Special Populations in Pivotal Clinical Trials: Eligibility and Supporting Evidence for Exclusion in EMA ‐Authorised Medicines

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Evidence on the efficacy and safety of medicines supporting marketing authorization is largely derived from randomized controlled trials, yet these trials often exclude populations likely to use the medications in clinical practice. This study assessed eligibility of special populations, defined as pregnant and breast‐feeding individuals, elderly individuals, and individuals with comorbidities, in pivotal clinical trials supporting centrally authorized products in the European Union between 2022 and 2024. It also examined whether exclusions of the special populations were supported by scientific justifications in the form of prior clinical or nonclinical evidence documented in regulatory sources. Among 24 products supported by 44 pivotal trials, pregnant and breast‐feeding individuals were most frequently excluded (16/24 products), followed by individuals with cardiovascular disease or hepatic impairment (13/24 products) and renal impairment (10/24 products). Exclusion of elderly individuals based on age alone was uncommon (1/24 products). Of the 24 products, 15 excluded more than one special population. While exclusions of pregnant and breast‐feeding individuals were largely supported by preclinical evidence suggesting safety concerns, those related to comorbidities were often not accompanied by prior evidence justifying exclusions. Broad exclusion criteria based on investigator judgment were also common. These findings reveal variation in how exclusion criteria are justified across special populations in regulatory documentation and suggest an opportunity for greater transparency and consistency in documenting the scientific and ethical justification for these criteria in clinical trials.