In the latest installment of the ongoing saga "Congress Discovers Drug Safety," lawmakers have started focusing on the pharmaceutical
industry's willingness to skirt the rules. They've noticed that companies frequently fail to complete promised Phase IV clinical
studies, and that opportunities to enroll in clinical trials have not been publicized as required. The result has been new
proposals to beef up FDA's enforcement powers, expand clinical trial registries, and require broader disclosure of study results.
Industry has responded with its own voluntary disclosure programs, but these efforts may be too little, too late to calm legislators,
regulators, and critics.
Push for Phase IV
The tone was set by a report on FDA's drug safety oversight program, issued by Congress' Government Accountability Office
(GAO) in April. GAO wants FDA to have the authority to require additional Phase IV studies of specific safety concerns, in
addition to giving the agency more tools to get companies to complete promised research. And last month, a House panel added
a provision to FDA's 2007 appropriations bill clarifying its authority to pull a drug from the market if the sponsor fails
to meet post-approval study commitments.
The GAO recommendation and similar proposals before Congress reflect industry's poor track record on post-approval study commitments.
The latest FDA report to Congress on Phase IV activity was issued in March and covered studies completed by September 30,
2005. It showed that 1,200 studies had been promised, but manufacturers had not even started 65 percent of them, and fewer
than 200 had been completed.
There are legitimate reasons for some delays and failures to complete: FDA officials explain that some studies turn out to
be less valuable than anticipated, and that it's difficult to recruit patients for controlled trials after a drug comes to
market. Public perception, however, is that sponsors will agree to any future study request from FDA just to get a drug on
FDA published a guidance in February clarifying Phase IV study timelines and disclosure policies, which officials hope will
placate critics. The agency also has signed up consultant Booz Allen Hamilton to evaluate the study commitment process and
obstacles to completing promised research. Even so, more proposals for strengthening FDA's post-approval study oversight are
expected in July from the Institute of Medicine panel reviewing FDA's drug safety program.
These recommendations may prompt Congress to stiffen penalties for companies that fail to meet research promises, as it considers
legislation to require companies to provide more information on clinical trials and their outcomes. Senators Charles Grassley
(R-IA) and Chris Dodd (D-CT) are backing a bill to require companies to register active trials of treatments for cancer and
other life-threatening diseases, with fines for those who don't.
The FDA Modernization Act of 1997 already requires sponsors to list active trials on the National Library of Medicine's (NLM)
clinicaltrials.gov/ Web site. Investigators affiliated with the National Cancer Institute have complied fully, but many commercial sponsors have
not—or have omitted important information, such as sponsor or drug name, indication, enrollment criteria, and study locations.
FDA's Office of Special Health Issues, which administers this program, managed to boost the listing rate up to 67 percent
for a group of cancer studies initiated in 2005, but it's still a pretty poor performance.
Registration is expected to improve because a group of leading medical journals, including the Journal of the American Medical Association, now require trial registration prior to enrollment in order for study results to be considered for publication. The policy
went into effect last September and expands registration requirements to more studies on more drugs.