10 Percent of New Drugs Approved Without Meeting Primary Efficacy End Points

Findings seen for 21 drug approvals between 2018 and 2021, with only one-third needing postmarketing studies

By Lori Solomon HealthDay Reporter

TUESDAY, Feb. 14, 2023 (HealthDay News) — From 2018 to 2021, 10 percent of drugs approved by the U.S. Food and Drug Administration were based on pivotal studies with null findings for one or more primary efficacy end points, according to a research letter published online Feb. 13 in JAMA Internal Medicine.

James L. Johnston, M.D., from Brigham and Womenâ€™s Hospital in Boston, and colleagues used the Drugs@FDA database to determine the frequency of and rationale for FDA approval of drugs based on pivotal trials with null findings for one or more primary efficacy end points.

The researchers found that between 2018 and 2021, the FDA approved 210 new drugs, of which 10.0 percent (21) were based on pivotal studies with null findings for one or more primary efficacy end points. These 21 approvals were for 21 unique clinical indications, 11 were first in class, 10 received orphan designation, and 13 received an expedited review designation. Overall, the 21 drug approvals were supported by 56 pivotal trials, but five approvals were supported by only one pivotal trial. The 56 trials included 74 primary efficacy end points, of which more than one-third (27) were null. These 27 end points included 13 clinical outcomes, seven surrogate markers, four clinical scales, and three composite end points. For one-third of drugs, the FDA required or requested postmarketing studies to address the null end point or a related clinical end point.

“Greater transparency regarding FDA decision-making could increase clinician, patient, and payer confidence in novel drugs and improve clinical use,” the authors write. “Timely completion of postapproval studies addressing areas of clinical uncertainty is also necessary.”

One author disclosed appearing as an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen.