Don’t be afraid to ask for help
Don’t be afraid to ask for help
Sandra L. Alfano
This case raises questions about risk analysis and about the expertise of the biomedical IRB, specifically focusing on whether such an IRB is qualified to evaluate socio-behavioral research projects. In thinking about this issue, one can easily expand the questions to apply to other ‘different’ types of research projects for which members do not have direct experience.
So what are the questions to be explored? It is helpful to start by examining the expectations for IRB review, which focus on protecting the rights and welfare of human subjects of research, and ensuring sound, ethical research. IRBs fulfill this mission by evaluating risks and plans to minimize risks, and by constituting a board with diverse membership that embodies expertise to evaluate projects from an ethical and scientific or scholarly perspective.
In designing and reviewing human research protocols, it is necessary to be cognizant of all the possible risks. Researchers should attempt to anticipate risks of harm that may occur, and incorporate the means to minimize those risks. It is important to recognize that evaluation of risks in a protocol needs to extend beyond the physical risks inherent in medical procedures, and can be thought of in terms of legal, social, and psychological risks. Examples include putting subjects at risk of civil or criminal liability, breach of confidentiality which may lead to threats to insurability or employability through discrimination if certain research results become known, and/or causing psychological distress or stigmatization. Consideration of the full spectrum of possible risks before the protocol is initiated should lead to better safeguards being built into the protocol.
Nonetheless, while an IRB is expected to safeguard subjects and ensure that risks are minimized, this does not mean that risks must be or can be eliminated. Indeed, Belmont 1 recognizes that “…even avoiding harm requires learning what is harmful; and, in the process of obtaining this information, persons may be exposed to risk of harm.” So it is reasonable to expect that thought be given to identifying potential risks, while understanding that not all risks will be anticipated prior to conducting the research. This recognition is acceptable in a setting where there is oversight of the ongoing research that results in rapid identification of unanticipated problems that might involve risk to subjects or others. Thus, a well thought-out data and safety monitoring plan will be necessary to mitigate any risks and their impact on human subjects. When a harm occurs, it is necessary for the researcher and the IRB to understand what has happened in order to analyze whether any new measures should be put in place to avoid similar occurrences. It seems in this case, this has occurred.
In order to ensure that the rights and welfare of research participants are adequately protected, the federal regulations set the minimum standard for constitution of an IRB:
“Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members and the diversity of the members, including consideration of race, gender and cultural backgrounds and sensitivity to issues such as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas… No IRB may consist entirely of members of one profession.
An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB. In order to fulfill the requirements of this policy, each IRB shall…review proposed research at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas.”2
From these standards, it follows that evaluation of each research study, including scientific review, needs to be relative to the complexity of the study. Outside review of the research (e.g., NIH review, Cooperative Group review, FDA review) can be acknowledged as contributing to the review, but should not be considered as the only scientific/scholarly review. It is the IRB’s responsibility to determine that risks are minimized through sound research design and that risks are reasonable in relation to anticipated benefits.
With this focus on expertise, however, the federal regulations do require that a nonscientist member be present for full board deliberations. It is not clear if one was present during the initial review of the case in question. So the essential question is whether the IRB had the appropriate expertise to evaluate the socio-behavioral protocol. Certainly, the IRB should seek the expertise of consultants or ad hoc reviewers if the IRB members lack the expertise to make approval determinations without such consultation. Consultants and ad hoc reviewers can be used to evaluate the research proposal for scientific or scholarly merit, and other issues as requested by the IRB. Such issues might include evaluation of research design, statistical power, subject selection process, risk assessment and benefit analysis, etc. When selecting a consultant or ad hoc reviewer, it is important that one not be chosen who has or may be perceived as having a conflict of interest. The consultant or ad hoc reviewer should provide a report to the IRB, and they may be requested to attend the Committee meeting for questions and clarification of issues, but should not be allowed to vote.
All risks/harms cannot be anticipated or avoided, but steps can be taken to promote safety and welfare for all research participants. In addition to thinking about risks, and putting in place efforts to minimize risks, it is important to also have a data and safety monitoring plan that will help researchers quickly become aware of harms so modifications can be made if necessary.
No IRB can have endless expertise. Diversity in membership brings different expertise and experiences to the table and allows for a broad scope of research to be reviewed. IRBs need to recognize when additional expertise is required and seek it out and find methods to incorporate it.
1. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report, Ethical Principles and Guidelines for the Protection of Human Subjects of Research, April 18, 1979. (Accessed February 25, 2010 at http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm)
2. Code of Federal Regulations. Title 45 Public Welfare Department of Health and Human Services; Part 46 Protection of Human Subjects, June 23, 2005. (Accessed February 25, 2010 at http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)