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Almost one-third of FDA-approved therapeutics had postmarket safety events

Nearly one-third of the 222 new pharmaceuticals and biologics approved by the FDA from 2001 through 2010 were subject to a postmarket safety event such as issuance of a safety communication, boxed warning, or withdrawal, according to research recently published in JAMA.

“Given the inherent limitations of premarket clinical evaluation for drug safety, there may be opportunities to enhance patient safety if factors associated with postmarket safety events could be identified at the time of FDA approval,” Nicholas S. Downing, MD, department of medicine, Brigham and Women’s Hospital, Boston, and colleagues wrote. “Additionally, monitoring efforts could focus on at-risk drugs to facilitate earlier detection of safety problems and prevent patients from unnecessary harm.”

Researchers conducted a cohort study of 222 novel therapeutics approved by the FDA between Jan. 1, 2001, and Dec. 31, 2010, and watched for developments through Feb. 28, 2017. Therapeutics indicated for the treatment of cancer and hematology were most commonly studied (47, or 21.2%), followed by those for infectious disease (37, or 16.7%) and those for CVD, diabetes and hyperlipidemia (26, or 11.7%). Of the 222 novel therapeutics, 77 (34.7%) had received priority reviews, 62 (27.9%) had been designated orphan drug status and 28 (12.6%) had received accelerated approval. The median total review time was 311 days (interquartile range [IQR] = 203-485), with total review time less than 200 days for 54 (24.3%) of the drugs studied, between 200 and 399 days for 90 (40.5%), 400 days or longer for 76 (34.2%) of them, and not available for 2 (0.9% of them. Also, 23.6% of the therapeutics were near–regulatory deadline approvals.

Downing and colleagues found there were three withdrawals, 61 boxed warnings and 59 safety communications during a median follow-up period of 11.7 years (IQR = 8.7-13.8 years), affecting 32% of the drugs studied. The median time from approval to first postmarket safety event was 4.2 years (IQR = 2.5-6 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 a multivariable analysis, postmarket safety events were significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06), those receiving accelerated approval (IRR = 2.2; 95% CI, 1.15-4.21), and those with near–regulatory deadline approval (IRR = 1.9; 95% CI, 1.19-3.05); events were significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87).

“The high frequency of postmarket safety events highlights the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle,” Downing and colleagues wrote. “These findings should be interpreted cautiously but can be used to inform ongoing surveillance efforts.”

Researchers suggested future research examine the dynamics between more rapid and near-regulatory deadline approval and drug safety.

These findings are particularly noteworthy given statements by President Donald Trump during his campaign and in his first address to a joint session of Congress where he called for accelerating the “slow and burdensome approval process” at the FDA. In statements prior to being nominated to run the FDA, Scott Gottlieb, MD, expressed support for speeding up the approval process for generic medications, but not for removing efficacy standards for original medications. – by Janel Miller

Disclosure: Downing reports no relevant financial disclosures. Please see the study for a full list of the other authors’ relevant financial disclosures.