Protect research subjects who have mental disorders

Advisory panel includes 20 guidelines in report

A presidential advisory panel, the National Bioethics Advisory Commission (NBAC), is in the final process of revising a draft of recommendations on protections for people with mental disorders selected as participants in research studies.

The report is expected to provide a framework for developing ethical research studies that do not unjustifiably exclude persons with men tal disorders from participation and offer needed protections to ensure that vulnerable patient groups are not exploited, says Patricia Backlar, research professor of bioethics at Port land State University and assistant director of the Center for Ethics in Health Care at Oregon Health Sciences University, both in Portland. Backlar is a member of the 17-person multi disciplinary panel.

Although a previous panel, convened in the mid 1970s, recommended similar guidelines, many of the recommendations were never implemented, she says. "That group did sets of recommendations for two groups of people who might have diminished capacity for consent or who may have impaired decision-making capacity: One was children; the other was the institutionalized mentally infirm.’"

The protections for children largely were implemented into law and public policy, but the ones for the "mentally infirm" were not, largely because of the rapidly changing focus of treatment for people with mental disorders and because the recommendations were seen as too restrictive to research, the professor adds.

"You can see one of the problems they had in the title," Backlar notes. "They used the word institutionalized’ just at the point when we were de-institutionalizing the mentally ill and these people were coming out into the community."

Although the final version of the report, Research Involving Persons with Mental Disorders that May Affect Decision-Making Capacity, is not yet complete, the 20 recommended guidelines have been drafted and the final wording and order to the recommendations is in its final stages. The report includes recommendations ranging from the establishment of governmental regulations at federal and state levels to guidelines for the institutional review boards who review and approve study protocols at the individual facility level.

The current committee’s work began partly in response to reported abuses of some people with mental disorders in research projects. Plus, the committee recognized that, as treatment and diagnostic methods became more and more advanced, more study of mental conditions was urgently needed.

"We know that there needs to be research, but we want to ensure that we have adequate protections in place for these subjects," Backlar explains. "Research is not the same as clinical treatment. The researchers are seeking generalized knowledge. The researcher’s obligation to the subjects is not that of a doctor to a patient, because in these situations they are not patients, but research subjects."

One of the most problematic issues in research involving subjects with mental disorders is the limited and sometimes fluctuating ability of the subjects to give informed consent to the study protocols.

"The issue is when you have people with fluctuating cognitive impairments, like schizophrenia or bipolar disorder, or prospective cognitive impairments, like people with Alzheimer’s disease, you really have to be careful about the design of the selection part of the protocol," Backlar says. "You need to get a really valid, voluntary consent. But because people with these disorders may lose the capacity [to understand and consent to the protocol], or it may come and go, you have to put ongoing protections in place in your protocol."

Impartial evaluation urged

The panel recommends that an independent health care professional evaluate each study’s protocol for evaluating the subjects’ ability to give consent.

Although people with mental disorders may have a more difficult time as a research subject, Backlar is quick to add that even people with seemingly severe impairments should be allowed to participate in research.

"Particularly because of new medications, many more people are going to be able to give consent," she says.

The guidelines cover issues such as these:

• how consent should be obtained;

• under what conditions the subjects should be informed if it is determined they are unable to give a valid consent;

• in what instances a legally authorized representative may give consent for the participant;

• how this process should be monitored to ensure the subjects’ consent is valid and remains so throughout the study.

Institutional review boards

A significant portion of the recommendations deal with the composition and role of the institutional review boards that will approve, evaluate, and monitor research studies.

Backlar particularly endorses the recommendation that review boards include two representatives who have personal experience with the illness being studied.

"I definitely feel that members of the population being studied should be on the institutional review board," she explains. "People who have these disorders often have periods of time when they are lucid and capable of decision making, and they should be included."

Another part of the guidelines establishes categories of risk for research studies. Under the current draft of the guidelines, studies would be subjected to different standards depending on whether they were of "minimal risk" or "greater than minimal risk" and whether they offered a possible direct benefit to the research subject. (For additional information, see related story, at right.)

"When you talk about research you can be talking about many different things," Backlar says. "You can be talking about minimal risk research. The kind of research I do on psychiatric advance directives involves just asking questions and getting psychiatric histories and so forth. The subjects come in, answer questions, and then go on their way."

Placebo or washout?

However, in some studies, the subjects may be asked to take a test drug or a placebo in a clinical trial for a new drug. "Those are the kinds of studies in which you would be concerned. You don’t know what is going to work. [You have to decide] what you are going to test it against and will you have a placebo or washout first?" she asks.

Standards on obtaining consent — and in what instances explicit consent is not necessary — vary according to the level of risk vs. benefit presented to the subjects.

A key part of minimizing unnecessary risk is appropriate subject selection, Backlar says. "Part of the guidelines states that you should not target people with mental disorders as study subjects when the study can be performed without them, for example, a study of a cancer drug. However, you don’t necessarily want to exclude them from a study if they genuinely want to participate and are capable."

Sources

For more information regarding the National Bioethics Advisory Commission recommendations, contact:

National Alliance for the Mentally Ill, 200 N. Glebe Road, Suite 1015, Arlington, VA, 22201. Phone: (703) 524-7600. Fax: (703) 524-9094. World Wide Web: http://www.nami.org.

• The draft report, Research Involving Persons with Disorders that May Affect Decision-Making Capacity, is available on the Web site of the National Bioethics Advisory Commission: http://www.bioethics.gov.