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 ŎIG 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. 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 clinics and physicians in private practice to participate in clinical research. Moreover, primarily because of federal clinical testing requirements for new products, clinical trials, especially industry-funded ones, now focus on multi-site studies involving thousands of human subjects. Without doubt, this increase in research conducted at multiple sites has allowed a greater understanding of the benefits and risks of a drug or device before marketing. Now more than ever, IRBs must have sufficient staff, expertise, and technical support to meet the demands of the changing research environment. II. RECOMMENDATIONS FOR IMPROVING THE CURRENT SYSTEM WIRB believes that the present IRB regulations can be effective in providing human subject protection, but because of the dramatic change in the research environment, it is appropriate to pause and reevaluate the process at this time. As the OIG draft report noted, there is no indication that the current regulatory system has resulted in harm to research subjects. However, we believe that even the perception of problems in the system will undermine public confidence and could adversely affect the advances in medical research. Therefore, the recommendations made by the OIG would be helpful in maintaining our country's leadership in the protection of the rights of research subjects. A. IRB Registration WIRB supports the concept of IRB registration. At present, NIH/OPRR and FDA lack basic information on the existence, location, and make-up of IRBs, and they must rely on IRB information that is either provided by sponsors or investigators in their applications to FDA or provided by institutions in assurance documents with NIH/OPRR. WIRB believes that requiring such basic information would help to improve protection of human subjects by allowing the agencies to manage their oversight efforts more effectively and to fully communicate with IRBs. B. Information Sharing WIRB also strongly supports the OIG's recommendation concerning "information sharing." There have been situations where certain sponsors or investigators were displeased with an IRB's review and switched to a new IRB without informing the new IRB about the previous review. While the majority of sponsors and investigators have demonstrated integrity during the IRB review process, WIRB believes that it is important that these parties be obligated to disclose any prior disapprovals of the research. Further, so that an IRB can effectively monitor the progress of research studies, copies of all FDA and OPRR inspection reports concerning clinical studies which the IRB has approved should be provided to the reviewing IRB. Finally, because clinical investigations are already subject to government and sponsor auditing and monitoring, we believe that extending the required "information sharing" between the parties would be helpful to the IRB's oversight of research without adding more oversight to an already overworked clinical investigator. C. Ethical Considerations: Structure of Board Concerns have been raised about the ability of IRBS to act independently of the sponsors or the institution to which they are affiliated. The issue of independence applies equally to institutional IRBs as well as independent IRBs. We strongly support formal studies that analyze actual conflicts of interests in all IRBS. Without knowing whether conflicts of interest bias IRB decisions, it would be difficult to implement meaningful regulatory change. It appears that the best way to control conflicts of interest is through organizational structures that eliminate the financial interest of the board members in their decision making. WIRB already practices this through separation of its administrative and review functions. Moreover, WIRB strongly supports the OIG's recommendation that IRBs should include more non-scientific and non-institutional members. WIRB highly values the important role that these members play in protecting human subjects and understands the OIG's view that present regulations requiring merely one non-scientific member and one non-institutional member may not be adequate. WIRB also strongly supports the OIG's recommendations for increased board member training. IRB members need initial and continuing education to understand and stay current with the complex scientific, regulatory, and ethical issues in today's research environment. WIRB also supports an increase in investigator training, both inside and outside of institutions. There are few educational resources available for investigators. and this contributes to the problem of investigator non-compliance with regulations. D. Common Policy Shared by FDA and NIH/OPRR We strongly support the concept of a "shared" policy between FDA and NIH/OPRR in oversight of IRBs. As discussed previously, regulatory mechanisms employed by FDA and NIH/OPRR vary. FDA oversight of IRBs is included in the process of evaluating the safety and efficacy of drugs, devices, and biologics. Its approach is more compliance-based, focusing on inspection of IRB research sites. In contrast, NIH/OPRR oversight of IRBS focuses on assurances. Each of these systems incorporates valid oversight tools. However, we agree with the OIG that similar oversight policies and close collaboration would strengthen the |