This monthly feature presents a variety of questions from clinical trial professionals with answers from WCG Clinical’s expert staff. This month features Yvonne Higgins, WCG IRB quality assurance adviser, and David Borasky, vice president of IRB compliance.

Question: As a sponsor, what do the regulations say about paying research subjects? What are acceptable practices for compensating subjects for participating in a clinical trial?

Answer: The FDA’s and other federal regulations on human subject protections do not specifically address payment. The regulations do require that informed consent must be obtained under circumstances “that minimize the possibility of coercion or undue influence.” The Office for Human Research Protections (OHRP) guidance states: “Paying research subjects is a common, and in general, acceptable practice.”

In fact, it is common for subjects to be paid for their participation in research. Sponsors, researchers and IRBs may consider the following as acceptable practices for compensating subjects.

1. Reimbursement of Study-Related Expenses Research participation should be cost-neutral. This helps to ensure the principle of distributive justice and that the risks and benefits of research participation are fairly distributed. A number of different models for covering out-of-pocket expenses are acceptable, including collection of receipts and reimbursement in cash or check, vouchers for taxis, payment for parking or meals, prefunded debit cards or per-diem payments based on average and expected expenses.
2. Compensation for Time and Effort Participants may be compensated for their time and effort, including study visits, tasks outside study visits (completing surveys or diaries) and even travel time to clinical sites. Some ethicists have proposed payment amounts based on local minimum wages, although others have pointed out that compensating at minimum wages may attract only lower-paid persons to participate in research.
3. Incentive Payments In some cases, a sponsor may wish to pay a certain amount of money to ensure that they were able to enroll the study with the necessary number of participants and in a reasonable amount of time. An IRB may consider and approve an incentive plan. — Yvonne Higgins, WCG IRB quality assurance adviser

Q: Many sites offer a referral program for their patients stating, for example, “Refer a friend to our center and receive a $25 gift card.” Is this an ethical practice?

A: The use of referral incentives, sometimes referred to as “snowball sampling,” can be an effective recruiting tool, particularly with hard-to-reach populations. The FDA and HHS regulations for human research protections are silent with respect to the payment of incentives in research, whether those incentives are paid to study participants or researchers. However, the regulations do require that the IRB determine that informed consent is sought “only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.” (21 CFR 50.20)

The FDA’s guidance on payment and reimbursement of research subjects notes that “paying research subjects in exchange for their participation is a common and, in general, acceptable practice,” but cautions that IRBs “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.”

In this case, the role of the person receiving the referral is minimized because they are not directly involved in the study and prospective subjects are being referred to the site, not to a specific study. In other cases, where the referral is for a specific study, there could be a concern that patients would put significant pressure (i.e., undue influence) on their friends or even engage in threatening behaviors (i.e., coercion) to ensure their enrollment in the research so that they would receive the referral incentive.

There are some practical measures that can be put in place to minimize the chance of coercion or undue inducement occurring. The OHRP suggests that “IRBs may restrict levels of financial or nonfinancial incentives for participation and should carefully review the information to be disclosed to potential subjects to ensure that the incentives and how they will be provided are clearly described.”

In the case of referral fees, IRBs may consider the structure of proposed referral plans and suggest limitations to referral plans that minimize the potential for coercion of undue inducement. Limitations might include restricting the number of referrals an individual may make or not having the referral payment be contingent on the enrollment of the referred individuals. Many IRBs do not allow payment of referral fees to medical professionals or research staff.

Finally, the consent process should minimize the chance of coercion or undue inducement occurring. Referred individuals should understand that the choice to participate is voluntary, and the role of the individual making the referral should be minimized. — David Borasky, vice president of IRB compliance

Q: Will an IRB allow reimbursement for co-pays for routine patient care costs associated with participation in a clinical trial when the costs are covered by insurance but the subject is responsible for a high co-pay? Examples of these costs include extra blood tests, scans or administration of medication other than the study drug.

A: The IRB can approve this but there may be other parties that have to weigh in. While it is not ethically objectionable to reimburse out-of-pocket expenses for research participation, there may be potential legal issues with reimbursement of co-pays. It is illegal to pay for co-pays under Medicare, and many private insurers have elected to follow suit. As a result, having a research sponsor reimburse co-pays could lead to legal issues for the research physician and the insured individual. — David Borasky, vice president of IRB compliance