IRB: Ethics & Human Research
Money, Coercion, and Undue Inducement: Attitudes about Payments to Research Participants
Researchers nearly always offer money to healthy individuals—and increasingly to individuals who are ill—as an incentive to enroll in research studies and as compensation for research participation.1Yet there is a tension between researchers’ use of payment as an incentive and the aim of institutional review boards (IRBs) to protect research participants by determining the ethical acceptability of payment practices. Anecdotal evidence suggests that IRB members and other professionals involved in research oversight are concerned that offers of payment may coerce or unduly influence individuals to enroll in research, thereby compromising the voluntariness of consent.2Insofar as they reflect sound ethical thinking, these concerns appropriately influence payment practices; if they are misguided, however, valuable research may be impeded because no payment—or insufficient payment—is being offered when such payment is compatible with informed consent.
Providing informed consent to participate in research requires a competent decision-maker, adequate disclosure and comprehension of relevant information, and finally, a voluntary decision. A considerable amount of regulation intended for the protection of human subjects has been aimed at promoting voluntary choice.3Although payment to participate in research is thought to influence decision-making and may thereby compromise voluntariness, the various laws, regulations, and ethical guidelines that govern the conduct of human subjects research offer relatively littlespecificguidance about payment. According to the Federal Policy for the Protection of Human Subjects (the Common Rule), “An investigator shall seek such consent only under circumstances that provide the prospective subject or representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.”4Yet the Common Rule does not define either coercion or undue influence. TheBelmont Report—upon which many rely for authoritative guidance—says that “Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance” and, by contrast, that undue influence “occurs through an offer of excessive, unwanted, inappropriate or improper reward or other overture in order to obtain compliance.”5Other documents and institutional guidelines make similar statements, but these sorts of guidance do not tell us how IRB members actually understand and apply these concepts. And while scholars have explored these concepts, we do not know to what extent their arguments have shaped the views of the crucial gatekeepers.6Thus, we conducted a survey of IRB members and research ethics professionals to address the lack of systematic data concerning attitudes about payment generally, and to determine how these individuals think about the concepts of coercion and undue influence specifically.
Study Design and Sample.We conducted a cross-sectional, descriptive, online survey of individuals randomly selected from the database of Public Responsibility in Medicine and Research (PRIM&R), a nonprofit organization advancing “the highest ethical standards in the conduct of biomedical, social science, behavioral, and educational research.”7PRIM&R’s membership includes IRB members and IRB professionals (IRB administrative staff), as well as researchers, institutional officials, and government personnel.
A random sample of 1,800 individuals was initially selected from approximately 23,000 U.S.-based individuals in the PRIM&R database of members and nonmembers who had previously identified themselves as interested in IRBs and human subjects protections. An additional 269 individuals were later added because of an unexpectedly high rate of returned mail or e-mail. Of 2,069 e-mails sent, 689 were undeliverable, leaving a usable sample of 1,380 individuals. In total, 610 surveys were completed, yielding an adjusted response rate of 44.2%.
Survey Process.A confidential, self-administered survey instrument was developed by the authors and pretested with 10 members of intramural IRBs at the National Institutes of Health (NIH). The University of Virginia Center for Survey Research transferred the instrument into a Web-based survey tool and pilot-tested the online survey, data collection, and entry techniques with 30 individuals from the same PRIM&R database.
A confidential, self-administered survey instrument was developed by the authors and pretested with 10 members of intramural IRBs at the National Institutes of Health (NIH). The University of Virginia Center for Survey Research transferred the instrument into a Web-based survey tool and pilot-tested the online survey, data collection, and entry techniques with 30 individuals from the same PRIM&R database. An advance letter mailed in May 2010 explained the nature and purpose of the survey and that an e-mail would follow with a link to an electronic survey. The advance letter included $5 as a token of appreciation and to improve recruitment. Approximately one week after the letters were sent, the 2,069 potential participants received an e-mail with an embedded HTML link to the survey Web site. Respondents entered the Web site using a unique log in that allowed for identification of nonresponders. Two subsequent reminder e-mails and one reminder postcard were sent to nonresponders.8Responses received by July 31, 2010, were included in our analysis.
Survey Content.The survey—available from the authors upon request—consisted of a maximum of 80 questions (depending on whether the respondent was currently an IRB member) and addressed five domains: 1) level of ethical concern about payment; 2) attitudes about coercion and undue influence; 3) reasons to offer money to research participants; 4) response to hypothetical scenarios; and 5) demographic information. In this paper, we focus on respondents’ attitudes about coercion and undue influence. Most questions were multiple-choice, but some allowed for free response. A five-point Likert-type scale (1 = not concerned and 5 = very concerned) was used to assess concerns about payment and its effects on participants. Unless stated otherwise, “not concerned” was combined with “a little concerned,” and “somewhat concerned,” “moderately concerned,” and “very concerned” were also combined. A separate five-point Likert-type scale (1= strongly agree and 5= strongly disagree) assessed respondents’ agreement with statements on payment to research participants. Categories of agreement were simplified to “agree” (strongly and somewhat agree), “neither,” and “disagree” (strongly and somewhat disagree).
Human Subjects Protections.The NIH Office of Human Subjects Research determined the study was exempt from the Common Rule, and a University of Virginia IRB approved it. The advance letter informed participants of the survey’s purpose and that completion was voluntary and responses anonymous.
Data Analysis.Survey data were exported from the Web-based application, cleaned, and analyzed using SAS version 9.2 (SAS Institute, Inc, Carey, NC). We summarized data using frequency distributions and descriptive statistics. Contingency tables with singly-ordered variables were analyzed using the Cochran-Armitage Trend Test, and doubly-ordered variables utilized the Jonckheere-Terpstra Test for Trend. These tests are modifications of the usual chi-square test used to incorporate the ordering in the effects of the categories and applied to our analyses of differences related to gender, education, and current IRB service.9
Respondent Characteristics.Respondents who provided demographic information were predominantly non-Hispanic white (84%) and female (70%), with an average age of 51 (±11) years. The majority (65%) held a masters or doctorate degree. Respondents were geographically diverse, representing the four U.S. Census regions (155 from the northeast, 232 from the south, 107 from the midwest, and 104 from the west). All but 42 (7%) reported they were employed in a job related to human subjects research (see Table 1). More than half (56%) had been an IRB member at some point, and the majority of these (36% of total) were currently IRB members. IRB members usually served on academic IRBs (64%), and about half reported that the majority of studies they review are government funded (52% government, 28% industry, 20% other).
Ethical Concerns about Payment.Respondents expressed varying levels of concern about offers of payment, nonmonetary goods, and medical care to research participants (Figure 1, Table 2). Sixty-one percent of respondents reported feeling somewhat, moderately, or very concerned that payment ofanyamount might influence a participant’s decisions or behaviors regarding research participation. Fewer—though over a third (37%) of respondents—expressed concern about payment described as “token,” as they defined it. On the other hand, 87% were concerned about payment described as “substantial,” as they defined it (Figure 2). In addition, 67% said they were concerned that offers of medical care provided in addition to research-related procedures might influence a participant’s decisions and behaviors. In contrast, fewer reported concern that gift cards (43%) and nonmonetary offers such as t-shirts or mugs (20%) would influence participants. Concerns about the possible influences of money, non-monetary incentives, or medical care did not vary significantly by gender, education, or IRB membership.
Most respondents expressed concern that substantial payment could compromise a participant’s ability to think clearly about study risks and benefits (85%), lead individuals to enroll in a trial they otherwise would not enroll in (88%), or remain in one from which they would like to withdraw (84%). Most (84%) also reported concern that offering participants a bonus to complete a study might compromise a participant’s right to withdraw from the study.
Coercion and Undue Influence.Although the majority (69%) of respondents agreed that there is a conceptual distinction between coercion and undue influence, about half (53%) agreed with the statement that they “could not judge whether payment was coercive or unduly influential without more specific guidelines.” Less than 20% expressed concern about possible coercion or undue influence from atokenpayment, while most were concerned about possible coercion (76%) or undue influence (84%) from an offer ofsubstantialpayment.
Table 3illustrates the views of respondents regarding coercion and undue influence. Nearly all agreed or strongly agreed with the statement that individuals are coerced if they are threatened with harm for not participating in a study (91%). The majority also agreed that coercion occurs if the offer of payment makes individuals participate when they otherwise would not (65%), or when the offer of payment causes them to feel that they have no reasonable alternative but to participate (82%). Women tended to agree more than men (p = 0.03) that participants are coerced if the payment offer makes them participate when they otherwise would not. No other trends were observed by gender, education, or IRB membership. Most respondents agreed that payment offers are an undue influence if they cause individuals to participate when they otherwise would not (81%), if an individual perceives he has no reasonable alternative but to participate (79%), or if the offer of payment distorts a prospective participants’ evaluation of risks and benefits (98%). Here, no trends were observed by gender, education, or IRB membership.
In addition to asking respondents about their general or abstract understanding of coercion and undue influence, we asked them to indicate whether hypothetical scenarios illustrated coercion or undue influence. Respondents exhibited considerable inconsistency between their abstract position and their response to the scenarios with respect to coercion, but they were more consistent with respect to undue influence (Table 2). One scenario described Mary as a resident of a U.S. inner city who was invited to participate in a phase I malaria vaccine study. She said that because she had lost her job and needed money, she felt she had “no reasonable alternative but to participate.” Even though 82% of respondents agreed that individuals are coerced if a payment offer makes them feel that they have no reasonable alternative but to enroll in a study, only one quarter (24%) thought Mary was coerced, and 17% were uncertain. For the same scenario, 64% thought Mary was unduly influenced and 15% were uncertain, which was more consistent with the 79% who agreed that payment is an undue influence if the individual perceives no reasonable alternative but to participate. Responses to scenarios involving John and Steve, who were described as enrolling in a leukemia treatment study that offered payment, were very similar. John said he needed the money to pay bills; 27% of respondents agreed and 12% were uncertain that John had been coerced. Steve said he had no health insurance; 27% of respondents agreed and 10% were uncertain that he had been coerced. Yet 70% agreed that John had been unduly influenced, and 61% said the same for Steve.
Differences by Type of Subject and Reason for Payment. Most respondents found it acceptable to offer money to healthy volunteers (87%), patient volunteers in studies with no prospect of benefit (78%), and patient volunteers in prospect of benefit studies (72%). Only 14% agreed that participants in studies that hold the prospect of direct benefit for their health should be paid less than those in studies with no prospect of benefit (68% disagreed; 19% neither agreed or disagreed). No differences were seen in these attitudes by gender, education, or IRB membership.
As illustrated byTable 4, almost all respondents agreed that researchers could offer money to reimburse expenses regardless of the study population (98% for healthy volunteers, 96% for patients in studies with no prospect of benefit, and 94% for studies with prospect of direct benefit). Many also agreed that offering money as compensation for time and inconvenience was acceptable for all three populations (94%, 91%, and 87%, respectively). In contrast, only about half agreed it was permissible to offer money as an incentive to participate (58%, 57%, and 51%, respectively), and even fewer thought it permissible as compensation for risk (37%, 38%, and 36%, respectively). In all cases, IRB members were less likely to agree that offering money as compensation for risk is permissible than individuals who had never been IRB members (p = 0.0006, p = 0.005, and p = 0.001, respectively). Nonetheless, approximately 30% of IRB members agreed that it is permissible to offer money as compensation for risk or to regard payment as a benefit in risk-benefit assessment.
This is the first national study to examine the attitudes of IRB members and human subjects protection professionals about the ethics of payment and, in particular, their beliefs regarding coercion and undue influence. Previous studies have examined institutional practices regarding payment, whether payment affects a subject’s perception of the risks of research, and the attitudes of IRB members towards the reasons and amount of payment.10Our data demonstrate 1) persistent ethical concern about the effect of offering payment to research subjects, 2) divergence between how individuals view the meaning of coercion and undue influence and how they apply these concepts to concrete situations, and 3) more acceptance of payment by IRB members as reimbursement or compensation for time and inconvenience than as an incentive to participate or as compensation for risk.
Concerns about Payment. Study respondents indicated pervasive ethical concern that offering payment to subjects will influence a prospective research participant’s decision to enroll or remain in a trial. Self-reported levels of concern increased as the amount of payment became more substantial. This is consistent with a belief pervasive in our daily lives: more money is generally more influential.
Coercion and Undue Inducement. A major purpose of our study was to probe respondents’ understandings of coercion and undue inducement, terms invoked but not defined by the U.S. regulations governing human subjects research. Interestingly, although over 90% of respondents agreed with a definition of coercion tied to threat of harm, substantial majoritiesalsoagreed that research participants are coerced when an offer of payment—not the threat of harm—gets them to participate when they otherwise would not or when they feel they have no alternative but to participate. Although responses to concrete scenarios were more consistent with theBelmont Report’s definition of coercion (noted above), substantial minorities of respondents characterized hypothetical research participants as being coerced by offers of payment.
Virtually all respondents agreed that an offer constitutes undue influence if it “distorts a subject’s ability to perceive accurately the risks and benefits of research.” However, a surprising 80% also judged that the offer of payment constitutes undue influence simply because it motivates someone to do something they otherwise would not. This view is an interesting counterpoint to reports in the literature that some research subjects view payment as highly effective or even essential to securing their participation.11Moreover, we suspect respondents are unlikely to think that a bioethicist isundulyinfluenced if the offer of $1,000 as an honorarium to give a presentation motivates him to do so when he otherwise would not.
How can these apparent inconsistencies be explained? We hypothesize that many of our respondents (perhaps implicitly) accept a form of “research exceptionalism” by adopting a conception of undue influence in research that is radically different from the conception they employ in most other areas of life. For example, everyone agrees that in the realm of work it is ethically permissible and not undue influence to offer money as an incentive to get people to perform activities that they would otherwise not. However, many IRB members and others involved in research oversight perceive the use of money as an incentive for research participation as ethically problematic undue inducement, even when payment does not distort a prospective research participant’s ability to weigh the risks and benefits of participation. A possible explanation for this perspective, not probed by our study, is an idealized view that research participation should be motivated by altruism; on this view, financial incentives—as distinct from compensation for time and burden—are seen as ethically worrisome. This view seems to be supported by our data, as respondents endorsed payment for reimbursement and compensation much more often than as an incentive or compensation for risk.
Although the connection between attitudes towards payment and IRB practices is unclear, survey respondents endorsed interpretations of coercion or undue influence that, if strictly applied, would stringently limit the amount of payment offered research participants. The extent to which these attitudes about payment effect recruitment to research is unknown.
Implications for Policy and Practice. Much valuable research is unlikely to be completed in a timely way or even conducted at all unless individuals are offered payment as a financial incentive to participate. Yet most respondents expressed ethical concerns that payment constitutes coercion or undue influence. Given that IRBs should not approve protocols—whatever their social or scientific value—unless the possibility of coercion or undue influence has been minimized, it is important that IRBs employ defensible views of the concepts of coercion and undue influence. If IRBs are employing excessively expansive or inconsistent views of these concepts when they make decisions about protocols, or if investigators believe that IRBs will disapprove payment practices for these reasons and therefore adjust their protocols to offer “acceptable” payments, then these views about coercion and undue inducement may unnecessarily interfere with recruiting research participants and thus impede valuable research. Policy guidance and educational efforts are needed to clarify coercion and undue inducement and to address “research exceptionalism” in order to advance the goals of research ethics to promote socially valuable research while providing appropriate protection for participants.
Limitations. Our survey probed the beliefs and attitudes of IRB members and other human subject professionals associated with PRIM&R. While the respondents are geographically and professionally diverse and have considerable experience in human subjects protections, they may have views that differ from others involved in the oversight of human subjects research.
Future Research. It is possible that many human subjects protection professionals “worry” that payment is coercive or constitutes undue influence, but that these worries have little impact on their decisions to approve or not approve research. Future research should examine actual IRB decision-making. The “research exceptionalism” hypothesis we have proposed should be tested, and it is necessary to consider whether this view can be defended. It would also be valuable to examine how investigators design their payment schedules and whether they adjust the amount of payment based on concerns about what IRBs will approve.
We conducted a national survey of the attitudes of IRB members and human subjects protection professionals toward payment of research subjects. Respondents indicated considerable ethical concern that payment could constitute coercion or undue inducement. Most agreed that individuals are coerced if the offer of payment makes them participate when they otherwise would not or when the offer of payment causes them to feel that they have no reasonable alternative but to participate. Most respondents had similar views about undue influence. The excessively expansive or inconsistent views about coercion and undue influence held by IRB members and human subjects professionals may interfere with the recruitment of research participants by needlessly limiting the payments offered to them and may thereby impede valuable research without true cause.
The views expressed are the authors’ own. They do not reflect any position or policy of the National Institutes of Health, U.S. Public Health Service, or the Department of Health and Human Services.
The authors thank Joan Rachlin and the staff of PRIM&R for their collaboration in providing the sample, the University of Virginia Center for Survey Research for conducting the survey, and the respondents for taking the time to answer our questions. We also thank David Wendler, Seema Shah, Joseph Millum, and an anonymous reviewer for helpful comments on the manuscript and Ninet Sinaii for her assistance with statistical analysis. These individuals were not compensated for their contributions.
Emily A. Largent, BSN,is a candidate in the PhD Program in Health Policy, Harvard University, Cambridge, MA;Christine Grady, PhD, RN,is Head, Section on Human Subjects, Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD;Franklin G. Miller, PhD,is Senior Faculty, Department of Bioethics, Clinical Center, National Institute of Health, Bethesda, MD; andAlan Wertheimer, PhD,is Senior Research Scholar, Department of Bioethics, Clinical Center, National Institute of Health, Bethesda, MD.
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4. Code of Federal Regulations. Protection of Human Subjects. 45 CFR 46.
5. See ref. 3, The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 1979.