DR. CHILDRESS: Our next speaker will be Stephen Post, Professor Stephen Post, representing the Alzheimer's Association.

For members of the commission he has made -- given us one copy of some materials. Those will be copied and distributed to the commission.

Stephen, I am not sure you were hear earlier. We are asking everyone to limit it to five minutes so we will have time for questions.

DR. S. POST: That is fine.

The chair of the National Bioethics Advisory Commission, Dr. Shapiro, wrote the Alzheimer's Association National Public Policy Office inviting testimony on research ethics involving subjects who are decisionally impaired. In response, the leadership of the association requested that I represent the association before you today.

The Alzheimer's Association and its network of over 200 chapters and 35,000 volunteers is the only voluntary health organization dedicated to research to conquer Alzheimer's disease and to providing support and assistance to people with the disease, their families and care givers.

Educating and informing the public and care professionals on ethical issues is one of the principle tasks of the association. Toward this end the association established several years ago a National Ethics Advisory Panel on which I have been honored to serve. With the guidance of panel member, Dr. Greg Sachs, this group has discussed research ethics in people with AD in great depth on numerous occasions and has issued a formal document entitled Ethical Issues in Dementia Research, which was approved by the association's board of directors in Chicago on May 18th, 1997, and I believe has been disseminated to all the association chapters as well as to this committee.

This document which then you have before you should be understood as an important contribution to the national debate on the issue, both because of its content and because of its source. It is not an end to discussion but it is a step forward. It attempts to balance the association's powerful commitment to delay prevention or cure of this horrible dementing disease which afflicts four million Americans directly and another 19 million as care givers with reasonable but not excessive protection for research subjects. Please consider it with care.

Because of limits in time I wish to highlight the three major paragraphs on categories of research and then offer some interpretation of these paragraphs based on lengthy panel discussions to which I was privy.

Category A: "For minimal risk research all individuals should be allowed to enroll even if there is no potential benefit to the individual. In the absence of an advanced directive proxy consent is acceptable."

Category B: "For greater than minimal risk research and if there is a reasonable potential for benefit to the individual the enrollment of all individuals with AD is allowable based on proxy consent. The proxy's consent can be based on either a research specific advanced directive or the proxy's judgment of the individual's best interests."

Category C: "For greater than minimal risk research and if there is no reasonable potential for benefit to the individual only those individuals who (1) are capable of giving their own informed consent or (2) have executed a research specific advanced directive are allowed to participate. In either case a proxy must be available to monitor the individual's involvement in the research. Note: This provision means that individuals who are not capable of making their own decisions about research participation and have not executed an advanced directive or do not have a proxy to monitor their participation cannot participate in this category of research."

Now as for the background discussion, which I think will help you interpret this, the conversations of the Ethics Advisory Panel indicate a wide definition in Category B of reasonable potential for benefit to the individual. The many new antidementia compounds under investigation would categorically be of reasonable potential benefit as would nearly all other current investigations. Thus the association endorses the proxy consent process currently in place in all the Alzheimer's disease research centers across the United States.

The ravaging nature of Alzheimer's disease, the strong desire of the association's grassroots constituency to make scientific advances, and the threat of AD to the well-being of millions and millions of people in our aging societies can permit nothing less. To quote the title of the association's 1996 annual meeting program, "A world without Alzheimer's."

But the association's document is highly protective of research subjects under Item C, that is in the clearly nontherapeutic context. Conversations of the Ethics Advisory Panel indicate that the research specific advance directive must include documentation of an explicit desire to participate in research beyond minimal risk that holds no potential to benefit the individual subject.

Further the panel and the association believe that for a considerable period of time after diagnosis people with AD ought to retain their capacity to complete such an advanced directive. The panel noted that there are many expressions of profound altruism in which individuals with the disease indicate an explicit desire to contribute to an eventual cure of AD for the benefit of future generations. Genetic risk factors suggest a concern for their children.

The association's position in Item C then is protective but it does not preclude such forms of altruism so long as informed consent is ensured. Monitoring by a proxy provides a fail safe mechanism consistent with comfort and dignity.

This document does not address the possibility of distinguishing between degrees of increase over minimal risk as the proposed Maryland legislation does but there is nothing in the association document inconsistent with efforts to define several levels of risk.

It should also be noted in the context of an irreversible and progressive dementing disease such as Alzheimer's family members eventually make decisions for their loved ones in all realms of life. The care of people with AD depends on trust and the association, which includes millions of care givers, has confidence in them.

On behalf of the association thank you for your kind consideration. The association and its Ethics Advisory Panel looks forward to close rapport with the National Bioethics Advisory Commission. AD has been called by Louis Thomas the disease of the century. Historian Arnold Toynbee said forty years ago that at the close of the century the greatest moral problem would not be death but the death of the mind before the death of the body.

No condition of severe mental dementia impacts on the present and the future as much as this one.

Thank you.

DR. CHILDRESS: Thank you.

Yes, Bernie?

DR. LO: I want to ask you a question about research advance directives. How feasible are they? Do you have a feeling for what percentage of Alzheimer's patients complete them. I want to put that in the context of the really disappointing response of the public at large to advance directives for their own medical treatment.

DR. S. POST: The use of research advance directives which occasionally occurs in the Alzheimer's population is by Dr. Sachs' acknowledgement extremely rare. This means, in fact, that in category C, clearly nontherapeutic research, the likelihood of an individual volunteering for such is really small. I think that is the subtext of this document if you will.

There have been remarkable cases, somewhat outlier cases, I have seen of individuals who consented to neurosurgery for research that held no therapeutic value to them personally and in one case an individual probably was harmed and wound up in a nursing home I think a year or two earlier than would otherwise have been the case. But I can only think of seven or eight of examples of that that I heard about anecdotally over the last five years. So these would be, if you want to call them, research groupies. They are an unusual breed and we view that Category C then as highly protective and is unlikely to be relevant to a great many individuals.

DR. LO: If I could just follow along, then is there an important research that would be foregone because of the impossibility of enrolling subjects for those kinds of studies?

DR. S. POST: I do not think so because the association, you know, you have to go to one of the association's board meetings to recognize, this association is hell bent on prevention or delay of the disease. The association's formal research policy statement is that if Alzheimer's disease could be delayed by five years it would effectively cut in half the number of people suffering from AD because they would die of other age related disorders before onset.

Almost anything you could imagine would be in Category B, that is to say potentially therapeutic, which raises some questions that I am sure you may want to consider and you probably have considered. But most of the research is, in fact, right now in the area of antidementia compounds and the association board and the panel believes that these compounds categorically as I said earlier are of potential benefit to any subject.

DR. CHILDRESS: Thank you very much.

DR. S. POST: Thank you very much.