Clinical Researcher—July 2021 (Volume 35, Issue 5)
Sean Horkheimer, JD, CIP
When recruiting participants for a clinical trial, the U.S. Department of Health and Human Services (HHS) regulations require that “An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence” (see 45 CFR 46.116 in the Code of Federal Regulations). Coercion occurs when there is an explicit or implied threat of harm used to obtain compliance. Undue influence occurs when an offer of an excessive reward or other benefit is used to obtain compliance.
Whether a potential clinical trial participant is vulnerable to coercion and/or undue influence is often situational. A potential participant may be vulnerable in one situation but not in another; this will depend on the context of the participant’s involvement and the relationship between the participant and the study team. For example: college students may be vulnerable when recruited for research conducted by their professors due to the power imbalance between the parties, but would not be considered vulnerable when recruited for research that is unrelated to their education or status as a student.
Coercion and undue influence can result in a situation where a potential participant feels pressured to enroll in a clinical study. This perceived pressure undermines a potential participant’s autonomy and ability to provide meaningful informed consent. Some participant populations are more susceptible to this pressure based on their unique circumstances—prisoners, military personnel, elderly patients in residential healthcare settings, and students can all face additional pressure to participate when asked to enroll in research.
In the case of prisoners and military personnel, the regulations directly address this situation by imposing additional requirements for study teams and institutional review boards (IRBs). In the other cases, the consent process can be designed to minimize the participant’s perceived pressure to enroll.
Let us examine the regulatory requirements and consenting best practices for these participant populations.
Prisoners are involuntarily confined or detained individuals in a penal institution (45 CFR 46.303(c)). Compared to non-prisoners, they have very little control over their daily activities. Prisoners are also subject to punishment by correctional officers for any misconduct or violation of strict prison rules. In this precarious situation, they have greatly reduced autonomy and are vulnerable to coercion and undue influence.
Subpart C of the Common Rule (Federal Policy for the Protection of Human Subjects) enacts additional regulatory protections for participants who are prisoners (45 CFR 46.301 et seq.). IRBs can only approve research that falls into specifically delineated categories (45 CFR 46.306(2)). To prevent undue influence, enrollment should not provide the participant with advantages in terms of living conditions, medical care, quality of food, amenities, and opportunities for earnings compared to the regular prison population that are of such a magnitude they undermine the potential participant’s ability to effectively evaluate the risks of the research (45 CFR 46.305(a)(2)). To prevent coercion, the consent process should inform potential participants that their involvement will have no impact on decisions made concerning their possible parole (45 CFR 46.306(a)(6)).
Aside from these regulatory requirements, there are some consent process best practices that can reduce a prisoner’s perceived pressure to participate. Members of the study team should identify themselves and their relationship to the prison at the start of the consenting process. If the study team includes members who are employees of the prison system, they should consider whether the person obtaining consent should be someone independent.
The warden and any prison administrators who have the ability to punish or reward participants should not be present during the consenting process, if possible. Their presence could be perceived as a subtle form of intimidation or possible promise of better treatment that will impact a potential participant’s decision to enroll in the research.
The consent form should outline the extent to which prison officials will be able to access and review the research records. Participants will be interested to know if they will be identified individually or if results will be collected and stored in aggregate form. If the research is designed to examine prohibited activities taking place in the prison system and participant anonymity is essential to protect the participant’s rights and welfare, the consent process for each individual participant should take place in private, outside the view of other inmates or correctional officers (this may also extend to the research activities, if necessary to protect participant privacy).
In many ways, military service is defined by rigid hierarchies, deference to authority, and the expectation that all orders from the chain of command are followed. As such, military personnel can feel additional pressure to participate in research when it is presented to them in the context of their service.
Federally funded research recruiting military personnel is governed by the Department of Defense (DoD) regulations (32 CFR 219.101, DoD’s adoption of the Common Rule). Additionally, DoD Instruction (DoDI) 3216.02 outlines additional requirements and guidance for research conducted involving DoD-affiliated personnel. This instruction document defines DoD-affiliated personnel as service members, reserve service members, National Guard members, DoD civilians, and DoD contractors.
Per DoDI 3216.02(3.9)(f)(3), military and civilian supervisors, officers, and others in the chain of command are prohibited from influencing their subordinates to enroll in human participant research. Subsection (4) requires these individuals not be present during recruitment sessions or the consent process. If potential participants are approached in a group setting, this means their superior officers should not be present.
For minimal risk research, an alternative consent process may be appropriate. For example, in a survey study for which results are aggregated and linking to individual participants is not required for data analysis, informed consent could be obtained from the participant via an electronic platform during a time when he or she is not on duty. If necessary, participants can contact members of the study team with any questions they have before consenting.
For more than minimal risk research where recruitment is conducted in a group setting, the DoDI outlines additional protections. The IRB must appoint an independent ombudsperson to supervise the recruitment activity and consenting process. This person should explain to participants that their involvement is voluntary. They should also ensure the IRB-approved recruitment script, digital materials, and consenting process are followed (DoDI 3216.02(3.9)(f)(6)(b)).
Members of the study team should identify themselves and their relationship to the DoD as part of the recruitment and consenting process. Participants should be informed of the extent to which the research records may be accessible by the military. If the research is covered by a Certificate of Confidentiality, the consent form should explain the scope of this protection along with any exceptions that may limit it.
Compensation of DoD-affiliated personnel while on duty is prohibited, with some limited exceptions defined by statute (DoDI 3216.02(3.9)(f)(7)). As such, study team members should be aware of what they can and cannot offer as compensation to these participants.
Elderly Patients in Group Healthcare Settings
The biggest area of concern for elderly participants who reside in a residential healthcare facility is their decisional capacity or ability to consent for themselves. Elderly patients may have reduced mental capacity that is temporary, progressive, or permanent due to any of the following: ongoing disease processes, acute urinary tract infections, neurological disorders like stroke or dementia, psychoactive medications, head trauma, or even past substance abuse. This means evaluation of an elderly patient’s mental capacity is an essential step in any consenting process and should be an ongoing consideration throughout the duration of a research study.
The regulations do not direct specific requirements for consenting participants with reduced mental capacity, but they do identify individuals with impaired decision-making capacity as likely to be vulnerable to coercion or undue influence (45 CFR 46.111(b)). As such, the study design should incorporate additional protections for these participants. The research procedures should involve regularly assessing the participant’s capacity throughout the study and obtaining consent with the help of the participant’s legally authorized representative (LAR).
Even if the planned research is short in duration and a potential participant is otherwise decisional, it is advisable to involve an LAR or family member in the process. An otherwise alert and decisional elderly patient may not feel comfortable asking questions or voicing his or her objections in this setting. The participant’s LAR or family member can serve as an advocate during the consenting process to voice any concerns or objections, if needed.
For research that presents more than minimal risk, the study team should plan for a longer consent process by conducting the discussion over multiple visits. This will provide the potential participant and his or her LAR with a chance to review the consent form in detail and formulate any questions they may have for the study team. This will also let the elderly patient discuss participation with the LAR privately. Because patients have an ongoing relationship with the care facility where they stay, they may be reluctant to refuse to participate for fear of upsetting their caregivers or the study team members who may also be providing them with clinical care. Extending the consent process to give the patient and LAR time to discuss their concerns reduces this feeling of pressure to participate.
For longitudinal studies that follow the progression of disease resulting in reduced capacity, it is advisable to have the participant’s LAR identified ahead of time even if he or she is not needed during the initial consenting. This is especially important if the disease progresses and the formerly decisional participant is no longer able to adequately evaluate his or her own needs and interests. Some progressive conditions have good days and bad days, and a participant’s capacity may vary along a spectrum. An LAR who is familiar with the participant’s personality and medical history will be able to step in for the participant to evaluate continued participation when necessary.
Although students are not granted additional protections by the regulations, they can still be considered vulnerable by virtue of their concern for their own academic well-being and the power differential between them and the study team working with their professor. As such, study team members should adopt the following best practices to reduce the pressure to enroll that these potential participants may feel.
The study team should not include the student’s professor as a member, since potential participants may be concerned that they will receive a bad grade or other punishment if they do not agree to enroll in the research. If this situation cannot be avoided, the study team should arrange to have someone other than the professor obtain consent from participants. Ideally, the professor should not be present during the recruitment and consenting activities.
If possible, the study team should design the protocol in such a way that the professor will not know who participates and who does not. For example, recruitment for research involving an anonymous survey could take place in person, but the study team could request a waiver of documentation of consent so participants will not have to provide their names on forms linking them to their participation.
For research that offers extra credit as compensation for participation, the study team should arrange to have an alternative option available to students who do not wish to participate, as some students may feel pressured to enroll in research that they would otherwise avoid to obtain the extra credit they need to get a good grade. This alternative option should involve a similar time commitment and level of effort—for example, a research survey that takes an hour to complete could be presented alongside an assignment that takes about the same amount of time.
Ideally, there should be protections in place to anonymize which students participated in the research and which students opted to complete the extra credit assignment instead. These protections should be clearly communicated to the potential participants as part of the consent process.
In addition to perceived pressure from the study team, students may also experience peer pressure to enroll (or not enroll), depending on their age. If this is a concern, study team members should conduct the consent process privately rather than in a group setting. Team members could also consider asking the students to not discuss their participation with each other until after the research activities are completed.
When conducting research in participant populations that are more susceptible to feeling pressure to participate, study teams need to be mindful of regulatory requirements and adopt a consent process that minimizes this pressure. Depending on the circumstances, this may require additional consent disclosures, identifying different individuals to conduct recruitment and obtain consent, changing the consenting setting, relying on the participation of an LAR, or designing the research procedures to limit who on the study team knows who participated. A well-developed consenting process will reduce a participant’s perceived pressure to enroll in the study.
Sean Horkheimer, JD, CIP, is Regulatory Chair at WCG IRB, which conducts ethical reviews of clinical research protocols and studies and has more than 200 members on boards accredited by the Association for the Accreditation of Human Research Protection Programs, Inc.