Since dementia patients and others with limited decision-making capabilities cannot defend their own interests when participating in a clinical trial, researchers and ethicists have called for policy-makers and stakeholders to develop concrete ethical and legal guidelines to protect this population.

According to a new study published in IRB: Ethics & Human Research, current regulations and guidelines provide insufficient direction to Institutional Review Boards (IRBs) or ethics review committees on how best to protect those who are incapable of making informed judgments about participating in research. The study also found that regulations lack clear guidance as to who can make decisions on behalf of these research subjects.

The study, called Research with Decisionally Incapacitated Older Adults: Practices of Canadian Research Ethics Boards, found a wide variability in ethics board practices for protecting human research subjects with Alzheimer’s disease and others with limited capacity to make decisions. The researchers discovered more than 20% of ethics boards surveyed don’t require additional protections for this population, such as assessing decision-making capacity, and none of the institutions called for particular monitoring of these types of studies once they were underway.

“The findings are significant because of the inability of many of these subjects to protect themselves, express discomfort or fears and, most importantly, withdraw from the study,” said Gina Bravo, Ph.D., the study’s lead author, a professor in the Department of Community Health Services at the University of Sherbrooke, and at the Research Centre on Aging, University of Geriatrics of Sherbooke, Quebec. “Close relatives are rarely available on a daily basis to oversee participation in the study and defend the interests of the subject. It makes little sense that the protection afforded to these subjects through the IRB system varies across IRBs, provinces or states.”

Bravo and her study co-authors called for the establishment of comprehensive regulatory criteria for research that involves this population in Canada and around the world. “We would like to see clearer—and more uniform—rules about who can provide third-party consent to research in place of a decisionally-impaired prospective subject, and in what circumstances,” said Bravo. “We’d also like to see obligations on the part of IRBs to more closely monitor protocols involving this population and clearer guidance regarding the use of research advance directives.”

The issue has moved to the forefront as many countries have made research on dementia a national health priority. According to Alzheimer’s Disease International, the umbrella organization of national Alzheimer’s Associations around the world, the worldwide costs of dementia exceeds $604 billion each year and a number of countries have started dementia programs that include a research component. Some of that research will include subjects with dementia who already are, or are likely to become, decisionally impaired.

In a separate report, Stefan Eriksson, associate professor of research ethics at the Centre for Research Ethics & Bioethics at Uppsala University, Sweden, said research with dementia patients and others with limited decision-making capabilities is necessary to develop future treatments to benefit these groups. Yet he found current guidelines allow for the possibility of vulnerable people to be exploited.

“There are ethical guidelines to guard their interests, but they are somewhat ill-guided,” said Eriksson, whose study, On the Need for Improved Protections of Incapacitated and Non-Benefiting Research Subjects, was published last year in the journal Bioethics.

Eriksson said ethical standards used in research often don’t make sense for adults who can’t give their informed consent. For example, he said ‘minimal risk standard’ builds on the idea that there is something ordinary or routine about the risks we take in our daily lives and that such risks should then be acceptable in research as well. “This kind of reasoning doesn’t work for someone with Alzheimer’s. The same is true for ‘very slight impact’ and ‘routine examination,’ notions that don’t translate well to a person who might very well react in a different way than a person without dementia,” he said.

The guidelines should be rewritten, said Eriksson, and include safeguards for subjects with limited capacity to make decisions. “We need to monitor this kind of research more closely and provide legal obligations to compensate for any injuries suffered,” he said. “We also need to consider other issues, such as how surrogate decision-makers can be of use to these persons and how to find ways to estimate a dementia patient’s capacity for autonomy. We need to continue the debate and do more research on the ethics of research on persons with limited decision-making capacity.”

--Karyn Korieth