Paying Research Subjects: An Analysis of Current Policies

Context Many investigators pay research subjects. Paying research subjects could inappropriately influence them to participate in studies. We know little about how research organizations handle payment of research subjects. Contribution This survey of 9 academic centers, 7 pharmaceutical companies, 8 contract research organizations, and 8 independent institutional review boards showed that most paid subjects but few had formal policies to guide the amount or circumstances of payment. Policy Implications Without standard policies for paying research subjects, there are uncertain safeguards against unfair or coercive payment. It is uncertain whether the organizations that participated are representative of all research organizations in the United States. The Editors Clinical research would be impossible without the participation of willing human subjects. Research institutions are recruiting more participants more quickly than ever before (1). Some researchers consider payment crucial to recruitment, as evidenced by the sheer number of advertisements for paid studies in newspapers, on the radio, and on the Internet. Although paying research subjects is a common and long-standing practice in the United States (2), it remains contentious. Decisions about when, why, and how much to pay research subjects continue to spark disagreement within the research community. Some have argued that paying subjects is unethical (3, 4), but most agree that it is acceptable in some cases. The prominent ethical concern is that money may unduly induce subjects to participate in research by compromising the voluntary nature of their decisions or their willingness to explore the risks and benefits of the study (5-7). Others worry that payment may target economically vulnerable persons or compromise scientific integrity by altering the makeup of the subject population. No empirical data exist on the validity of these concerns. Federal regulations and guidelines provide minimal guidance on payment of research subjects. The U.S. Code of Federal Regulations never specifically mentions payment (8). The Official IRB Guidebook simply advises that the local institutional review board (IRB) should determine whether the rewards offered for participation in research constitute undue inducement (9). Information sheets from the U.S. Food and Drug Administration state that payment is not a benefit, [but] a recruitment incentive and advise IRBs to review both the amount of payment and the method and timing of disbursement to assure that neither are coercive or present undue influence (10). It is unknown how investigators or IRBs use these guidelines in designing and evaluating payment in research proposals. Given the pervasiveness of the practice of paying research subjects, the disparate views on its appropriateness, and the sparseness of regulations, we examined and describe guidance that research organizations actively engaged in clinical research use to decide about payment of research subjects. Although alternate forms of payment raise similar ethical concerns (11), we focused on guidance regarding monetary payment of research subjects. Methods The study included 32 geographically diverse organizations involved in the development, conduct, and review of biomedical research. We selected 12 academic research centers, 3 in each of the 4 census regions, from the 50 centers that receive the most funding from the U.S. Public Health Service; of these 12 centers, 9 agreed to participate. We contacted 20 of the largest pharmaceutical companies in the United States, and 7 agreed to participate; the others refused, citing the proprietary nature of the information. Eight of 12 contract research organizations (CROs) identified from the Centerwatch Web site agreed to participate (12). Nine independent IRBs (freestanding, for-profit IRBs that review commercially funded as well as federally funded and community research) were identified from the Web site of the Health Industry Manufacturers Association (now called AdvaMed) (13), and 8 agreed to participate. The project was explained over the telephone to the chair of the IRB, the vice president for research, or the equivalent person at each organization. Participation was requested, and a follow-up letter was sent. Data were collected in 1998 and 1999. We asked organizations to provide 1) the total number of clinical research studies initially approved in 1997; 2) the total number of studies that paid subjects in the same year; and 3) all organizational policies, guidelines, or rules of thumb regarding paying research subjects. Respondents were asked to send official copies of policies and guidelines (defined as written rules formally authorized by the organization) and to describe rules of thumb (defined as unwritten rules that had become standard practice at the organization) in a return letter. We clarified written submissions through follow-up telephone calls. Responses were analyzed to determine the type of guidance used by the organization; descriptions of the purpose of payment; and specific requirements regarding advertising, informed consent, and determination of how much to pay subjects. We had previously identified these categories as important for analysis through literature review and discussion with IRB members, ethicists, and clinical researchers. This study received IRB exemption from the Office of Human Subjects Research at the U.S. National Institutes of Health. Data are aggregated to protect the confidentiality of participating organizations. The Department of Clinical Bioethics, W.G. Magnuson Clinical Center, National Institutes of Health, funded the study, and members of the department were responsible for the collection, analysis, and interpretation of the data and the decision to submit the results for publication. Results Thirty of 32 organizations paid subjects in at least some clinical studies that were initially approved during 1997. One organization reported no paid studies, and 1 could not determine whether any subjects had been paid. Few organizations (18.8%) were able to provide a confident estimate of the proportion of studies that paid subjects. Six of 9 academic research centers provided the total number of studies approved in 1997. Of these, only 4 had an electronic method of identifying paying studies; for the other 2 centers, we collected information from the cover page of the study description or from IRB minutes. At these 6 academic research centers, 23% of studies approved in 1997 offered payment to subjects. Most pharmaceutical companies and CROs could not provide the total number of studies approved in 1997 or provided it only for units that do phase I studies and pay almost all participants. Of 8 independent IRBs, 4 did not release the total number of studies approved because of proprietary reasons and none could determine the precise number of studies that paid subjects. However, 2 independent IRBs described the proportion of paid studies as most and 1 described it as close to 80%. Existence of Guidance on Payment Only 37.5% of organizations (12 of 32) reported having written policies or guidelines about payment of research subjects. Three pharmaceutical companies reported having written guidance that applies only to phase I units and not to other studies that the companies support. In contrast, 31 of 32 organizations reported having unwritten rules of thumb. One pharmaceutical company with no written guidelines or rules of thumb reported that it leaves decisions about payment of subjects entirely to the site investigators and the IRB. Participating pharmaceutical companies and CROs reported having little involvement with decisions about paying subjects in off-site studies. Study budgets are generally negotiated among sponsors, CROs, and study sites. Site investigators and staff typically determine the details of subject recruitment and payment, and the IRB is the ultimate arbiter in deciding whether a particular payment strategy is appropriate. Content of Guidance Guidance reflected wide variation in reasons for offering payment (Table 1). Slightly more than half of the organizations with payment guidelines or rules of thumb (58%) described payment as an incentive. Academic institutions, compared with the other three types of organizations, were least likely to do so (44% vs. 62.5% to 66%, respectively). Overall, most organizations said that subjects were paid for the time (87%), inconvenience (84%), or travel (68%) associated with research participation. Thirty-two percent reported that subjects were paid for incurring risk. Independent IRBs were more likely than other organizations to report that risk level affected payment decisions (75% vs. 0% to 33%, respectively). Notably, written guidance described payment almost exclusively as compensation for time and inconvenience. Half of the written guidelines explicitly stated that subjects should not be paid for risk, and only 4 of 12 written guidelines (33%) described payment as incentive for participation. Table 1. Content of Guidance on Payment to Research Subjects Only 8 of 32 organizations (2 academic institutions, 3 pharmaceutical companies, and 3 CROs) reported using a particular formula to calculate amount of payment (Table 1). For the 3 pharmaceutical companies and 3 CROs, the payment formula applies only to on-site phase I studies. Seven organizations with written guidance but no specific formula for calculating payment advise against excessive payment to avoid undue inducement; however, they do not specify what should be considered excessive. The eight formulas varied both in level of specificity and basis for calculating payment. Four organizations calculate payment for time by the hour, ranging from $4 to $10; the other four calculate payment per inpatient day or outpatient visit. Three of the organizations pay a flat rate per day or visit (range, $25 to $125) that is not altered for procedures performed