Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010

• Published in: JAMA : the journal of the American Medical Association 2017-05, Vol.317 (18), p.1854-1863
• Main Authors: Downing, Nicholas S, Shah, Nilay D, Aminawung, Jenerius A, Pease, Alison M, Zeitoun, Jean-David, Krumholz, Harlan M, Ross, Joseph S
• Format: Article
• Language: English
• Subjects: Biological products; Biological Products - adverse effects; Cohort Studies; Drug Approval; Drug-Related Side Effects and Adverse Reactions; Drugs; FDA approval; Food safety; Humans; Incidence; Management; Original Investigation; Pharmaceuticals; Product Surveillance, Postmarketing; Regulatory agencies; Risk; Safety; United States; United States Food and Drug Administration
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2017.5150

IMPORTANCE: Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. OBJECTIVES: To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. DESIGN AND SETTING: Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. EXPOSURES: Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. MAIN OUTCOMES AND MEASURES: A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. RESULTS: From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P