Among more than 200 new pharmaceuticals and biologics approved by the FDA from 2001 through 2010, nearly one-third were affected by a post-marketing “safety event,” such as the issuance of a boxed warning or safety communication, according to a new study published in JAMA.
Joseph S. Ross, MD, MHS, of the Yale University School of Medicine, and colleagues examined safety events (a composite of withdrawals due to safety concerns; FDA issuance of incremental boxed warnings added during the post-marketing period; and FDA issuance of safety communications) for all new therapeutics approved by the FDA between January 2001 and December 2010, with follow-up through February 2017.
During this period, the FDA approved 222 new therapeutics (183 drugs and 39 biologics). The authors identified 123 new post-marketing safety events (three product withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years, affecting 32% of the new therapeutics. The median period from approval to the first post-marketing safety event was 4.2 years, and 31% of the new therapeutics were affected by a post-marketing safety event at 10 years.
In a multivariable analysis, post-marketing safety events occurred significantly more often among biologics (incidence rate ratio [IRR], 1.93; P = 0.03); among therapeutics indicated for the treatment of psychiatric diseases (IRR, 3.78; P < 0.001); among those given accelerated approval (IRR, 2.20; P = 0.02); and among those with near-deadline approval (IRR = 1.90; P = 0.008). Safety events were significantly less frequent among therapeutics with regulatory review periods of less than 200 days (IRR = 0.46; P = 0.02).
Most of the pivotal trials that form the basis for FDA approval for therapeutics (both drugs and biologics) enroll fewer than 1,000 patients, with follow-up periods of six months or less, which may make it challenging to identify uncommon or long-term serious safety risks, the authors note.
These risks may become evident when new therapeutics are used in much larger patient populations and for longer periods during the post-marketing period. Post-marketing safety events can change how these therapeutics are used in clinical practice and can inform patient and clinician decision making, the authors write.
“The high frequency of post-market safety events highlights the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle,” the researchers conclude.