A Review of Methods Used to Assess Treatment Tolerability in Clinical Trials

Clinical tolerability refers to the degree to which patients can endure side effects without discontinuing treatment. Despite its frequent inclusion alongside efficacy and safety, tolerability in clinical trial publications is typically reported without a clear description of the methods used to assess it. We examined how treatment tolerability is evaluated in clinical trial publications. A targeted review of PubMed was conducted for publications of phase I, II, or III clinical trials published in 2024 and including tolerability in the title. Methods used to assess tolerability were extracted along with claims related to treatment tolerability. Of 339 identified publications, 154 met the inclusion criteria. Tolerability was referenced in the study objective or conclusion in ~95% of publications; fewer than half (n = 72 [46.8%]) reported these methods specifically in the methods section, and 38 (24.7%) reported tolerability findings. Over 85% of included studies implicitly or explicitly equated tolerability with safety. Clinical outcome assessments for tolerability were included in 22 trials (14.3%), with six incorporating preexisting clinical outcome assessment tools. Tolerability was predominantly described favorably, e.g., 'well tolerated' (n = 126 [85.7%]) or 'tolerable' (n = 17 [11.6%]). This review highlights opportunities to improve the scientific utility of tolerability data in clinical trial publications. Methods for assessing tolerability are often inconsistently described in publications and the terms safety and tolerability are frequently used interchangeably, which can obscure important distinctions. Future research should focus on developing methodological guidance and promoting clinical trial standards that clearly define how tolerability is assessed. Such advances will strengthen regulatory decision making, support clinical practice, and ultimately enhance patient care.