Subjects’ decision-making capacity must be part of the selection process

Don’t confuse competency with capacity, experts warn

Clinical trial investigators and research staff have a responsibility that goes beyond obtaining IRB approval when working with vulnerable adult populations and making certain all research subjects are capable of making decisions related to their participation in a study, experts say.

"This really is a developing area," says Virginia D. Buckles, PhD, research associate professor of neurology and executive director of the Alzheimer’s Disease Research Center at Washington University in St. Louis.

"Capacity assessment is an extra protection," she adds. "Where people sometimes get into trouble is in when there is pressure to recruit subjects and they think they have to get people into the study, so they’re not paying attention to this stuff."

While there have been more published data about decision-making capacity in recent years, the clinical trial industry still has a way to go in implementing the knowledge at the study level, says James M. DuBois, PhD, DSc, an associate professor and PhD program director at Saint Louis University.

To learn more about vulnerable study populations, he has conducted focus groups with people who have mental health disorders and who participated in research.

"One participant said he had attempted suicide while in a study," DuBois explains. "He was very calm about it, and he said, They did mention there was this risk that I could become suicidal.’"

Other participants said they were never told or else they had forgotten some information about the clinical trial, DuBois continues.

"One person talked about participating in a trial where they allowed them to smoke crack cocaine because they wanted to study the effects on the brain, and that raises ethical issues," he notes.

In designing studies for vulnerable populations — which DuBois defines as participants who have a compromised ability to grant voluntary informed consent because of cognitive or other difficulties — a variety of factors need to be considered, DuBois and Buckles say.

For one, investigators should avoid using the term mental competency because it has legal connotations, Buckles advises. Instead, researchers should assess decision-making capacity, which has four elements:

1. Expressing a choice

The research participant needs to be able to express a choice, saying, "Yes" or "No," or saying, "I want to" or "I don’t want to." This can be difficult for aphasic patients, she explains.

2. Reasoning ability

"They have to have reasoning ability so they are able to talk about and think about benefits and risks and weigh them," Buckles adds.

3. Appreciation/interpretation

Research subjects also need to be able to demonstrate higher level reasoning, deciding what their participation in a study will do for them personally, she says.

This may be the toughest element of decision-making capacity to measure because it is so subjective, Buckles notes. "When someone is considering treatment for a life-threatening disease that will extend life only a little longer, that gets to their appreciation of whether living like that is worth it to them," she says.

4. Basic understanding

Do the subjects have a basic understanding of what they’re being told by research staff? This includes an understanding of both written informed consent and a discussion with investigators about it.

While it’s ideal for subjects to meet all of these elements of decision-making capacity, for vulnerable populations capacity is determined on a sliding scale, DuBois says.

"When a research project is considered likely to benefit an individual and is of low risk, then a lower threshold for capacity is used," he adds.

"For example, in minimal-risk research, it might be enough that the person understands the information and agrees to it," DuBois points out.

"In very high-risk research, you want to make sure the person really understands how the research relates to them and that they’re capable of reasoning with the information, weighing risks and benefits," he says.

It’s also important to not assume that someone with a severe mental disorder lacks decision-making capacity, DuBois says. "Someone with a mental disorder may retain these capacities."

While a court decides whether a person is mentally competent, decision-making capacity is not as rigid a determination. It can come and go, DuBois continues. "In recent years, a fair amount of research has been conducted on ways to improve decision-making capacity.

"And I think the most promising approach is to quiz participants on the information that’s communicated; and [for] any pieces of information that participants do not understand, you have to provide further education," he says.

Education could include several repetitions of the information, which has been found to improve participants’ ability to understand and retain the information, DuBois notes.

Additionally, there are two types of tools available for assessing decision-making capacity, Buckles explains:

  • the vignette method;
  • a test tailored to an actual protocol.

The vignette method works this way — The patient is told a story about a person who has a brain tumor and who has two choices to make.

One choice is to try treatment with a drug or surgery, and the storyteller provides risks and benefits of each, leading the patient through the vignette, Buckles says. "Then they say, Pretend you’re this person. What should this person do? And what does it mean when they talk about the risks of this drug or surgery?’" she adds.

However, the problem with the vignette method is that it’s difficult to use in a population of people with dementia, Buckles notes.

"For one thing, you’re telling people with cognitive impairment to suspend reality. A couple of the patients who were told the brain tumor vignette asked the interviewer: You’re telling me I have a brain tumor problem?’ They couldn’t make this leap," she says.

"The vignette tool has good literature to support it, but there are downsides to it in terms of appreciation and telling some one who has cognitive impairment to assume or interpret relative to their own personal feelings," Buckles adds.

Another problem with this method is that decision-making capacity is a very specific concept. So someone might have the ability to manage his or her finances, but cannot make a health care decision, she explains.

The other method for assessing decision-making capacity is to tailor a test to an actual protocol, hitting on the four decision-making capacity elements discussed previously, Buckles suggests.

With this method, the person making the assessment would look for the following:

  • Does the person comprehend what he/she was told?
  • Does the person think about the risk and what it means to him/her personally?
  • Does the person make a choice?

"The good thing about this method is it’s valid and it has a specific application," Buckles says. "The downside is you have to tailor it to every person."

However, it may not have to be tailored a great deal. There is an available tool for determining capacity for clinical research, called the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), developed by Paul S. Appelbaum, MD, and Thomas Grisso, PhD.

This tool contains a set of questions requiring some adaptation to ask potential subjects, adds Buckles.

"It’s not a criterion-based tool; it’s a norm-based tool," she notes. "You compare their scores to your control group, but a lot of times clinical trials don’t have a normal control group."

Nonetheless, the MacCAT-CR is the most popular and most studied of the tools available for assessing decision-making capacity, DuBois says.

"You can use it with mental health and substance abuse populations, and its purpose is to determine whether or not they have the capacity to make decisions," he says. "Capacity is determined on a sliding scale with no fixed cut-off point."

Use of study partners

The Washington University Alzheimer’s Disease Research Center provides an example of another safeguard for dealing with vulnerable populations in research: an informant, who can be a family member or close friend.

About 90% of the time, this close informant is a spouse or adult child and meets the state of Missouri’s legal requirements of being a legally authorized representative, Buckles says.

"Usually when doing clinical trials in dementia, there is a study partner because participants forget things, and sponsors want someone there who can remind and help them," she explains.

"We try to educate our subjects and informants about research proxies, a concept that depends on state law to determine who can be a research proxy or designated surrogate," Buckles says.

"In Missouri, they have a clause for the medical research of determining who can give consent to participate." But this law only goes into affect if the person cannot consent for him- or herself, she adds.