Jill Wechsler

Regulating and monitoring clinical trials has become an increasingly complex and challenging business for the Food and Drug Administration and other government agencies that fund and oversee biomedical research. There are more clinical studies in the United States and abroad, many involving multiple sites, complex study designs, and more research participants. Many studies deal with complex biotech therapies, medical devices, and combination products and call for greater participation of vulnerable subjects, including children.

Efforts to better manage the flood of data from these research programs is generating a number of electronic record keeping and processing methods and systems that, in turn, require new rules. These developments impose new challenges for IRBs and research institutions, which continue to evolve to meet new requirements.

Regulatory overhaul

Who Will Lead SACHRP?

To cope with these developments, FDA has launched an initiative to update its Human Subject Protection and Bioresearch Monitoring (HSP/BIMO) program to reflect this larger, more decentralized global research enterprise. Announced by Deputy Commissioner for Operations Janet Woodcock in June [View from Washington, August 2006], the project aims to safeguard study participants and ensure that trials produce high-quality data, while also bolstering public confidence in clinical research activities and in FDA's oversight.

An HSP/BIMO steering committee headed by Woodcock has established working groups to tackle key issues, which include:

• Updating inspection and compliance policies to establish a more risk-based approach to selecting research sites for inspection and better defining what constitutes quality clinical data.
• Revising investigator disqualification procedures to facilitate the removal of unethical researchers more quickly while ensuring due process.
• Clarifying adverse event reporting policies to help IRBs deal with the overwhelming volume of adverse event reports they now receive and advising investigators more clearly on what information has to be filed.
• Revising FDA's internal governance of BIMO programs across centers to establish a more unified system.
• Finalizing a proposed rule for ensuring that sponsors maintain ethical standards in foreign clinical studies not conducted under IND rules.

Changing roles

Linda Tollefson, FDA assistant commissioner for science and deputy director of the Office of Science and Health Coordination, who reports to FDA Associate Commissioner for Science Norris Alderson, now is more involved in the BIMO initiative as the acting director of FDA's Good Clinical Practice Program. Tollefson also directs FDA's Offices of Women's Health and Orphan Product Development and chairs the agency's internal IRB, which oversees human subject research conducted by FDA scientists.

David Lepay, who has headed the Good Clinical Practice Program (GCPP) for the past decade, remains a special assistant to Alderson, but now is working out of FDA's San Diego office and focusing more attention on international clinical research policy and programs. A main project for Lepay has been to develop a final rule on FDA acceptance of data from foreign clinical trials, which is moving through the review process. Lepay is also involved with efforts to extend harmonized standards on good clinical practices (GCPs) beyond the United States, Europe, and Japan as a way to achieve common oversight approaches in the developing world. To this end, Lepay is working with the World Health Organization and conducting educational programs in Asia and South America on research ethics policies and practices.

Lepay also seeks to finish a number of FDA guidances and policies under development at FDA. In recent months, the agency has issued guidance documents on IRB registration, use of data monitoring committees, and dealing with falsification of information and exceptions from informed consent for emergency research. In addition to a final rule on foreign clinical data, Lepay is involved with updating policies to assure the integrity of clinical information in computerized data systems and on reporting adverse events to IRBs.