UI Study Examines Informed Consent Among People with Schizophrenia, HIV

An important first step in any research study involving human subjects is confirming that the potential participants are capable of making an informed decision whether or not to enroll in the study, after being told of all procedures, risks and benefits.

Known as providing informed consent, the process helps ensure that participants are acting of their own free will, that they understand what they are agreeing to do, and that they will be treated ethically during the study. But what happens when an investigation aims to involve people with an illness that can affect decision-making abilities? How can one be sure these individuals really have the capacity to decide for themselves?

To examine this question of competency, University of Iowa Health Care investigators used a hypothetical drug trial to compare the capacity for providing informed consent among 25 potential participants with schizophrenia and 25 participants with HIV (some of whom had been diagnosed with AIDS). The findings, published in the July issue of the American Journal of Psychiatry, reveal that most people with either condition were able to provide consent, although one in five people with schizophrenia had significantly decreased capacity to do so.

In addition, in an interesting corollary, the results suggest that the ability to decide to participate in a research study must be carefully assessed in all potential participants, regardless of the topic under investigation or known mental condition of the subjects.

"Patients with schizophrenia and HIV were compared because both can have problems with thinking, memory and attention," said David Moser, Ph.D., UI assistant professor of psychiatry and lead author of the study. "These types of cognitive dysfunction can obviously bring about problems with the ability to provide informed consent."

Moser said that while HIV is not a psychotic illness, individuals with the condition, as a group, share some similarities with people who have schizophrenia. In addition to the potential for cognitive dysfunction, both illnesses are ongoing and are accompanied by similar levels of anxiety and depression, and individuals in the two groups are often demographically similar in age and education. Both groups are often invited to be in research studies, as well.

Impetus for the UI study also came in part from a 1998 National Bioethics Advisory Commission report that detailed 21 ways to protect research participants who have conditions that might impair mental status.

"I think the commission's intention was good, without a doubt, but the report focused on psychiatric diagnoses, as if just having a psychiatric diagnosis said much about a person's decisional capacity," Moser said. "In fact, decisional capacity can vary quite a bit across health conditions whether they are psychiatric conditions or not."

The investigation built on informed consent studies by other researchers, notably Will Carpenter, Jr., M.D., professor of psychiatry and pharmacology at the University of Maryland School of Medicine, and Paul Appelbaum, M.D., professor of psychiatry at the University of Massachusetts Medical School, who also was part of the UI-led study. Previous research has shown that people with schizophrenia, as a group, can make informed decisions about research participation. However, they tend to perform more poorly compared to people who do not have a mental illness.

Moser said the UI study focused on finding the extent of this vulnerability in people with schizophrenia and, if they were vulnerable, what might be underlying their decision impairment.

The study involved asking individuals with schizophrenia or HIV to pretend they were potential candidates for a study of a made-up cognition-enhancing drug called Synaptoclear. No deception was involved. Individuals read and considered informed consent materials, similar to actual materials, that described the hypothetical six-week trial as a randomized, double-blind, placebo-controlled study that would also involve hospital visits and possible side effects. Decision-making capacity was then quantitatively assessed using a structured interview, and subjects were also given neuropsychological and psychiatric assessments.

The study found that 80 percent of the people with schizophrenia (20 of 25 individuals) and 96 percent of those with HIV (24 of 25 individuals) showed "adequate capacity to consent" to the hypothetical medication study. However, the people with schizophrenia had, on average, significantly lower scores in several important markers that relate to a person's decision-making ability. Moser said the team was interested to find that, of the various symptoms of schizophrenia, problems with thinking, apathy and avolition (behavioral slowing or shutting down) were related to a decreased ability to provide consent, yet hallucinations and delusions were not.

"A common but, as it turns out, inaccurate view is that hallucinations and delusions have a major affect on one's ability to make decisions," Moser said. "In fact these seem to play a relatively minor role. Cognitive dysfunction and symptoms such as apathy and avolition seem to play a much larger role. These are problems that are not unique to schizophrenia, but occur across a wide range of conditions."

The questionnaires used to test the competency of each subject for the hypothetical trial included the MacArthur Competence Assessment Tool for Clinical Research, and the Evaluation to Sign Consent (ESC). The ESC also was used to get actual informed consent for the study about consent. All the participants passed that assessment.

"We definitely got informed consent for people to participate in our actual study about the hypothetical study," Moser said. "Everyone passed our actual study consent requirement likely because those procedures were relatively easy to understand, and the actual risks and benefits were less complex those in the hypothetical study. The actual risks included boredom or possible confusion about whether the hypothetical study was real."

The fact that the hypothetical study was so much more complex allowed the investigators to ensure they were not studying subjects who would necessarily be "competent" in all situations. "Everyone demonstrated adequate decision-making capacity for the actual study but some failed to do so with regard to the hypothetical study," Moser noted.

While the findings may not apply to all people with schizophrenia, they do apply to people who would at least consider being in a study, regardless of their decisional capacity. Moser said it is also very likely that some of the individuals who did not prove immediately competent in giving informed consent for the hypothetical study could, with cognitive remediation, be able to give informed consent. Such remediation would typically involve giving the potential subject an enriched opportunity to review consent form information and discuss these materials at greater length.

"Cognitive remediation, as it relates to competency, is not about 'fixing' a person's reasoning in general," Moser said. "However, it's possible to improve decisional capacity as it specifically relates to being in a given research study."

Moser said informed consent is a crucial issue because science is designed to improve treatment.

"The scientific world is continually struggling to figure out how to develop ethical guidelines and informed consent guidelines that provide adequate patient protection and at the same time not be so overly restrictive -- that is, stand in the way of scientific advance and information-gathering that can ultimately help these conditions," he said.

Moser's current studies examine the effects of medication on decision-making capacity in schizophrenia and how best to help those individuals with impaired capacity. He also is studying decision-making and susceptibility to coercion in mentally ill prison inmates, as this population has traditionally been considered vulnerable from a research ethics standpoint.

In addition to Moser and Appelbaum, the study involved UI researchers Susan Schultz, M.D., associate professor of psychiatry; Stephan Arndt, Ph.D., professor of psychiatry; Michelle Benjamin, research assistant in psychiatry; Frank Fleming, nurse manager in psychiatry; Colleen Brems, nurse practitioner in psychiatry and internal medicine; Jane Paulsen, Ph.D., professor of psychiatry, and neurology; and Nancy Andreasen, M.D., Ph.D., the Andrew H. Woods Chair of Psychiatry and director of the UI Mental Health Clinical Research Center.

The study was funded in part by a grant from the Nellie Ball Charitable Trust in Iowa City.