How to Read an Article about a Systematic Review Maribeth Chitkara, MD Rachel Boykan, MD Stony Brook Long Island Children’s Hospital

How to Read How to Read an Article an Article

about a about a Systematic Systematic

ReviewReview

Maribeth Chitkara, MDMaribeth Chitkara, MDRachel Boykan, MDRachel Boykan, MD

Stony Brook Long Island Stony Brook Long Island Children’s HospitalChildren’s Hospital

Session ObjectivesSession Objectives

Demonstrate understanding of general EBM principles.

Demonstrate understanding of validity measures specific to articles about a systematic review.

Critically appraise an article about a systematic review and describe its clinical applicability.

Clinical ScenarioClinical Scenario

You are on inpatient service and have been You are on inpatient service and have been taking care of a 4 month old with bronchiolitis. taking care of a 4 month old with bronchiolitis. The infant was initially admitted to the ICU for The infant was initially admitted to the ICU for respiratory distress, but was transferred to the respiratory distress, but was transferred to the general pediatric ward on the 4general pediatric ward on the 4thth hospital day hospital day with resolved increased work of breathing but a with resolved increased work of breathing but a persistent O2 requirement. Your attending persistent O2 requirement. Your attending suggests starting the child on systemic suggests starting the child on systemic corticosteroids because she is getting inpatient corticosteroids because she is getting inpatient with the prolonged length of stay. You are with the prolonged length of stay. You are skeptical, and decide to see where the medical skeptical, and decide to see where the medical evidence lies. evidence lies.

Systematic ReviewsSystematic Reviews

A summary of the medical A summary of the medical literature literature

Uses explicit methods to Uses explicit methods to systematically search, systematically search, critically appraise, and critically appraise, and synthesize the world synthesize the world literatureliterature


GoalsGoals::Minimize BiasMinimize Bias

randomized trialsrandomized trialsseeks multilingual published and seeks multilingual published and

unpublished reportsunpublished reportsMinimize random errorMinimize random error

by amassing very large numbersby amassing very large numbers


MayMay include some statistical include some statistical method for combining the method for combining the results of individual studiesresults of individual studies

““Meta-analyses”Meta-analyses”

Appraisal of Systematic Appraisal of Systematic ReviewsReviews

Is the Systematic Review Is the Systematic Review ValidValid??

What are the What are the ResultsResults??

Can I Can I ApplyApply the results to my the results to my patient?patient?

Is the Systematic Review Is the Systematic Review ValidValid? ?

Is this a systematic review of Is this a systematic review of randomized trials?randomized trials?

Were the results consistent Were the results consistent from study to study?from study to study?


Randomized trials reduce biasRandomized trials reduce bias

Combining all relevant Combining all relevant randomized trials further randomized trials further reduces bias and random errorreduces bias and random error

Provides the highest level of Provides the highest level of evidence currently achievableevidence currently achievable


Systematic Reviews of Non-Systematic Reviews of Non-Randomized Trials Can:Randomized Trials Can:

Compound the problems of Compound the problems of individually misleading trialsindividually misleading trials

Produce a lower quality of Produce a lower quality of evidenceevidence


If a systematic review includes If a systematic review includes both both Randomized and Non-Randomized and Non-Randomized Trials, Randomized Trials, avoid itavoid it unless these types of trials are unless these types of trials are separated in the analyses.separated in the analyses.


Does the study have a Methods Does the study have a Methods SectionSection

Seek a description of Seek a description of howhow the the investigators found all the investigators found all the relevant trialsrelevant trials

If not present If not present STOP STOP

The Methods Section The Methods Section

Seek reassurance that the Seek reassurance that the search went beyond standard search went beyond standard bibliographic databasesbibliographic databases

Should include hand-searching Should include hand-searching journals, conference journals, conference proceedings, theses, databanks proceedings, theses, databanks of pharmaceutical companies, of pharmaceutical companies, and contacting authors of and contacting authors of published articlespublished articles

The Methods SectionThe Methods Section

Negative trials are less likely Negative trials are less likely to be submitted and selected to be submitted and selected for publicationfor publication

A Systematic Review A Systematic Review restricted to restricted to published published trials trials can result in a false-positive can result in a false-positive conclusionconclusion

Restriction to a single Restriction to a single language can bias the language can bias the conclusionsconclusions


How did the investigators assess How did the investigators assess the validity of the individual the validity of the individual studies?studies?Randomized?Randomized?Follow-Up sufficient?Follow-Up sufficient?Intention to treat analysis?Intention to treat analysis?Blinded?Blinded?Were the groups similar at the start?Were the groups similar at the start?Were the groups treated equally, Were the groups treated equally,

apart from the experimental tx?apart from the experimental tx?

What are the What are the ResultsResults? ? Forest PlotsForest Plots

Each study is a lineEach study is a line Black square is Black square is

point estimatepoint estimate Size of square is Size of square is

weightweight Line is 95% Line is 95%

confidence intervalconfidence interval Pooled analysis is Pooled analysis is

combined effect combined effect and CIand CI

What are the What are the ResultsResults? ? Funnel Plots and Publication BiasFunnel Plots and Publication Bias

Vertical AxisVertical Axis Measure of study Measure of study

precisionprecision Higher up: more precise, Higher up: more precise,

smaller CIsmaller CI

Horizontal AxisHorizontal Axis Measures treatment Measures treatment

effecteffect

Center LineCenter Line Combined treatment Combined treatment

effecteffect

No publication bias: No publication bias: Inverted funnel shapeInverted funnel shape


Is our patient so different from those in Is our patient so different from those in the study that the results cannot apply?the study that the results cannot apply?

Is the treatment feasible in our setting?Is the treatment feasible in our setting?What are our patient’s potential benefits What are our patient’s potential benefits

and harms from the therapy?and harms from the therapy?What are our patient’s values and What are our patient’s values and

preferences for both the outcome we preferences for both the outcome we desire and the potential side-effects of desire and the potential side-effects of treatment?treatment?


A Systematic Review provides an A Systematic Review provides an overall, average effect of therapy which overall, average effect of therapy which may be derived from a heterogeneous may be derived from a heterogeneous population.population.

SR’s may provide precise information on SR’s may provide precise information on sub-groups that may help individualize sub-groups that may help individualize evidence to our own patients.evidence to our own patients.

BUT...BUT...


A qualitative difference in treatment efficacy A qualitative difference in treatment efficacy among subgroups is likely only when ALL the among subgroups is likely only when ALL the following questions can be answered “YES”:following questions can be answered “YES”:

Does it really make biological and clinical sense?Does it really make biological and clinical sense?

Is the qualitative difference both clinically and Is the qualitative difference both clinically and statistically significant?statistically significant?

Was it hypothesized before the study began (rather Was it hypothesized before the study began (rather than a product of dredging the data) and has it than a product of dredging the data) and has it been confirmed in other independent studies?been confirmed in other independent studies?

Was it one of just a few subgroup analyses carried Was it one of just a few subgroup analyses carried out in this study?out in this study?

Practice CasesPractice Cases

Review the case scenarios in your handoutReview the case scenarios in your handout

Articles for each clinical question have been Articles for each clinical question have been providedprovided

Use worksheet to help guide your appraisal Use worksheet to help guide your appraisal for each article for each article

Practice Case Practice Case ReferencesReferences

Case 1: Case 1: Garrison MM. et al. Systemic Corticosteroids in Infant Bronchiolitis: A Meta-analysis. Pediatrics, 2000; 105:e44.

Case 2: Case 2: Wooditch AC, Aronoff SC. Effect of Initial Corticosteroid Therapy on Coronary Artery Aneurysm Formation in Kawasaki Disease: A Meta-analysis of 862 Children. Pediatrics, 2005;116:989.

Case 3: Case 3: Figuls MR, Giné-Garriga M, Granados Rugeles C, Perrotta C. Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database of Systematic Reviews 2012.

EBM EBM References/ResourcesReferences/Resources

Friedland DJ, Shilpak MG, Subak LL, Bent Friedland DJ, Shilpak MG, Subak LL, Bent SW, Mendelson T. Evaluating Integrative SW, Mendelson T. Evaluating Integrative Literature. Literature. Evidence-based medicine: a Evidence-based medicine: a framework for clinical practiceframework for clinical practice, Appleton , Appleton and Lange, 1998: 222-227. and Lange, 1998: 222-227.

Straus SE, Glasziou P, Richardson WS, Haynes RB. Therapy: Reports of Systematic Reviews. Evidence-based medicine: how to practice and teach it, 4th ed, Churchill Livingston Elsevier, 2011: 98-108.

Documents

How to Read an Article about a Systematic Review Maribeth Chitkara, MD Rachel Boykan, MD Stony Brook Long Island Children’s Hospital