The Food and Drug Administration is under pressure to approve drugs faster, but researchers at the Yale School of Medicine found that nearly a third of those approved from 2001 through 2010 had major safety issues years after they were made widely available to patients.
Seventy-one of the 222 drugs approved in the first decade of the millennium were withdrawn, required a “black box” warning on side effects or warranted a safety announcement about new risks to the public, Dr. Joseph Ross, an associate professor of medicine at Yale School of Medicine and colleagues reported in the Journal of the American Medical Association . The study included safety actions through Feb. 28.
It took a median of 4.2 years after the drugs were approved for these safety concerns to come to light, the study found, and issues were more common among psychiatric drugs, biologic drugs, drugs that were granted “accelerated approval” and drugs that were approved near the regulatory deadline for approval.
Drugs ushered through the FDA’s accelerated approval process were among those that had higher rates of safety interventions. These approvals typically rely on surrogate endpoints, meaning that researchers measured something other than survival, such as tumor size, to determine whether the drugs worked.
“This [finding on surrogate endpoints] has the greatest relationship to policy today,” Ross says. “In the 21st Century Cures Act, there’s a push to have the FDA move to further support the use of surrogate markers … [but] they’re more likely to have concerns in the post-market setting.”
Former President Barack Obama signed the 21st Century Cures Act into law on Dec. 13. It offers ways to speed drug approval by pushing the FDA to consider different kinds of evidence beyond the three phases of traditional clinical trials. The new process has made some researchers worry that it will open the door for approvals of drugs that haven’t been adequately tested.
The FDA’s system for reporting drug- and device-related health problems is voluntary. The reports are not verified, and critics say this system is underutilized and filled with incomplete and late information. The FDA also monitors other available studies and reports to determine whether it needs to take action a particular drug.
FDA spokeswoman Angela Hoague said the agency is reviewing Ross’s findings.
“All too often, patients and clinicians mistakenly view FDA approval as [an] indication that a product is fully safe and effective,” said Dr. Caleb Alexander, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness who did not work on the study. “Nothing could be further from the truth. We learn tremendous amounts about a product only once it’s on the market and only after use among a broad population.”