Mr. SHAYS. At this time, I recognize our witnesses before swearing them in, just introduce them: George F. Grob, Deputy Inspector General for Evaluation and Inspections, U.S. Department of Health and Human Services, accompanied by Dr. Mark R. Yessian, Regional Inspector General for Evaluation and Inspections. A second testifier will be Dr. Eric Meslin, Executive Director of National Bioethics Advisory Committee, U.S. Department of Health and Human Services; and Dr. Gary Ellis, Director, Office of Protection from Research Risks, Office of Extramural Research, National Institutes of Health. [Witnesses sworn.] Mr. SHAYS. Note for the record that all our witnesses responded in the affirmative. And let me just say, before recognizing you, Mr. Grob, we have before us four reports done by your office, the Office of Inspector General. One is entitled "Institutional Review Boards: The Emergence of Independent Boards." Another is "Institutional Review Boards: Their Role in Reviewing Approved Research." Another is "The Institutional Review Boards Promising Approaches." And another is "Institutional Review Boards," titled now, "A Time for Reform." It's original draft was "A System in Jeopardy." And I would like to say that while I believe these are very balanced reports, if anything, I think they understate the concern we have about the IRBS. Mr. Grob. STATEMENTS OF GEORGE F. GROB, DEPUTY INSPECTOR GENERAL FOR EVALUATION AND INSPECTIONS, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, ACCOMPANIED BY MARK R. YESSIAN, PH.D., REGIONAL INSPECTOR GENERAL FOR EVALUATION AND INSPECTIONS, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES; ERIC MESLIN, PH.D., EXECUTIVE DIRECTOR, NATIONAL BIOETHICS ADVISORY COMMITTEE, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES; GARY B. ELLIS, PH.D., DIRECTOR, OFFICE OF PROTECTION FROM RESEARCH RISKS, OFFICE OF EXTRAMURAL RESEARCH, NATIONAL INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Mr. GROB. Thank you, Mr. Chairman, and members of the committee. Again, I would like to introduce Dr. Mark Yessian, who is our regional director in Boston, and it was he and his team that prepared these reports that we're discussing here today. Mr. Shays, I think you did an excellent job of summarizing the findings of our report, that it will make it a little easier for me to deal with the reports in the brief time I have for my oral testimony. Perhaps, I can supplement what you have said by providing a little bit more background about their origin and their implications. And, perhaps, I could begin by addressing the question you raised in the change in title. The original title was "A System in Jeopardy," and we did change it because some of our reviewers, while not disagreeing with what we found, felt that they might have been too alarmist. And it was our feeling that it would be better to concentrate our discussions on what should be done about the problem than on the particular language that was used in the title. So we were more than happy to change the title for that reason so we could get down to the business of making the repairs that we think are made. We do come before you with a feeling that we need to give you a warning that the system that we have relied on for many years to protect human research subjects may not be adequate to the job now, and perhaps even less in the future. I myself would liken it to a shield, which has been hardy in the past but may be outdated now. It is brittle, strained, and, I think, even cracked. We certainly need a better one. The four reports that you highlighted before are the ones primarily on which our testimony is based. But I think that it is worthwhile to recall an earlier report that we did 3 years ago. This report, "Investigational Devices For Case Studies," was actually the origin of our work here. We prepared this at the request of the Food and Drug Administration who were concerned about the way trials were being conducted for investigational devices and particularly their premature commercial application. So we worked with them to review four case studies, and I think a brief summary of what we found there would be in order here. We found in one of the trials, or in one of the research centers, that there were three times as many patients that had implanted in their bodies a device that was a device for testing, three times more than were approved in the research protocol. We found another research site that continued to conduct the research on a device 6 weeks after the IRB had asked them to halt. We found another one in which the researchers did not make the changes to the informed consent forms that the IRB had asked them to make. And, generally, we found some missing or problematic consent forms for some of the research subjects. It was these findings of these particular problems that led us to do the broader study that is the subject of our hearing today. The things we found there are just not supposed to happen. So we thought well let us take a look then at the system under which that did happen. The system is one that was built for a research world that largely does not exist anymore. Originally when it was designed, it was for research conducted at a single site by a single investigator with small cohorts of subjects under Government-funding and primarily at a university or teaching hospital. Today, research tends to be multi-site trials, across the country, some even across the world, involving tens or hundreds of researchers, thousands of research subjects. We see an increased use of commercial sponsors of the research and we see research done in new sites, such as doctors' offices, managed care organizations, in-vitro fertilization clinics, and diet and weight loss centers. We see, as well, an increase in interest in the research subjects wanting to participate in the research, wanting to get drugs that are available, perhaps wanting to make some money to help them through school. And we see new types of research that are coming to the fore. The IRBS are faced with these research challenges. They are also faced with a great increase in the amount of research that is being conducted in this country, and perhaps at a pace that has outpaced their ability to deal with them. Perhaps one of the strongest findings we have is what we consider an inadequacy in the role of continuing to review the research protocols, as opposed to the initial approval of the protocols. We identified threats to the independence of the boards, a lack of training, and a lack of evaluation and oversight. In response, Mr. Shays, to your request that we try to deal with coming to grips with the problem, we concentrated in the reports on offering a framework for solution. In this report we offer, I think, a lot more recommendations than we usually do in our reports; and we tried to present them in a framework that the research community could use to consider some of the problems that we raised in the report. I won't repeat them now because they are in the report and they respond to the findings that we have here. Mr. SHAYS. Let me just say to you, I'm going to roll over the clock, and just expect that you'll stop between the 5 and 10 minute framework. Mr. GROB. OK. I think I can summarize now, perhaps, if you will allow me to put things in perspective. In the most recent reports, we did not attempt to systematically identify the extent of the problem that was out there. We thought that the problems that we had found earlier were enough to warrant a look at the system itself and that's where we concentrated our efforts. In this report, we don't claim that the research abuses are particularly widespread. We just haven't done enough random studies to know that that is the case. And we recognize very much the dedicated and conscientious board members often working long hours as volunteers to deal with these problems. In fact, we even went out of our way to produce one report that showed innovations and promising approaches that these IRBS themselves were developing to improve the way that research is done. Nevertheless, we end with a feeling that this is the time for the reform of this system; and we would urge action to be taken as soon as possible. Thank you very much. [The prepared statement of Mr. Grob follows:] Good morning. I am George Grob, Deputy Inspector General for Evaluation and Inspections in the U.S. Department of Health and Human Services (HHS). I am pleased to testify at today's hearing on Institutional Review Boards (IRBs). With me is Dr. Mark Yessian, Regional Inspector General for Evaluation and Inspections in our Boston office. Mr. Chairman, the IRB system, which has provided important protections for human subjects for so many years, needs to be reformed. While I bring you no evidence of widespread harm to research subjects at this time, I do feel obligated to call your attention to weaknesses inherent in the system that was designed to protect them. Research and medicine have changed dramatically in the past decade. However, our system for ensuring human-subject protections has not kept pace with these changes. Its shortcomings could become more apparent and significant in light of future developments. These include plans to increase the Federal investment in cancer and other biomedical research and a number of recent proposals recommending greater responsibilities for IRBs in the areas of genetics and patient confidentiality. My testimony is based on more than a year of inquiry into the work of IRBs that we have just completed and on an earlier study performed by our office. Today we are releasing four reports that describe the results of our recent work. Our total effort reveals a brittle system Human Resources Subcommittee June 11, 1998 and even a few cracks. I call these to your attention now in the hopes of preventing more serious problems in the future. Background on Our Inquiry We initiated the broad, systemic review in response to concerns raised in a prior Office of Inspector General study. In that study, we examined clinical trials involving four investigational medical devices, and, in each case, discovered limitations related to IRB review. These concerned serious matters such as the implantation of a device in three times the number of human subjects specified in the IRB-approved research protocol, the initiation of a research effort without the changes called for in the informed consent document, and the continuation of a research project for six weeks beyond when the IRB had suspended it. We were also aware of concerns about the IRB system raised by others. For instance, in its 1995 report, the Advisory Committee on Human Radiation Experiments questioned the adequacy of the IRB review process and the effectiveness of Federal oversight. In that same year, the General Accounting Office issued a report identifying numerous factors inhibiting IRB performance. Human Resources Subcommittee House Government Reform and Oversight Committee June 11, 1998 Page 2 |