BACKGROUND: Most randomized controlled trials (RCTs) and meta-analyses of RCTs examine effect modification (also called a subgroup effect or interaction), in which the effect of an intervention varies by another variable (e.g., age or disease severity). Assessing the credibility of an apparent effect modification presents challenges; therefore, we developed the Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN). METHODS: To develop ICEMAN, we established a detailed concept; identified candidate credibility considerations in a systematic survey of the literature; together with experts, performed a consensus study to identify key considerations and develop them into instrument items; and refined the instrument based on feedback from trial investigators, systematic review authors and journal editors, who applied drafts of ICEMAN to published claims of effect modification. RESULTS: The final instrument consists of a set of preliminary considerations, core questions (5 for RCTs, 8 for meta-analyses) with 4 response options, 1 optional item for additional considerations and a rating of credibility on a visual analogue scale ranging from very low to high. An accompanying manual provides rationales, detailed instructions and examples from the literature. Seventeen potential users tested ICEMAN; their suggestions improved the user-friendliness of the instrument. INTERPRETATION: The Instrument for assessing the Credibility of Effect Modification Analyses offers explicit guidance for investigators, systematic reviewers, journal editors and others considering making a claim of effect modification or interpreting a claim made by others.
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