Study: “Safety Events” Common for Drugs and Biologics After FDA Approval

Treatments should be monitored throughout their life cycles, authors advise

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.

Sources: Medical Xpress; May 9, 2017; and JAMA; May 9, 2017.