Post-market Safety Issues Not Obvious in Review: Study

FDA researchers say that although drugs approved with a Boxed Warning or priority review are more likely to experience post-marketing safety events, other information provided during the FDA drug review that is easy to quantify is generally not associated with such post-marketing events. “It appears that these post-marketing events are not discernible during a pre-marketing review and therefore might not be avoidable using current review data,” the researchers write in the journal Drug Safety.

The study used an internal agency database listing every new small molecule drug submitted to CDER on or after 11/21/97 and approved and commercially launched before 12/31/09. The researchers looked at 219 new molecular entities for post-marketing Boxed Warnings or withdrawal from the market due to safety concerns. In the sample, 30 received Boxed Warnings by 7/31/16 and 11 were withdrawn for safety reasons.

“Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing Boxed Warning or safety withdrawal,” the authors write. “However, we do find that new drugs approved with either a Boxed Warning or priority review are more likely to experience post-marketing Boxed Warnings. Furthermore, drugs approved with Boxed Warnings tend to receive post-marketing Boxed Warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a Boxed Warning are 3.88 times more likely to receive a post-marketing Boxed Warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing Boxed Warning.”