Good Clinical Practice: A Question & Answer Reference Guide - May 2014 - 450

GCP: A Question & Answer Reference Guide
related directly to the study. Payment information, including the amount and schedule of payment(s), as well as any
possible costs to volunteers who participate in a study, are discussed with potential participants during the informed
consent process, and documented in the informed consent form."
A general-but perhaps the lengthiest-agency discussion on the topic is provided in an FDA information sheet titled,
"Payment to Research Subjects," which establishes that the IRB must review and approve all payments and payment
methods/schedules, and that all payment-related information must be set forth in the informed consent document:
"It is not uncommon for subjects to be paid for their participation in research, especially in the early phases of
investigational drug, biologic or device development," the agency's information sheet states. "Payment to research
subjects for participation in studies is not considered a benefit, it is a recruitment incentive. Financial incentives are often
used when health benefits to subjects are remote or non-existent. 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]."
A search of the FDA Inspection database (BMIS) in March 2014 shows only 24 inspections that include the
deficiency code for inappropriate payment to volunteers, but none resulted in a Warning Letter. It is interesting to
note that all of the letters are from the 1980-1990s time period.
Much of the agency's discussion focuses on the scheduling, rather than the amount, of payments to study subjects.
"Any credit for payment should accrue as the study progresses and not be contingent upon the subject completing the
entire study," the agency notes. "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of the study) had they not withdrawn.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to allow a single payment date at the end of the study, even to subjects who had withdrawn before that date. 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."
Given that the FDA has itself cited studies for "inappropriate payments," however, payments are not just an IRB
concern as implied in the passage above, although some agency officials today believe they should be addressed
solely by IRBs (see discussion below). It is difficult to get FDA officials to speak candidly about the types and
methods of payments that they consider to be inappropriate inducements. In an informal discussion with an FDA
field inspector who focuses on bioresearch monitoring issues, the inspector noted that he will become suspicious
if, for example, he notices a study recruitment advertisement that seems to overemphasize financial incentives
involved in a study (e.g., a particularly large or frequently recurring "$$$$" sign in the ad, a bolded statement of
"money for your time"). The inspector noted, however, that he will not generally include suspected undue influence
of financial incentives on the 483-Inspectional Observations form-in fact, he notes that he has never seen such
a citation on a 483. Rather, the inspector communicates any suspicions back to headquarters for evaluation, and
allows FDA compliance officials to determine if the payments were inappropriate and whether the study should
be cited. Other FDA inspectors note that they will not formally assess payments during inspections, but rather
simply allow FDA headquarters to make such assessments through the copy of the informed consent form routinely
forwarded in the inspection report.
In instructions to FDA field staff conducting clinical investigator inspections, the previous version of FDA
Compliance Program Guidance Manual 7348.811 (CPGM 7348.811) noted that inspectors should assess "media
ads for patient/subject recruitment" and related "promotional material." CPGM 7348.811 did not mention payments
to trial subjects, however, and instructed FDA inspectors to focus on whether the IRB approved media recruitment
ads and whether the investigator represented the test article as safe and effective in related promotional materials.
It is important to note that the current (December 2008) version of CPGM 7348.811 does not appear to make any
references to "media ads for patient/subject recruitment" or related "promotional material."
Given the lack of formal FDA guidance or written agency policy on the appropriateness of payments offered
to potential subjects, it is not surprising that CDER compliance officials themselves struggle in this area. In some
cases, say CDER officials, they will even contact medical officers in CDER's drug review divisions (e.g., an FDA
reviewer who is also a board-certified psychiatrist regarding a trial involving an antidepressant) for input on the
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