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Federal Guidance Confirms a Narrowed Investigator Reporting Obligation to IRBsThe Office for Human Research Protections (OHRP) of the U.S. Department of Health and Human Services (HHS) has declared that investigators have only a narrow obligation to report adverse events and other safety information to institutional review boards (IRBs). In a draft guidance issued on October 11, 2005, OHRP acknowledges that under current HHS regulations pertaining to IRB review (45 CFR Part 46), investigators only need to report "unanticipated problems involving risks to subjects or others" to an IRB. OHRP concludes further that only a small subset of the many adverse events that typically occur during the course of a clinical study need to be reported to the IRB as "unanticipated problems." The OHRP guidance is the first product of a multi-agency effort to harmonize and clarify federal human subject protection regulations with respect to safety reporting requirements. Even though the OHRP guidance technically extends only to the oversight of federally funded studies, OHRP and FDA have pledged to develop a harmonized approach to the issue. At the November 1, 2005 meeting of the Secretary's Advisory Committee on Human Subjects Protections (SACHRP), Dr. David LePay, a senior official at the FDA, confirmed that the FDA intends to publish a similar position regarding the reporting of adverse events. The OHRP guidance (and promised FDA guidance) should bring a measure of relief to IRBs struggling under the weight of the thousands of adverse event reports circulated annually. The OHRP guidance declares that "[i]n OHRP's experience the vast majority of adverse events . . . do not need to be reported under the HHS regulations for the protection of human subjects." Instead, the regulations require only that "unanticipated problems involving risks to subjects or others" need to be reported to IRBs. OHRP acknowledges that the regulations do not define "unanticipated problems." According to the draft guidance, "unanticipated problems" include those events that (1) are not expected given the nature of the research and the subject population, and (2) indicate that the research poses a greater risk of harm or discomfort than was previously known or recognized. In the draft guidance, OHRP illustrates with the following diagram that only a subset of adverse events qualify as unanticipated problems that must be reported to the IRB:
The draft guidance goes on to establish that an investigator does not need to report expected adverse events or events that are not related to participation in the research. According to OHRP, the vast majority of adverse events are expected. Some are expected in light of the known toxicities and side effects of the research procedures. Other adverse events occur due to the natural progression of a subject's underlying disease or condition as opposed to resulting directly from the subject's participation in research. The draft guidance emphasizes that investigators do not need to report to the IRB expected adverse events or adverse events that are unrelated to the research. The draft guidance concludes that three categories of adverse events must be reported to the IRB:
The guidance also provides instruction to investigators for the reporting of "external" adverse events to IRBs; that is, reports of adverse events that arise at sites other than the investigator's site. In multicenter studies, sponsors receive reports of serious adverse events from a reporting investigator and then distribute those reports to all sites involved in the study as IND Safety Reports, MedWatch Reports, etc. Investigators in turn often submit these IND Safety Reports and other reports to their IRBs. Consequently, IRBs have become buried under a deluge of external adverse event reports, most of which the IRBs cannot meaningfully evaluate. The draft guidance clearly acknowledges that IRBs do not have expertise, resources, or the regulatory responsibility to undertake the data and safety analysis of external adverse event reports, such as IND Safety Reports. Accordingly, with respect to such reports, the draft guidance states that "the vast majority of reports of external adverse events do not need to be submitted to the IRB." Many IRBs already have developed forms and reporting procedures consistent with OHRP's draft guidance. Researchers can expect more and more IRBs to begin screening adverse event reports and to accept only those events that qualify as potential unanticipated problems involving risks to subjects or others. Some IRBs have developed checklists and guidelines to help investigators determine whether an event is reportable or not. For more information on Quorum Review IRB's safety reporting requirements, please visit www.quorumreview.com. The OHRP draft guidance is an important declaration that should help IRBs, investigators and sponsors reassess the type of safety information to submit to the IRB. For many, adopting OHRP's position will require a fundamental shift in thinking about the role of an IRB in monitoring adverse event data. For others, OHRP's position is just the first step in a comprehensive, multi-agency effort to reform safety reporting requirements. In the end, the changes being undertaken by IRBs, OHRP, FDA and other federal agencies are designed to improve the ability of IRBs, investigators and sponsors to collaborate on their shared mission of protecting human subjects participating in clinical studies. To read the OHRP draft guidance in its entirety, please visit www.hhs.gov/ohrp/requests/com101105.html. Learn the latest about adverse event reporting at our upcoming Educational Seminars |
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