EMA pivotal trials often excluded kidney, liver and heart disease without stating why

Design

Review of regulatory documents and pivotal trial eligibility criteria

Population

24 EMA centrally authorised products (2022–2024), 44 pivotal trials

Primary outcome

Exclusion of special populations and documented justification

Effect

Pregnancy excluded in 16/24; cardiovascular or hepatic disease 13/24; renal impairment 10/24; age alone 1/24

This review examined 44 pivotal trials behind 24 medicines centrally authorised in the EU between 2022 and 2024, looking at whether pregnant or breastfeeding people, older adults and people with comorbidities were eligible, and whether exclusions were scientifically justified in regulatory documents.

Pregnancy and breastfeeding were the most common exclusions (16 of 24 products), followed by cardiovascular disease or hepatic impairment (13 of 24) and renal impairment (10 of 24). Exclusion by age alone was rare (1 of 24). Fifteen products excluded more than one group. Pregnancy exclusions were usually backed by preclinical data; comorbidity exclusions often were not, and broad 'investigator judgement' exclusions were common.

The consequence for prescribers is that the patients most likely to receive a new drug, older people with kidney, liver or heart disease, are often those in whom it was least studied.

• Check whether your patient's comorbidities were excluded from the pivotal trials before relying on the headline efficacy and safety.
• Look for dedicated renal and hepatic impairment pharmacokinetic studies in the label.
• Start low and monitor closely when prescribing a new drug to a patient outside the trial population.
• Report adverse effects in these groups; post-marketing data are often the only evidence.

Why it matters

It shows the gap between who is studied and who is treated is often a choice, not a necessity.

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