Preserving Public Trust: Accreditation and Human Research Participant Protection Programs (2001)

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APPENDIX B 118 Institutional/ An individual within the organization who has the responsibility for and authority Organiza- over the Human Research Protection Program (HRPP). tional Offi- cial Institutional Committees or boards that review research to ensure the protection of human Review subjects. The term includes, but is not limited to Institutional Review Boards (per Boards the Common Rule, 45 CFR 46), Central Review Boards, Independent Review (IRBs) Boards, and Cooperative Research Boards. Investigator Any individual who has responsibility for the design, conduct, management, or analysis of research. OrganizationThe entity with an HRPP. Organizations include but are not limited to corporations, private research entities, hospitals, universities, colleges, institutions, and governmental agencies. The functional arrangement of the HRPP may vary depending upon the type of organization. There are circumstances when the sponsor of the research (e.g., a pharmaceutical firm) may be the logical organization responsible for the HRPP. Research A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge, or, any experiment that involves an FDA-regulated test article. Research An individual about whom an investigator conducting research obtains (1) data Participant/ through intervention or interaction with the individual, or (2) identifiable private Subject/ information. The term “subject” is traditionally used in the literature and in Individual federal regulations to describe these individuals. In these Standards, the term Studied in “subject” will be used when the individual has not had an opportunity to consent Research to the research, “participant” or “research participant” will be used when the individual has consented to be part of the research, and “individual studied in research” will be used in a general sense when either may be the case. Sponsor Any entity that provides funds or other resources to support the research. This entity could be a federal agency, corporation, foundation, institution, or an individual. PROPOSED STANDARDS Section 1—Organizational Responsibilities 1.1 Protection of individuals studied in research must be a core value within the organization. COMMENTARY on Standard 1.1: Officials at the highest level of the governing body of an organization shall demonstrate to the organization the importance and value of the protection of the individuals studied in 

APPENDIX B 119 research by the development and support of a system of protections. This principle should become a basic tenet in the organization. 1.2 The organization must uphold ethical principles underlying the protection of individuals studied in research. COMMENTARY on Standard 1.2: The Belmont Report—Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1979) provides the philosophical basis for federal regulatory requirements. It should be noted that the Common Rule in many ways “operationalizes” the principles of the Belmont Report. 1.3 The organization must assure compliance with applicable legal requirements, including state and local laws. COMMENTARY on Standard 1.3: Organizations must comply with applicable federal regulations including the Common Rule, 45 CFR 46 (DHHS regulations), and 21 CFR 50 and 56 (FDA regulations) in all research conducted within the organization, regardless of the type of study, the source of funding, or the locale. 1.4 The organization must place the responsibility for the HRPP in an institutional official with sufficient standing and authority to ensure implementation and maintenance of the program. COMMENTARY on Standard 1.4: An organization demonstrates that the protection of individuals studied in research is a priority by investing overall responsibility in an institutional official with demonstrated authority in the organization, with access to adequate resources to support the HRPP, and without conflicting responsibilities in other aspects of the organization's activities. 1.5 Individuals responsible for the HRPP must identify and minimize conflicts of interest, and/or competing interests, which may compromise the goals of the HRPP. COMMENTARY on Standard 1.5: Institutional officials responsible for the HRPP should have clearly defined and institutionally supported responsibilities and authority in order to maximize their ability to achieve the goals stated in 1.5 without interference. 1.6 Any delegation of authority for the HRPP by the responsible institutional official (see 1.4 above) must be assigned to qualified individuals and documented in writing. 

APPENDIX B 120 COMMENTARY on Standard 1.6: Any delegation of authority by the responsible institutional official to others requires serious and thoughtful attention. The institutional official must only delegate authority to qualified individuals and in situations that enhance the HRPP. Written documentation of delegation of authority is required to promote clear communication among the organization's constituencies and to establish an organizational record. 1.7 The governance of the organization must assure the independence and credibility of the IRB(s). COMMENTARY on Standard 1.7: IRBs are one of several critical elements in an organization's HRPP. A successful HRPP requires that IRB members and chair(s) possess knowledge about ethical, regulatory, and institutional requirements. The IRB must be supported by the organization, which would necessarily exclude inappropriate influence by powerful officials, researchers, and potential funding sources. The IRB should have a clear mechanism for managing any influence that blocks or otherwise interferes with its functions. 1.8 The organization must have conflict of interest policies and must enforce those policies to minimize real, potential, or perceived conflicts from interfering with the protection of individuals studied in research. COMMENTARY on Standard 1.8: Organizations must have a mechanism to address real or perceived conflicts of interest that could interfere with the protection of individuals studied in research. Organizational policies need to define conflicts of interest, provide mechanisms for disclosure of conflicts, establish a process for evaluating whether a conflict of interest may interfere with protection of the individuals studied in research, and institute actions to manage conflicts of interest determined to have the potential to interfere with that protection. Organizations need to disseminate these policies to individuals responsible for the conduct of research involving humans and they need to determine what role the IRB should play in monitoring the application of these policies. The existence and enforcement of the organization's conflict of interest policies further demonstrates its commitment to place the protection of individuals involved in research above financial, professional, and other concerns. 1.9 The organization must have and follow clearly written policies and procedures governing all human research. The policies and procedures must specify applicability. The policies and procedures must be re 

APPENDIX B 121 viewed periodically and updated as necessary. The policies and procedures must be disseminated appropriately within the organization to all staff involved with protection of individuals studied in research. COMMENTARY on Standard 1.9: Mechanisms should be established regarding when new policies and procedures are needed, and how existing policies and procedures should be reviewed and revised. Appropriate intervals for this review and revision must be specified. New research personnel must also be provided with this information and all staff must be kept apprised of any changes. 1.10 The organization must assure that all personnel conducting or supporting human research or involved in the HRPP demonstrate and maintain sufficient knowledge of the protection of individuals studied in research appropriate to their role. COMMENTARY on Standard 1.10: The organization must assure the provision of acceptable educational activities for principal investigators, other research personnel, IRB chairs, IRB members, IRB staff, appropriate institutional officials, and others in the organization as appropriate. The organization needs to assure that: (1) educational programs for professional development in the area of protection of individuals studied in research are appropriate to the investigator's role in the research; (2) mechanisms exist to provide additional education as needed; (3) procedures exist for demonstrating the effectiveness of these activities; and (4) individuals receive ongoing education at intervals determined appropriate in consideration of their research endeavors. Appropriate procedures for these individuals may involve attendance at courses, participation in seminars, and/or completion of computer-based training. Supplemental techniques such as performance feedback, monitoring, supervision, or mentoring are also acceptable. (Please note that the NIH Required Policy for IRB Review of Human Subjects Protocols in Grant Applications [Notice: OD-00-031: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-031.html] describes the minimum requirement for NIH grantees.) 1.11 The organization must establish the number of IRBs appropriate for the volume and types of human research that the IRBs review. COMMENTARY on Standard 1.11: The trend in many research organizations is toward establishing more than one IRB. In large organizations conducting many research studies, it may be difficult for one IRB to provide an adequate level of review of the protocols, particularly if they are complex or originate from different disciplines (e.g., biomedical versus social and behavioral sciences). In determining the appropriate num 

APPENDIX B 122 ber of required IRBs, the organization should take into account the volume, complexity, and types of research it reviews. Organizations with multiple IRBs require additional thought and consideration to ensure that all human research subject protection issues are taken into account in a uniform manner. 1.12 The organization must provide sufficient and appropriate staff, space, equipment, finances, technology, and other resources for the HRPP. COMMENTARY on Standard 1.12: The organization must determine what constitutes adequate resources. Input from the IRB(s) chairs, members, and staff is a critical ingredient in this determination (see further discussion of this issue in Section 2 of these Standards). In addition to staffing needs, IRB administrative offices require enough space to maintain secure storage of records, to enable private communication, to provide current computer technology and support services, and to provide adequate space for meeting with investigators and IRB members. 1.13 The organization must recruit and retain IRB chair(s), members, and staff who have both experience and knowledge appropriate to their respective roles on the IRB team, and who represent all fields of science applicable to their organization. COMMENTARY on Standard 1.13: The organization must both recruit and maintain a quality IRB by having high-caliber chairs, members, and staff. The organization's policies must foster the retention of individuals knowledgeable of and sensitive to the principles of the organization's human research protection program sufficient to assure continuity of high levels of performance. Appropriate and meaningful recognition, including but not limited to adjustments to compensation or organizational responsibilities, are central to the retention of knowledgeable and committed individuals. 1.14 The organization must have procedures for timely identification and dissemination of new information that may affect the HRPP, including laws, policies, and procedures, as well as emerging ethical and scientific issues. 1.15 The organization must have and follow written policies and procedures for addressing allegations and findings of non-compliance with the requirements of the HRPP, and management of research harms. The policies and procedures must be reviewed periodically and updated as necessary. 

APPENDIX B 123 COMMENTARY on Standard 1.15: There must be a clear and public policy concerning identification and reporting of research harms and for the compassionate and efficient management of such events. These procedures must include a fair and reasonable process for all parties involved. Any accused individual should have the right to appear in person to defend himself/herself. The procedures should also include a mechanism that determines those violations serious enough to inform regulatory agencies and funding sources. The organization must have and follow a written policy that protects from retaliation those who in good faith report allegations of non-compliance. (Please note that the Office for Research Integrity's Notice of Proposed Rulemaking can be found at 65 Fed. Reg. 70830 (2000) and may be accessed by clicking on News on the ORI home page, http://ori.hhs.gov.) 1.16 The organization must utilize a system for regularly assessing outcomes of and improving the performance of the HRPP. The system developed to examine results or outcomes of the HRPP's activities must also include the identification of problems, implementation of interventions, and measurement or evaluation of the effect of interventions. COMMENTARY on Standard 1.16: Performance evaluation and assessment of programmatic outcomes in other disciplines are well known and have become generally accepted as organizational best practice. Until now, they have neither been widely applied nor implemented by HRPPs. Two reports, one by the Advisory Committee on Human Radiation Experiments (ACHRE) and the other by the DHHS Office of the Inspector General (OIG), concluded that an adequate system of human research protection “would require that the system be subjected to regular, periodic evaluations that are based on an examination of outcomes and performance and that include the perspective and experiences of research [subjects] as well as the research community.” The OIG's Report recommended that IRBs be given more flexibility by the FDA and OPRR (now OHRP), with concomitantly a greater accountability for results by taking “concrete actions . . . to assess and verify the actual results of their efforts in protecting human subjects.” The Report described a small number of creative efforts currently undertaken by some IRBs. Persistent problems in human research protection and the changing nature of clinical research, public expectation, and organizational best practices have thus necessitated that the organization, IRBs, and investigators regularly evaluate their performance and assess outcomes. An organization seeking accreditation must propose its own methods/procedures for evaluating the performance of all aspects of the HRPP.