Open-labelantidepressant
6-8 weeks
Responders randomized to stay on AD/switch to placebo Nonrespond
ers are discontinued
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.00 100 200 300 400 500
Days since randomization
Est
imate
d s
urv
ival
pro
bab
ilit
y
citalopram
placebo
-Robust results in depression trials-Example of enrichment of patient population
DSM-IV and anxietyDSM-IV and anxiety
The activity todayThe activity today
You will be allocated all the antidepressant You will be allocated all the antidepressant relapse prevention trials (n=3-6) for a specific relapse prevention trials (n=3-6) for a specific anxiety disorderanxiety disorderYou need to extract data (You need to extract data (n relapsen relapse and and n n randomizedrandomized) for each of the trials and enter this ) for each of the trials and enter this into RevManinto RevManCalculate Calculate Odds RatiosOdds Ratios for the relapse prevention for the relapse prevention effect of antidepressantseffect of antidepressantsUse the relapse data to also calculate NNTUse the relapse data to also calculate NNTPrepare a brief (Prepare a brief (<<3 slide) presentation of your 3 slide) presentation of your output to present to the whole group.output to present to the whole group.
Collecting your dataCollecting your data
This exercise skips several of the key This exercise skips several of the key steps involved in a systematic reviewsteps involved in a systematic review Literature searchLiterature search Selection of appropriate studies based on Selection of appropriate studies based on
explicit criteria (i.e. protocol)explicit criteria (i.e. protocol) What data were collectedWhat data were collected Analytical MethodsAnalytical Methods
Literature search termsLiterature search termsWhen did you search…
How did you search…
Where did you search…
How did you explore further…
Inclusion criteriaInclusion criteria
Data CollectionData Collection
Are you comparing like with like?
Are endpoints the same?f
Analysis MethodsAnalysis Methods
Sorting out data from your searchSorting out data from your search
Titles identified from electronic databases and screened for retrieval (n=5424)
Full text articles assessed for eligibility (n=72)
Excluded (n=5289)
Excluded (n=63) Combination therapy (n=10) Placebo control only (n=22) Duplicate data (n=12) Different patient group (n=15) Review article (n=3) Unusable data (n=1)
Publications screened (n=135)
Studies included in meta-analysis (n=9)
Using RevManUsing RevManOpen RevManOpen RevMan
Open up a review from file Open up a review from file anxiety-relprev-4-10.rm5anxiety-relprev-4-10.rm5
2: Study titles have already been entered
3: Then click on Data and analyses
1: Click on Studies and References
Click on Add Comparison
… and click Next
Panic disorder, GAD etc
Click on Add an outcome….
….then click Finish
Choose Dichotomous (relapse vs non-relapse)
…and click Next
Fill in labels
Click next
Select M-H
Click next
Random effects model
Odds Ratio
Edit new outcome
Click finish
A blank table shell is created Click here to
enter studies
Highlight multiple studies to enter with CTRL
And click finish
Relapse on AD
Enter data from each study
Total on AD
Total PBO
Relapse on PBO
Stats
Generate a graph for presentation
Study weight
Forest plot
Individual and pooled ORs
Can uncheck to assess effects of individual studies
(sensitivity analysis)
Presentation Forest Plot generated by RevMan
Calculating NNTCalculating NNT
NNT = 1NNT = 1 (nonrelapsers on ADs/all AD)-(nonrelapsers on PBO/all PBO) (nonrelapsers on ADs/all AD)-(nonrelapsers on PBO/all PBO)
Round NNT up to next whole number
NNT 2-4 – strong effect for treatmentNNTs >10 may still be useful for prophylaxis
Go!Go!