by private sources, not the NIH and not Federal sources. We find ourselves in situations where private sources are beginning to put restrictions on information that is available to not only subjects but to IRBS.

And in this area in particular I'd like to note for the Chair that we've had incidents where private companies have now stepped forward and said research cannot be published because it is held as a secret or that it has been contracted with an institution, that it will be done with condition that the company must sign off. A recent example of this was Boots, now the Knoll Pharmaceutical Co., with its drug Synthroid-is one such example of restriction of information.

Mr. Chairman, if an IRB cannot get all the information that it needs to have about conflict of interest, financial sources of funding, if a firm is in a position to say that it will not publish legitimate findings about a particular drug or device, then the interest of subjects cannot be protected. So if we need to-and I feel we must-we have to ensure that IRBs have the information available to them so they can know when a researcher has a conflict of interest. We need to make sure that secrecy and provisions of restriction on findings of information are not part of what goes on in American institutions. In the end, to fail to publish findings and I say this knowingly and deliberately-but to fail to publish findings that you have is a betrayal of what is owed to human subjects. If you don't get results out, if you don't put them in the peer reviewed literature, then you've asked people to carry burden, be involved in risk, face a sacrifice in coming to and from experimentation, for no purpose.

And so for me, one of the most sad and unfortunate consequences of what we're asking our IRBS to do is we're asking them to work sometimes without the information, without the access that they need to have to do the job right.

That makes me cite a secondary issue, which I think the chair should pay close attention to. I'm very impressed with the previous panel and its comments about the role of IRBS and making sure that informed consent forms are understandable and that people have information.

But Mr. Chairman, I feel we have a system now that is spending too much time at the front end of research, looking at the written informed consent forms-that's what IRBS do. And the ones that I've served on-I would estimate that 97 to 99 percent of the time is spent in a room looking at an informed consent form, trying to translate medical jargon back to English. Sometimes that works and sometimes it doesn't. Sometimes subjects know more than you think because they've been involved with the disease process and have learned a lot about medical issues. So what looks difficult to understand to the outsider may be understandable to those subjects.

But where the system is not doing its job is in monitoring and making sure that what is on that form is actually taking place in the research setting. Very rarely do IRBS spend any time talking to subjects. Very rarely do they debrief anybody. Very rarely, if ever, do they find themselves in contact with researchers, actually going out and saying, did you sign this form, did you understand

this form, is it capturing the things that turned out to have been of interest and concern to you as you were a subject in research? In other words, the feedback loop that ought to be there between actual subjects and actual research, and what goes on in practice, and what you see at the front end when someone says, here is what I propose to do, and here is what the form is to accompany it, is broken. It is simply broken. And we have to do something to restore that loop of information so that when an IRB is taking a look at a research protocol it can say, we've been out and talked to some of these subjects, we know that the researchers are doing what they told us they would do.

We need more audit. We need more oversight. We need to get more time available for IRB members to spend talking with subjects. In this era—and I'm just going to make two more points and then I'll stop in the interest of time-in the era of IRB and informed consent work, there's something else that's missing, Mr. Chairman.

If you were to ask any of the officials who were with us in the previous panel, tell me; who is in research? What is the composition in America of who participates? What are the statistics about who is involved in the military? From the ranks of those with mental disability or mental illness? Minority people? Poor people?

That can't be answered. We have never insisted as a Nation that we collect basic statistics and demographics on who is involved. Are women over or underrepresented? Are the elderly over or underrepresented? Are Native Americans getting the access that they might have? We don't know. There is no data collected. In fact, sadly, incredibly, we collect more standardized data on animal use than we do for people in this country. And it seems to me some of the questions of informed consent, the adequacy of how research proceeds, and fairness and equity and access to research and, how well people are treated, require basic information for answers.

That leads me to the last point I'd like to make. In looking at research and informed consent it is clear to anyone who wants to look out here and you've talked about some of this this morning already, and I have to confess given the tone of direction of some questions, I'm on that Presidential Advisory Committee for Gulf War Illnesses, and the interest of research in the military has been of special concern to me as a member of that committee. But, I have to tell you, Mr. Chairman, that for our vulnerable populations-people who are impaired or unable to consent on their own for reasons of age or mental disability or institutional settings like a prison or service in the Army or even being a student, a medical student dare I say it is clear that informed consent has its limits, that there are just people out there who want to be in research, who want the opportunity to be in research, who, one way or other, are not going to be able to give a full informed consent to their participation in research.

We have not yet, I think written the regulations and put the kind of oversight in that would help those people. I'm sorry to tell you, Mr. Chairman, I don't think we have a policy today that is any different from what we had in 1990 prior to the Gulf war about research in the military. I think the issue could arise tomorrow as to what could or couldn't be done with soldiers or sailors or people

in the armed forces with respect to research and who would approve that and how that would proceed. We are operating with an interim, temporary rule in that area right now. We have been for 6 years.

And it seems to me we ought to fix that. When we look at issues involving research with the mentally ill or people who are institutionalized with Alzheimer's and see the number of problems and scandals and difficult cases that have arisen-at UCLA, the Medical College of Georgia-there are many, many settings where people have, I would say, been taken advantage of or not understood what is happening to them in terms of recruitment to research. The time has come, I think, to toughen those regulations and perhaps to add more than just IRB oversight. It may be time to say that we need to have some national or regional review of certain kinds of high risk groups involved in research and certain types of high risk research itself, that local IRB review may not be enough.

So Mr. Chairman, in summary, I think that the system we've got is better than what we once had, but it hasn't been much changed since 1981. That's the last time the rules of informed consent and IRB review got a thorough going over. I think it's overdue. I think there are some concrete steps that could be taken to toughen those regulations and afford better protection to those who make the gift of themselves to participate in research so that they and others may benefit.

[The prepared statement of Mr. Caplan follows:]

Mr. Chairman and distinguished subcommittee members, I very grateful for the opportunity to testify before this committee. The question of whether the time has come to consider changes in the way Americans are recruited to and participate in biomedical research is of obvious importance. This hearing is an especially important one since recent scientific advances continue to demonstrate the value of research with human subjects. Research is crucial to the high level of care that Americans can receive in our health system. However, research also requires the participation of subjects if progress is to continue to be made. Thus, it is essential that Congress remain vigilant with respect to the adequacy of the protections afforded those involved as subjects in biomedical research.

This nation has not always done what it should to insure the welfare and dignity of those who altruistically make themselves available as subjects so that medicine can learn and advance in the battle against disease and disability. the troubling revelations of the exploitation of subjects including children with mental retardation, the elderly and soldiers in the 1950s and 1960s in research involving the study of radioactive substances and the outright deception and fraud perpetrated by our government upon poor African American men infected with syphilis in rural Alabama for four decades in the notorious Tuskegee study, this nation's ethics have not always been what they ought to have been in the area of biomedical research.

As a result of these and other scandals coming to light, debate ensued in this nation concerning the ethics of human experimentation. In the past two decades We have as society made a commitment to do better to those involved in research as subjects. And we have.

In my view our current system of laws, regulations and teaching programs insures more protection of the rights and welfare of those involved in human research than exists anywhere else in the world.

Still, Congressman Shays, I believe that still more can be done. It is time to revisit the adequacy of human subjects regulation in the United States for three reasons; a rapidly changing research environment that casts doubt on the adequacy of informed consent and IRB review, a lack of basic information about who is involved in research and inadequate attention to the needs of those who are most vulnerable in research contexts. These reasons provide both a basis for a reexamination of human research ethics and for some recommendations I wish to offer this committee about reforms and changes that might help stregthen our existing protections of informed consent and peer review by IRBS to meet the moral challenges that have already and will continue to appear in biomedicine.

Shifts in Financing. Organization and Purposes of Human Research

For thirty years research in the United States has been subject to policies and regulations imposed by the Federal government. In the wake of scandals in the late 1960s and early 1970s such as the Tuskegee syphilis Study, the Brooklyn Chronic Disease Hospital cancer study, and the Willowbrook hepatitis vaccine trials two sets of protections were created for those recruited to serve as subjects in biomedical research. The first, informed consent, requires that participation in research be voluntary, informed and freely chosen. The second, review by local institutional review boards (IRBS), insures that the scientific marit, risk/benefit ratio and informed consent documents associated with individual research proposals are approved by the peers