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.
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 the market.
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.