MONEY, COERCION, AND UNDUE INDUCEMENT: A SURVEY OF ATTITUDES ABOUT PAYMENTS TO RESEARCH PARTICIPANTS

The practice of offering payment to research participants exhibits a tension between the aims of investigators to recruit subjects and the aims of IRBs to protect them by determining the ethical acceptability of protocols and payment schedules. On the one hand, payment is offered – nearly universally to healthy participants and increasingly to patient participants – to incentivize enrollment and compensate for participation.¹ On the other hand, institutional guidance often cautions against undue inducement through offers of payment, and anecdotal evidence suggests that members of Institutional Review Boards (IRBs) and professionals involved in research oversight are concerned that payment may coerce or unduly influence prospective research participants, thereby compromising the voluntariness of consent.² Insofar 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.

Provision of informed consent to participate in research requires: a competent decision maker; adequate disclosure and comprehension of pertinent information; and a voluntary decision. While payment is thought to influence decision-making and may thereby compromise the voluntariness of consent, the various laws, regulations, and ethical guidelines that govern the conduct of human subjects research offer relatively little specific guidance about payment. According to the Federal Policy for the Protection of Human Subjects or 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.”³ Yet, the Common Rule does not define either coercion or undue influence. The Belmont Report, upon which many rely for authoritative guidance, states, “Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance;” by contrast, undue influence “occurs through an offer of excessive, unwanted, inappropriate or improper reward or other overture in order to obtain compliance.”⁴ Although other documents and institutional guidelines make similar statements and scholars have explored these concepts, we do not know how IRB members actually understand and apply these concepts.⁵

To remedy this gap in our understanding of research regulations, we undertook 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 they think of coercion and undue influence specifically.

Methods

Study design and sample

We conducted a cross sectional, descriptive, on-line survey of individuals randomly selected from the database of Public Responsibility in Medicine and Research (PRIM&R), a non-profit organization advancing “the highest ethical standards in the conduct of biomedical, social science, behavioral, and educational research.”⁶ PRIM&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 1800 was initially selected from approximately 2,300 U.S.-based individuals in the PRIM&R database of (members and non-members) who had previously self-identified as interested in IRBs and human subjects protections; an additional 269 were later added because of an unexpectedly high rate of returned mail or email. Of 2069 emails sent, 689 were undeliverable, leaving a usable sample of 1380. 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 NIH IRBs. 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 email would follow with a link to an electronic survey. The advance letter included $5 as a token of appreciation and to improve recruitment. The 2069 potential participants received an email with an embedded html link to the survey approximately 1 week after the letters. Respondents entered the website using a unique login which allowed for identification of non-responders. Two subsequent reminder emails and one reminder postcard were sent to non-responders.⁷ Responses 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 their attitudes on coercion and undue influence. Most questions were multiple-choice; 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. For analysis, “not concerned” was combined with “a little concerned”; and “somewhat concerned,” “moderately concerned,” and “very concerned” were combined. A separate 5 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 exempt, 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). Data are summarized by 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.⁸

Results

Respondent characteristics

Respondents (n= 610) were predominantly non-Hispanic white (84%) and female (70%), with an average age of 51 ((±11) years. The majority (65%) had a masters or doctorate education. Respondents were geographically diverse, representing the 4 US Census regions (155 Northeast, 232 South, 107 Midwest, and 104 West). All but 42 (7%) reported a current job related to human subjects research (see Table 1). More than half (56%) had been an IRB member at some point, the majority of whom (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).

Table 1.

Respondents’ Current Roles Related to Human Subjects Research

Role	Frequency	Percent
IRB Member	222	67.68%
Researcher	157	25.74%
Academic, Non-Researcher	79	12.95%
Clinician, Non-Researcher	46	7.54%
Research Nurse	21	3.44%
Ethicist	58	9.51%
Sponsor	13	2.13%
Regulator	122	20.00%
Evaluate Grants	67	10.98%
Write Policy	120	19.67%
Other	209	34.26%

NOTE: Respondents could choose more than one role.

Ethical concerns about payment

Respondents expressed variable levels of concern about offers of payment, non-monetary goods, and medical care to research participants (see Figure 1, Table 2). The majority (61%) of respondents reported feeling somewhat, moderately, or very concerned that payment of any amount might influence a participant’s decisions or behaviors regarding research participation. Fewer respondents expressed concern (37%) about payment described as “token” – as they defined it – but most (87%) were concerned about payment described as “substantial” – as they defined it (Figure 2). The majority (67%) were also concerned that offers of medical care provided in addition to research-related procedures may influence a participant’s decisions and behaviors. In contrast, fewer reported concern that gift-cards (43%) and non-monetary 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.

Figure 1.

Percentage of respondents reporting that they were concerned about possible influences on participant decision and behavior

Table 2.

Levels of Concern About the Influence of Different Offers

	Not Concerned	A Little Concerned	Somewhat Concerned	Moderately Concerned	Very Concerned
Non-Monetary Offers	53.69%	25.94%	11.49%	6.73%	2.13%
Medical Care	12.97%	19.70%	27.91%	22.50%	19.91%
Gift Cards	19.90%	36.68%	22.37%	14.64%	6.41%
Payment in Any Amount	7.91%	31.30%	27.35%	20.92%	12.52%
Token Payment	33.61%	29.65%	19.11%	13.51%	4.12%
Substantial Payment	2.98%	9.59%	19.01%	26.61%	41.82%

Figure 2.

Percentage of respondents reporting they were concerned about the influence of payment on participant decision and behavior

Most 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 that otherwise they would not enroll in (88%), or remain in one from which they would like to withdraw (84%). Most (84%) also reported concern that completion bonuses compromise a participant’s right to withdraw.

Coercion and undue influence

Although the majority (69%) of individuals surveyed 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 a token payment, while most were concerned about possible coercion (76%) or undue influence (84%) from an offer of substantial payment.

Table 3 illustrates the views of respondents regarding coercion and undue influence. Nearly all agreed or strongly agreed with the statement that subjects are coerced if they are threatened with harm for not participating (91%). The majority also agreed that participants are coerced if the offer of payment makes them 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 participants to participate when they otherwise would not (81%), if a participant perceives he has no reasonable alternative but to participate (79%), or if the payment offer distorts participants’ evaluation of risks and benefits (98%). Here, no trends were observed by gender, education, or IRB membership.

Table 3.

Views about coercion and undue influence

% of respondents who agreed or strongly agreed that if the research participants …	Then …it is coercion	Then …it is undue influence	% who thought Mary* was coerced unduly influenced		% who thought John** was coerced/unduly influenced		% who thought Steve*** was coerced/unduly influenced
…are threatened with harm	91.2%	-----
…will participate when otherwise they would not if offered payment	64.8%	81.0%
…feel they have no reasonable alternative but to participate because offered payment	81.6%	79.2%	24.3%	64.4%	26.7%	70.2%	6.5%	60.5%
…ability to accurately perceive risks and benefits is distorted when offered payment	---	98.2%

^*Mary, a resident of a US inner city, said about the malaria vaccine study “I would not normally have enrolled, but I recently lost my job and I need the money. I don’t feel like I have any alternative but to participate”

^**John was offered $2500 to enroll in the leukemia drug study and said “The bills have piled up since I got sick, and I feel like my only option is to participate in this study. I need the money”

^***Steve also enrolled in the leukemia treatment study that offered $2500. He said “I don’t have health insurance. I don’t care about the money, but by enrolling in this study, I can get the medical care I need. I feel like I have no alternative but to participate”

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 were more consistent with respect to undue influence (Table 2). For example, Mary, described as a resident of a US inner city invited to participate in a phase 1 malaria vaccine study, said that because she lost her job and needed money, she felt she had “…no reasonable alternative but to participate.” Even though 82% agreed that subjects are coerced if a payment offer makes them feel that they have no reasonable alternative but to participate, 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 subject 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% agreed and 12% were uncertain that John had been coerced. Steve said he had no health insurance; 27% agreed and 10% were uncertain that he had been coerced. The majority agreed that both John (70%) and Steve (61%) had been unduly influenced.

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 by Table 4, almost all respondents agreed that researchers could offer money for reimbursement of expenses regardless of the study population (98% for healthy volunteers, 96% for patients in no prospect of benefit studies, 94% in prospect of direct benefit studies), or as compensation for time and inconvenience for all three populations (91%, 91%, 87% respectively). In contrast, only about half agreed it was permissible to offer money as an incentive to participate (58%, 57%, 51% respectively), and even fewer as compensation for risk (37%, 38%, and 36% respectively). In all cases, IRB members were less likely to agree that it is permissible to offer money as compensation for risk 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 regard payment as a benefit in risk-benefit assessment.

Table 4.

Acceptable reasons to offer money to research participants of different types

% who agree or strongly agree that it is acceptable to…	Healthy Volunteer	Patient-subjects in studies with no prospect of benefit	Patient-subjects in studies with a prospect of benefit	Considered in choosing payment amount for phase 1 malaria vaccine trial, which involved 3 doses of experimental vaccine, blood, urine, vitals and P&E over 7 months, in participants from:			Considered for choosing amount in leukemia treatment study, which involved an experimental drug, research PET, bone marrow biopsy, blood, and 6 visits every 4 weeks
				A US affluent suburb	A US inner city	Rwanda
Offer Money	86.5%	78.2%	71.8%	----	----	----	-----
Reimburse for expenses	97.7%	95.8%	93.8%	67.1	66.7	65.9	65.7
Compensate for time, effort, inconvenience	94.2%	90.9%	87.1%	80.1%	82%	78.4%	80.2
Offer money as an incentive	58.3%	57.2%	50.6%	30.5%	31	31	30.5
Offer money to compensate for risk or benefit in risk-benefit assessment	37.0%	37.8%	35.5%	30%	31.6	31.2	36.6%

Discussion

This is the first national study to examine the attitudes of IRB members and subject 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.⁹ Our 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

Our 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 that 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 majorities also agreed 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 the Belmont 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.¹⁰ Moreover, we suspect respondents are unlikely to think that a bioethicist is unduly influenced 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 have effects on 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 unless research subjects are offered payment as a financial incentive to participate. At the same time, most survey 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 these concepts. If IRBs are employing excessively expansive or inconsistent views of these concepts when they make decisions on protocols, or if investigators believe that IRBs will disapprove payment schedules for these reasons and therefore anticipatorily adjust their protocols to offer “acceptable” payments, then these views about coercion and undue inducement may unnecessarily interfere with the recruitment of research participants and 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 subject protection 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 subject professionals “worry” that payment is coercive or constitutes undue influence, but that when faced with a decision to approve or not approve research, these worries have little impact. 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.

Conclusion

We conducted a national survey of the attitudes of IRB members and human subjects protection professionals towards payment of research subjects. Respondents indicated considerable ethical concern that payment could constitute coercion or undue inducement. Most agreed that subjects 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 thereby impede valuable research without true cause.