Informed Consent Concerns for Study Participants with Neurological Disorders

By Stacey Kusterbeck

Despite clear ethical and regulatory mandates to obtain informed consent before research enrollment, multiple barriers exist for prospective participants in neurological research, according to Lauren R. Sankary, JD, MA, associate director of the Neuroethics Program at the Cleveland Clinic Center for Bioethics. These include cognitive impairments, aphasia, and fluctuations in cognitive function over the course of study participation.

Sankary and colleagues surveyed 113 research staff and identified these frequent barriers to informed consent: communication and cognitive impairments and research participants having unrealistic expectations, mistrust of research, time constraints, literacy barriers, and lack of social support.¹

Many of the research staff viewed the informed consent process as an opportunity to establish rapport, trust, and expectations related to study participation, notes Sankary. Researchers should consider these strategies:

• integration of social support in the informed consent process;

• collaboration with experienced research team members;

• encouraging participants to review consent materials in advance.

Informed consent tools “should support research personnel in emphasizing information related to study-related risks, voluntariness, and study duration,” says Sankary.

Adults with neurological disorders, particularly those who lack capacity to consent, are chronically underrepresented in the research setting, says Tara Coffin, PhD, MED, CIP, regulatory chair/vice chair at WCG. One challenge is that research staff must engage not only participants, but also their caregivers. “You essentially have to recruit two people, doubling the potential barriers,” Coffin explains.

These recruitment barriers have serious implications for studies that explicitly focus on individuals with neurological conditions. “When recruitment targets are unmet, clinical trials are stopped in their tracks,” says Coffin.

Careful design of study protocols can avoid some issues. Study protocols should include a plan to obtain consent from a legally authorized representative if the study participant lacks decision-making capacity, says Edward Kuczynski, director of the Human Research Protection Program at University of California, San Francisco.

However, research staff should not automatically assume the participant lacks the ability to provide consent. Researchers should turn to surrogates only if the participant meets objective criteria showing lack of decision-making capacity, says Kuczynski. Additionally, research staff should reevaluate the participant’s cognitive ability across the duration of the study. This is because for some individuals, the ability to consent may fluctuate during the course of the study.

For clinical trials focusing on degenerative neurological conditions, study protocols typically address these unique informed consent challenges. This is because all participants have neurological conditions that may affect cognitive functioning. However, all clinical trials should ensure that people with neurological conditions are included if eligibility criteria are met, asserts Kuczynski. That means research teams need specialized training to assess participants’ ability to provide informed consent. Research staff must plan to reassess this ability periodically, especially when there is a change in a participant’s cognitive status. “IRBs [institutional review boards] should be evaluating protocols for this longitudinal assessment of cognitive capacity,” says Kuczynski. IRBs also should verify that study teams are competent to assess decision-making capabilities and that documentation of such assessments is included in the study materials.

Some research staff wrongly assume that participants with neurological conditions are unable to engage in the informed consent process at all. “Certain neurological conditions may impact the participant’s ability to engage in an informed consent process. But this is not always the case,” says Coffin.

If a potential participant has impaired ability to provide informed consent, and the research team has not planned for evaluating cognitive functioning and surrogate consent, these individuals will be excluded from study participation. “Many studies include among the inclusion criteria that the individual must be capable of providing informed consent,” notes Kuczynski.

Sometimes, a legally authorized representative is required to obtain initial and ongoing informed consent. Even so, research staff should continue to involve the participant in that process to the greatest extent possible. For example, researchers can use a structured assent process. Research staff explain the purpose of the research, its risks and benefits, and what will be asked of the person if they choose to participate. “The individuals should be offered ample opportunity to discuss the research with their healthcare providers, friends, and family, and ask questions,” says Coffin. Assent then can be documented in a manner determined by the study protocol and the IRB. That may include verbal confirmation or written confirmation. “It is not always a regulatory requirement to obtain assent,” acknowledges Coffin. “But from an ethical perspective, it is critical to respect the individual’s autonomy.”

REFERENCE

1. Sankary LR, Zelinsky ME, Ford PJ, et al. Overcoming barriers to informed consent in neurological research: Perspectives from a national survey. Res Ethics 2023;19:42-61.