Are there ethical or data integrity concerns for foreign clinical trials used for FDA drug approvals? Are the research standards as high as in the United States? What are the challenges facing developing countries in conducting clinical trials? Two recent reports discuss the issue. One report is by the Inspector General of the U.S. Department of Health and Human Services on “Challenges to FDA’s Ability to Monitor and Inspect Foreign Clinical Trials.” It was reported on in an article by Gardiner Harris of the New York Times. The report noted that FDA isn’t able to conduct foreign inspections at the same level as at domestic clinical trial sites and that trials were dramatically increasing in places such as Latin America that lack strong regulatory oversight. The report recommends “FDA should continue to explore ways to expand its oversight of foreign clinical trials.”
The second report I learned about when I attended a session at the recent meeting of the Drug Information Association (DIA). The session discussed the challenges of international clinical research, particularly in developing countries. In a report of the Multi-Region Clinical Trials (MRCT) project, problems were discussed and practical recommendations suggested for improving the quality of clinical trials in resource-deprived countries.
I was impressed with the panelists who presented to DIA on the MRCT project. The focus was on how clinical trials could be conducted in developing countries with resource challenges. How could the rights, safety, and welfare of research participants be protected? The session was chaired by Mildred Solomon, EdD, Associate Clinical Professor of Medical Ethics at the Harvard Medical School. She discussed the formation of the MRCT project and the report that resulted. Other panelists included Allan Johansen, DVM, Susan D’Amico, and Janet Wittes, PhD. According to the report the MRCT project was:
“Initiated by Pfizer, the Multi-Regional Clinical Trial (“MRCT”) Project began with a Summit Meeting in July 2009 to identify ways to enhance the planning and conduct of multi-regional trials and the integrity of these trials. The Project has involved experts from large and small companies, clinical research organizations (CROs), non-industry sponsors of research (such as participants from the National Institutes of Health), non-industry researchers and bioethicists, and others. The discussions have focused on opportunities to enhance research ethics, ensure respect for study subjects, strengthen fairness and equity in clinical trials, protect subject safety, and identify other opportunities to improve MRCTs involving the developing world.”
The project formed work groups to cover five areas:
1. Efficiency and quality of ethical review
2. Data & safety monitoring
3. Site selection and investigator
4. Monitor performance
5. Transparent contract amendments
The report discusses the problems in each area and offers some solutions. For example, work group one proposed to “Include an ethics section accompanying each/certain protocols (to help ethics committee review the proposal, as needed).” Work group 4, which focused on monitor performance, proposed to: “Establish a comprehensive set of recognized and expanded core competencies for monitors.”
The report concluded by noting:
“This Report has focused on outcomes that sponsors and CROs have the ability to impact and, thereby, improve research ethics and data integrity in their own operations or through collaboration. Since there is already broad acceptance of foundational ethical principles, the next important step is to ensure operational alignment with those principles.
Predominantly, the MRCT Work Group proposals focus on achieving that alignment through greater professional competence of the many players who must contribute to the global research enterprise. Professionalism is essential to the ethical conduct of clinical research. Just as scientifically unsound research is unethical, so too is research conducted in a manner that cannot ensure the integrity of the science, the quality of the data, and respect for and safety of research participants. Assuring all individuals engaged in research are properly qualified through education and experience is a theme throughout this Report.”
The report also noted that developed countries and the pharmaceutical industry need to assist with resources to achieve this goal. This is certainly an important point. However, the devil is always with the details. Finding a way to finance improvements may prove difficult.
My own viewpoint is that we should stop referring to “foreign” clinical trials. Clinical research is globalized and we need a strong international component. Not all of the answers are in the United States and we would do well to listen to those from outside our borders, particularly those from the developing world. To me, referring to clinical trials from outside the U.S. as “foreign” infers that they are inferior to trials conducted in the U.S. I don’t think that is always the case. Why don’t we call them “international” or even “multi-regional” trials instead? If we view international research as something that is a shared responsibility then perhaps there would be less concern over “foreign” clinical trials.