Differences Between Trial Populations and Approved Label Populations of New Drugs in the United States and Europe (2012 to 2023) : A Cross-Sectional Study

Drugs are approved when their benefits outweigh their risks based on the results of clinical trials. It remains unclear how often regulatory agencies extrapolate or restrict the approval compared with the trial.

To analyze the differences in the characteristics of enrolled patients between trial populations and approved label populations in the United States, European Union (EU), and Switzerland for new drugs.

Cross-sectional study.

Inclusion of all new drugs that were approved by all 3 agencies from 2012 to 2023 and comparison of trial populations with the approved label populations.

Aggregated and anonymized patient data included in trial data and approved label information were analyzed.

The eligibility criteria of the trial population with the approved label population in the United States, EU, and Switzerland were compared for 5 categories: age, disease subtype, disease severity, patient fitness, and prior therapy. Linear regression models were performed, and the proportions of more extensive and more restrictive evaluations were determined.

263 drugs (278 indications) were included in the study cohort. Overall, approved label populations were broader than trial populations and more pronounced in the United States compared with the EU and Switzerland. Patient fitness was the most often at variance with 276 approved indications (99.3% [95% CI, 99.2% to 99.4%]) in the United States and EU, and 275 (98.9% [CI, 98.8% to 99%]) in Switzerland, followed by disease severity with 143 approved indications (51% [CI, 49% to 54%]) in the United States, 119 (43%, [CI, 40% to 46%]) in the EU, and 111 (40% [CI, 37% to 43%]) in Switzerland.

Reporting of trial eligibility criteria lacked uniformity.

Postapproval trials and surveillance are indicated for drugs for which broadening has occurred to ensure safety and efficacy for patient subpopulations that were not included in the trials.

Kaiser Permanente Institute of Health Policy; Swiss National Science Foundation (SNSF).