educational problems, were used to expedite appropriate educational assistance. The study helped provide a foundation for a new approach to help parents raise children who are at risk for behavioral problems. Studies to examine the utility of these interventions are now underway with Federal support, including a recent grant from the Department of Education. This is the goal of research, to lead to the development of effective services and treatments. Again, we appreciate the opportunity to testify at this hearing. We would be happy to respond to your inquiries. [The prepared statement of Dr. Oldham follows:] UNITED STATES HOUSE OF REPRESENTATIVES SUBCOMMITTEE ON CRIMINAL JUSTICE. DRUG POLICY AND HUMAN RESOURCES DECEMBER 9. 1999 HEARING “DO CURRENT FEDERAL REGULATIONS ADEQUATELY PROTECT PEOPLE WHO PARTICIPATE IN MEDICAL RESEARCH?" Written Testimony of John M. Oldham, M.D. Professor of Clinical Psychiatry, College of Physicians & Surgeons, Columbia University Director, New York Psychiatric Institute B. Timothy Walsh, M.D. Professor of Psychiatry, College of Physicians & Surgeons, Columbia University Chairman Mica, members of the Government Reform Subcommittee on Criminal Justice, Drug Policy and Human Resources, I would like to thank you for the opportunity to testify today about this important topic. It has been approximately 25 years that Institutional Review Boards (IRB's) have been formally carrying out their functions. This is a time of unprecedented advancement in medical science, and it is also an appropriate time to review the federal regulations and the IRB's that are at their center. The federal regulations provide rules for institutional review boards (IRBs), which are based on a set of ethical principles outlined in a document known as the Belmont Report'. The 'The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, produced by The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 1979). federal research regulations include detailed regulatory requirements for all research, and mandate specific additional protections for children, prisoners, pregnant women and fetuses. Currently institutions such as New York Psychiatric Institute that conduct federally funded studies are required to enter into a Multiple Project Assurance (MPA) with the Office for Protection from Research Risks (OPRR), an agreement which governs research at that facility. Under an MPA, reporting mechanisms are established for unanticipated problems involving research risks and for suspension or termination of IRB approval of specific research protocols. OPRR provides oversight of research programs conducted under an MPA. It also conducts investigations of allegations of violations of human subject regulations. One area of the examination of IRBs and federal research regulation which could be considered is that their coverage is not universal. With the exception of FDA-regulated research, some nonfederally funded research may be conducted without the application of federal regulations. While New York Psychiatric Institute, like other major academic institutions, has chosen to apply the federal regulations to all of its research, regardless of whether the studies are federally funded, many studies conducted today fall outside the scope of the federal research regulations. The IRB serves an important and useful role in the system of protecting human research subjects. New York Psychiatric Institute has a highly committed and responsible IRB. As this committee is aware, the New York Psychiatric Institute was the subject of allegations filed with OPRR regarding a portion of a particular study carried out in 1995 at the Institute, and Dr. Walsh and I testified before the Subcommittee on Human Resources in June, 1998, about that study. A copy of that testimony is attached to today's testimony. OPRR conducted a lengthy and thorough investigation to determine whether NYPI complied with the detailed federal regulations that applied to the research. They were provided with extensive documentation of the study and its IRB review and oversight. They made multiple requests for additional information and received lengthy responses to detailed questions. In March 1999, a team of six OPRR staff and three outside consultants questioned NYPI investigators, IRB chairs and members, and institutional representatives at length and reviewed their decisions and actions in light of federal regulations. After 16 months of investigation, OPRR concluded that not only were there no deficiencies in the IRB's review of the research and the human subjects protections provided, it also commended the Psychiatric Institute's IRB: for its "detailed understanding of the specific requirements of the [federal] human subject regulations," for its members who are "enthusiastic and dedicated to the protection of human subjects" and have "the diversity, including consideration of race, gender and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects, as required under [federal] regulations," and for its "established procedures [for ensuring that] additional safeguards have been included in research to protect the rights and welfare of vulnerable subjects.” The study in question was one component of a larger study which sought to identify factors that contribute to the development of antisocial and violent behavior in young boys, a concern of pressing importance in our country today. It has been established in adults that violent behavior is correlated with low levels of a brain chemical called serotonin. Serotonin can be indirectly measured by blood tests after the administration of a drug called fenfluramine, a test for serotonin--much like a glucose tolerance test is a test for diabetes or a cardiac stress test is a test for heart irregularities. For many years prior to the study at NYPI, fenfluramine studies were a well-established mechanism for measuring serotonin. Researchers outside of NYPI had described experiences with more than 2,000 research subjects, including over 200 children and adolescents, who had participated in fenfluramine studies. At the time of the study in question, fenfluramine was FDA-approved for use in large daily doses for the treatment of obesity over a period of several months. Even after concerns about the drug's safety led to its withdrawal from approved use for such treatment-- something which did not occur until almost two years after the NYPI study was concluded-- the FDA still allowed it to be used in small, single-dose research studies since this had always been judged to be entirely safe, and indeed, the FDA continues to permit this use today. |