Effect modification goes by many other names: “subgroup effect,” “statistical interaction,” and “moderation,” to name a few. Regardless of what it’s called, the existence of effect modification in the context of an individual study means that the effect of an intervention varies between individuals based on an attribute such as age, sex, or severity of underlying disease. Similarly, a systematic review may aim to identify effect modification between individual studies based on their setting, year of publication, or methodological differences (often called a “subgroup analysis”).
As many as one-quarter of randomized controlled trials (RCTs) and meta-analyses examine their findings for potential evidence of effect modification, according to a paper by Schandelmaier and colleagues published in the latest edition of CMAJ. However, it is not uncommon for claims of effect modification to be later proved spurious, which may negatively affect the quality of care in those subgroups of patients. Potential sources of these claims range from simple random chance to issues with selective reporting and misguided application of statistical analyses.
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In “Development of the Instrument to assess the Credibility of Effect Modification in Analyses (ICEMAN) in randomized controlled trials and meta-analyses,” the authors present a novel tool for evaluating the presence of a potential modifier. While several sets of criteria have been developed in the past for this purpose, the ICEMAN is the first to be based on a rigorous development process and refined with formal user testing.
First, the authors conducted a systematic survey of the literature to ensure a comprehensive understanding of the previously proposed criteria for evaluating effect modification. Thirty sets were identified, none of which adequately reflected the authors’ conceptual framework. Second, an expert panel of 15 members was identified randomly from a list of 40 identified through the systematic survey. These experts then pared down the initial list of 36 candidate criteria to 20 required and eight optional items. After developing a manual for its use, the authors tested the instrument among a diverse group of 17 potential users, including authors of Cochrane reviews and RCTs and journal editors using a semi-structured interview technique.
Schandelmaier, S., Briel, M., Varadhan, R., Schmid, C.H., Devasenapathy, N., Hayward, R.A., Gagnier, J., ... & Guyatt, G.H. 2020. Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and meta-analyses. CMAJ 192:E901-906.
Manuscript available at the publisher's website here.