Research
Ethical Issues in Recruitment and Payment of Research Participants
Summary: The goal of the series of conceptual and empirical projects described here is analysis of ethical issues and enhanced understanding of practices related to recruitment of and payment of research participants.
| Section: | Ethics of Human Subjects Research | ||||||||||||||||||
| Principal Investigators: | Christine Grady, R.N., Ph.D. Ezekiel Emanuel, M.D., Ph.D. David Wendler, Ph.D. |
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Background: Clinical research depends on the successful recruitment and retention of participants. Fundamental to avoiding exploitation and demonstrating respect for research participants is care and attention to the selection, recruitment, and enrollment of groups and individuals in research. Decisions about who should be invited to participate in research take into consideration not only scientific objectives, but also dynamics of risk and benefit, and vulnerability. People participate in research for a variety of reasons. Understanding these reasons can help in recruitment as well as careful enrollment. The social value of research and the imperative to ensure scientific validity justify strategies to enhance recruitment of eligible participants to research protocols.
However, recruitment strategies pose ethical issues insofar as they threaten to distort the physician-patient relationship, exploit potential research participants, influence risks and benefits, interfere with informed consent, or violate confidentiality or privacy. Recruitment techniques represent the initial communication or contact with potential participants and may influence their understanding and expectations of research and the voluntariness of their participation. Despite the potential issues, participant recruitment has received relatively little attention in the bioethics literature.
Although evidence is limited, payment may enhance recruitment to clinical research by providing an incentive or enabling participation with a lesser amount of financial sacrifice. Offering payment to participants of clinical research is a long-standing but uneven and contentious practice in the United States. Despite the reality that people have been paid for participation for decades in the United States and are paid in a wide range of studies today, concern remains about money unduly inducing participation and as such obscuring risks, impairing judgment or encouraging misrepresentation. Limited data exist to support or refute these concerns.
Departmental Research Initiative: The Department has undertaken several projects related to recruitment and payment of participants in clinical research. We engaged in a series of related conceptual and empirical studies to better understand ethical issues involved in paying participants, policies and practices regarding payment of participants, and the influence of payment on participants' perceptions of research. Other projects aimed to better understand what motivates people to participate in research as well as the extent to which participants feel pressure, either from others or from their health or social circumstances. A better understanding of the motivations and reasons for research participation could increase efficiency and specificity of recruitment efforts, enhance the process of informed consent, foster subject satisfaction and compliance, and ultimately improve the quality of clinical investigation. This information could potentially benefit researchers, trial managers, recruiters, and health care team members.
Payment of Research Participants: Although there remains some controversy over the ethics of paying for research participation, many agree that payment is acceptable especially if offered as reasonable reimbursement for time and expenses. Our conceptual work examined the presumptive reasons that people are paid for research participation, moral concerns about payment as a possible ‘undue influence’ on the decision to participate in research, and different models to justify and formulate payment. We proposed three different models for justifying and calculating payment to research participants, a market model, a wage payment model and a reimbursement model (Dickert & Grady). In a subsequent conceptual analysis of the ethical issues when considering payment to children in research, we described a fourth possible model of payment, that of appreciation (Wendler et al. 2002).
In a target article in the American Journal of Bioethics, Grady considered whether payment jeopardizes informed consent. Some are concerned that money could possibly be “coercive” or unduly influential and thus capable of distorting the judgment of potential research participants or compromising their voluntariness. Grady recognizes that more often than not there are multiple factors influencing research participation decisions, even if money is one among them. She briefly explored the concept of undue influence, as well as the question of whether or not there is something uniquely distorting about money as opposed to a chance for treatment or medical care. She argues that a modest amount of money calculated on the basis of time or contribution may, rather than constituting an undue inducement, be an indication of respect for the contributions that research participants make.
The empirical aspects of the payment project included the following projects. First, we analyzed institutional policies and rules of thumb regarding payment to research participants from research organizations, including academic medical centers, clinical research organizations (CROs), pharmaceutical companies, and independent IRBs. In this analysis, we discovered that guidance about payment of research participants for IRBs and investigators is sparse. Although few institutions had written guidance regarding payment, most have rules of thumb. These rules of thumb are often nonspecific and based on the regulatory requirement to avoid 'undue' influence, yet rarely include explicit formulae or specifications for how to calculate payment or recognize what might be undue (Dickert et al. 2002). The second project involved reviewing and extracting data from research protocols themselves to describe the practice of paying participants in the United States. In this analysis of 467 paying protocols from around the United States, we found that both patient participants and healthy participants are paid in similar amounts for participation in a wide range of studies including phase three clinical trials. There is limited documentation regarding how amounts are calculated and consequently considerable variation in payment, sometimes even within a single institution or a single study. The median total amount paid across all 467 studies was modest at $150 (Grady et al. Contemporary Clinical Trials 2005).
Undue Inducement: In another project, Dr. Emanuel distinguished different ways of understanding the concept of undue inducement. He suggested that undue inducement requires 1) a welcome offer that is 2) excessive or irresistible, 3) leads to bad judgment, which results in 4) participating in ethically, legally, or prudentially undesirable activities that harm ones interests. He argues that in research appropriately approved by an IRB and found to have acceptable risks, undue inducement is a misplaced worry (Emanuel, JLME 2004, Emanuel, AJOB 2005, Emanuel et al. Lancet 2005). In collaboration with Jen Hawkins, he also undertook a re-examination of the concept of coercion (Hawkins, Emanuel 2005).
Payment and Response Rates: Although there have been previous studies measuring the impact of financial incentives on survey response rates, little is known about the effect of a cash lottery on response rates. In a recent national survey study of non-physician clinicians, we randomized the cohort into three incentive groups ($5 cash, a chance to win a lottery, and no incentive) to determine the effect of these incentives on response rates. A small cash payment of $5 had a significant effect on response rate (64.2 percent) whereas those given the chance of participation in a cash lottery responded no more frequently than the control group (44.7 percent and 42.2 percent, respectively). (Ulrich et al. Nursing Research 2005).
Impact of Research: The Department’s studies and resulting publications regarding payment of research participants have had a noticeable impact on the debate about payment of research subjects. Some have adopted a model based on our recommended “wage payment model” for determining how to pay research participants. The paper on models of payment has had over 75 citations. Publishing the paper on payment as a target article in AJOB invited further debate on the topic.
The critique of undue inducement, and publishing a target article on undue inducement in AJOB has influenced the field and invited further debate on the topic.
Future Research Initiatives: We continue to be interested in various influences on decisions to participate in research.
- We hope to further explore the influence of financial compensation on participants’ perspectives of research, and on the quality of their informed consent, including whether offering payment could reduce any “therapeutic misconception.” Dr. Wertheimer, is developing an analysis of monetary payment for research participants in which he first recognizes that the common perception which regards payment as sometimes necessary but generally to be discouraged and minimized in research is at odds with most common practices and with liberal political philosophy. Recognizing that in most activities people are free to engage in any behavior they choose so long as their conduct does not negatively affect others, he analyzes payment in research by critically examining — and rejecting — four principal arguments against the use of monetary incentives in clinical research: 1) the argument from voluntariness; 2) the argument from commodification; 3) the argument from justice or exploitation; and 4) the argument from institutional integrity or trust.
- Through our study with economically disadvantaged participants (see Vulnerable Populations), we plan to explore the influence that lack of health care options has on perceptions of research, decision making and willingness to participate in research. We will also investigate motivations and what is important to decision making in our study of adolescent research participants and their parents (also see Vulnerable Populations). Through our study with ESPRIT, we are examining the factors that influence individuals to stay in a study after they are enrolled, especially if they are assigned to the no-intervention arm (see Multinational Research).
- We are also embarking on a project to examine the justifications for certain exclusion criteria. A paper addressing the unique risks and benefits of cancer chemoprevention studies discusses concerns about who is included as sufficiently ‘at-risk’ for a particular disease based on selected criteria. This paper has been accepted at IRB (Slutsman et al. 2006). In another project, we are arguing in support of no categorical exclusion for HIV infection for cancer clinical trials. We also plan to explore whether the predictable costs of including particular individuals might permissibly influence decisions about eligibility for clinical research.
Publications:
Dickert N, Grady C. What's the price of a research subject? Approaches to payment for research participation. New England Journal of Medicine. 1999;341(3):198-203.Grady C. Money for Research Participation: Does it Jeopardize Informed Consent? American Journal of Bioethics. 2001;1(2):40-44.
Dickert N, Emanuel E, Grady C. Paying Research Subjects: Analysis of Current Policies. Annals of Internal Medicine. 2002;136(5):368-393.
Wendler D, Rackoff J, Emanuel E, Grady C. The Ethics of Paying for Children's Participation in Research. Journal of Pediatrics. 2002;141:166-171.
Emanuel E. Ending Concerns about Undue Inducement. Journal of Law, Medicine & Ethics. 2004;32(1):100-105.
Ulrich C, Grady C. Financial incentives and response rates in nursing research. Nursing Research. 2004;53(2):73-4.
Grady C, Dickert N, Jawetz T, Gensler G, Emanuel E. An analysis of U.S. practices of paying research participants. Contemporary Clinical Trials. 2005;26(3):365-375.
Emanuel, EJ. Undue Inducement: Nonsense on Stilts? American Journal of Bioethics. 2005;5(5):9-13.
Emanuel, EJ. Response to Commentators on “Undue Inducement: Nonsense on Stilts?” American Journal of Bioethics. 2005;5(5):W8-W11.
Emanuel EJ, Currie XE, Herman A, on behalf of Project Phidisa. Undue Inducement in clinical research in developing countries: is it a worry? Lancet. 2005;366:336-340.
Hawkins J, Emanuel E. Clarifying Confusions about Coercion. Hastings Center Report. 2005;35(5):16-19.
Grady C. Payment of clinical research subjects. Journal of Clinical Investigation. 2005;115:1681-1687
Ulrich C, Danis M, Koziol D, Garrett-Mayer E, Hubbard R, and Grady C. Does it pay to pay? A randomized trial of prepaid financial incentives and lottery incentives in surveys of non-physician health care professionals. Nursing Research. 2005;54(2):2-6.
Hull SC, Glanz K, Steffen A, Wilfond B. Recruitment Approaches for Family Studies: Attitudes of Index Patients and Their Relatives. IRB: Ethics and Human Research. 2004;26(4):12-18.
Slutsman J, Buchanan D, Grady C. Ethical Issues in Cancer Chemoprevention Trials: Considerations for IRBs and Investigators. IRB: Ethics and Human Research. (in press)
Ulrich CM, Wallen GR, Feister A, Grady C. Respondent Burden in Clinical Research: When Are We Asking Too Much of Subjects? IRB: Ethics and Human Research. 2005;27(4):17-20.
Hull SC, Glanz K, Steffen A, Wilfond B. Recruitment Approaches for Family Studies: Attitudes of Index Patients and Their Relatives. IRB: Ethics and Human Research. 2004;26(4):12-18.
