• Alexandra B Spicer, Alexandre B Cavalcanti, and Fernando G Zampieri.
• Department of Medicine: Allergy, Pulmonary and Critical Care Division; UW School of Medicine and Public Health.
• Curr Opin Crit Care. 2024 Oct 1; 30 (5): 427438427-438.

Purpose Of ReviewTo date, most randomized clinical trials in critical care report neutral overall results. However, research as to whether heterogenous responses underlie these results and give opportunity for personalized care is gaining momentum but has yet to inform clinical practice guidance. Thus, we aim to provide an overview of methodological approaches to estimating heterogeneity of treatment effects in randomized trials and conjecture about future paths to application in patient care.Recent FindingsDespite their limitations, traditional subgroup analyses are still the most reported approach. More recent methods based on subphenotyping, risk modeling and effect modeling are still uncommonly embedded in primary reports of clinical trials but have provided useful insights in secondary analyses. However, further simulation studies and subsequent guidelines are needed to ascertain the most efficient and robust manner to validate these results for eventual use in practice.SummaryThere is an increasing interest in approaches that can identify heterogeneity in treatment effects from randomized clinical trials, extending beyond traditional subgroup analyses. While prospective validation in further studies is still needed, these approaches are promising tools for design, interpretation, and implementation of clinical trial results.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

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