Informed Consent in Research and Individuals with Impaired Decision-Making Capacity

Food and Drug Administration (FDA) regulations and the Common Rule require that the selection of participants in research is equitable. “Equitable selection” generally refers to the idea that no one group should bear all the burdens of research or reap all the rewards. This term also refers to the idea of ensuring marginalized populations have access to research.  

These regulations also require that research include additional safeguards when some or all of the study participants are likely to be vulnerable to coercion or undue influence.  

The principle of equitable selection and the requirement for additional safeguards for certain vulnerable groups can seem at odds. We see this tension in the example of adults with impaired decision-making capacity. While these adults might be considered vulnerable to coercion and undue influence, and thus in need of additional protections, institutional review boards (IRBs), sponsors, and investigators must also be cognizant of not unduly limiting these individuals’ research participation in an effort to protect them. 

Putting It Together: Neurological Disease Research Example 

Consider the example of research on neurological diseases. Researchers continue to chip away at this challenging field, seeking new treatments and potential cures for these conditions. This research is urgently needed: In the U.S., neurological diseases create nearly $800 billion annually in healthcare costs. The economic, social, and emotional costs of these conditions will continue to grow with our aging population. 

When conducting clinical research on neurological diseases, researchers often must provide additional safeguards for the research participants. Conditions like Alzheimer’s disease, Parkinson’s disease, and others can cause both physical and mental impairment, making individuals vulnerable to coercion or undue influence. 

Researchers must be careful to ensure individuals with impaired decision-making capacity (and, if appropriate, their legally authorized representatives) are fully informed about a study and can provide legally effective informed consent to participate in research. A legally authorized representative (LAR) is any individual, judicial body, or other body who are authorized under applicable law to consent to research participation on behalf of a designated person (45 CFR 46.102(i)). Depending on where the research takes place, an acceptable LAR might be a health care proxy, medical power of attorney, or a caregiver. 

Understanding “Capacity” 

In this context, “capacity” refers to a potential research participant’s ability to: 

• Make and express a choice 
• Understand relevant information 
• Appreciate the significance of the information relative to the participant’s own situation 
• Reason with this relevant information in making decisions 

Decision-making capacity is a spectrum, with some individuals more capable of understanding and reasoning than others. With this in mind, “impaired decision-making capacity” can include anyone who is incapable of giving legally effective informed consent. This could be because of a neurological condition that affects an adult’s decision-making capacity, a developmental disability (e.g., autism spectrum disorder), an injury leading to temporary incapacity (e.g., an injury that causes someone to become unconscious), or even because a person has been put under legal guardianship by a judicial body.  

Don’t assume that just because an individual’s decision-making capacity is diminished that he or she cannot provide legally effective consent. Decision-making capacity is variable within groups and may change throughout the course of a study: Someone with early Alzheimer’s disease may be capable of providing consent, but as the disease progresses, their capacity will likely diminish. 

Regulatory Guidance 

In its draft guidance Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors, the FDA recommends additional safeguards for participants with diminished decision-making capacity, such as: 

• Using an independent “qualified professional” to assess the consent capacity of potential participants at the time of consent and in an ongoing manner 
• Establishing a waiting period to allow additional time for decision making 
• Using methods to enhance consent capacity, such as repetition, simplification, and/or enlisting a participant advocate or trusted family members 
• Using questionnaires to assess understanding 
• Reassessing a participant’s decision-making capacity for progressive disorders 
• Involving LARs as cognition declines 
• Including an assent mechanism 
• Involving the IRB or another third party to observe the consent process and/or the research 

Vulnerabilities like impaired decision-making capacity are critical aspects of clinical research. Vulnerabilities have driven the regulations governing research, and honoring that mandate gives us continued permission to conduct research.  

Regulations can’t cover every person or situation, so it’s essential for research professionals to have a working mental construct for identifying vulnerability, along with practical ways to mitigate its influencing factors. 

Note: This article was originally published on August 30, 2017, and has been updated to include new and clarifying information. 

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