By Gary Evans
The Secretary’s Advisory Committee on Human Research Protections (SACHRP) used a series of questions in crafting recommendations on the complex issue of requiring research subjects to “pay to participate.”
While still subject to some wordsmithing, the unpublished, finalized draft discussed at the SACHRP meeting included the following five questions and committee answers.
1. Does the study meet relevant thresholds of scientific quality?
The question of a study’s scientific validity is integral to the IRB assessment of whether a study’s benefit justifies its risk and burdens. Because pay-to-participate studies typically lack the well-established peer review processes that generally precede IRB review, the IRB’s responsibility to evaluate the evidence of scientific validity of such proposals is heightened. The IRB should be prepared to confirm the scientific validity and value of the proposed study and its design, either directly when they have the expertise to do so, or through reliance on expert consultants or other institutional committees. An IRB that lacks access to sufficient expertise to conduct the necessary review of scientific quality may decline to review any study, including a pay-to-participate trial.
2. Is the risk-benefit balance justifiable?
Assuming the threshold of scientific quality has been confirmed, the IRB must continue to evaluate the study’s risk in relation to its benefits to subjects and society. Just as payment to subjects is not to be considered a benefit that could balance research risks, payment to participate should not be considered as a harm in the risk-benefit equation. Instead, the IRB should evaluate a study’s risk and benefits first without considering payment. If the balance is unacceptable on that account, the study should not be approved. However, if the balance appears to be acceptable independent of any payment to participate, the IRB should consider whether payment raises other concerns that must addressed to satisfy ethical and regulatory criteria for approval.
3. Why are traditional research funding sources not used? Could the study potential be funded by means other than charging subjects?
The IRB should require investigators to specifically explain and justify the rationale for charging subjects, including whether traditional funding was sought and why other funding sources are not available or appropriate.
Although it should not be necessary for investigators to demonstrate that all other funding options have been exhausted, they should demonstrate an adequate and reasonable justification for charging subjects. IRBs should examine each trial’s potential to exploit subjects for profit-seeking motives. Investigators should be expected to provide a detailed breakdown of the amount charged and a description of what subjects pay for. They also should explain whether the payment is expected as a lump sum or installments, as well as conditions under which a subject would receive a partial or complete refund (e.g., what will happen if a subject withdraws partway through the research or the investigator removes a subject from the study for medical or noncompliance reasons). This information should be included in the consent form.
4. Will requiring payment for participation influence equitable subject selection?
Where the justification for charging is seen as acceptable, the IRB should then consider whether or how study results may be affected by an expectation of payment by subjects. Investigators should try to mitigate concerns regarding generalizability and equitable subject selection, potentially considering efforts to include some subjects who cannot pay their own way (e.g., a sliding payment scale or an approach where economically disadvantaged subjects are subsidized by those who can pay).
5. Is requiring payment from subjects likely to exacerbate the possibility of therapeutic misconception? If so, how can that concern be mitigated?
Is the pay-to-participate study scientifically valid? Does the study carry an acceptable harm-benefit reaction and a strong rationale for charging subjects? Is there a plan for equitable subject selection? If the answer is “yes” to all these questions, the next consideration is how to minimize the potential for a payment requirement to interfere with subject’s informed decision-making process
When subjects are charged for participation, they may regard trial participation as a means of gaining further access to a promising new treatment. This raises concerns about their adequate consideration of and reflection about important study features, such as risk, burdens, discomforts, and uncertainty.
IRBs (and investigators and sponsors) should pay special attention to whether the informed consent process will provide clear and complete information about the study and support adequate consideration and comprehension of that information. Similar consideration should be given to any recruitment materials.
Although individuals are free to make decisions outside of the research settings that reflect misunderstanding or insufficient consideration of key information (e.g., when accepting a job offer or making a purchase), IRBs and investigators fail to fulfill their responsibilities for subjects’ protection if they do not strive to assist potential subjects in reasoned decision-making. IRBs need not monitor the enrollment process of each individual subject, but should encourage investigators to adopt approaches that will support high-quality decision-making. These may include:
- Setting aside sufficient time for knowable study staff to review the entire consent form with potential subjects and answer any questions, rather than permitting a passive consent process in which potential subjects are expected to review materials on their own;
- Including tests of comprehension or teach-back methods that will provide an indication that potential subjects are aware of and understand key information about the study, such as the difference between research and clinical care, the uncertainty of benefit, and the amount they will be required to pay;
- Incorporating a waiting period for potential subjects to reflect on their desire to participate and potentially discuss the study with trusted others;
- Facilitating prospective subjects’ explicit consideration of their interests (e.g., asking for reflection about the possibility that the intervention may have no beneficial effects, may be harmful, or if available alternative treatments may be preferable);
- Providing further support for any individual who expressed that he or she “has no choice” but to enroll because of his or her medical circumstances.