Payment for patient participation has long been debated, analyzing the ethical as well as practical implications. The primary concern is whether payment would unduly influence a patient’s evaluation of the risks involved with participation.
This article will look at the relevant arguments to assess current best practice of patient compensation.
The FDA, as with many trial sponsors, notes that payment can act as a useful recruitment incentive. However, as referenced in its recent guidance, trials need to have an institutional review board (IRB) look at each case to determine what is ethically appropriate and whether it influences a patient’s informed consent.
Issues to address include both the amount of money paid to patients and what needs to happen in order to get paid. So, factors like total time spent, inconvenience experienced and discomfort suffered by the patient need to be considered.
Of course, the FDA already condones compensation for travel and accommodation costs incurred while participating in a trial. Its opinion here is that this compensation does not unduly influence people to enroll in a trial.
Payment amounts should be “just and fair,” with those numbers together with payment schedules submitted to the IRB for review to ensure they are neither coercive nor seem likely to unduly influence trial participants.
However, the decision as to whether a proposed amount is too high or too low is not simple. In a paper published by The Hastings Center, Holly Fernandez Lynch, J.D. and Emily Largent, J.D., Ph.D., at the University of Pennsylvania School of Medicine, say the tendency is “payment conservatism,” offering lower pay to safeguard against undue influence on informed consent.
The problem with this approach is that the vast majority who are unlikely to be unduly influenced will be undercompensated. While the practice minimizes the likelihood of influencing some in their decision to participate, it comes at the cost of fair payment to many who would not be influenced in the same way.
“This better-safe-than-sorry approach, however, fails to reflect the fact that coercion is not a payment problem, that IRB review itself serves as some protection against undue influence, and that whether an offer of payment is ‘too high’ should not be the only—or even the most prominent—consideration. Real ethical and practical concerns associated with payments that are ‘too low’ should also command IRBs’ attention," Lynch and Largent write.
They argue that risking undue influence on a small number of participants by offering higher compensation is favorable to the majority suffering financially.
A major reason that reimbursement has become a hot topic again is because the makeup of clinical trials has changed, Lindsay McNair, M.D., chief medical officer of WIRB-Copernicus Group, explains.
It used to be that patients were paid train or taxi fare or had their parking expenses covered when travelling to a nearby clinical site. Today, trials are often carried out in specialist centers with patients travelling from all over the country, requiring airfare and accommodation reimbursement for the patients and accompanying family members.
McNair says this shift has brought about the conversation to which type of reimbursement is considered coercion. Still, an IRB plays an important role here in determining what is reasonable risk.
Putting patients first is an emerging trend underway in the clinical trial community. And transparency with regard to compensation is an important part of this, says Anna Hrovat-Staedter at Forte Research.
First, it’s important to note that the FDA now recognizes the difference between compensation and reimbursement. And while the requirement to ensure a balance between undue influence and just compensation remains paramount, it stands to reason that simply by communicating the fact that all travel and lodging payments will be reimbursed, trials can be opened to a potentially far bigger pool of patients, many of whom may otherwise not have participated without this knowledge.
The result is more inclusive trial populations and better results from a broader reaching trial.
Global pharma company Pfizer has a clear policy about how patients should be paid.
A key consideration is that compensation is based on “consistent criteria,” so all participants in the same country or the same treatment group receive payment as outlined in the study budget. Of course, compensation must be consistent with the laws and guidelines of the country or region.
Payment should also not be so high that patients might be compromised in their assessment of the study’s risks. Rather it should be proportionate to the discomfort and inconvenience a patient will experience and extended to caregivers of incapacitated adults and children.
Additionally, it should not be offered on condition of completion of the trial.
Amounts and schedules of payments should be included in the informed consent form (ICF) and these should be reviewed and approved by an IRB.
While openly advertising compensation is more common in the US, compensation practices vary considerably among countries in Europe, according to the European Patients’ Academy.
Some countries won’t pay at all, while others will agree to a fair compensation, based on review from an Ethics Committee.
According to EU Clinical Trial Directive (2001/20/EC)1 and Regulation (536/2014)2, pregnant women, children and incapacitated adults, along with their caregivers, will not receive any compensation except to cover expenses and loss of earnings while participating in the trial. And as with the US, there is a clear message that payment should not exert undue influence on a patient’s evaluation of a trial’s risks.
While some studies opt for non-compensation, patient recruitment solutions provider Trial Facts suggests this is practice is not a fair one. It’s unreasonable to expect patients to participate, devoting time and energy, without being compensated. Plus the reality is that compensation leads to “easier, faster, and more reliable recruitment.”
While the conversation about what constitutes ethical payment is vital for fair treatment of patients in trials, another issue stems from this — how and when patients get paid.
Research organizations that delay reimbursement can cause patients a great deal of hardship and distress, including driving them into debt. “For all that patients sacrifice to participate in a study, the least we can do is pay them back promptly,” Kristina Lopienski at Forte Research writes.
Part of the problem is that many organizations still pay using checks, Lopienski notes. Those most adversely impacted by delays associated with this method of payment tend to be lower-income patients, who can least afford to be out-of-pocket.
In fact, delayed reimbursement can cause patients to become unable to continue in the trial, Lopienski argues. “Just as sites don’t want the money that is owed to them by sponsors to be delayed, patients take a similar position.”
Electronic payment options, and allowing patients to choose one from several methods, is an easy fix. Patients will be reimbursed or compensated in a timely manner and will be able to at least financially be in a position to continue participating in the trial.
Ed Miseta at Clinical Leader writes about a cancer patient who racked up $10,000 in expenses when participating in a trial. Not only did she have to wait much longer to get paid than what had been agreed to, she also only received $3,000 in the end.
Distressed by this story, Miseta notes that payment is a common issue for trial sites, but this was the first he’d heard of patients struggling in the same way.
“It angers me that companies can seem so lackadaisical in reimbursing patients that are a necessity for a trial, and then bemoan the fact that patient participation in trials is not higher,” Miseta says.
There have been cases in which patient stipends are “camouflaged within the per-patient contract,” cosmetic surgeon Jeffrey Adelglass, founder of clinical research organization Research Across America, writes. This is important because blended stipends can be as high as 13 percent of the per-patient cost.
Those figures can result in the “impression of an inflated budget,” he adds, in which the patient may not get a fair amount paid as a stipend relative to the overall per-patient budget.
Itemizing study budget expenses allows sponsors to clearly determine whether site managers are allocating funds in accordance with the study’s various requirements.
Payment does not necessarily translate into patient participation, science and health reporter Donald G. McNeil Jr. at The New York Times, writes. This was proved in a study by the HIV Prevention Trials Network in which patients in New York and Washington D.C. were paid to take their medication, submit to testing and attend a follow-up consultation.
The $2.8 million experiment with 9,000 participants failed, with only a 5 percent improvement in patient adherence noted in clinics that paid patients over those that didn’t.
Part of the problem may be that the study was so large, Anna Rose Welch at Clinical Leader writes. She says that researchers trialled this approach in “smaller clinics enrolling poorly performing patients” with a 13 percent improvement.
Another issue is that the amount paid to patients was $280, far less than the $5,000 per year which mathematical modeling suggested would be cost effective, McNeil writes. However, as Welch points out, that kind of compensation is prohibitive to most sponsors, especially in light of rising trial costs.
While high payments like the above example are unfeasible for most trial sponsors, it is essential that patients be compensated fairly for their time and potential discomfort. Balancing payment with fair treatment is key. Sponsors that take a patient-centric approach and adhere to FDA guidance and IRB input should be safe in making the correct patient compensation decisions.
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