- •While differences are expected in a meta-analysis, these may be negligible, and a pooled estimate can guide the clinical decision. However, when the differences are large, this estimate may mislead.
- •The danger of reporting pooled estimates is that readers may overlook the overall picture—some studies having bigger effects than the other studies, some effects with different directions (harm) from the benefit shown by most studies. A careful inspection of the forest plot can help detect these differences; we refer to as heterogeneity.
- •Visual inspection should be used together with measures of heterogeneity–I2 and Q. High values of I2 and small P-values associated with Q may suggest heterogeneity. But large P-values do not mean the absence of heterogeneity. It is more informative to report the confidence interval of I2.
- •If heterogeneity is detected, an explanation must be sought, and analysis using study-level characteristics (subgroup analysis or meta-regression) may be done. Although intensive, analysis using individual-level data (Individual Participant Data) may also be done.
- •In case of unexplained heterogeneity, a pooled estimate using the random-effects model may be used. This estimate no longer estimates a single unknown effect but the average of the effects of the intervention in the populations represented by the studies. If precise enough (narrow confidence interval), this estimate, together with the prediction interval (a measure of uncertainty in the effect one might see in a particular context), can guide clinical and policy decisions.
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2. Detecting heterogeneity
3. Dealing with heterogeneity
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Declaration of No conflict of interest: Authors Cynthia Cordero and Antonio Dans do not have any conflict of interest related to this manuscript.
Authors’ statement: As authors of this article, we both conceived, developed, and finalized the manuscript. We thank our students and colleagues—they are the inspiration of this article, which is meant to guide readers on what to look for in a meta-analysis as a user and what to report as a doer. We thank our reviewers for their valuable comments, which we think made the article more informative and relevant. The process from conceptualization to the current version of the article required hours of literature review and drawing from our collective research and teaching experience. No funding or monetary support was needed. The article is the authors’ original work, has not been previously published, and is not under consideration for publication elsewhere.