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Boston—The last year and a half was an embarrassing and humbling period for institutional review boards (IRBs).
First came reports and recommendations by the President's National Bioethics Advisory Commission, the General Accounting Office, and the National Institutes of Health (NIH) Office of the Inspector General, all of which were critical of the current IRB system's ability to deal effectively with increasing workloads and changes in the way research is conducted and of its ability to adequately protect human subjects participating in research.
Then, to general surprise, the NIH Office for Protection from Research Risks (OPRR) shut down clinical research for brief periods at some of the nation's most prominent medical centers because their IRBs failed to follow all the rules regarding the research review process.
With this background of low confidence ratings and a sudden push into the limelight with disclosures of shirked responsibilities, IRB members and other human research watchdogs came here in December seeking affirmation and guidance on how to avoid future slings and arrows from the OPRR and a dissatisfied public. A record-setting 1300 registrants attended the 25th annual meeting of Public Responsibility in Medicine & Research (PRIM&R) and its membership organization, the Applied Research Ethics National Association (ARENA). These two groups have assumed the leadership role in education and training programs for IRB members.
Despite the cloud of criticism hanging over the IRB system, the overall meeting and the breakout discussion sessions did not give way, as one might expect, to defensive arguments. There was general acceptance that IRBs are in trouble, that changes are necessary, and that their primary task is to find reasonable solutions to the problems at hand. Those who came to the meeting with thoughts that IRBs had been chastised by a group of nitpicking bureaucrats left with a very different impression.
Suspension and cleanup
Rush-Presbyterian-St Luke's Medical Center in Chicago was one of more than a dozen institutions at which the OPRR shut down research activities. David Clark, PhD, the center's director of research affairs, said that "OPRR staff were consistently clear and direct in their communications, willing to explain and educate, and were friendly, helpful, and encouraging."
The OPRR simply found that for the amount of research being conducted at Rush, there was inadequate staff, budget, and space to do what had to be done. "This made the institution vulnerable," Clark said, because it led to "too much responsibility concentrated in one administrator, too much administrative presence on the IRB, and too few people who understood the regulations."
Jerome Sugarman, MD, MPH, director of the Center for the Study of Medical Ethics and Humanities at Duke University School of Medicine, described what it was like to be called in to rectify the suspension of new clinical research at Duke earlier this year. Using a clip from the film Pulp Fiction, Sugarman likened his task to that of Harvey Keitel's character, the Cleaner, who specialized in cleaning up the bungled outcomes of gangster activities. Despite the comedic analogy, there was nothing funny about Duke's quick and decisive response to the OPRR, which Sugarman compared to Kubler-Ross's four stages of dying: denial, anger, bargaining, and acceptance.
Within a matter of days, Sugarman said, the cleanup had alerted all investigators, ceased all research, assembled a task force, developed an action plan, named an interim IRB administrator, met with the OPRR, and had the suspension lifted by day four.
The suspension, however, is just the beginning, Sugarman said. "As we move forward, there will be mandatory educational programs for everyone involved in research, and the use of consultants for specific areas of concern. Resources for IRB staff have been increased from 1 to 6 and eventually to 12 [positions]. A second IRB has been formed and a third is planned for the near future. A national search is under way for a full-time IRB administrator, and continued conversations with, and reporting to, OPRR are now in place," he said. "We have gone from talking about what the rules should be to falling in line with what the rules are."
Many IRB failures to meet OPRR requirements result from the pressure cooker environment under which the IRBs operate. Nonetheless, the OPRR's response and philosophy are simple. As OPRR Director Gary Ellis, PhD, was quoted as saying in the New York Times following the Duke action, "In medicine, all doctors know that if something isn't documented in the medical records, it wasn't done. That's a good standard for medical research as well."
Efforts have begun to remedy some of the shortcomings of IRBs. ARENA is starting a certification program for IRB professionals (including office administrators as well as committee chairs and members) that will aim to advance the quality of services to human subject protection programs. The first credentialing test will be given this fall, and up to three times a year thereafter at various locations around the country.
To help relieve IRBs of the extra burden experienced with the growth and complexity of new research projects, some institutions are appointing data monitoring committees (DMCs) to review interim study data as they accumulate, focus on analysis of study design and protocol issues, and recommend continuation, modification, or termination of the study after each review.
According to Susan S. Ellenberg, PhD, of the US Food and Drug Administration's Center for Biologics Evaluation and Research, DMCs have traditionally been used for trials with mortality or major morbidity end points. Today, with the increasing number of industry-sponsored trials with major end points, Ellenberg suggested that DMCs could inform IRBs about the status of ongoing trials, particularly with regard to reporting adverse events and suggesting modifications in trial design.
More institutions expect to reduce the IRB operational deficit by charging for IRB review. Ernest D. Prentice, PhD, associate dean at the University of Nebraska Medical Center in Omaha, noted that "pharmaceutical companies already pay fairly large IRB review fees to independent IRBs, which are growing in both size and number. Additionally," he said, "the number of academic institutions that charge for IRB review has increased dramatically. Institutional review board review fees are rapidly becoming the standard of practice and may, in fact, help an institution become more competitive."
As more patients view research studies as their last or only hope for treatment, attitudes are changing regarding the appropriateness of billing private insurers or Medicare for the costs of clinical research trials. Traditionally, Medicare has prohibited such reimbursement. However, Robert Forrester, of Price Waterhouse Coopers LLP in Boston, pointed out that as more research is conducted in conjunction with and as a part of the care of patients, the costs of usual patient care and studies, analyses, surveys, and related activities that serve the provider's administrative and program needs are allowable costs in the determination of payment under Medicare.
New efforts are being explored to offer payment directly to patients for their participation in research studies. Christine Grady, RN, PhD, head of the Section on Human Subjects Research in the NIH's Department of Clinical Ethics, described three models: market, wage payment, and reimbursement. Grady favors the wage-payment model, which operates on the notion that participation in research "requires little skill but does require time, effort, and the endurance of undesirable or uncomfortable procedures." She emphasized the need, however, to investigate the ways that money may affect a patient's decision making, the quality of a subject's informed consent, and the recruitment of a disproportionate number of poor subjects.
Updating the system
Regulations for current IRBs were conceived as a system involving solo investigators working with government grants in a single institution with a distinct cohort of subjects. This scheme reflects a small percentage of today's research projects. Many are privately funded preclinical or basic research projects involving multisite trials using large numbers of subjects. This change has created gaps in applying and monitoring assurances for the protection of subjects. Attention that used to be paid to increasing the number of women and minorities in clinical trials is now shifting to the challenges of ensuring new or additional safeguards for vulnerable populations, such as the "decisionally impaired," children, prisoners, and patients involved with emergency care research.
On a larger scale, several study groups have recommended that the OPRR be moved from the NIH to the Department of Health and Human Services and that the office receive more federal funds to do its work. Those changes would help improve the regulation of research that is already subject to IRB review. There has been some talk of extending similar types of review to cover the current unregulated research carried out or financed by state governments and the private sector.
A number of speakers at the meeting here alluded to the need for changing the culture of institutions with respect to human subject protections. But as Rush Medical Center's Clark noted in his presentation, this is "akin to an enormous oil barge making a 180-degree turn mid-ocean," a process that will take a very long time.
Coping with pressure
In summary, the pressure cooker analogy still holds for the IRB system, with the pot being the IRBs in which the research process cooks. The pressure of increased work loads will continue, as will the heat from the OPPR and government oversight. Nonetheless, as the PRIM&R meeting showed, new escape valves seem to be opening in the form of education and training of IRB members and staffs, additional financial and material resources, and better information management systems.
Phillips DF. IRBs Search for Answers and Support During a Time of Institutional Change. JAMA. 2000;283(6):729–730. doi:10.1001/jama.283.6.729
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