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
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.