INSTITUTIONAL REVIEW BOARDS: A SYSTEM

IN JEOPARDY

THURSDAY, JUNE 11, 1998

HOUSE OF REPRESENTATIVES,

SUBCOMMITTEE ON HUMAN RESOURCES,

COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT,

Washington, DC. The subcommittee met, pursuant to notice, at 9:30 a.m., in room 2154, Rayburn House Office Building, Hon. Christopher Shays (chairman of the subcommittee) presiding.

Present: Representatives Shays, Snowbarger, Pappas, Burton, Towns, Barrett, and Kucinich.

Staff present: Lawrence J. Halloran, staff director and counsel; Anne Marie Finley and Robert Newman, professional staff members; Jesse S. Bushman, clerk; and Cherri Branson, minority counsel.

Mr. SHAYS. I call this hearing to order and welcome our witnesses and our guests.

The history of human subject protection follows a fitful journey between trust and tragedy: from the Hippocratic Oath to the Holocaust, from the Nuremberg Code to Tuskegee, from the common rule to the irresponsible administration of pyridostigmine bromide, PB, to United States troops in the Gulf war.

The bond of trust between researcher and subject, between doctor and patient, between Government and the governed, demands we heed warning signs before, not after, another tragic chapter in that history must be written.

Today, the Department of Health and Human Services [HHS], Inspector General [IG], sounds such a warning. Institutional Review Boards [IRBs], the local committees responsible for protecting the safety and dignity of persons participating in clinical research, are in jeopardy of being overwhelmed by the weight and complexity of their work. As a result, the 25-year-old system of review and oversight intended to ensure ethical design and implementation of research protocols is in need of structural reforms.

These important findings and recommendations by the HHS Inspector General confirm and amplify testimony we heard in May 1997, that the safety net to protect human research subjects was showing signs of age and disrepair even then. In this hearing, we ask what steps must be taken to strengthen Institutional Review Boards before the system is strained to the breaking point.

A quarter century ago, most biomedical research was conducted at an academic medical center or hospital by a single investigator studying a small number of subjects. The scientific merit, inherent

risks, research protocol, and informed consent materials were reviewed, approved, and monitored by local review board members who knew the community, the patients, the doctors, and the procedures involved.

But today's research environment has changed dramatically. Institutional Review Boards have not.

Large, multi-site studies involving thousands of participants challenge both the concept and practice of local IRB control. Increasingly sophisticated studies, involving biochemical and genetic concepts, considered scientific fiction just a few years ago, demand time and expertise IRBS often lack. Complex science can pose subtle, yet profound, ethical questions about risk assessment and the ability of subjects to consent; questions often beyond the capacity of altruistic, overworked, but ill-trained, IRB members.

Examples of systemic weaknesses in subject protections are readily available. I know Mr. Towns, the ranking member of this subcommittee, is particularly concerned about IRB approval of inequitable subject selection and lax informed consent procedures in a "fenfluramine challenge" study of childhood aggression conducted by the New York Psychiatric Institute.

And today, the entire membership of this subcommittee joins in introducing legislation to make sure U.S. soldiers will never again be required to take an experimental drug without first being given basic information, in writing, about the drug, the reasons for its use, known side effects, and possible interactions.

In both these instances, giving fenfluramine to children and giving PB to U.S. soldiers, the current system of bioethical review failed miserably.

To remain effective in an era of entrepreneurial research and managed health care, IRBs need greater expertise, broader representation, more resources, and effective Federal oversight. Many of these reforms are within the power of the IRB sponsors and administrators to implement immediately. The IG found promising approaches to IRB training, workload management, performance evaluation and broadened membership already being implemented. Still lacking, however, is the basic coordination needed to transform isolated innovation into systemic reform. Incredibly, Federal regulators know more about lab animals than they do about the human beings who subject themselves to medical research. The IG, and others testifying today, support central registration of IRBs to capture empirical data about practices and trends now discerned only through anecdotal evidence. We ask our witnesses today to discuss the feasibility and efficacy of this modest proposal.

When the footings of a highway bridge show signs of structural stress, we close the road and make repairs. While the IRB system continues in the main to perform admirably, a structure built on the fragile foundation of trust will not be repaired by self-congratulation or statistical quibbles about the extent of the problem. We look to all our witnesses today for your help in sustaining and strengthening Institutional Review Boards, and recommend any other ways to protect those who participate in medical research. Again, I welcome our witnesses and I look forward to our testi

mony.

At this time, I'd like to recognize the chairman of the full committee, Mr. Burton. And it's a real pleasure to have you here, Mr. Burton.

Mr. BURTON. Thank you, Mr. Chairman. I really appreciate the opportunity to be with you.

On April 22nd of this year, the full committee held a hearing focusing on the FDA's responsibility to oversee and protect clinical trial participants. It was apparent to me then, as a result of some compelling witnesses' testimony, that a real problem exists within the scientific community in providing meaningful protections to clinical trial subjects.

Several problems were discussed in the context of clinical trials. One was the use of placebos and/or wash-out phases in clinical trials which place subjects at high-risk for relapse in the case of psychiatric patients and for irreversible physical damage in the case of patients with heart disease and hypertension. Another was the non-beneficial experimentation on young minority children in New York City by several prestigious medical centers of the drug fenfluramine, which has been banned by the FDA as unsafe for use in adults. And that was very troubling.

The subject of meaningful oversight by Institutional Review Boards was also discussed and the experts who testified, as well as many members, expressed serious concerns over the conflicts of interest that exist among members of IRBs and the overload of protocols that they must review and approve. Thus, it is not surprising to me that the HHS IG, Inspector General, has determined in her draft report that IRBS are not living up to the standard of protection required by Government regulation. Of course, within Health and Human Services, the National Institutes of Health, including the Office of Protection Against Research Risks, as well as the Food and Drug Administration, are charged with the responsibility to oversee these review boards. And when I questioned the FDA about this, there was a lot of finger pointing and shifting of the blame to somebody else.

Thus, I'm pleased to see that some representatives of other potentially responsible parties are here today. I am concerned that the head of the FDA is not present, nor is the Director of NIH, nor HHS. I certainly hope that after this hearing, critical followup will be done to make sure that those agency heads are involved in the sharing of responsibility for this very serious and potentially growing problem.

And I thank you, Mr. Chairman.

Mr. SHAYS. I thank the chairman of the full committee, and assure him that this will not be our only hearing and that we will have the FDA, HHS, and NIH here.

Thank you very much.

At this time, the Chair would recognize the ranking member of this committee, a full partner in all our investigations and not only a tremendous friend but a wonderful Member of Congress.

Mr. TOWNS. Thank you very much, Mr. Chairman. Thank you for your kind words. I want to thank you for holding this hearing today. The report of the Department of Health and Human Services' Inspector General raises serious issues concerning the oversight these boards exercise in reviewing and approving research

study applications. The IRBs play an important role in approval of federally funded research. However, where research is privately funded, the IRBs are the only safety net protecting the human volunteer from unnecessary risks or harm.

In the course of preparing for this hearing, we have reviewed a New York case which is very, very disturbing. The research plan specifically included only African American or Hispanic male children between the ages of 6 and 10. The research plan excluded white children. In a document dated February 18, 1994, the researchers informed the IRB that all of the children have been selected for the study. Two weeks later, in a document dated March 2, 1994, the IRBs told the researchers to "reformat" the criteria to eliminate previous references to race or ethnicity. At this point, the researchers had spent 2 years selecting the children for the study. All evidence points to the conclusion that these selections were based on the original research plan. The institution has repeatedly stated that these selections were based on chance. Today, we know that those assertions are false. I would like to enter into the record the research plan and these memos. They provide clear proof that these children were chosen by design, not by chance. They were selected because of the color of their skin and the actions of their siblings.

Additionally, Mr. Chairman, let me add there are serious questions about the voluntariness of the participants, of the parents and the children. Government employees were used to interview the parents and enlist the children. The use of Government employees would give anyone the idea that the Government had condoned this experiment or that failing to comply could bring serious consequences.

Mr. Chairman, you and I know we would be foolish to refuse an invitation from the IRS. These parents would have been foolish to decline this invitation from the State government and officials.

Furthermore, there are problems about the payment mechanisms. The researchers provided separate payments for each test. This created an economic incentive for the parents and children to participate in as many tests as possible.

Finally, there is something very shameful here about compensation received by the children. Here, the children received gift certificates for food and toys as compensation for their participation. Mr. Chairman, these researchers have taken the purest innocent motivation of children, a desire to help, and have transformed it into a snare for the unwary.

Given all of these problems, the IRB voted unanimously to approve the study. The Inspector General's report finds that the IRB process needs reform. Well, I'd like to help it. If this case is indicative of the IRB's process, it needs to be torn down, rebuilt from scratch. Reforming is not enough.

It has been 20 years since a horrified Nation learned of the Tuskegee syphilis experiments. The IRB process was designed to assure that there would never, never, never be another Tuskegee situation. Yet, we are here today to listen to testimony about nontherapeutic, non-beneficial, medical experiments that involved only African-Americans and Hispanic male children. I'm left with a feel

ing of déjà vu all over again, and I'm saddened that we have again arrived at this point.

Finally, Mr. Chairman, following this hearing, we must-and I say we must-take strong and decisive action to assure that the Federal oversight process holds researchers and the IRB accountable, especially where experiments are improperly racially motivated or place children at risk without any possible benefit.

Thank you for holding this hearing, and I look forward to working very closely with you in the days ahead to be able to clean up this situation.

Mr. SHAYS. I thank the gentleman. Mr. Pappas, do you have an opening statement?

Mr. PAPPAS. No, Mr. Chairman.

Mr. SHAYS. Let me just get some housekeeping out of the way and ask unanimous consent that all members of the subcommittee be permitted to place any opening statement in the record, and that the record remain open for 3 days for that purpose. Without objection, so ordered. I ask further unanimous consent that all witnesses be permitted to include their written statements in the record. And without objection, so ordered.

And also you, Mr. Towns, want to submit for the record a document. Is that the document right there?

Mr. Towns. That's correct.

Mr. SHAYS. And without objection, we'll submit that for the record.

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