Have the Conversation Early: Research Proxies in Alzheimer’s Disease

      Many patients with Alzheimer’s disease can still identify a trusted individual to make decisions about participation in research, even when their cognitive abilities have declined to the point that they may not be able to give informed consent for participation in a particular research protocol.
      This preserved ability can leave a window of time during which physicians and others caring for individuals with AD can offer patients the opportunity to identify a “research proxy” who can help the patient make future decisions about research participation.
      Patients’ core values and “authenticity of character” are often relatively preserved even after cognitive abilities and memory have begun to decline, according to research conducted by Scott Kim, MD, PhD, a senior investigator in the department of bioethics at the National Institutes of Health.
      Speaking in Minneapolis at the University of Minnesota’s ethics forum entitled “Research with Human Participants: the National Debates,” Dr. Kim shared findings from a study examining decisional capability in patients with AD.
      Dr. Kim and his colleagues interviewed 188 people with AD to determine their capacity to appoint a proxy and to consent to a lower-risk and a higher-risk clinical trial. They used a widely adopted competence assessment tool, along with an instrument they designed to assess capacity to appoint a proxy. Capacity determinations were made by five psychiatrists who each independently viewed all interviews (Arch Gen Psychiatry 2011;68:214–20).
      Overall, fewer than half of patients (82 of 188) were deemed capable of consenting to the low-risk trial and fewer than one in five (31 of 188) were found capable of consenting to the high-risk trial. However, 38% (40 of 106) of patients who couldn’t consent to the low risk trial were still found capable of identifying a research proxy, as were 54% (86 of 157) of those incapable of consenting to the high-risk trial.
      Dr. Kim and his colleagues concluded that “providing for an appointed surrogate even after the onset of AD, which might best be done in the very-early stages of the illness, may help address key ethical challenges to AD research.”

      Proxy Can Guide Research Decisions

      Clarifying a proxy for research decision-making is an important and separate process from designating a power of attorney for health care. Although clauses about research decision making can be written into power-of-attorney documents, participation in research is a separate — and slightly thornier — question than health care decision making. Not only do many research studies offer no direct benefit to participants but also participating in research may carry some risk for the patient.
      Still, many individuals with AD wish to participate in research, Dr. Kim said. Some may hope for some direct benefit from a particular clinical trial; others hope knowledge learned will help family members who may be at risk for dementia; for some, their desire to participate is purely altruistic.
      Using a legally appointed representative as a research proxy can lend flexibility and authenticity to these choices, without diminishing the legal and ethical clarity these decisions require, Dr. Kim said. If the proxy is appointed early and functions as a “concurrent proxy” — meaning that decisions are made jointly early in the course of AD — then that proxy can learn more about the patient’s core values and wishes through the shared decisions they make. Although this joint process doesn’t fit well into our “relentlessly individualistic” view of competence, it can work very well, said Dr. Scott.
      Whether an individual has decision-making capacity is a functional decision that should be based on the task-specific abilities that are relevant to the decision at hand, Dr. Kim said. Most adults are presumed to have capacity to give consent for research participation.
      In current thinking about who is or is not capable of giving consent for participation in research, decisions about capacity should not be based on a diagnosis, such as dementia, or a label, such as having an “unsound mind.” Rather, the threshold for capacity is fluid, and is affected by context, especially the balance of risk and benefit.

      Ideology vs. Reality

      Still, when it comes to research participation, “ideological concerns often trump careful review of clinical data and realities,” said Dr. Kim.
      Addressing a real-world concern, Dr. Kim said in an interview, “Health disparities often translate into the stage at which people seek help.” This means that for those with barriers to health care access, the window of capacity to appoint a research proxy may have closed by the time dementia is first diagnosed, shutting the patient out of research participation.
      The Alzheimer’s Association also addresses the question of capacity and proxy appointment, noting that “the proxy’s consent can be either a research-specific advance directive or the proxy’s judgment of the individual’s ‘best interests.’”
      Physicians interested in drawing up a research proxy, Dr. Kim said, should work with their institutional review boards to devise a format that includes information about the types of research and the degree of risk the patient is willing to undergo. Dr. Kim recommended leaving some flexibility in these documents to be used “only as guidance, not as a hard and fast rule.”
      As genetic underpinnings are being found for more and more neurodegenerative diseases, a greater number of patients will be offered the opportunity for research participation. For Dr. Kim, the research proxy offers a path to participation in research for many of these patients. “Even after the diagnosis of Alzheimer’s disease, it is usually possible to obtain a valid proxy directive,” he said. “As much as possible, involve the patient with dementia in the decision-making process; there are many, retained, preserved abilities that are ethically relevant.”
      Dr. Kim’s study was supported by a grant from the National Institute of Mental Health.
      Kari Oakes is with the Midwest bureau of Frontline Medical News.