Nearly one-third of novel therapies have a post-market safety event, according to a study published in JAMA.1 These safety events occur most frequently with biologics, psychiatric agents, and accelerated and near-regulatory deadline approvals.
The design of most pivotal clinical trials makes it difficult to identify uncommon or long-term safety signals. This study characterized post-marketing safety events of new agents approved by the US Food and Drug Administration (FDA) between 2001 and 2010.
The cohort study evaluated 222 novel biologics (17.6%) or pharmaceuticals (82.4%). The therapeutic areas included cancer and hematology (21.2%); infectious disease (16.7%), cardiovascular, diabetes, and hyperlipidemia (11.7%); autoimmune, musculoskeletal, and dermatology (7.7%); genitourinary and renal (7.7%); psychiatry (6.8%); other (20.7%).
Priority review was granted to 34.7% and accelerated approval for 12.6%. The total median time of regulatory review was 311 days (interquartile range [IQR], 203-485 days). The majority of agents were reviewed for 200 to 399 days (40.5%).
Post-market safety events affected 71 (32%) of novel agents, which resulted in 3 withdrawals. The median time to first post-market safety event was 4.2 years (IQR, 2.5-6.0 years).
There were 61 incremental box warnings added to 43 agents. Safety communications were sent regarding 44 different agents.
Psychiatric agents were most likely to result in a safety event at 10 years (60.0%), whereas anticancer agents were least likely (21.4%; P = .006). Biologic agents were more likely to result in a post-market safety event compared with pharmaceuticals.
Post-market safety events were more likely to occur with agents that received accelerated or near-regulatory deadline approvals compared with other approval types. Priority review and orphan status were not associated with frequency of post-market safety reports.
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The authors wrote that “collaboration between the FDA and other stakeholders is necessary to develop and maintain an effective system for detecting postmarket safety events.”
- Downing NS, Shah ND, Aminawung JA, et al. Postmarket safety events among novel therapeutics approved by the US Food and Drug Administration between 2001 and 2010. JAMA. 2017;317:1854-63. doi: 10.1001/jama.2017.5150