By Gary Evans, Medical Writer

Research subjects often are paid for their participation in trials, but there is little standardization and accessible data about compensation.

The current dearth of data on incentives for research participation raises ethical issues in such areas as informed consent and potential exploitation of vulnerable populations, says Brandon Brown, PhD, MPH, a researcher and assistant professor at the Center for Healthy Communities at the University of California, Riverside.

“This is a huge issue,” he says. “Informed consent documents will usually specify payment amounts to participants. While IRBs do not consider payment a benefit, many participants might see the payment as a benefit, and some might even enroll into a study due to the payment.”

To address these problems, Brown and colleagues are building a framework for determining appropriate payment for research subjects in HIV clinical trials.1 Some vulnerable populations may be more likely to have low income, putting them at risk of exploitation due to underpayment. Conversely, they also may be at risk of exploitation for joining higher-risk studies due to the lure of higher compensation, he explains.

“Right now, since we don’t have data, we only have a sense that ‘we will know it when we see it’ for inadequate or excessive incentives,” he says. “How is that ethical?”

In guidance updated this year, the FDA states that “all information concerning payment, including the amount and schedule of payments, should be set forth in the informed consent document.”2

To Brown’s point on payment and benefit, the FDA notes that “payment to research subjects for participation in studies is not considered a benefit that would be part of the weighing of benefits or risks [of the research]. It is a recruitment incentive.”

Participation payment “may raise difficult questions that should be addressed by the IRB,” the FDA states. These include the amount of payment and what should be factored into the compensation.

For example, the FDA does not consider reimbursement for travel and lodging costs for research an “undue inducement.” This pressure can arise, however, if payment undermines the “subjects’ ability to give voluntary informed consent.”

In any case, the amount and schedule of payments should be presented to the IRB at the time of initial study review. IRBs should weigh the issues and come up with a payment plan that is “just and fair,” the FDA concludes.

That goal may be somewhat aspirational given the many factors at play. For example, the possible effects of undue inducement include research subjects’ concealing contraindications to gain enrollment, Brown notes. Concerned about undue inducement, some IRBs and researchers may overcorrect and provide low compensation that fails the fairness test.

A Payment Framework

The payment framework under development by Brown and colleagues will focus on incentives in HIV clinical trials. The framework will be based on input from researchers, ethicists, former study participants, IRB members, and people living with HIV. It will include a database that allows for tracking payment practices.

The idea is to develop baseline data that can inform payment practices going forward. The researchers hope to identify “what types of payments in various contexts might constitute undue inducement to participate in HIV research.”

Ultimately, the system developed for HIV research should be transferable to other areas of research, guiding ethical decisions on compensation for participation across other types of trials, Brown says.

Q&A

IRB Advisor asked Brown to provide more detail on the incentive issue and the proposed framework in the following interview.

IRB Advisor: You cite a number of factors and variables that have made this historically difficult. For example, IRB documentation of payment for research participation varies, listing payment is not required on ClinicalTrials.gov, and academic journals do not routinely publish the data.

Brown: The lack of payment data as a separate variable in electronic IRB forms and on ClinicalTrials.gov and the underreporting of payment in publications mean that these data are not accessible. We aim to develop a database of payment data.

But instead of collecting payment data alone, which would not reflect the complexity of the different types of studies and study populations, we will collect payment data with relevant contextual and study-related variables.

But choosing the variables is important, and we need all the major stakeholders in that conversation, including participant community members, IRB members, and researchers. When at all possible, we should defer to the participant community. Having a payment framework itself is a good idea, but if data are not collected, it will continue to be an abstract idea.

IRB Advisor: Would this be something that individual IRBs could adopt and begin requiring of researchers?

Brown: I think so. Why not require researchers to describe how and why they choose payment amounts with a justification statement? Or how they worked with a community advisory board to make the decision? In addition, the type of payment should be specified, whether it be reimbursement, incentives, or compensation. Adding this question to applications will enrich research and bring the issue of payment to the forefront. Researchers themselves need to start thinking of this and how what they are providing might be inadequate or excessive.

IRB Advisor: Just to clarify, are you implementing the framework you propose to begin collecting financial incentive data in your research with HIV?

Brown: We have not yet implemented the study that we propose, but the planned study is under consideration for funding by a federal agency. Locally, at my own IRB, we have begun collecting incentive data from studies along with a variable list to have pilot data on payment in research. Variables collected along with payment data include risk level, IRB review type, review category, number of visits, time commitment, type of research, online or in person, and population type.

In my own studies, I work closely with the potential participant population to decide upon incentives. This is one of the benefits of working with wonderful community partners who have taught me a great deal in my community-based participatory research. I also make it a point to describe the incentives in our publications.

IRB Advisor: Is more consensus needed on efficacy before the framework is implemented?

Brown: There have been several grants funded to examine the impact of incentives in specific research areas, including, for example, cancer, HIV, cardiovascular health, and kidney disease. While these projects examine the impact of incentives in their individual research projects, we will examine trends across projects.

So yes, we are planning a study using this framework. More consensus is needed, but that step — the consensus step — is built in as part of the study. We are also planning a first look at consensus on different aspects of payment in research in separate studies with participants, researchers, and IRB members. Then we will take a retrospective look at previous research and create a database that can aid incentive decision-making.

REFERENCES

1. Brown B, Galea JT, Dubé K, et al. The Need to Track Payment Incentives to Participate in HIV Research. IRB Ethics and Human Research 2018;40(4). Available at: https://bit.ly/2LRAEjL.

2. FDA. Payment and Reimbursement to Research Subjects - Information Sheet. Guidance for Institutional Review Boards and Clinical Investigators, Jan. 25, 2018. Available at: https://bit.ly/2slP3Ao.