* Agency limiting use of "non-inferiority" clinical trials
* FDA being more selective with trials
* GAO concerned about "biocreep," or waning effectiveness
By Susan Heavey
WASHINGTON, Aug 27 The U.S. Food and Drug
Administration is cracking down on use of certain clinical
trials that show a new drug is no worse than another already on
the market, according to a government report released on
Such trials, known as non-inferiority trials, are used when
drugmakers want to compare their experimental product to
another one that is already FDA-approved. By showing that their
new drug is no worse than another, it can also show some
potential benefits such as fewer side effects.
But some critics question the benefit of approving a new
drug if it is simply shown to be no worse than something
already available to patients, especially if any additional
benefits are slight.
The report, conducted by the Government Accountability
Office and released by a bipartisan group of U.S. lawmakers,
found the FDA is taking a tougher line in the wake of industry
guidelines it issued in March.
"GAO's review of FDA's guidance showed that the agency has
become more conservative in allowing evidence from
non-inferiority trials to demonstrate a drug's effectiveness,"
the report said.
"First, FDA has limited the indications for which these
trials may be used. Second, the agency has also become more
rigorous in its review of evidence from non-inferiority
trials," according to the GAO, which analyzed such trials
looked at by the FDA between 2002 and 2009.
Additionally, the GAO said that repeatedly using
non-inferiority trials for certain kinds of drugs can lead to
"biocreep," in which successive approvals lead to drugs that
are less and less effective and eventually "no more effective
than a placebo."
Drugmakers can work with the FDA to choose from a variety
of clinical trial designs when developing a new therapy, but
other kinds of studies are not without their weaknesses.
Placebo-controlled trials only prove a drug is better than
a sugar pill -- that is, no treatment at all. Superiority
trials can show a therapy is better than another one, but can
take more time and be expensive, and are tougher to prove.
Proving a drug is actually no worse than another can also
be challenging. According to the GAO, "non-inferiority trials
are more complicated to design and their results are more
difficult to interpret than other types of clinical trials."
In March, FDA officials gave pharmaceutical manufacturers
advice on how to set up such trials. They can be used to prove
a drug is no worse than another in people with certain
infections, HIV, cancer and a few other conditions.
FDA objected to using non-inferiority trials in three cases
but ultimately approved the drugs: Merck & Co Inc's (MRK.N)
antibiotic Noxafil, Bristol-Myers Squibb Co's (BMY.N) HIV drug
Reyataz and Novartis' NOVN.VX anemia drug Exjade.
Fifteen other drugs were also approved using such trials
during 2002 through 2009, the GAO said.
Democratic lawmakers and Senate Finance Committee ranking
Republican Charles Grassley said in a statement the GAO's
finding shows the agency needs to proceed with caution when
evaluating such trials.
"The GAO report shows that these so-called non-inferiority
trials have often proved to be an inferior means of reviewing
the safety and efficacy of new drugs," said Representative Ed
Markey, a Democrat.
"While the FDA has made strides to improve evaluations
relying on non-inferiority trial data, the GAO report
highlights important limitations of non-inferiority trials."
FDA officials had no immediate comment on the report.
(Editing by Jerry Norton)