Nature Medicine 12, 153 (2006)
Published online: 31 January 2006; | doi:10.1038/nm0206-153
Earlier drug tests on people could be unsafe, critics warn
Meredith Wadman
Washington, DC
The FDA has set new guidelines to speed up drug development.
The US Food and Drug Administration (FDA) in January announced a
significant loosening of the rules that govern at what stage
experimental drugs can first be tested in people. The changes are
intended to speed up drug development, but critics say they might expose
research participants to unwarranted danger.
The FDA's announcement comes as the embattled agency, which has been
without a permanent leader for more than three of the last five years,
is trying to salvage its tarnished public image. On 18 January, the
agency also unveiled a long-awaited overhaul of drug-labeling
guidelines, intended to make the labels more accessible to doctors and
consumers. Those won wide praise, but also raised a thorny legal issue
involving lawsuits against drug makers.
The new rules on drug development will allow scientists to test small
doses of experimental drugs in people before full-scale clinical trials
begin, and before standard in vitro and animal tests are complete. The
idea is that companies would be able to identify failing candidates and
jettison them before they invest millions of dollars in costly clinical
trials. The data from these early human studies might also help them
design smarter trials for promising drugs.
A parallel set of guidelines on manufacturing will allow smaller
companies and academic labs to make modest amounts of experimental drugs
without the financial investment needed to meet industrial-scale
manufacturing standards. Under previous guidelines, only companies with
substantial resources were able to make drugs for human clinical trials.
With the manufacturing changes, academic researchers will get much more
information about these compounds early on, says Janet Woodcock, the
agency's deputy commissioner for operations. "And the industrial sector
will have a much broader range of compounds to evaluate coming out of
academic labs," she adds.
Much of the response to the changes has been optimistic.
"I think this is a very positive, realistic step by the agency," says
Raymond Woosley, chief executive officer of the Arizona-based C-Path
Institute, a nonprofit that aims to speed drug development. "With small
companies, it may make the difference between the life and death of the
company or of the potential therapy," he says.
Woosley and others see the changes as a step toward fixing a broken
model of drug development.
Since 1995, the number of new drug candidates brought to the FDA for
approval has fallen dramatically (see graph) even as the drug industry
has doubled its investment in drug development. About nine out of ten
drugs that appear safe and effective in laboratory and animal tests fail
in subsequent clinical studies.
The new rules would allow scientists to give low doses of an
experimental drug for seven days or less to a small number of
individuals. These 'exploratory' studies would not test the drug's
safety or effectiveness, but would assess how it acts in the body and is
metabolized. Based on how rapidly it is broken down, for instance,
scientists could quickly identify and discard inappropriate candidates.
The drug giant Pfizer, in consultation with the FDA, in September 2005
conducted a pilot study in eight volunteers to evaluate the effects of a
candidate anticoagulant. Testing the drug early in people shaved five
months off the development time, says Liam Ratcliffe, senior vice
president of global clinical research and development at Pfizer. Equally
important, he says, the study allowed the company to determine the
dose-response relationship, a key piece of information for deciding
whether and how to move forward with a drug candidate.
Still, not everyone is convinced that the changes are completely positive.
"It's no secret that the FDA is too cozy with the drug industry, so I'm
concerned for those who will be receiving these experimental drugs,"
Republican Senator Charles Grassley said in a statement.
"The whole purpose of preclinical studies is to ensure that the drug is
safe enough to put in humans," adds Sidney Wolfe, a physician and
director of health research at the Washington, DC–based advocacy group
Public Citizen. "If you do fewer safety checks, there are more
possibilities that the drug will not be safe enough when it goes into
people," he says.
But that criticism is misplaced, say supporters of the new rules. "If
you're Sid Wolfe, you only see the increased risk," says Woosley. "But
if you're a patient who is sitting there waiting for a medicine to solve
their health problem, you want people taking acceptable risks as often
as possible."
Separately, the agency also came under fire for announcing—in
conjunction with the new drug-labeling guidelines—that people injured by
FDA-approved drugs that meet the agency's labeling requirements should
not be able to sue the drug's makers in state courts. Companies have
argued that the labeling changes open them to increased legal liability,
and that they should in return receive more explicit federal protection
from lawsuits.
Scott Gottlieb, the agency's deputy commissioner for medical and
scientific affairs, says state courts don't have the scientific
knowledge to second-guess the FDA's decisions. "I would say this is not
a new policy position for the agency," he says. But critics say the FDA
is protecting industry at the expense of consumers.
Published online: 31 January 2006.
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