WASHINGTONThe National Institutes of Health (NIH) and the Food and Drug Administration (FDA) have made little progress in implementing recommendations to reform the Institutional Review Board (IRB) system to ensure the protection of patients participating in medical research, according to a new report by the Office of the Inspector General (IG) at the Department of Health and Human Services (HHS).
The report is a follow-up on how the two agencies have responded to recommendations contained in a previous IG report released in June 1998. That investigation discovered disturbing inadequacies in IRB oversight of clinical trials involving investigational medical devices, the new report said.
Nearly 2 years after the first report, the IG said, few of our recommended reforms have been enacted.
A Sensitive Time for Researchers
The new evaluation comes at a sensitive time for clinical and epidemiologic researchers. HHS, at the mandate of Congress, has proposed a lengthy series of rules aimed at protecting the privacy of patients.
Many researchers are gravely concerned that some provision would hinder or prevent their work, and some have argued that any privacy problems can be handled through the IRB system and particularly the informed consent process.
The report acknowledges a substantial increase in enforcement efforts by NIH and FDA intended to ensure protection of patients participating in experimental trials. It noted, for example, that between April 1997 and May 1998, NIHs Office of Protection from Research Risks (OPRR) made only one on-site investigation of a research institution.
Between June 1998 and March 2000, OPRR carried out on-site investigations at 10 institutions. FDA increased its routine on-site investigations of IRBs from 213 in fiscal year 1997, to 253 in FY 1998, and to 336 in FY 1999.
OPRRs reviews, which have occurred at major medical centers and resulted in the suspension of federally funded research at seven institutions, have been particularly influential in drawing attention of the national research community to the adequacy of IRB oversight and human-subject protection, the report said.
The document also acknowledged that several other promising steps have been taken to improve protection. Foremost, NIH and FDA have enacted two recommendations made earlier: NIH now requires data safety monitoring boards to share summary information with IRBs, and FDA now informs sponsors and IRBs about its findings of clinical investigator misconduct. In addition, both agencies have ongoing initiatives, particularly in the area of education.
Six Areas of Reform
Otherwise, the report found that NIH and FDA had enacted only a few of the IGs reform recommendations. It cited six specific areas and suggested that congressional legislation might be necessary to push the reform process:
Flexibility and accountability. The two agencies have made minimal progress in recasting federal requirements so that IRBs have greater flexibility and are held more accountable for research results. Too much IRB attention now focuses on review responsibilities of questionable protective value, the report said.
Oversight and protection. The IG found minimal progress in strengthening protections for research subjects. Continuing IRB review of a research project after the initial review receives a low priority at many institutions, and IRBs know little about what occurs during informed consent and the research trial.
Education. Despite some progress in this area, neither NIH nor FDA has enacted educational requirements for researchers or IRB members. The most important continuing protection for human subjects is the presence of well-trained and sensitized investigators and IRB members, the report said.
Conflicts of interest. The commercialization of research and the increasing importance of research revenues to institutions heighten the potential for conflicts of interest in clinical research. Yet neither agency has made any progress toward insulating IRBs from conflicts that can compromise their mission in protecting human subjects.
Workload. NIH and FDA have made only minimal progress in easing the workloads of IRBs, which are overloaded with protocols and adverse events reports. Because of limited help and resources, many boards find it difficult to give each review proper attention.
Federal oversight. Reorganization of the federal oversight process also got a low rating. Federal oversight of IRBs is not equipped to respond effectively to the changing pressures and needs of the current system of protection, the report argued.
The Common Rule
The IGs office also called the Common Rulethe core regulations used by 17 federal agencies as the basis for protecting research subjectsa significant barrier to HHS implementing needed reforms, because any changes require agreement by all 17 agencies.
While acknowledging the importance of the Common Rules goals, the report also noted that it inhibits timely responses to rapidly changing developments in clinical research. As a result, the report said that achieving a timely implementation of the IGs recommendations might require Congress to enact new legislation.
Looking ahead, the IG report urged that initiatives taken to tighten the supervision and conduct of gene therapy trials be extended to the broad universe of clinical trials, particularly those in which patients face significant risks. One of these is a new requirement that study sponsors submit plans for gene transfer trials to FDA. Another is a planned symposia series on the directions and safety of such trials.