February 5, 2018
The FDA has updated its guidance to institutional review boards and clinical investigators clearly allowing reimbursements to patients in clinical trials for lodging and travel.
While paying subjects for participation in clinical research may raise difficult questions that should be addressed by an IRB, reimbursements for travel expenses to and from trial sites are not considered to raise issues regarding undue influence, according to the agency’s Office of Good Clinical Practice.
FDA Commissioner Scott Gottlieb highlighted the new passage in the guidance on travel reimbursement, saying the agency hopes “this clarity encourages recruitment in clinical trials.”
The change in the FDA’s guidance reflects how the industry has begun to shift how it conducts clinical trials, said Lindsay McNair, chief medical officer of WIRB-Copernicus Group.
“It used to be that people who were participating in clinical trials were very near a clinical site,” McNair said. “They would have some parking expenses, or they might have taxi fare.”
“But especially as we move into rare disease areas — where people may be coming from other parts of the country to special treatment centers to participate in research — the amount of reimbursement for travel expenses becomes plane tickets for someone and their spouse and two nights in a hotel.”
For instance, a study on hypertension may have many potential participants available locally; studies in Duchenne muscular dystrophy patients carrying a particular genetic mutation, however, would require a larger recruiting footprint, she said, meaning a higher likelihood of paying travel expenses.
In contrast to reimbursement, the guidance states that ethics reviews should continue to examine how much compensation participants receive, including for reasons such as time, inconvenience or discomfort.
“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,” the guidance said, adding that payments should be just and fair.
IRBs should receive the amounts and schedule of all payments, including end-of-study bonuses, during the initial review to ensure that they are not coercive according to federal regulations, including 21 CFR 50.20, the agency said. All information concerning payment should be spelled out in the informed consent document.
Credits for payment should accrue as the study continues, and not be contingent on study completion; however, a small proportionate payment to incentivize completion is acceptable, as long as it is not coercive, according to the guidance.
The question of what type of reimbursement crosses the line into undue influence or coercion has typically caused more stress for sponsors and researchers than IRBs, McNair said.
By comparison, IRBs — as well as Phase I research units with experience recruiting healthy volunteers to studies — all have a pretty good idea of what kind of compensation amounts will be considered appropriate.
“It’s something they’ve been very used to considering,” McNair said. “We very rarely see anything come through where we need to push back on a payment plan,” especially in a study that an IRB has already decided has a reasonable risk.
Many research organizations and sponsors keep payment schedules — detailing how much they compensate for blood draws, nights spent in the clinic and other study procedures, for example — creating a guide to what they know IRBs have considered appropriate in the past.
But sponsors in all phases of clinical trials can be very concerned with the optics of offering patients money to participate in research, and often seek IRB input.
The FDA guidance is a welcome update, McNair said. “It’s nice to have them explicitly clarify the difference between compensation and reimbursement.”
“The previous guidance didn’t really separate those two things out, and I think it did cause some confusion to people in trying to plan what they wanted to do in a study,” she said, adding that it probably won’t change how IRBs weigh the issue.
When examining a submission, the boards typically break those two considerations apart to judge them individually, even if the two are not explicitly described by the sponsor in the protocol or consent form.
“We do think it’s generally appropriate for people not to have to pay out-of-pocket expenses to participate in research,” said McNair. “We don’t want the subject to incur those expenses, and we also look at it from the concept of justice and equitable subject selection.”
If only the people who can participate in research are those who can afford the travel expenses upfront, that could greatly limit who can be recruited into a study, she said. The larger issue of research subject compensation has had a tremendous amount of discussion in the IRB space, and how study protocols should balance the issue of undue influence and respect for patients.
The full FDA guidance is available here: https://www.fda.gov/RegulatoryInformation/Guidances/ucm126429.htm.
—by Conor Hale @conorhale