Who Provides Informed Consent?
While informed consent from the research subject is possible when he or she is competent to give it, many persons with AD are no longer able to provide consent by the time they are diagnosed and could potentially be entered into a research program. Rather than deny these persons access to new treatments that are being studied, researchers usually proceed by surrogate consent, i.e., another person, generally the primary caregiver, consents on behalf of the subject. (A notable exception to this rule is the National Institute of Aging, which requires that researchers on its own premises gain the direct consent of the prospective subject while competent to do so for all forms of AD research.)
The Alzheimer's Association is dedicated to research to conquer AD and to providing support and assistance to people with the disease, their families and caregivers. The Association strongly endorses surrogate consent. Toward this end, the Association has approved a statement, Ethical Issues in Dementia Research (18 May, 1997) that attempts to balance the Association's powerful commitment to delay, prevention, and cure with reasonable but not excessive protection for research subjects. It's essential features are:
- "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 advance directive, proxy consent is acceptable.
- "For greater than minimal risk research and if there is 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 advance directive or the proxy's judgment of the individual's best interests."
- "For greater than minimal risk research and if there is no reasonable potential for benefit to the individual, only those individuals who (a) are capable of giving their own informed consent or (b) have executed a research specific advance 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 advance directive or do not have a proxy to monitor their participation, cannot participate in this category of research . ."
The above recognition of surrogate consent includes all except research which is greater than minimal risk and for which there is no likely therapeutic benefit for the subject. Certain critics of this policy, which reflects current practice, argue that it might lead to enrollment of subjects in research that they would not have consented to were they still competent.
What is Greater than Minimal Risk?
There is much debate about how to define minimal risk and greater than minimal risk. For example, drawing blood might be considered minimal risk, but for the person with AD who has no insight into the purpose behind a needle stick, the draw may be more emotionally stressful than would ordinarily be the case. A lumbar puncture (spinal tap), for example, while minimal risk for many subject populations, might cause considerable confusion and agitation in a person with dementia. Some position statements on AD research define minimal risk quite widely, while others are more restrictive.
When is There a Reasonable Potential for Benefit to the Subject?
The conversations of the Association's Ethics Advisory Panel indicate a wide definition of "reasonable potential for benefit to the individual." The many new anti-dementia compounds under investigation would categorically be of "reasonable potential benefit," as would nearly all other current investigations. But some critics assert that "reasonable potential benefit" should be defined very narrowly so as to protect persons with AD from research abuse in which they are enrolled in greater than minimal research on the grounds that it is potentially therapeutic for them when, in fact, it is not.
The Association's document is highly protective of research subjects being considered for enrollment in studies that pose greater than minimal risk and have no reasonably expected benefit for the individual subject (i.e., subjects who fall under 3 above). Conversations of the Association's Ethics Advisory Panel indicate that the research specific advance directive must include documentation of an explicit desire to participate in such research. Further, the Panel and the Association believe that for a considerable period of time after diagnosis, people with AD often retain their capacity to complete such an advance directive. The Panel noted that there are many expressions of 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, then, is protective, but it does not preclude such forms of altruism so long as informed consent is assured. Monitoring by proxy provides a fail-safe mechanism consistent with comfort and dignity.