of the members of this subcommittee or their staff on our activities as we move forward. Mr. SNOWBARGER. Mr. Grob. Mr. GROB. Yes. Thank you, Mr. Snowbarger. I am concernedI know Chairman Shays said he wasn't concerned-about the affects of the title change that happened between the draft report and the final report but I think I'm concerned about it now because of the gist of some of the comments that have been made here. And I would like to in parting emphasize that we stand by everything that we said in those draft reports. We offered up some language that we felt would be more conducive to getting to discussing these results. But since I won't be around when the next panel meets, I don't want anyone to forget these final words that the change to that language was not a steering away in any way from the conclusions of our study, of the findings of our study, about the inadequacy of the system that we have, or the jeopardy of that system. We stand by that. The findings are in there. And I just want to really make that very clear so that the discussions about it won't be off the mark. Mr. SNOWBARGER. Dr. Ellis. Mr. ELLIS. I think that we stand poised at this time to finish the job that we started 30 years ago in protecting human subjects formally and which has been evolving ever since. And it is time to establish a prevailing ethic across the land that irrespective of funding sources for the research, you don't do something to or with someone for the purpose of obtaining generalizable knowledge without asking their consent and without making sure that a group of unbiased observers-an IRB-reviews it ahead of time. Mr. YESSIAN. I would just offer the simple point that the IRB system has done many good things over the years and is based fundamentally on system of trust. There's much that's very good about that. A good part of our critique is that along with the trust must go some verification. So how do we have a system that has appropriate degrees of verification, along with a system of trust that's there. I think the seriousness of the issues warrants that. Mr. SNOWBARGER. Thank you, gentlemen, very much. We appreciate your input into this hearing and with that I think we're ready to go on to panel two. So we'll have a little brief interlude here while we get panels shifted around. Before the members of panel two get too settled, we're going to have you rise again and take an oath so you might want to just remain standing for a minute. In this second panel, we're going to have Dr. Angela Bowen from the Western Institutional Review Board; Dr. Timothy Walsh, Institutional Review Board of the New York Psychiatric Institute; and he's accompanied by Dr. John Oldham, who is the director of the New York Psychiatric Institute; Dr. Bert Spilker, who is senior vice president, Scientific and Regulatory Affairs for the Pharmaceutical Research and Manufacturers of America; Dr. Robert Levine, professor of medicine at Yale University School of Medicine, and he's speaking on behalf of the American Association of Medical Colleges; then Dr. Moreno, who's professor of biomedical ethics, the director for the Center of Biomedical Ethics, University of Virginia; finally, Dr. Paul Appelbaum, the American Psychiatric Association. [Witnesses sworn.] Mr. SNOWBARGER. Note for the record that all the witnesses responded in the affirmative. And with that, Dr. Bowen. STATEMENTS OF ANGELA BOWEN, M.D., PRESIDENT, WESTERN INSTITUTIONAL REVIEW BOARD, OLYMPIA, WA; B. TIMOTHY WALSH, M.D., CO-CHAIR, INSTITUTIONAL REVIEW BOARD, NEW YORK PSYCHIATRIC INSTITUTE, ACCOMPANIED BY JOHN OLDHAM, M.D., DIRECTOR, NEW YORK PSYCHIATRIC INSTITUTE; BERT SPILKER, PH.D., M.D., SENIOR VICE PRESIDENT, SCIENTIFIC AND REGULATORY AFFAIRS, PHARMACEUTICAL RESEARCH AND MANUFACTURERS OF AMERICA; ROBERT J. LEVINE, M.D., PROFESSOR OF MEDICINE, YALE UNIVERSITY SCHOOL OF MEDICINE, ON BEHALF OF THE AMERICAN ASSOCIATION OF MEDICAL COLLEGES; JONATHAN D. MORENO, PH.D., PROFESSOR OF BIOMEDICAL ETHICS, DIRECTOR OF THE CENTER FOR BIOMEDICAL ETHICS, UNIVERSITY OF VIRGINIA; AND PAUL S. APPELBAUM, M.D., AMERICAN PSYCHIATRIC ASSOCIATION Dr. BOWEN. Thank you, Mr. Chairman. The Western Institutional Review Board commends the committee for its interest in human subject protection, and as president of Western, I am pleased to present our views concerning the oversight of Institutional Review Boards and the Inspector General's proposals. Western was privileged to participate in the OIG's study and to review the draft report. Western was established in 1968 and is the oldest and the largest of the independent boards. This 30 years of experience has afforded us the opportunity to know the present oversight process intimately, and especially in the FDA arena. Since the IRB regulations were implemented 20 years ago, biomedical research has changed dramatically. The expansion of technology and regulatory focus on multi-site studies for product approvals has caused the number of clinical trials to increase dramatically. This has necessitated increased staff, board expertise, and technical support to meet these needs. We have worked diligently to adapt to these changes. While we believe that the present IRB regulations continue to be effective in providing human subject protection, it is appropriate that we should pause and re-evaluate the process at this time because even the perception of problems in the system will undermine public confidence. The OIG has made several recommendations that we support. The recommendation to require IRBS to register with FDA and/or OPRR would improve protection of human subjects by allowing these agencies to manage their oversight efforts more effectively. It would also aid IRBS in communicating with each other and sharing information. Therefore, Western strongly supports IRB registration. While the overwhelming majority of sponsors and investigators have demonstrated high integrity during the IRB review process, we believe it is important that these parties be obligated to inform the IRB of any prior disapprovals. Further, so that an IRB can effectively monitor the progress of research studies, it should be provided copies of all FDA and OPRR inspection reports. Finally, be cause clinical investigations are already subject to auditing and monitoring by other parties, information sharing between these parties and IRBS could be extremely helpful. Concerns have been raised about the ability of IRBS to act independent of sponsors or the institution to which they are affiliated. This issue of independence applies equally to institutional IRBs and to independent IRBS. We believe it is best to minimize these potential conflicts of interest through appropriate corporate or institutional structure that eliminates financial interest as part of the ethical review process. For example, through separation of administrative and review functions. We also support the OIG's recommendation that IRBs should include more non-scientific and non-institutional members and that all members should be adequately trained. We highly value the important role that these non-scientific members play in protecting human subjects. This composition, however, does require a very structured board member education program. We agree with the OIG that similar oversight policies between FDA and OPRR would strengthen the protection of human subjects. A common policy would result in a more efficient regulatory scheme that would improve the ability of IRBs to comply with Federal regulations. America continues to be the international leader in both protection of human subjects and in biomedical research and development. And although congressional efforts in the 1970's established an excellent system of oversight, your review is needed to address changes in the research process and to provide consistent continuing oversight. The central issue for IRBs is to ensure the protection of human research subjects, using efficient and consistent review processes. We thank you for the opportunity to present our views and we look forward to continuing to work with you to protect the rights of human research subjects. [The prepared statement of Dr. Bowen follows:] Statement of Dr. Angela J. Bowen President, Western Institutional Review Board Before the Subcommittee on Human Resources Hearing On "Institutional Review Boards: A System in Jeopardy?" June 11, 1998 Western Institutional Review Board® (“WIRB*") commends the Committee for its interest in human subject protection and, as President of Western Institutional Review Board, I am pleased to present our views concerning the present system of oversight covering institutional review boards ("IRBs") and our proposals to address future human subject protections. WIRB is the oldest and largest of the independent boards. It was established in 1968 and has operated continuously since that time. Our work is primarily Food and Drug Administration ("FDA")-regulated research, and the majority of our clients are small hospitals and clinical investigators who do research in private settings. We also serve as part of the University of Rochester's IRB system. I. PRESENTATION OVERVIEW The Office of the Inspector General (“OIG”) of the Department of Health and Human Services ("HHS") has conducted an extensive study of IRBs over the past year. This study involved the voluntary participation of a number of IRBs, both institutional and independent, and has resulted in the drafting of four reports. WIRB was one of the IRBs interviewed by OIG and was privileged to review the draft reports. A. The History and Function of the IRB System The OIG's draft report entitled “Institutional Review Boards: A System in Jeopardy" contains an excellent history of IRBs in the scientific review process. While separate regulations govern federally-funded research and FDA-regulated research (i.e., research conducted to support FDA approval of new drugs, medical devices, and new food substances), the IRB responsibilities are the same. First, IRBs are responsible for an initial review of the research plan presented by the clinical investigator. Without IRB approval, the investigator cannot commence clinical trials. The initial review encompasses the research protocol, the informed consent document to be signed by subjects, any advertisements to be used in recruiting subjects, and any other relevant documents. IRBs are responsible for ensuring that the research meets specific regulatory and ethical requirements. The risks to human subjects must be reasonable in relationship to the anticipated benefits, and the risks must be minimized. The selection of subjects must be equitable and justified. In addition, IRBs must ensure that the informed consent document clearly provides the information necessary for the potential subject to make a decision about whether or not to participate in the research, ensure that advertisements to recruit human subjects are not misleading, and ensure that there are adequate protections for the subjects, especially vulnerable subjects. After the IRB approves the research study, it is then responsible for providing continuing review of the research. The continuing review includes review of all study amendments and reports of unexpected adverse experiences to ensure that the risk-benefit ratio remains acceptable. The FDA and NIH/OPRR regulations require at least yearly review. The FDA has oversight jurisdiction concerning research conducted as part of its product approval process, while the Office of Protection from Research Risks (“OPRR”), which is located within the National Institutes of Health (“NIH”), has oversight jurisdiction concerning federally-funded research. However, the two federal agencies approach oversight very differently. The FDA relies on an inspection process. FDA inspects IRBs, research sponsors, and research investigators. In its inspection of IRBS, FDA reviews IRB records, examines written procedures, and audits the research protocols and informed consent documents approved by the IRB. The NIH/OPRR relies primarily on assurances as its oversight mechanism. An "assurance" is a document in which the institution commits to compliance with Federal regulations for human-subject protections. To ensure compliance with an assurance once it is filed, OPRR can limit, suspend, or withdraw an institution's assurance or require special reporting. While OPRR has the authority to conduct investigations, these are usually conducted only in response to subject complaints, or as a result of other information indicating protection breakdowns. B. Recent Changes in the U.S. Research System Biomedical research has changed significantly since the IRB regulations were first implemented. At that time, most clinical trials involving human subjects were federally-funded and conducted within a single institution, by a single investigator. However, due to a number of factors, including an increase in regulatory requirements for premarket clinical testing, the number of research studies funded both by public and private sources has increased dramatically. These factors have encouraged medical -2 |