Study: FDA more likely to approve drugs for broader populations than EMA, Swissmedic

The US Food and Drug Administration (FDA) more frequently approved drugs for a broader population than the population in which the drug was studied in clinical trials, compared to the European Medicines Agency (EMA) and Swissmedic.

The study, which was published in the Annals of Medicine on Tuesday, evaluated 263 drugs that were approved by all three regulators for 278 different indications between 2012 and 2023, and compared the approved labels across five categories (age, disease subtype, disease severity, patient fitness, and prior therapy) against those evaluated in pivotal efficacy clinical trials. Their analysis found that US regulators were more likely to approve drugs for a broader population than the pivotal trial population than their European counterparts.

On average, all three agencies consistently approved drugs for a broader population than the trial populations, though FDA did so to a greater degree than the other regulators.

“Overall, approved label populations were broader than trial populations and more pronounced in the United States compared with the EU and Switzerland,” said the study authors. “For almost all drugs, broader approved label populations were seen for the category patient fitness in all 3 jurisdictions, followed by—but substantially less pronounced for—the category severity.” In the US, disease subtype was the least frequent category for broader population labeling, whereas for both the EU and Switzerland, age was the least frequent.

The researchers noted that it was far more unlikely that regulators restricted drug approvals to a population that were narrower than the population the drug was tested in. When the approved labeling was more restrictive, the authors found that it was most often restricted in terms of disease severity. For example, all three regulators approved Pfizer’s Braftovi (encorafenib) to treat patients with unresectable or metastatic melanoma, despite the pivotal trial enrolling some patients with locally advanced disease. The authors note that “restrictions based on subgroup analyses from the pivotal trials may be clinically appropriate, particularly when the subgroups are prospectively defined.”

The study also found that since 2016, FDA more frequently stated in its approval whether a drug was only indicated for adults or children and adults, which is a trend that researchers didn’t see with EMA approvals.

The researchers said that regulators often ask manufacturers for post-approval studies and surveillance of drugs approved for broader populations to ensure they can monitor the safety and efficacy of the products in subpopulations that the drugs were not tested on during clinical trials. They noted that it could be helpful to patients and physicians if regulators specified the extent to which the intended population of a drug matches the population in which it was tested in their drug approval.

The study was led by Kerstin Vokinger, a professor of law and medicine at the University of Zurich. Kaiser Permanente Institute of Health Policy and the Swiss National Science Foundation (SNSF) funded it.

AoM study

Study: FDA more likely to approve drugs for broader populations than EMA, Swissmedic

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