Research involving cognitively impaired patients requires researchers to take extra precautions to protect these patients. There are a number of reasons a patient may be considered cognitively impaired—psychiatric illness, a medical or neurological disorder which may temporarily impair decision making , and dementia to name a few. According to the New York Times, the population of Americans over the age of 65 will nearly double by the middle of the century—a trend which has been referred to as the graying of America. With an increasingly elderly population, more potential research subjects will suffer from various forms of cognitive impairment and there will be a greater demand for treatments for age-related conditions. The likely result is the need to incorporate larger numbers of cognitively impaired patients in research studies.

As researchers, we need to consider how we simultaneously protect patients who are cognitively impaired or may become cognitively impaired during a study with the need to include this population as part of our research. Unlike children, pregnant women, and prisoners, the current Code of Federal Regulations for the Protection of Human Subjects (45 CFR Part 46) does not contain specific guidance for the protection of subjects with cognitive impairment in clinical trials.

Informed Consent

One key issue related to cognitively impaired subjects is informed consent.  Many of the items discussed here are related to consent.  If a research subject has substantial cognitive impairment, they cannot provide informed consent.  In this case, a legally authorized representative (LAR) must provide consent on their behalf.  The standard for an LAR to provide consent is substituted judgment—what is in the best interest of the subject and what would the subject want.  If possible, the subject should assent.  In situations where a subject refuses to provide assent, the subject should generally not be included in the study.

Deciding if a Patient is Cognitively Impaired

Dementia is often a matter of degree, and in mild forms of cognitive impairment, a patient may still be capable of providing consent.  How do we decide when a patient is competent to consent and when an LAR is needed?  This certainly isn’t a settled matter, but one option is to include an assessment which would be performed by the investigator as part of the screening process to make this determination.  The assessment should check the patients understanding of potential risks, potential benefits, that participation is voluntary, and what will be involved in participating (study procedures, additional visits).

Consent is a Process, Not a One Time Event

In many cases involving dementia, a patient’s decision making ability may degrade over the course of a study.  It may be that a patient is capable of providing informed consent at the beginning of a study, but is not as the study progresses.  This is something investigators should keep in mind.  You may want to plan for reassessment later in the study.

Identifying LARs

There is not a single standard for determining who can act as an LAR.  Some states have enacted laws specifying who can act as LAR, but the laws are not all the same.  In states where there isn’t a law, identifying an LAR can be trickier.  In other countries and cultures, views on who can make decisions for the cognitively impaired vary greatly from common views in the US.  Make sure at the start of the trial that you are aware of local laws and standards related to LARs.

Limiting Risk

Study designs should take extra care in limiting risk exposure in studies which will be using cognitively impaired patients, particularly when there is little or no potential for direct benefit. In most cases, studies involving these patients that don’t offer the potential of direct benefit should be limited to those involving minimal risk.

In conclusion, because formal guidance on conducting clinical research in subjects with cognitive impairment has not yet been standardized or incorporated into law, it is important to take extra care to protect these patients. We’d be interested in knowing how other organizations are responding to this issue. Is this a topic your organization is actively addressing? If so, please share in the comments.