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!