In responding to the OIG report, FDA deputy commissioner and chief medical officer Janet Woodcock pointed out that BIMO inspections are just one narrow component of the agency's broader efforts to protect human participants in clinical research. More important is FDA's careful scrutiny of proposed research protocols, a process that usually leads to protocol revisions to ensure human subject safety before the trial begins. And even though FDA visits only a small fraction of sites, "the possibility of an inspection helps keep all parties aware of their responsibilities," Woodcock noted.

Because its resources for site inspections are limited, FDA is looking to apply risk-based approaches to all its field inspection programs, including BIMO activities. The aim is to target FDA oversight to those sites and operations involved in more vital or difficult research activities. This approach also involves establishing quality systems for BIMO activities that provide incentives for sponsors to ensure adherence to good clinical practices.

Registration & disclosure

The details for expanding the existing clinical trial registration program [ClinicalTrials.gov/] were uncertain until FDAAA was finalized and still require considerable explanation to be fully implemented. Registration now extends to all trials for drugs, biologics, and medical devices beyond Phase I intended to support a market application to the agency—and not just those for products that treat serious and life-threatening conditions. Trial listings have to fully describe each study, including name of intervention, start and completion dates, eligibility criteria, target number of subjects, and expected outcome measures. Listings also must provide information on site location, contacts, and updates on recruitment status.

Each listing will have a protocol identification number to facilitate tracking and eventual links to a results database. NIH will begin to establish this data bank in 90 days with information from FDA's application review process. This may include clinical trial data considered by advisory committees or posted in review packages. NIH will link to drug labels posted on its product label database, plus to publications found in its Medline Plus database.

Within a year, the results data bank will expand to include a listing of basic data elements for approved drugs: study participant demographics, trial outcomes, and any agreements between sponsors and investigators limiting results disclosure. During this period, FDA also will work with NIH to post additional information on serious and frequent adverse events of registered test drugs.

The legislation gives FDA, NIH, and sponsors three years to explore ways to provide more complete trial results information to the public. Issues to be decided are whether trial results should be posted for medical products never approved by the FDA; whether there should be nontechnical lay summaries of trials, as well as technical summaries; how much detailed protocol information would be required; time frames for submitting results information (e.g., if results of early trials have to be submitted before filing a market application); and how to register studies supporting new product uses.

FDA will hold a public meeting to discuss these issues and will conduct a pilot project on how best to verify that sponsor information is accurate and not false or promotional. Sponsors want clear rules and an effective information system because they will face fines and legal action for failure to comply with registration requirements.

Jill Wechsler is the Washington editor of Applied Clinical Trials,(301) 656-4634 jwechsler@advanstar.com