Patient payment in clinical trials: US FDA flags undue influence, reimbursement and consent

According to​ the US Food and Drug Administration (FDA), the institutional review board (IRB) – a committee designed to ensure ethical practice in research – should determine that risks to subjects are "reasonable" in relation to anticipated benefits.

In the update​, the Administration highlighted that payment to research subjects is “not considered a benefit that would be part of the weighing of benefit or risks,”​ adding any payment offered be treated a “recruitment incentive.” ​ 

Such payment may raise questions for the IRB, said the FDA, citing “how much money should research subjects receive, and for what should subjects receive payment” ​– such as their time, inconvenience, and discomfort – as factors that should be considered by the board.

Undue Influence​

Undue influence in clinical trials occurs when an offer of payment causes a participant to undertake or continue a trial, where they otherwise may not have.

The FDA urged IRBs be sensitive to proposed payment for participation, in order to determine whether undue influence could be interfering with a patient’s consent: “Payment for participation in research should be just and fair,” ​according to the guidance.

Further, if a monetary bonus is offered for completion of a study, the IRB should deem the monetary amount reasonable, and demand all information regarding payments be included in informed consent document, the FDA said.

Reimbursement​

In the update, the Administration said it does not consider reimbursement for travel expenses, including airfare and parking costs, as an influence for patient consent.

Assistant professor of Medical Ethics at the University of Pennsylvania Holly Fernandez Lynch said she supports payments to subjects, as clinical trials can involve real burdens and risks for research participants.

“They [the subjects] should at least be reimbursed for any out-of-pocket costs they incur and compensated for their time and contributions to science,” ​she told us.

Out-of-pocket costs can serve as a barrier to trial enrollment, said Fernandez Lynch, who explained such expenses may mean “only those who are well-off enough to afford to the costs themselves will participate.”​

Potential benefits that may come from trial participation ought to be shared fairly, she added.

Payments too low?​

According to Fernandez Lynch, the guidance conflates undue influence and coercion – when a subject feels they have no reasonable alternative but to consent – and suggests that other types of payment, beyond reimbursement, can be ethically inappropriate.

“For the most part, however, if an IRB is doing its job evaluating a study’s risks and benefits, payment for participation beyond reimbursement is ethically acceptable,” ​she told us.

The guidance also fails to acknowledge the ethical problem of payments that are too low, said Fernandez Lynch, “which can be exploitative of research participants and fail to encourage adequate enrollment in trials,” ​she said.