A systematic review of 12 randomized controlled trials on a new antihypertensive drug shows a pooled relative risk reduction of 25%. However, the Cochran Q test yields p = 0.003 and I² = 78%. The most appropriate interpretation of these findings is:

• A The drug reduces cardiovascular events significantly across all populations
• B A fixed-effects model should be used as data come from RCTs
• C The I² value of 78% indicates publication bias, requiring a funnel plot correction
• D There is substantial heterogeneity; pooling may be inappropriate without exploring its source ✓

Explanation

An I² value >75% indicates substantial statistical heterogeneity in a meta-analysis; the significant Cochran Q (p < 0.05) confirms true between-study variability rather than chance. In such scenarios, a simple pooled estimate is potentially misleading, and sources of heterogeneity (subgroup analyses, meta-regression) should be explored. I² measures heterogeneity, not publication bias (which is assessed by funnel plots and Egger's test); fixed-effects models are inappropriate when heterogeneity is substantial regardless of study design.

Reference: Park's Textbook of Preventive and Social Medicine, 27th ed.

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