Institutional Review Boards: A System in
Jeopardy?
Testimony
June 11, 1998
Dr. Angela J. Bowen
President, Western Institutional Review Board
Western Institutional Review Board® ("WIRB®") commends
the Committee for its interest in human subject protection
and, as President of Western Institutional Review Board, I
am pleased to present our views concerning the present system
of oversight covering institutional review boards ("IRBs")
and our proposals to address future human subject protections.
WIRB is the oldest and largest of the independent boards.
It was established in 1968 and has operated continuously since
that time. Our work is primarily Food and Drug Administration
("FDA")-regulated research, and the majority of
our clients are small hospitals and clinical investigators
who do research in private settings. We also serve as part
of the University of Rochester’s IRB system.
I. PRESENTATION OVERVIEW
The Office of the Inspector General ("OIG") of
the Department of Health and Human Services ("HHS")
has conducted an extensive study of IRBs over the past year.
This study involved the voluntary participation of a number
of IRBs, both institutional and independent, and has resulted
in the drafting of four reports. WIRB was one of the IRBs
interviewed by OIG and was privileged to review the draft
reports.
A. The History and Function of the IRB System
The OIG’s draft report entitled "Institutional
Review Boards: A System in Jeopardy" contains an excellent
history of IRBs in the scientific review process. While separate
regulations govern federally-funded research and FDA-regulated
research (i.e., research conducted to support FDA approval
of new drugs, medical devices, and new food substances), the
IRB responsibilities are the same. First, IRBs are responsible
for an initial review of the research plan presented by the
clinical investigator. Without IRB approval, the investigator
cannot commence clinical trials. The initial review encompasses
the research protocol, the informed consent document to be
signed by subjects, any advertisements to be used in recruiting
subjects, and any other relevant documents. IRBs are responsible
for ensuring that the research meets specific regulatory and
ethical requirements. The risks to human subjects must be
reasonable in relationship to the anticipated benefits, and
the risks must be minimized. The selection of subjects must
be equitable and justified. In addition, IRBs must ensure
that the informed consent document clearly provides the information
necessary for the potential subject to make a decision about
whether or not to participate in the research, ensure that
advertisements to recruit human subjects are not misleading,
and ensure that there are adequate protections for the subjects,
especially vulnerable subjects. After the IRB approves the
research study, it is then responsible for providing continuing
review of the research. The continuing review includes review
of all study amendments and reports of unexpected adverse
experiences to ensure that the risk-benefit ratio remains
acceptable. The FDA and NIH/OPRR regulations require at least
yearly review.
The FDA has oversight jurisdiction concerning research conducted
as part of its product approval process, while the Office
of Protection from Research Risks ("OPRR"), which
is located within the National Institutes of Health ("NIH"),
has oversight jurisdiction concerning federally-funded research.
However, the two federal agencies approach oversight very
differently. The FDA relies on an inspection process. FDA
inspects IRBs, research sponsors, and research investigators.
In its inspection of IRBs, FDA reviews IRB records, examines
written procedures, and audits the research protocols and
informed consent documents approved by the IRB.
The NIH/OPRR relies primarily on assurances as its oversight
mechanism. An "assurance" is a document in which
the institution commits to compliance with Federal regulations
for human-subject protections. To ensure compliance with an
assurance once it is filed, OPRR can limit, suspend, or withdraw
an institution’s assurance or require special reporting.
While OPRR has the authority to conduct investigations, these
are usually conducted only in response to subject complaints,
or as a result of other information indicating protection
breakdowns.
B. Recent Changes in the U.S. Research System
Biomedical research has changed significantly since the IRB
regulations were first implemented. At that time, most clinical
trials involving human subjects were federally-funded and
conducted within a single institution, by a single investigator.
However, due to a number of factors, including an increase
in regulatory requirements for premarket clinical testing,
the number of research studies funded both by public and private
sources has increased dramatically. These factors have encouraged
medical clinics and physicians in private practice to participate
in clinical research. Moreover, primarily because of federal
clinical testing requirements for new products, clinical trials,
especially industry-funded ones, now focus on multi-site studies
involving thousands of human subjects. Without doubt, this
increase in research conducted at multiple sites has allowed
a greater understanding of the benefits and risks of a drug
or device before marketing. Now more than ever, IRBs must
have sufficient staff, expertise, and technical support to
meet the demands of the changing research environment.
- RECOMMENDATIONS FOR IMPROVING THE CURRENT SYSTEM
WIRB believes that the present IRB regulations can be effective
in providing human subject protection, but because of the
dramatic change in the research environment, it is appropriate
to pause and reevaluate the process at this time. As the OIG
draft report noted, there is no indication that the current
regulatory system has resulted in harm to research subjects.
However, we believe that even the perception of problems in
the system will undermine public confidence and could adversely
affect the advances in medical research. Therefore, the recommendations
made by the OIG would be helpful in maintaining our country’s
leadership in the protection of the rights of research subjects.
A. IRB Registration
WIRB supports the concept of IRB registration. At present,
NIH/OPRR and FDA lack basic information on the existence,
location, and make-up of IRBs, and they must rely on IRB information
that is either provided by sponsors or investigators in their
applications to FDA or provided by institutions in assurance
documents with NIH/OPRR. WIRB believes that requiring such
basic information would help to improve protection of human
subjects by allowing the agencies to manage their oversight
efforts more effectively and to fully communicate with IRBs.
B. Information Sharing
WIRB also strongly supports the OIG's recommendation concerning
"information sharing." There have been situations
where certain sponsors or investigators were displeased with
an IRB's review and switched to a new IRB without informing
the new IRB about the previous review. While the majority
of sponsors and investigators have demonstrated integrity
during the IRB review process, WIRB believes that it is important
that these parties be obligated to disclose any prior disapprovals
of the research. Further, so that an IRB can effectively monitor
the progress of research studies, copies of all FDA and OPRR
inspection reports concerning clinical studies which the IRB
has approved should be provided to the reviewing IRB. Finally,
because clinical investigations are already subject to government
and sponsor auditing and monitoring, we believe that extending
the required "information sharing" between the parties
would be helpful to the IRB's oversight of research without
adding more oversight to an already overworked clinical investigator.
C. Ethical Considerations: Structure of Board
Concerns have been raised about the ability of IRBs to act
independently of the sponsors or the institution to which
they are affiliated. The issue of independence applies equally
to institutional IRBs as well as independent IRBs. We strongly
support formal studies that analyze actual conflicts of interests
in all IRBs. Without knowing whether conflicts of interest
bias IRB decisions, it would be difficult to implement meaningful
regulatory change.
It appears that the best way to control conflicts of interest
is through organizational structures that eliminate the financial
interest of the board members in their decision making. WIRB
already practices this through separation of its administrative
and review functions.
Moreover, WIRB strongly supports the OIG’s recommendation
that IRBs should include more non-scientific and non-institutional
members. WIRB highly values the important role that these
members play in protecting human subjects and understands
the OIG’s view that present regulations requiring merely
one non-scientific member and one non-institutional member
may not be adequate.
WIRB also strongly supports the OIG's recommendations for
increased board member training. IRB members need initial
and continuing education to understand and stay current with
the complex scientific, regulatory, and ethical issues in
today's research environment. WIRB also supports an increase
in investigator training, both inside and outside of institutions.
There are few educational resources available for investigators.
and this contributes to the problem of investigator non-compliance
with regulations.
D. Common Policy Shared by FDA and NIH/OPRR
We strongly support the concept of a "shared" policy
between FDA and NIH/OPRR in oversight of IRBs. As discussed
previously, regulatory mechanisms employed by FDA and NIH/OPRR
vary. FDA oversight of IRBs is included in the process of
evaluating the safety and efficacy of drugs, devices, and
biologics. Its approach is more compliance-based, focusing
on inspection of IRB research sites. In contrast, NIH/OPRR
oversight of IRBs focuses on assurances.
Each of these systems incorporates valid oversight tools.
However, we agree with the OIG that similar oversight policies
and close collaboration would strengthen the protections to
human subjects. Moreover, a common policy would result in
a more efficient regulatory scheme that would be advantageous
to both the federal government and to IRBs. We believe that
a shared policy between FDA and NIH/OPRR will improve the
ability of IRBs to comply with federal policies, regardless
of whether the research protocol is regulated by NIH/OPRR
or by FDA. We also support the OIG's recommendation that NIH/OPRR
and FDA involve other departments in the Department of Health
and Human Services, as well as non-federal parties such as
IRBs, sponsors, and clinical investigators, in development
of a shared policy.
III. CONCLUSION
Congressional efforts in the 1970s established an excellent
system of oversight. The United States continues to be an
international leader in both oversight of human subjects participating
in clinical trials and biomedical research and development.
However, WIRB supports a review that seeks to address changes
in the research environment and to provide consistency in
oversight of clinical trials, whether funded by the federal
government or the private sector. The central issue is to
ensure human subject protection through the use of an efficient
and consistent oversight policy.
Independent IRBs have responded to the legitimate needs of
the medical research community by providing an independently
based assurance of human subject protection. As independent
IRBs, we play a critical role in protecting rights of research
subjects as well as facilitating the development of new medical
therapies.
We thank you for the opportunity to present our views and
we look forward to continuing to work with Congress, HHS and
FDA to protect the rights of human subjects who choose to
participate in clinical research.
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