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CAT 5: CAT 5: How How to Read an to Read an
Article about a Article about a Systematic Systematic
ReviewReview
Maribeth Chitkara, MDMaribeth Chitkara, MDRachel Boykan, MDRachel Boykan, MD
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 11N respiratory distress, but was transferred to 11N on the 4on the 4thth hospital day with resolved increased hospital day with resolved increased work of breathing but a persistent O2 work of breathing but a persistent O2 requirement. Your attending suggests starting requirement. Your attending suggests starting the child on systemic corticosteroids because the child on systemic corticosteroids because she is getting inpatient with the prolonged she is getting inpatient with the prolonged length of stay. You are skeptical, and decide to length of stay. You are skeptical, and decide to see where the medical evidence lies. see where the medical 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
Systematic ReviewsSystematic Reviews
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unpublished reportsunpublished reportsMinimize random errorMinimize random error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
Systematic ReviewsSystematic Reviews
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”
Systematic Reviews - Systematic Reviews - ValidityValidity
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?
Is the SR Valid?Is the SR Valid?
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
Is the SR Valid?Is the SR Valid?
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
Is the SR Valid?Is the SR Valid?
If a systematic review includes If a systematic review includes both both Randomized and Non-Randomized and Non-Randomized Trials, Randomized Trials, avoid it avoid it unlessunless these types of trials are these types of trials are separated in the analyses.separated in the analyses.
Is the SR Valid?Is the SR Valid?
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
Seek reassurance that the search Seek reassurance that the search went beyond standard went beyond standard bibliographic databasesbibliographic databasesNegative trials are less likely to Negative trials are less likely to
be submitted and selected for be submitted and selected for publicationpublication
A Systematic Review restricted to A Systematic Review restricted to published published trials can result in a trials can result in a false-positive conclusionfalse-positive conclusion
Restriction to a single language Restriction to a single language can bias the conclusionscan bias the conclusions
Is the SR Valid?Is the SR Valid?
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?
Results: Forest PlotsResults: Forest 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 Diamond is Diamond is
combined effect combined effect and CIand CI
Publication Bias: Funnel Publication Bias: Funnel PlotsPlots
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
ApplicabilityApplicability
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?
ApplicabilityApplicability
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...
ApplicabilityApplicability
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?