Responsible Research A Systems Approach to Protecting Research Participants (2003) / Chapter Skim
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3 Back to Basics: A Scientific, Conflict of Interest, and Ethical Review of Research Protocols
3 Back to Basics: A Scientific, Conflict of Interest, and Ethical Review of Research Protocols
Pages 70-107
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From page 70... ...
THE NEED FOR RESEARCH ETHICS REVIEW BOARDS As detailed in this chapter, Institutional Review Boards (IRBs) should be reshaped and reformed to serve the role for which they were originally intended ensuring participant protection through the careful ethical review of research protocols.
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From page 71... ...
This committee urges all research organizations (as well as free-standing IRBs) to signal their commitment to reform by changing the name of the bodies serving the functions of IRBs to "Research Ethics Review Board" 1In addition to these designations in use at the Duke University Medical School and the Albert Einstein College of Medicine, respectively, Johns Hopkins University also uses the terms "Joint Committee on Clinical Investigation" and "Committee on Human Research" within their medical school and school for public health.
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From page 72... ...
Recommendation 3.2: Research organizations and research sponsors should ensure that Human Research Participant Protection Programs utilize distinct mechanisms for the initial, focused reviews of scientific and financial conflicts of interest. These reviews should precede and inform the comprehensive ethical review of research studies by the Research Ethics Review Board (Research ERB)
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From page 73... ...
In some cases, particularly when no federal funds are used to sponsor the research, scientific review may not occur or may be conducted only cursorily by a group internal to the research organization. In other cases, ethics review may not occur if the research is not subject to the various federal regulations governing the conduct of research with human participants.4 As stated in Chapter 2, the committee believes that all research involving human participants, regardless of site or funding source, should be subject to an independent review and a common system of protections (Recommendation 2.1~.
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From page 74... ...
Some institutions "crossfertilize" various review committees to maintain communication and promote awareness of the relevant issues within each committee's purview (Dretchen, 2001~. The Research ERB should use this information to determine if and how participant protection could be negatively affected, whether the recommended conflict management plan is sufficient to ensure participant protection, what information pertaining to any conflict should be disclosed to participants through the informed consent process, and whether ongoing review is required in the event that the research goes forward.
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From page 75... ...
Therefore, the focused reviews of scientific merit and the evaluation of potential financial conflicts of interest should feed into the ethics review process for each protocol, and the Research ERB should have the ultimate authority regarding participant enrollment. ENSURING DISCRETE SCIENTIFIC REVIEW OF PROTOCOLS Scientific and ethical reviews of research protocols are both essential because each considers different sets of questions and therefore each can yield different determinations.
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From page 76... ...
is free of significant conflicts of interest. Elements of Scientific Review All protocols involving human participants should undergo an independent and rigorous scientific review to assess scientific quality, the importance of the research to increase knowledge, and the appropriateness of the study methodology to answer a precisely articulated scientific and, in some cases, clinical question.
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From page 77... ...
Research ERB review should continue to include some consideration of a protocol's scientific merit; however, delegating the in-depth scientific review to an upstream mechanism should facilitate the Research ERB's more focused consideration of the ethical elements of particular protocols. One advantage of ensuring a distinct scientific review mechanism is the opportunity to identify protocols that are not yet suitable for Research ERB consideration.
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From page 78... ...
Research sponsored by established industrial entities typically undergoes rigorous scientific review (FDA, 2001c; Spilker, 2001~. For example, protocols designed by pharmaceutical companies often go through numerous and prolonged iterations before ultimately being approved by an internal oversight committee of physicians and scientists.
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From page 79... ...
BACK TO BASICS 79 agency. The guiding principles for the initial review of research project grant applications submitted to NIH are based on the Public Health Service Scientific Peer Review Regulations, which state that peer review groups are to make recommendations concerning the scientific merit of applications.
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From page 80... ...
Finally, when commercial Research ERBs are called upon to review research protocols, their standard operating procedures should provide the mechanisms to ensure that scientific review of proposed research occurs and that their primary function remains focused on the ethics review and the integration of the scientific and financial conflict of interest review elements pertinent to the research. Currently, most protocols reviewed by independent IRBs undergo intensive scrutiny by the same group for both scientific merit and ethical safeguards, with reliance on external content experts as necessary.
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From page 81... ...
Secondary gains from the use of this particular scientific review mechanism include an additional level of mentoring for new and junior investigators, continuing education of reviewers, a mechanism for monitoring and developing departmental research programs, and departmental investment in and responsibility for its research program and the consequent human participant protection needs. The organization's standards should become an integral component of the mentoring that senior investigators provide to less experienced investigators and reviewers.
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From page 82... ...
FINANCIAL CONFLICTS OF INTEREST AND PROTOCOL REVIEW As stated in Chapter 2, Research ERBs should not bear the primary responsibility for identifying and managing financial conflicts of interest, as they lack the necessary resources, expertise, or authority to do so (AAMC, 2001; Glass and Lemmens, 1999; NBAC, 2001b; NHRPAC, 2001)
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From page 83... ...
In addition, subconscious biases and preconceptions may lead to a flawed informed consent process. These conflicts, although less quantifiable than those with financial implications and not subject to conflict of interest committee financial reviews, should be considered by the Research ERB during the review of research involving human participants.
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From page 84... ...
In the meantime, it is essential for Research ERBs within academic centers to protect and maintain their independence within organizational structures in order to reduce the risk that participant protections will be compromised by institutional interests. To signify the importance of this realignment, the committee encourages academic centers and other constituencies in the research community to begin to structure their IRBs as "independent" review boards rather than "institutional" review boards in addition to renaming the board, as suggested in Recommendation 3.1.
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From page 85... ...
If even remotely relevant, these potential conflicts should be shared with the Research ERB (as a committee or with the chair) , or the board member should state that a potential conflict of interest exists and recuse her- or himself from the discussion and from voting on a particular protocol, as required in federal regulations.9 Similar problems could arise in the case of proprietary Research ERBs (i.e., established by a company to review its own research)
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From page 86... ...
ETHICS REVIEW: CLARIFYING THE ROLES AND RESPONSIBILITIES OF RESEARCH ERBS Independent review of proposed research by Research ERBs to determine ethical acceptability should provide a comprehensive ethical assessment of protocols from the perspective of the local community and the institution. However, despite the central role of these review boards in the federal regulations and the research review process, their ability to keep pace with the enormous volume of work and the high-quality services expected of them has been in question for some time (AAU, 2001; GAO, 1996; Levine, 2001a; NBAC, 2001b; OIG 1998a, 2000a)
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From page 87... ...
In addition, it should consider to what extent and in what manner conflict of interest information should be communicated to potential participants if that information might influence the investigator's, institution's, or participant's assessment and judgment about the risks and potential benefits of the proposed study. In general, Research ERBs are responsible within the protection program for the functions listed in Box 3.3.
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From page 88... ...
Although these functions are important in the protection of research participants, they should be addressed by other program units or collaborating units within an organization (e.g., Office of Technology Transfer for Material Transfer Agreements, see Chapter 6~. In addition, training is an institutional responsibility, not that of the Research ERB (see Chapter 2~.
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From page 89... ...
Recommendation 3.3: The Office for Human Research Protections. with input from a broad spectrum of research disciplines and participant groups, should coordinate the development of guidance for risk classification.
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From page 90... ...
A major challenge facing any HRPPP is determining how to appropriately and efficiently manage this variety of activity. Although the same ethical principles apply to participant protection regardless of the methodologies employed, a "one size fits all" approach to the review and oversight of heterogeneous studies can cause inefficiency and frustration, which unacceptably diminish a program's capacity to provide adequate protection.
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From page 91... ...
Is the current system of stratification adequate, or would a more refined form of staging be useful? Systematic empirical evidence regarding these questions is lacking and needs to be developed, perhaps by using inter-rater reliability studies that compare the disposition of similar protocols across sets of review boards.
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From page 92... ...
. Research Ethics Review Board Focus on Informed Consent Recommendation 3.4: Forms signed by individuals to provide their legally valid consent to participate in research should be called "consent forms" rather than "informed consent forms." Research Ethics Review Boards should ensure that the focus of the informed consent process and the consent form is on informing and protecting participants, NOT on protecting institutions.
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From page 93... ...
First, traditional informed consent often does not appropriately inform and empower the participant, because the information in the consent document increasingly serves institutional rather than participant needs. In other words, consent forms have been hijacked as "disclosure documents" for the risk management purposes of research organizations.
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From page 94... ...
, alternatives to the research, clarification that this is research not treatment, relevant investigator or institutional conflicts of interest, and opportunities for recourse in the event of problems during the course of the study. Research ERBs should require that disclosure language regarding liability, indemnification, and business agreements be removed from the consent form altogether, or at a minimum, be moved to an appendix in order to clearly distinguish the informed consent discussion from risk management information.
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From page 95... ...
Finally, the Research ERB should emphasize that the act of obtaining informed consent from a potential research participant should be interactive and ongoing and that obtaining written "informed consent" is tangential to the process of informed consent and merely provides a mechanism to document and record that communication with the participant regarding relevant considerations to enrollment in a protocol has taken place. Research Ethics Review Board Membership, Qualifications, and Voting System The effectiveness of the review process depends on the experience and commitment of board members.
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From page 96... ...
However, it is sometimes not clear whose interests such members represent and if one individual can represent more than one community (Hog", 2001; MacQueen et al., 2001~. In order to address the lack of guidance, NBAC recommended that Institutional Review Boards should include members who represent the perspectives of participants, members who are unaffiliated with the institution, and members whose primary concerns are in nonscientific areas.
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From page 97... ...
The depth of knowledge necessary in the particular areas correlates to the position of the issue within the pyramid, moving from the base to the top tier. The committee agrees that the composition of the Research ERB should reflect its ultimate function as the ethical review body for human research protocols.
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From page 98... ...
Under the committee's proposed refocusing of the ethics review, responsibility for the initial in-depth scientific review would lie elsewhere, enabling the Research ERB to focus on its primary functions of providing ethical review of proposed research and integrating the scientific and financial conflict of interest reviews. Consistent with this mission, the most important roles of the board chair are to constitute a proper and balanced membership, facilitate open discussion, and promote consensus.
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From page 99... ...
Research ERB Member Education The need to educate board members has been discussed by every major national body charged with the review of human research protections, with each clearly stating the need for additional resources and educational programs (ACHRE, 1995; National Commission, 1978; NBAC, 2001b; President's Commission, 1983~. In addition, a 1998 survey documented strong support for increased board member education (Bell et al., 1998~.
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From page 101... ...
The committee supports these efforts because they encourage the development of professional staff who can facilitate the ethics review function of the Research ERB. ORGANIZING AND INTEGRATING THE REVIEW PROCESSES In this chapter, the committee has proposed that separate and independent scientific review and conflict of interest review mechanisms should be available to the Research ERB, and that relevant findings from those reviews should be communicated to the Research ERB to inform its comprehensive ethical assessment.
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From page 102... ...
Recommendation 3.7: The review of multisite trials should be streamlined, as allowed by current regulations. One primary scientific review committee and one primary Research Ethics Review Board should assume the lead review functions, with their determinations subject to acceptance by the local committees and boards at participating sites.
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From page 103... ...
and Research ERB or could designate one of the SRCs and Research ERBs as the "primary SRC and Research ERB." The organization that has primary responsibility for obtaining the assurances should also assume the responsibility for acting decisively should violations occur, including termination of the study or the site and/or reporting violations and violators to authorities. In FDA-regulated trials, it should not be assumed that the industry sponsor has primary responsibility for the program; it would be preferable for the medical institutions involved to share that responsibility, since they are most directly and closely involved with the research participants.
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From page 104... ...
Effective use of communication tools, such as the use of protocol Web sites that would enable local Research ERBs to follow the lead Research ERB's progress, will be fundamental to successful collaboration. Sharing Responsibilities: Alternative Review Models Models exist in the United States for sharing program responsibilities among collaborating institutions and their Research ERBs for example, MACRO and BRANY.30 Similarly, the United Kingdom relies on regional committees for review of multisite research, and Denmark handles multisite studies by assigning the review responsibility to a lead committee (Albert)
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From page 105... ...
Time and focus are needed to accomplish these tasks, and if their difficult and demanding nature is to be taken seriously, the members and not just the administrative staff of scientific review groups and Research ERBs should be compensated for their efforts. This compensation may be monetary, may support academic promotion, or may provide release time from other duties.
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From page 106... ...
Need for a Common Body of Knowledge Recommendation 3.8: The Office for Human Research Protections and the National Human Research Protections Advisory Committee should convene conferences and/or establish working groups to develop and disseminate best practices, case presentations, and conference proceedings for use by local protection programs and their Research Ethics Review Boards. Intellectual and educational resources are as important as financial resources in ensuring protections.
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From page 107... ...
Robust, ethical review by the Research ERB could be enhanced by better employing risk-stratification, allowing boards to deal with minimal risk studies efficiently and devote more attention to high-risk studies. The review of multisite protocols could be streamlined by designating lead scientific review and ethics review committees, whose judgments would be subject to acceptance by the local review boards (this would include the sharing of conflict of interest determinations with the lead Research ERB)
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