Commentary: FDA Guidance on Payment and Reimbursement to Research Subjects

Summary

This article breaks down FDA guidance related to payment and reimbursement to clinical trial participants (patients) and provides commentary by Zac Carr, CEO and co-founder of Block Clinical Inc. The full FDA guidance can be found here.

Patient Travel Support and Reimbursements

Section 1:

“Paying research subjects in exchange for their participation is a common and, in general, acceptable practice. Payment to research subjects for participation in studies is not considered a benefit that would be part of the weighing of benefits or risks; it is a recruitment incentive. FDA recognizes that payment for participation may raise difficult questions that should be addressed by the IRB. For example, how much money should research subjects receive, and for what should subjects receive payment, such as their time, inconvenience, discomfort, or some other consideration.”

Commentary: Payments to trial participants are common, acceptable, and used as a recruitment incentive. It is clear the FDA acknowledges use of payment as a recruitment incentive and that the IRB has final say regarding how much and for what purpose payments may be used. The FDA gets it, patients are more likely to join trials where they are adequately supported and the burdens of participation don’t outweigh the benefits.

In a separate and similarly styled post we’ll explore the “The Belmont Report” by the Office of the Secretary that looks at Ethical Principles and Guidelines for the Protection of Human Subjects of Research which puts forth guiding principles for IRBs. Of the three basic ethical principles, “Justice” seems to require that the benefits AND burdens be equal across all people. Low stipend amounts exponentially affect those with limited financial resources and creates an unfair burden for this population of people, leaving only those with ample resources to participate in life saving research. This doesn’t leave a very diverse population of trial participants.

 

Section 2:

“In contrast to payment for participation, FDA does not consider reimbursement for travel expenses to and from the clinical trial site and associated costs such as airfare, parking, and lodging to raise issues regarding undue influence.”

Commentary: It’s important to define the difference between a stipend payment, and a reimbursement. Stipend payments count as taxable revenue, and they are payment for a participant’s “time, inconvenience, discomfort, or some other consideration.” Reimbursements are non-taxable and generally require proof (receipt) the participant spent what they claim. Reasonable participant reimbursement categories include, mileage, parking, and travel to and from the research sites, and depending on other factors may include everything in between including meals and child care.

Section 3:

“Other than reimbursement for reasonable travel and lodging expenses, IRBs should be sensitive to whether other aspects of proposed payment for participation could present an undue influence, thus interfering with the potential subjects’ ability to give voluntary informed consent. Payment for participation in research should be just and fair. The amount and schedule of all payments should be presented to the IRB at the time of initial review. The IRB should review both the amount of payment and the proposed method and timing of disbursement to assure that neither are coercive or present undue influence [21 CFR 50.20].”

Commentary: “Payment for participation in research should be just and fair.” Trial participants are volunteers, so let’s start there. They give up time they could be working or spending with friends and family. Even with all out of pocket expenses covered as reimbursements, a fair and just stipend amount would be greater than the “time, inconvenience, discomfort, [and] other consideration.” If not, we have a diversity issue. Only those with ample resources (support network, money, time, etc…) are able to participate in clinical research without adding undue hardship on themselves and those around them. Those with limited resources may initially join a study and drop out when the hardships outweigh the benefits.

 

Section 4:

“Any credit for payment should accrue as the study progresses and not be contingent upon the subject completing the entire study. Unless it creates undue inconvenience or a coercive practice, payment to subjects who withdraw from the study may be made at the time they would have completed the study (or completed a phase of the study) had they not withdrawn. For example, in a study lasting only a few days, an IRB may find it permissible to allow a single payment date at the end of the study, even to subjects who had withdrawn before that date.”

Commentary: Taking this a little further, payments to patients should be made as quickly as possible, and paid using a payment method of their choosing. Steps should be taken to reduce time to payment, for example by leveraging integrations with EDCs and ePROs that deliver status information and by automating remittance approvals for certain payments. Payment methods should be dictated by the patient, our job is to make them available, this could be direct deposits, reloadable debit cards, Paypal, Venmo, check, etc…Bitcoin soon?

 

Section 5:

“While the entire payment should not be contingent upon completion of the entire study, payment of a small proportion as an incentive for completion of the study is acceptable to FDA, providing that such incentive is not coercive. The IRB should determine that the amount paid as a bonus for completion is reasonable and not so large as to unduly induce subjects to stay in the study when they would otherwise have withdrawn. All information concerning payment, including the amount and schedule of payment(s), should be set forth in the informed consent document.”

Commentary: We have seen successful implementation of this concept for example with eDiary completion. But how much is fair and just and not inducive? 10% of total stipends paid? If stipend payment amounts increase as they should maybe the bonus doesn’t have to be as large but until then…

 

Conclusion

The FDA provides clear guidance and clear ownership (IRB) of who determines what is, and is not appropriate regarding participant payments in clinical research. Payments for participation (stipends) are common and accepted. There is a balance between keeping payment amounts just and fair while not unduly inducing trial participation. Reimbursements are paid in addition to stipends and not considered inducive and therefore should be universally covered without issue. Reducing participant out of pocket expenses as close to $0 as possible should be our collective goal.