When research subjects’ capacity to consent is absent, diminished, or fluctuating, additional consent enhancements, safeguards, and support may be required by the IRB. AAHRPP Standard II-4 requires IRBs to provide additional protections for vulnerable subjects in research, including policies and procedures to protect subjects whose capacity to consent is potentially absent, diminished, or fluctuating. The regulations, however, are generally silent on the specifics of these additional protections.

In January 2018, PRIM&R hosted a webinar, Capacity to Consent to Research: Assessing and Improving your HRPP’s Strategy, to offer strategies, best practices, and resources for HRPP professionals who are tasked with implementing institution-wide policies to address capacity to consent issues. Speaker Tamyra Armbrust, CIP, education coordinator at the Mayo Clinic IRB, discussed core competencies as well as the ethical and regulatory background of capacity to consent to research. Courtney Jarboe, MS, MA, CIP, education and outreach specialist in the human research protection program at the University of Minnesota, highlighted strategies for implementing new or revised policies to advance human research protections. Both speakers provided examples of how their institutions established best practices, oversight activities, education and outreach approaches, and strategies for engaging the community in policy development.

After the webinar, speakers provided additional scenarios to further assist attendees in understanding and applying these concepts. We’re pleased to share these scenarios with the readers of Ampersand.

Scenario 1:
A researcher proposes a clinical research study involving a population of subjects with a condition which outrightly affects their capacity to consent to research. The focus of the research study is to better understand a rare genetic condition. The study involves multiple procedures that generally pose minimal risk of harm to subjects. However, one procedure involves a skin biopsy, which poses a minor increase over minimal risk. The researcher provided rationale for including this procedure, indicating that it is necessary in order to answer the research question.

In reviewing the study, the IRB has determined that the study overall does not hold a prospect of direct benefit to subjects, but will likely yield important information about the subjects’ condition.

What should the IRB consider?
Courtney Jarboe (CJ): There are multiple questions that must be answered before considering approval of this study. Ideally, the proposed research study would have a prospect of direct benefit to subjects. However, in this case there is not a prospect of direct benefit to subjects. The IRB needs to make a decision as to whether this study can be ethically carried out. In order to make this decision, the IRB should consider whether:

• The IRB has appropriate expertise to evaluate the study and whether additional consultation is required before making a decision.
• The objectives of the research can be met by involving subjects that have the capacity to consent (in this scenario, this is not an option, as the entire population with this condition lacks capacity to consent).
• The information needed is well-justified and is necessary.
• If needed, the information can be gathered by any other procedure or method that does not pose greater than minimal risk of harm to subjects.
• The study is not prohibited under any law.
• The subjects will be sufficiently and closely monitored.
• The study includes appropriate plans for withdrawing subjects who are unduly distressed.
• The information gathered by the procedure will yield valuable information about the subjects’ condition that could benefit others with the same condition.
• Sufficient additional protections are in place to ensure the safety of subjects during the procedure.
• The consent process for obtaining permission from the legally authorized representative (LAR) is substantial and appropriate, conveying the risks of study. This may include the ability for LARs to decline the subject’s participation in the procedure that poses greater than minimal risk of harm

Scenario 2:
The IRB receives a call from an investigator about a consent discussion that just occurred. She mentions that the subject shared that he had a clinical procedure earlier that day where conscious sedation was administered. The investigator shared that they didn’t think the subject showed any signs of impaired judgement, but is seeking IRB guidance as to whether the subject can be enrolled.
Tamyra Armbrust (TA): The IRB specialist might advise the investigator to reschedule the consent discussion for another day under these circumstances:

• If time permits
• If the subject is local (easy to return)
• If rescheduling does not interfere with a study with a potential for benefit that would influence the course of the potential subject’s care
• If the study does not have a potential for benefit

If rescheduling is not feasible or not in the potential subject’s best interest, the IRB specialist can advise the investigator to conduct and document a consent capacity assessment.

• If, after the assessment, there is a concern that the subject may have an impairment, the investigator should either decline enrollment or request IRB approval for surrogate consent.
• If the potential subject clearly understands the study and is capable of making a decision, the subject may be enrolled. However, the investigator should explain that conscious sedation can affect people differently and while the subject is fully capable of making a decision today, they may not remember doing so later. The investigator should suggest the subject have a friend or family member sit in on the consent conversation. The investigator should also contact the subject within a day or two to confirm that the subject still wants to be in the study and understands what they agreed to.

Scenario 3:
An investigator proposes a study that involves subjects with advanced kidney disease. The study poses greater than minimal risk of harm to subjects. The investigator plans to include subjects that do and do not have capacity to consent to research. However, the investigator notes that only those subjects that have capacity to consent to research will be asked to participate in procedures that pose greater than minimal risk of harm. Those that lack capacity to consent will only participate in the study procedures that are minimal risk in nature, and the legally authorized representative’s permission will be sought. How does the IRB determine if this separation of activities is appropriate?
CJ: If the objectives of the research can be met by involving subjects that have the capacity to consent, then this approach may be very appropriate. The investigator’s approach allows those that have the ability to make a decision to decide as to whether they want to participate in procedures that pose greater than minimal risk of harm. The investigator should address how this separation of activities may affect data outcomes and if it may be more appropriate to separate the study into two separate studies.

PRIM&R thanks Ms. Armbrust and Ms. Jarboe for sharing their expertise.

The recording of this webinar is available for individuals to purchase in PRIM&R’s online store. If you would like to purchase the webinar for group viewing, please download the order form (PDF) and send it to registration@primr.org.