An examination of pharmacological and biological therapeutics approved between 1996 and 2012 revealed that the number of Food and Drug Administration–approved therapeutic agents given black box warnings skyrocketed in the wake of the 2004 withdrawal of Merck’s rofecoxib (Vioxx) from the market.
During this time, there were 522 novel therapeutics approved, including 441 pharmacological and 81 biological products, with 180 (136 pharmacological and 44 biological) receiving a black box warning. Premarket warnings were issued for 105 products, postmarket warnings were issued for 50 products, and 25 had both pre- and postmarket warnings associated with them. In total, there were 89 postmarket boxed warnings, with 11 withdrawals, most of which (81%) occurred after 2004, when the FDA launched initiatives to strengthen drug safety surveillance, Christine Cheng, Pharm.D., and her colleagues said in a report in JAMA Internal Medicine (2014 Aug. 15 [doi: 10.1001/jamainternmed.2014.4854]).
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Black box warnings issued to FDA-approved medications have increased since 2004.
"Our study demonstrates that boxed warnings are common, affecting more than one-third of recent drug approvals. ... Our findings that half of biological products had boxed warnings is consistent with literature suggesting that biologic products pose a greater risk of serious adverse events compared to other drug types," wrote Dr. Cheng, of First Databank in San Francisco, and her colleagues.
A proposed rule issued by the FDA in June could undermine that communication of risk using the boxed warning, according to Dr. Sidney Wolfe, senior adviser at Public Citizen’s Health Research Group, Washington, D.C.
In an editorial accompanying Dr. Cheng’s report, Dr. Wolfe noted that the draft guidance would allow drug companies that "believe that the FDA-approved drug labeling information overstates the risks of their drug to tell physicians that the risks are, in fact, lower," adding that the draft guidance "may encourage companies to promote the supposed evidence of lower risk in a peer-reviewed article directly to physicians without the FDA ever having been informed, so that the agency can review the data" (2014 Aug. 15 [doi: 10.1001/jamainternmed.2014.4547]).
Dr. Wolfe called on the FDA to maintain current regulatory requirements that would have a company report evidence to the FDA first in support of risk reduction and get the label changed that way.
"Off-label risk reduction is a misguided approach," he said.
Dr. Cheng is employed by First Databank, a commercial drug knowledge vendor. No other authors of the research or the editorial reported any financial disclosures.