volume 44, number 5
Temple UniversityFaculty Herald

IRB: A Necessary Good

By Mike Jacobs, Professor of Pharmaceutical Studies

Professor Jacobs stepped down from the medical intervention IRB after serving for 11 years as its chair and over 30 as a member. The Editor asked him to reflect on what his long (and selfless!) service had taught him.

 

   Call it what you like, the Human Research Protection Program, the Ethics Committee, or the Institutional Review Board (IRB); it is the committee that apparently all clinical researchers across the country love to hate. It doesn’t matter if it is medical or social-behavioral research. Any researcher who has had to deal with this committee will at one time or another face some level of frustration in having to deal with the IRB. But a well-functioning IRB is essential to a robust program for protecting the rights and welfare of human research participants, itself crucial to the good clinical research at the heart of Temple’s mission.
    Excellence in research is identified as one of the primary missions of Temple University. A variety of components must be integrated to achieve excellence in any endeavor, and this is particularly true of research. First among these is the commitment of the University to provide the direction and support necessary to achieve excellence. This support can be provided in a number of ways including the recruitment of highly skilled faculty as investigators, creation and maintenance of first-rate research facilities, and providing an infrastructure that accelerates the transition of ideas into concrete investigations. While these elements of support are necessary for both basic science and clinical research, clinical research requires the additional component of ensuring protection of the rights and welfare of human research participants.
    Having served as a member of the Temple medical intervention IRB for over thirty years and having chaired this committee for the last eleven, I felt it was well past time to leave and submitted my resignation last August. After all, most prison sentences are not that long. None the less, I found my work on this committee to be one of the most fascinating and enjoyable experiences I have had as a faculty member at Temple. It has also fashioned my views on the roles of the University, and faculty members, both individually and collectively, to create and promote a culture of research compliance at Temple. These are my opinions. Not all will agree with them. Whether you agree or disagree with these views, it is crucial that the wider university community engages in the discussions to make the clinical research enterprise at Temple function more efficiently and effectively to achieve excellence in research.
    At most universities a single individual, the Institutional Official (IO), assumes ultimate responsibility for the Human Research Protection Program (HRPP). The reporting line for this position closely follows the structure adopted by the university to direct other research-related activities. In some universities this is the Office of the Provost; while in others it may be in the Office of the Vice-President for Research, or a similar position. Temple’s HRPP is centered in the Office of the Provost. The major component of a well-functioning HRPP is the IRB; however, it is not the only component. HRPPs also have responsibilities to educate investigators, oversee research by audits and direct observation, and to facilitate research when possible. During my time on the IRB, individual schools and even departments have suggested the need to constitute their own IRB to review research proposals directly related to their areas of interest. These schemes typically gather some traction when individual researchers or groups of researchers experience delays in approval, or feel that the IRB is making unnecessary or burdensome requests. The reality is that starting an IRB outside of the University structure would lead to diversion of scarce resources, and would possibly create inconsistencies in the application and enforcement of human research regulations. The unavoidable problem of a school or department committee reviewing their own research is a conflict of interest. The potential for a conflict of interest might be better understood when considering the operation of “for profit” IRBs. Payment for review (and approval) is how these organizations stay in business. I am not suggesting that for-profit IRBs are bad. Temple has had a long standing agreement with one of the largest, accredited, for-profit IRBs in the country, which supports our own human research protection program by reviewing certain studies sponsored by the pharmaceutical industry. Conflicts of interest that might occur at the school or department level could be financial but might also be influenced by the position or stature of the investigator whose research is being reviewed. It is unreasonable to believe that any committee functioning below the level of a university committee would be immune from conflicts of interest. In fact, the university, with all of its resources and experience, may find it challenging to protect itself from real or perceived conflicts of interest.

   Contrary to the feelings of the investigator who has received a third deferral notice for her IRB submission, IRB members do not consider themselves obstructionists with the single-minded intent of derailing the research enterprise. There are situations where receiving approval for a study is more difficult, typically because of the nature of the intervention and the overriding need to ensure the safety of the participant. During my service on the IRB there were a few occasions where studies were rejected because the proposed research was considered unethical. In those situations where research was deferred by the IRB it, was always the result of failure to provide adequate information about the study and how it was to be conducted. More specifically, during the time I served as chair, studies were deferred because of one or more of the following reasons: the background information did not support the need for the research; no testable hypothesis was stated; a primary outcome parameter was not identified; eligibility criteria were vague or non-existent; study procedures were not presented in sufficient detail; methods for monitoring participant safety were not provided; no statistical analysis plan was submitted; the method for determining the sample size was missing. Why did this happen and left unattended why will it continue to happen? In the words of Pogo: “We have met the enemy and he is us.” To significantly enhance the efficiency of research review process requires the combined efforts of university administrators, deans and department chairs, IRB members and staff, and individual faculty members. Collectively we need to commit to a culture of research compliance.
    The two most common questions I have been asked by first-time investigators at Temple are, “What do I need to submit to the IRB?” and “How do I submit to the IRB?” To me this is a symptom of a larger underlying problem. Individuals have been recruited presumably to get a research program together, but the basic tools for success might not have been provided. I am not sure what materials are provided to new faculty members by schools or departments related to the intricacies of developing a protocol for submitting to the Temple IRB, if any. Even seasoned researchers arriving from other universities will run into trouble because once you know how to submit to one IRB, you know how to submit to one IRB. Every institution has its own mechanisms for getting the protocol in. Given the fact that one of Temple’s primary missions is to achieve excellence in research, faculty awareness of Temple research policies and procedures seems too important to be left to chance.

   A notable deficiency in the research review process in most departments (at least on the Health Sciences Center) is the failure of the protocol to undergo scientific review. This most directly relates to investigator-initiated studies, as multicenter trials and industry sponsored research typically have had several levels of review prior to being submitted to the IRB. Scientific review is probably best carried out at the department level, although school committees might be preferable in some instances. A strong scientific review would go a long way to help researchers avoid the common reasons for protocol deferral and allow the IRB to focus its attention on the assessment of the risks and benefits to research participants.
    As mentioned above, the IRB should assume roles beyond that of reviewing and approving research applications, including education, observation, and facilitation. These activities are important to the research mission, but difficult to implement given the current workload and staffing of the IRB. The IRB website provides access to all of the policies, procedures, worksheets, checklists, and other documents relevant to conducting research and how research is reviewed at Temple. This is useful information, but the IRB could do more to educate all members of the research team not just about what to do, but how to meet regulatory requirements. Other areas where education is needed include adherence to good clinical practices and systems to maintain confidentiality of participant information. Observation falls under the “police function” of the IRB. It includes everything from examining the qualifications of the researchers, the capabilities of the research site, assessing how data is collected and stored, and to how informed consent is obtained. This activity requires significant staff time, but is essential in determining areas where improvement is needed. Finally, with regard to facilitating research, it might be reworded as, “to make it as easy as possible.” It’s a tough job, especially when the IRB needs to ensure adherence to all regulatory requirements. It can be done with regular communications among the faculty, the IRB, and research administration.
    This brings me to what individual faculty members can do to create and maintain a culture of research compliance. First, if you are unsure about how to go about conducting any aspect of your research, ask someone on the IRB staff that can provide the correct answer. Too often an investigator comes to a decision based on what “seems right” to him or her or a consensus is developed with colleagues. If you aren’t sure, ask the IRB. Second, do what you can to ensure that those currently involved in research are following the regulations. If you become aware of an issue of noncompliance with research policies and procedures discuss it with the individual directly and help to get the problem resolved. Situations related to research noncompliance can get ugly, and many are aware of problems encountered at other institutions. To a lesser extent they have happened at Temple, too. One individual’s violation of the regulations becomes a reflection on all of Temple. Lastly, faculty members should consider actively participating in the research review process, whether at the level of scientific review or through service on the IRB.
    One thing I have learned in my years of service on the Temple University IRB is that adherence to the institution’s policies and procedures and federal regulations as they relate to human subject research are essential. I have also learned that everyone has a stake in creating a culture of research compliance, even if they are not directly involved in human subject research. The alternative is not an option. •