The FDA Is Approving Drugs After Fewer Trials and Providing Less Information to the Public
By OREGON STATE UNIVERSITY
While experts agree on the importance of
fast-tracking potentially life-saving treatments, especially for critical
conditions such as cancer, they say their findings point to a need for greater
transparency around how drugs receive approval.
For many drugs that have been tested in
multiple clinical trials, pharmaceutical companies are only required to share
the results from two trials, leaving questions about why they chose those two
for submission and what happened in the other trials, study co-author Veronica
Irvin said.
“We’re not saying that cancer drugs need a
lot more studies; just that they should show all the results or trials that are
completed,” said Irvin, an associate professor in OSU’s College of Health. “It
doesn’t mean they wouldn’t get approved, but it means we’d have a more complete
picture.”
21st Century Cures Act and Its Impact
The research team focused on the period after
implementation of the federal 21st Century Cures Act, passed with bipartisan
support in 2016 and meant to accelerate approval of new medicines so patients
could gain access to life-saving drugs that would otherwise take years to
become available.
As part of that law, the FDA relaxed some
standards to allow treatments for priority health conditions such as cancer to
be approved with fewer supporting studies, and placed less emphasis on
randomized clinical trials, allowing pharmaceutical companies to rely on
surrogate markers instead of clinical outcomes in certain cases. Surrogate
markers are used as substitutes when the direct clinical outcomes take a long
time to study, and they should be related to the clinical outcomes.
For example, Irvin said, it might take years
of following patients in a long-term clinical trial to determine if a drug
reduces their risk of a heart attack, so measuring the surrogate marker of
blood pressure enables the drug to move through the approval process more
quickly. However, reduced blood pressure does not assure reduced risk of death
from heart disease, she said.
Comparative Analysis of Drug Approvals
The studies, published in the Journal of the American Medical Association Network Open and Health Affairs Scholar, reviewed FDA approvals for
novel drugs in 2017 and 2022 to determine how many trials were used to evaluate
each drug prior to receiving approval from the FDA.
Researchers also looked at the availability
of drug trial results on the public-facing ClinicalTrials.gov,
a database maintained by the National Institutes of Health that
patients can use to learn more about drugs they may be prescribed.
Of the 37 drugs approved by the FDA in 2022,
24 (about 65%) were approved based on a single study. Four of the 37 drugs
(about 11%) reported three or more studies before approval. Roughly half of the
413 studies available for analysis were classified as randomized clinical
trials, while results were publicly posted on ClinicalTrials.gov for only 103
of the 413 studies.
In 2016, prior to the Cures Act, only four of
20 novel drugs (20%) were approved based on a single trial.
In the Health Affairs Scholar article,
researchers found that of the 46 novel drugs approved in 2017, 19 (41%) were
approved based on results from a single study — though the drugmakers conducted
an average of 2.2 studies per drug, including 165 studies for the popular
weight-loss drug Ozempic.
Despite drugmakers completing an average of
5.82 studies per drug prior to FDA approval, results were disclosed on
ClinicalTrials.gov prior to approval for only 1.42 studies on average.
Public Accessibility of Trial Results
That doesn’t necessarily mean the FDA is
denied access to those full results, Irvin said, but the public cannot read the
results until they are posted publicly.
For 33 of the 46 medications (72%), at least
one brand-new result was posted on ClinicalTrials.gov within nine months after
approval had been given, but in many cases the studies had been completed prior
to FDA evaluation.
“Everything is supposed to be transparent
with this FDA process,” Irvin said. “The purpose of ClinicalTrials.gov was to
have a way for the non-scientific community to access the trials and their
results, in a way that people can understand.”
When the FDA states that it has reviewed
drugmakers’ two submitted studies, consumers are missing information about how
many other studies were conducted, what those results showed, and why those
specific two studies were chosen for evaluation, Irvin said.
“We want doctors and patients to be able to
see the whole picture,” she said.
References: “Review of Evidence Supporting
2022 US Food and Drug Administration Drug Approvals” by Robert M. Kaplan,
Amanda J. Koong and Veronica Irvin, 8 August 2023, JAMA Network Open.
DOI: 10.1001/jamanetworkopen.2023.27650
“Food and Drug Administration novel drug
decisions in 2017: transparency and disclosure prior to and 5 years following
approval” by Robert M Kaplan, Amanda J Koong and Veronica Irvin, 19 July
2023, Health Affairs Scholar.
DOI:
10.1093/haschl/qxad028
Lead author on both papers was Robert Kaplan
from Stanford University, with co-author Amanda Koong, a medical student at the
McGovern School of Medicine in Texas.