protections to human subjects. Moreover, a common policy would result in a more efficient regulatory scheme that would be advantageous to both the federal government and to IRBs. We believe that a shared policy between FDA and NIH/OPRR will improve the ability of IRBs to comply with federal policies, regardless of whether the research protocol is regulated by NIH/OPRR or by FDA. We also support the OIG's recommendation that NIH/OPRR and FDA involve other departments in the Department of Health and Human Services, as well as non-federal parties such as IRBs, sponsors, and clinical investigators, in development of a shared policy. Congressional efforts in the 1970s established an excellent system of oversight. The United States continues to be an international leader in both oversight of human subjects participating in clinical trials and biomedical research and development. However, WIRB supports a review that seeks to address changes in the research environment and to provide consistency in oversight of clinical trials, whether funded by the federal government or the private sector. The central issue is to ensure human subject protection through the use of an efficient and consistent oversight policy. Independent IRBs have responded to the legitimate needs of the medical research community by providing an independently based assurance of human subject protection. As independent IRBs, we play a critical role in protecting rights of research subjects as well as facilitating the development of new medical therapies. We thank you for the opportunity to present our views and we look forward to continuing to work with Congress, HHS and FDA to protect the rights of human subjects who choose to participate in clinical research. Mr. SNOWBARGER. Thank you, Dr. Bowen. Next is Dr. Timothy Walsh from the Institutional Review Board for the New York Psychiatric Institute. Dr. Walsh, welcome to the committee. Dr. WALSH. Mr. Chairman, and distinguished members of the committee, I'm here with Dr. John Oldham, who is chairman of our Institute. We very much appreciate the opportunity to testify about the critical issue of protection of human subjects in research. In my remarks, I'd like to highlight a few important issues about the study that have already been raised in the remarks this morning. The research study that we've been asked to discuss was focused on violence and anti-social behavior among youth. The recent deadly shootings at schools across our country and the rising tide of youth suicide are tragic reminders that we must do more to understand and to prevent violence among young people. The purpose of the study conducted at Psychiatric Institute was to learn more about the origins of such problems. The broad goal of the project was to identify psychological, environmental, and biological factors which increase a child's risk of developing anti-social behavior. The hope was that, if successful, this research would lead to targeted interventions to help prevent these difficulties from developing in youngsters at risk. In its review of this proposal, our IRB carefully considered both the scientific merits of the study and the potential risks and benefits to the subjects, and concluded that approval of the study was consistent with Federal and State regulations, as well as with accepted ethical principles. The study was carried out and to the best of our knowledge, it was concluded without any harm to any participant. The fenfluramine study was one part of a larger project which involved 126 boys with an older brother who had been adjudicated a juvenile delinquent. Because the research involved numerous meetings with families over several years, the investigators sought potential participants living in proximity to our Institute, which is at the northern end of Manhattan adjacent to the Bronx, and so they obtained information on eligible families from the family courts of those two boroughs. The overwhelming majority of individuals in this system, and, therefore, the overwhelming majority of participants in these studies were from minority ethnic groups. The investigators recognized that such work should be more broadly based and this study was planned as the first phase of a larger research program. Consistent with this plan, the investigators later submitted to the IRB and to NIH a proposal to conduct similar research in a larger and more geographically and ethnically diverse sample. One major concern which has been raised about this study is its use of fenfluramine. There is strong evidence that the brain chemical, serotonin, plays an important role in the regulation of violent behavior. And by giving participants a single oral dose of fenfluramine, a pill, on one occasion, and then measuring changes in hormone levels in the blood, investigators could obtain an indirect measure of brain serotonin function. The procedure is very analogous to the widely used glucose-tolerance test. At the time the study was proposed, fenfluramine had been on the market as Pondimin for approximately 20 years for obesity, and was commonly used in research to assess brain serotonin function. The IRB thoroughly reviewed the potential risks, and concluded they were minor at most. Fenfluramine studies were carried out in 36 youngsters and to the best of our knowledge, none experienced significant problems. Concern about the use of fenfluramine subsequently developed because of the association between its use as Redux and heart valve abnormalities. These concerns first emerged in 1997, well after the conclusion of the Psychiatric Institute study in 1995. The concerns about valve damage are about obese individuals who took fenfluramine for months, almost always in combination with another medication, phentermine, the Fen-Phen combination. FenPhen was not used in the studies at Psychiatric Institute, only a small single dose with a pill of fenfluramine. There is no indication that this use of fenfluramine is associated with any risk of cardiac damage. In closing, we would emphasize our belief that research on the development and the prevention of violent behavior among young people is critical for our country. Studies in this sensitive area, as in all research, must be carried out with the strictest attention to safeguards for all the participants. We welcome the opportunity to provide information to the committee, and we'll be happy to answer your questions. [The prepared statement of Dr. Walsh follows:] UNITED STATES HOUSE OF REPRESENTATIVES "INSTITUTIONAL REVIEW BOARDS: A SYSTEM IN JEOPARDY?" Written Testimony of B. Timothy Walsh, M.D. Co-Chair, New York Psychiatric Institute Institutional Review Board, 1990-1997 Professor of Psychiatry, College of Physicians & Surgeons, Columbia University John M. Oldham, M.D. Director, New York Psychiatric Institute Professor of Clinical Psychiatry, College of Physicians & Surgeons, Columbia University Overview of the Research and the IRB Review The research study which we have been asked to discuss was focused on violence and antisocial behavior among youth. The recent deadly shootings at schools across our country and the rising tide of youth suicide are tragic reminders that we must do more to understand and to prevent violence among young people. The purpose of the study conducted at New York Psychiatric Institute (NYPI) was to learn more about the origins of troubled behavior among young people, in particular, the development of antisocial behavior. At present, no effective treatment exists for such behavior, and the broad goal of the project was to identify factors-psychological, environmental, and biological-which increase a child's risk of developing such problems. The hope was that, if successful, this research would lead to targeted interventions to help prevent these difficulties from developing in youngsters at risk. After receiving the investigators' initial application, the NYPI Institutional Review Board (IRB) requested additional materials to evaluate both the scientific merits of the study and the potential risks and benefits to subjects. These issues were carefully considered, as was the process of seeking consent from and providing information to the participants and their families. During its review, the IRB applied the governing federal regulations as well as the underlying ethical principles. Time does not permit a comprehensive discussion of all the issues involved, but we have previously provided the Subcommittee with extensive documentation which was submitted to the Department of Health and Human Services' Office for Protection from Research Risks. Who Participated The fenfluramine study was one component of a larger, foundation-funded project which involved 126 boys with an older brother who had been adjudicated a juvenile delinquent. The investigators provided the IRB with strong scientific evidence that such younger brothers were at significant risk for the development of antisocial behaviors. The study of risk factors is important in many fields of medicine. For example, individuals in families at high risk for heart disease may be studied to determine how factors such as elevated cholesterol contribute to the later development of the heart disease. The investigators believed that a study of youngsters at risk for developing antisocial behavior would increase understanding of the factors that contribute to this problem, and thereby provide leads toward interventions to prevent it. The IRB was convinced that the proposed study had scientific merit. Because the research involved numerous meetings with these families over several years, the investigators sought potential participants living in proximity to NYPI. Officials of the Family Courts of Manhattan and the Bronx provided information on eligible families from the court records, in accordance with New York law. The overwhelming majority of individuals in this court system and, therefore, the overwhelming majority of participants in these studies were from minority ethnic groups, primarily African-American and Hispanic. The investigators |