Jill Wechsler
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As the Food and Drug Administration celebrated its 100th birthday in June, it unveiled a major initiative for overhauling
how it regulates clinical trials and protects participants in research studies. In outlining the plan for the Human Subject
Protection and Bioresearch Monitoring (HSP/BIMO) initiative at the annual meeting of the Drug Information Association (DIA),
Deputy Commissioner for Operations Janet Woodcock noted that it reflects the emergence of an "increasingly large, decentralized,
and global" research enterprise. She cited the need to respond to dramatic changes in the nature and conduct of clinical research
characterized by:
- a steady increase in the number of clinical trial studies and sites in the United States and abroad
- larger trials involving many small, individual sites
- proliferation of different electronic record-keeping methods and systems for data collection and processing
- more complex trial methods and designs
- greater participation of vulnerable subjects, including children
- increased use of contract research organizations (CROs) to manage studies
- more variation in institutional review board (IRB) structure, including centralized, free-standing, and for-profit entities
- increase in human specimens, requiring new policies for storage and handling
- more studies involving complex medical devices and combination products.
Woodcock regards this undertaking as an important component of the Critical Path Initiative, which highlights the need to
streamline and improve clinical research processes. By taking steps to safeguard study participants and ensure that trials
produce high-quality data, FDA also hopes to bolster public confidence in research activities and stem criticism of lax FDA
enforcement. Some observers have raised concerns that increased commercialization of human subject research has fostered unethical
recruitment practices, particularly in foreign trials. And allegations of research fraud related to clinical studies for Sanofi-Aventis'
antibiotic Ketek (telithromycin) have raised questions about FDA's research monitoring program.
Seeking coordination
From Thalidomide to Globalization
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FDA first began inspecting clinical trial sites in the 1970s, primarily to verify the accuracy and integrity of investigator
data (see sidebar "From Thalidomide to Globalization"). The importance of also protecting the rights and safety of research
subjects became more visible in the 1980s, following publication of the Belmont Report in 1979 and subsequent adoption of
the "Common Rule" by the Department of Health and Human Services and other federal agencies. That policy requires researchers
to obtain and document informed consent; provides special protections for children, women, and prisoners; and sets policies
for institutional review boards (IRBs) to oversee research proposals and operations.
The need to monitor a growing clinical research enterprise has generated different bioresearch monitoring (BIMO) programs
in each FDA Center. This has created a highly decentralized system and a variety of compliance programs for field inspectors
to follow when auditing investigators, sponsors, CROs, and IRBs. Now, the agency seeks to modernize and better coordinate
this program, noting a lack of resources to inspect every research site and a continued reliance on a paper-based system in
an automated world.
Over the past year, Woodcock and agency staffers have been assessing BIMO programs and identifying opportunities for improvement.
She notes a lack of databases and electronic information systems, as well as too few guidances for implementing good clinical
practices.
The announcement of the BIMO initiative was not news to many agency observers, as FDA has been discussing these problems during
the past year while moving forward with a number of changes in research policies and practices. The agency has issued guidances
on using centralized IRBs to oversee multicenter clinical trials and for establishing Data Monitoring Committees to better
ensure subject safety. Several information sheets for the research community were published at the beginning of this year,
and a new draft guidance involving safeguards for children in clinical trials was published in May 2006.
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