The Food and Drug Administration is under pressure from the Trump
administration 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 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millennium were withdrawn, required a “black box” warning on side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, Yale professor Dr. Joseph Ross and his colleagues
reported in JAMA on Tuesday. The study included safety actions through Feb.
“While the administration pushes for less regulation and faster
approvals, those decisions have consequences,” Ross said. The
Yale researchers’ previous studies concluded that the FDA
approves drugs faster than its counterpart agency in
Europe, and that the majority of pivotal trials in drug approvals
involved fewer than 1,000 patients and lasted six months or less.
It took a median time period of 4.2 years after the drugs were
approved for these safety concerns to come to light, 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 said. “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 act into law on Dec. 13.
Among other things, 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
more unsafe approvals.
“I’m actually sympathetic to the idea that there are ways in
which the FDA can be more streamlined and do a quicker job,” said
Dr. Vinay Prasad, a hematologist-oncologist and professor at
Oregon Health and Sciences University who did not work on the
study. “The one place you don’t want to cut a corner is safety
and efficacy prior to coming to market.”
Given criticism of the FDA’s mostly voluntary system for
reporting new drug- and device-related health problems, it’s
possible there are more unknown adverse side effects of which
neither the FDA nor the general public is aware. 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 on a particular drug.
FDA spokeswoman Angela Hoague said the agency is reviewing Ross’
“In general, the FDA does not comment on specific studies, but
evaluates them as part of the body of evidence to further our
understanding about a particular issue and assist in our mission
to protect public health,” she said.
Regardless, some observers may find the proportion of safety
concerns alarming and others may be breathing a sigh of relief
that it’s not higher, Ross said.
“That’s the million-dollar question: What’s the right amount?
What’s the appropriate level of safety concerns to have
identified only once the product is out of the gate?” said Dr.
Caleb Alexander, co-director of the Johns Hopkins Center for Drug
Safety and Effectiveness. He did not work on the study.
Surprisingly, drugs approved in under 200 days were less likely
to have safety issues, which the authors speculate could be
because “some approval packages provide clearer evidence of
safety, allowing for more rapid regulatory approval.”
The study included market withdrawals of three drugs: the
anti-inflammatory drug Bextra, a drug called Zelnorm that treats
irritable bowel syndrome and the psoriasis drug Raptiva. Bextra
and Zelnorm were withdrawn over cardiovascular risk, and Raptiva
was withdrawn because of increased risk of a rare and fatal
infection that damages material in the brain.
Still, it’s important to keep in mind that the post-approval
safety issues cover the spectrum from relatively minor to
serious, Alexander said. A good next step would be to dig into
the extremely serious safety problems, determine whether the FDA
could have flagged them sooner and how they might have been
missed, he said.
Alexander commended the researchers, saying their study
“underscores the importance of surveillance” after a drug has
been launched. This helps researchers find new problems — and new
benefits — associated with a drug.
“All too often, patients and clinicians mistakenly view FDA
approval as [an] indication that a product is fully safe and
effective,” he said. “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.”
KHN’s coverage of prescription drug development, costs and
pricing is supported in part by the Laura and John
Read the original article on Kaiser Health News. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation Copyright 2017. Follow Kaiser Health News on Twitter.
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