The ethical anatomy of payment for research participants

Paying research subjects for their participation in biomedical studies is an increasingly common practice across different types of research involving healthy volunteers and patients (Grady et al. 2005; Largent and Lynch 2017a). Nevertheless, the payment continues to raise numerous conceptual, ethical and practical controversies among bioethicists, investigators, research ethics committees/institutional review boards (RECs/IRBs), and other members of the research community. Although prominent international guidelines and national regulations call attention to the crucial moral issues that payment raises (in particular, the risk of undue influence), they offer little substantive guidance on how to pay research subjects in an ethical way, and if they do so, they often provide contradictory advice. For instance, the World Medical Association Declaration of Helsinki (2013) does not address payment for research participation directly. It only mentions that information on “incentives for subjects” must be contained in the study protocol (par. 22). Also, the U.S. “Common rule” (Department of Health and Human Services 2018) and the European Union “Clinical Trial Regulation” (2014) offer very limited guidance on payment for participants. All these regulatory lacunas and contradictions are reflected in considerable variation in local payment policies and practices around the world (Dickert et al. 2002; Grady et al. 2005; Fry et al. 2005; Ndebele et al. 2008; Pasqualetti et al. 2010; Roche et al. 2013; Largent and Lynch 2017a).

One of the factors which adds to this confusion is the diversity and ambiguity of terminology used in the literature and guidelines on research payment. For example, the International ethical guidelines for health-related research involving humans of the Council for International Organizations of Medical Sciences (CIOMS) make a distinction between “reimbursement” for reasonable direct costs incurred by research subjects and “compensation” for the time spent and other inconveniences resulting from study participation (2016, Guideline 13 and Commentary). The Guideline for good clinical practice issued by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use speaks of “payments and compensation” (2016, par. 3.1.2., 3.1.8., 3.1.9.) with no further explanation. The U.S. Food and Drug Administration Guidance for institutional review board and clinical investigators: payment and reimbursement to research subjects (2018) makes a distinction between “reimbursement” for direct costs and other “payment” for participation, which it considered to be more ethically challenging as in some cases it may constitute an undue influence to prospective subjects. The Council of Europe’s Additional Protocol to the Convention on human rights and biomedicine, concerning biomedical research mentions „payments and rewards” without any additional differentiations, in the Appendix containing a template of an information sheet for the ethics committee (2005a). The term is “unpacked” in the Explanatory Report to Article 12 of the Additional Protocol dealing with undue inducement which refers to “compensation” for burdens and inconveniences and “reimbursement” for expenses and financial losses (Council of Europe 2005b, sec. 64). Australian guidelines on Payment of participation in research: information for researchers, HRECs and other ethics review bodies issued by the National Health and Medical Research Council (2019) divide “payment” for participants in four analytical categories: “reimbursement” for any research-related expenses; “compensation” for any documented financial losses resulting from participation in research, including loss of wages, or from an injury suffered as a direct consequence of participation; “remuneration” paid to participants in recognition of their service for the time spent and other inconveniences resulting from participation; and “incentive or inducement” provided to individuals simply to encourage their enrolment or continuation in research. In the United Kingdom, the NHS Health Research Authority guidance (2014) follows terminology developed by the Nuffield Council on Bioethics. The Council, in its report Human bodies: donation for medicine and research (2011) distinguishes three forms of payment: (i) “recompense” offered in recognition of losses incurred which may take a form of “reimbursement” of direct financial expenses, lost earnings, or “compensation” for non-financial losses, such as time, inconvenience and discomfort; (ii) “reward” defined as a “material advantaged gained by a person …that goes beyond ‘decompensating’ the person for losses they incurred”; “reward” becomes “remuneration” when calculated as a wage or equivalent”; and (iii) “purchase”—money given in exchange of a “thing” (e.g., biological material for research) (Nuffield Council on Bioethics 2011, p. 2).

In order to bring an end to this terminological (and conceptual) chaos, in this analysis, “payment” is used as an overarching term that encompasses all forms of financial and in-kind support provided to research participants.¹ It covers two sub-categories, which will be referred to as “recompense” and “remuneration”. These categories are distinguished by a different impact each of them has on the participant’s economic position as evaluated ex post.

The term “recompense” stands for any payment that entails no net benefit to recipients. Recompense amends to research participants for financial and non-financial losses or injuries resulting from their participation in research. Thus, this type of payment does not constitute a gain or profit, but merely covers—understood in broad terms—costs of the participation. Recompense may include three sub-categories of payments: (i) reimbursement of direct financial expenses incurred as a result of participation in research (e.g. costs of travel, accommodation, meals, childcare); (ii) compensation for indirect financial expenses, i.e., losses, that arise from participation in research (e.g. loss of wage in result of taking unpaid leave from work); and (iii) compensation for financial and non-financial losses resulting from injuries suffered as a direct consequence of participation in research.

“Remuneration” refers to any payment provided to individuals for their service as research participants, which exceeds expenses, losses or injuries experienced by participants as a result of their participation, and brings net benefit (gain, profit) for recipients. The remuneration for research participation (same as for “regular work”) may be understood either as a reward given in recognition of and as an appreciation for participants’ valuable contribution; or as a price—money given in direct, market-driven exchange for a service provided by participants (cf. Moriarty 2020; Różyńska 2021). If the remuneration is understood as a reward, the payment should be adequate to the desert, i.e., to the value of participants’ contribution. The latter value necessary depends on various factors, including (i) time allotted to research; (ii) efforts or types of services rendered (e.g., performing psychological or physical tests, taking drugs or using device as instructed, conducting self-monitoring or gathering other research-relevant information); (iii) discomfort, burdens or inconveniences associated with participation (e.g., stress, pain, suffering, but also burdens related to sticking to a dietary regime or inconveniences caused by the expected lifestyle changes); (iv) the level of risk involved in research, and (v) special/unique value of the input of the specific subject (e.g. due to rarity of a disease suffered by the person or her genetic make-up). If remuneration is considered as a price for participation, the amount of payment is determined by market forces—supply and demand, and it does not have to be proportionate to the value of the subjects’ contribution. In literature and guidelines, the latter way of thinking about payment if often concealed under the concept of “incentive” or “inducement”, although—as it will be explained later—these labels are far from being adequate and should be abandoned.

The above typology of payments for research participation is preferable over other schemes proposed in the literature and regulatory documents at least for three reasons. First, it is built upon one clearly defined, objective and disjoint divisional criterion, thereby avoiding a mistake of mixing entirely different criteria in one scheme. Such a mistake affects all typologies of research payments which, alongside recompenses and remunerations, distinguish “incentives” or “inducements” payments. This mistake originates from the fact that the former two categories of payments are defined by the payment impact on the subject baseline economic position, the latter is based on the researcher’s intention. Secondly, by rejecting the term”compensation”, the proposed typology avoids conceptual and normative confusion stemming from ambiguity of this notion in legal terminology, where it stands for both money received in return for services rendered, especially salaries or wages, and for payment of damages for loss or injury (Różyńska 2021). The ambiguity undermines the conceptual and normative value of highly popular payment scheme advocated by Gelinas, Largent, Lynch, and collaborators (Gelinas et al. 2018; Persad et al. 2019; Lynch et al. 2021; Bierer et al. 2021). Following Christine Grady’s terminology (2005), the authors separate “reimbursement”, “compensation”, and “incentive”. Trapped by the ambiguous language of “compensation”, they frame remuneration as recompense for losses, arguing that “participants' time, as well as their assumption of research-related burden and inconvenience … are critical contributions experienced as losses by participants; they are giving up or accepting unfavorable as a result of participation. Thus, the same justifications applicable to reimbursement applied here” (Lynch et al. 2021, p. 16). At the same time, applying the logic of remuneration, they reject compensating participants based on their opportunity costs, noting that “rather, research compensation is an acknowledgement of participants’ contributions to research, which leads to the conclusion that there generally should be equal pay for equal work” (Lynch et al. 2021, p. 16).

Finally, the advocated typology allows for separating payments form small gifts given at the conclusion of a study (such as chocolates, T-shirts, cups, pens, cinema-tickets) that have minimal market value, serve only as token of appreciation, and have likely zero impact on recruitment (Grady 2005).

Having clarified basic terminological and conceptual issues, we can move on and explore the ethical anatomy of payment for research participants. It would be useful, however, to indicate briefly—from the outset—the scope of the forthcoming analyses.

The paper deals with the widespread practice of paying research participants in exchange for their valuable service without determining whether the service should be treated as an unskilled labor, “regular” work, body renting, or a unique sui generis endeavor (cf. Lemmens and Elliott 1999, 2001; King Reame 2001; Anderson and Weijer 2002; Elliott 2008; Abadie 2015; Phillips 2011b; Lynch 2014; Różyńska 2018). For the sake of the analysis to come, it is assumed that paid participation in biomedical research is a form of paid bodily services, and it should be “no more worrisome to commodify a person’s labor [bodily service—JR] as a research subject than to commodify a person’s labor in other contexts, which happens all the time” (Lynch 2014, p. 159). Therefore, commodification concerns against research payment, raised by some commentators (Macklin 1989; Chambers 2001; Abadie 2010, 2015; Cooper and Waldby 2014; Walker and Fisher 2019) will not be explored here.

Since the paper focuses on the most fundamental ethical basis of payment practice, it is limited to monetary offers (paid in cash, cheques or pre-paid credit cards) as a paradigmatic case of payment, leaving aside all forms of in-kind support. This paper also leaves aside payments to participants unable to give consent, because those raise additional, substantive issues, as well as recompenses for research-related injuries as they would require in-depth legal analysis. The presented analysis applies to research which RECs/IRBs would consider scientifically and ethically sound thus presenting arguments that payment is offered to overshadow or mask some ethical deficiencies of a study project, especially those regarding its risk–benefit profile or criteria of subjects selection. In other words, it considers “research which ethics committee would allow to proceed, were the subject not paid” (Wilkinson and Moore 1997, p. 375).

The main “pragmatic” reason (Largent and Lynch 2017a, p. 77 fn. 22) for offering payment to research participants is to boost recruitment and retention rates. This “efficiency”-driven (Phillips 2011a) rationale is widely acknowledged. It is, however, rarely recognized as having not only practical, but also an ethical facet. Since progress in biomedical science and healthcare is not ethically discretionary, this section argues that neither efficient enrolment nor payment for research subjects, being conductive to the latter, are value-neutral practices. On the contrary, they are ethically grounded in and governed by the principle of social beneficence that calls for maximization of a common good, i.e. good which has two characteristics: it is non-exhaustible (one person’s use does not diminish another’s use) and is beneficial for all or almost all members of a society.²

Biomedical research is social practice aimed at generating such a common good—generalizable scientific knowledge that may contribute to the improvement of healthcare interventions and public health measures, thus leading to the advancement of human health (cf. Schaefer et al. 2009; Rhodes 2010; London et al. 2010). Health is highly valued by all individuals and societies primarily “because of what it enables us to do” (Duncan 2010, p. 321). A minimum threshold of physical and mental capacities is necessary (though not sufficient) for an individual to be able to pursue her particular life goals, plans, and projects that express her vision of a good life. Since all liberal and democratic societies share a fundamental moral (and political) commitment to protecting and respecting each person’s right to lead her life in accordance with her personal views of what is valuable in human life, they also share a moral obligation to encourage forms of social collaboration useful in fulfilling basic health needs of their members (London 2003, 2006; Rawls 1971; Nussbaum 2013). This includes the practice of healthcare as well as biomedical research, because the capacity of a society to satisfy its members’ basic health interests is conditional upon progress in biomedical sciences, which in turn is crucially dependent on various types of research, including human research. Thus, societies have a prima facie moral obligation to promote the conduct of biomedical research, including research involving human subjects.

Human biomedical research is a complex, collaborative social “enterprise”, involving various institutional and individual stakeholders with various, often conflicting, interests (London et al. 2010; Różyńska 2015). Therefore, in order to fulfill their obligation to promote biomedical research, societies should develop, implement and support normative and institutional mechanisms aimed ensuring the existence, stability and effectiveness of research practice in attaining the common good (London et al. 2010; Resnik 2011; Różyńska 2015). These mechanisms should enhance all stakeholders’ trust and willingness to support and invest in the research enterprise, including prospective research participants without whom biomedical research would not be able to achieve its goals.

Socially valuable human biomedical research is critically dependent on successful enrolment and retention of a sufficient number of appropriate participants, and on their willingness to comply with study procedures and conditions. Failure to recruit or retain participants may lead to invalid or inconclusive research data, it may result in premature termination of a study, increase research costs, and—what is the most important—delay or even hinder scientific progress and the anticipated development of safer and more effective diagnostic, prophylactic and therapeutic interventions (Altman 1980; Halpern et al. 2002; Gul and Ali 2010; Williams et al. 2015; Carlisle et al. 2015). Insufficient or slow recruitment and poor retention rates are, however, a common problem within biomedical research, especially in randomized controlled trials (Salman et al. 2014). A systematic review shows that less than half of trials achieve their original recruitment target goal in time (Campbell et al. 2007; cf. Sully Ben et al. 2013; Parkinson et al. 2019). Additionally, only very small portion of eligible adult oncological patients choose to enroll into trials—depending on a source the portion range from 3 to 5% or 8% (Bell and Balneaves 2015; American Cancer Society Cancer Action Network 2018)—leading to a conclusion that “if the proportion of patients with cancer who agree to participate in clinical trials were to increase from its current 5% to 10%, the usual study completion rate would decrease from around 4 years to 1 year. Another estimate suggests that at least 16 million more individuals are needed to participate in research trials each year” (Schaefer et al. 2009, p. 70).

Many different factors contribute to the low participation and retention rates. Although barriers of structural and clinical character, such as access to trials and eligibility requirements, seems to be the most important, concerns regarding financial costs and benefits linked to research participation also play a significant role in prospective subjects’ decision-making (Friedman et al. 2015; Hamel et al. 2016; American Cancer Society Cancer Action Network 2018; Nipp et al. 2019a, Unger et al. 2013, 2019). Recent statistics published by the Center for Information and Study on Clinical Research Participation show that information about potential costs and their reimbursement as well as information about compensation for time off from work are among the most important factors influencing a decision to participate in research for—respectively—58% and 40% potential subjects (2019). And the prospect of receiving monetary compensation is one of three top reasons (34% mentioning) impacting a decision to enroll into a study (Center for Information and Study on Clinical Research Participation 2019). These data are consistent with results of numerous empirical studies on subjects’ motivations for volunteering, conducted among patients and healthy volunteers. They all indicate that although the payment is not the only reason why people agree to participate in biomedical research, it is definitely one of the top motivates for enrollment, especially among healthy volunteers (Tishler and Bartholomae 2002; Almeida et al. 2007; Abadie 2010; McCann et al. 2010; Stunkel and Grady 2011; Grady et al. 2017; Fisher et al. 2018; Manton et al. 2019).

Thus, although it is rightly stressed in the literature that the exact impact of paying for participation on the rates of research enrollment and retention remains still under-investigated, it is reasonable to assume that payment can make a positive difference in this respect (Dunn and Gordon 2005; Watson and Torgerson 2006; Caldwell et al. 2010; Probstfield and Frye 2011; Treweek et al. 2013; Nipp et al. 2019b; Parkinson et al. 2019). Money may remove participation barriers for those individuals who are unable or unwilling to cover direct costs associated with research, such as costs of traveling, lodging or hiring a babysitter. The payment may attract people who would be otherwise discouraged from the participation by the necessity of taking unpaid leave from work and resulting loss of wages. It may help to make a positive enrollment decision for those, who feel forced by their low social-economic status (SES) to dedicate time and efforts for searching for a job or earning their living, instead of altruistically contributing to the development of science. Additionally, an offer of payment could convince to participation persons who believe that their private or professional time is particularly valuable (for example due to their unique responsibilities, competences, or skills), and, therefore, they should not allot it to alternative causes without an adequate remuneration. In all these cases, payment may enhance recruitment, provided it is designed in a way that targets the underlying barriers, needs, or expectations.

Insofar as these factual assumptions about inducing potential of money are true—and we concede them for the sake of the argument—the principle of social beneficence provides fundamental ethical rationale for paying research subjects. Offering payment to participants is an ethically right and prima facie obligatory practice because it increases research recruitment and retention, thereby contributing to the common good produced by the research enterprise. From a broader perspective, “it is useful in fulfilling society’s obligation to meet the essential [health-related] needs of its members” (Ackerman 1989, p. 1). The strength of the obligation to offer payment for participation grows in relation to studies which are urgently needed, e.g., to address acute public-health emergencies (such as a dire pandemic), or when there is strong evidence that without payment recruitment, retention and completion of socially valuable studies would be doomed or severely compromised. The strength of the obligation weakens when—due to study-specific features—payment offers are not needed to secure an adequate number of participants, i.e., where it is reasonable to assume that people will be willing to join the study for non-economic and social reasons, e.g., the prospect of direct or ancillary medical benefits, the wish to make a contribution to medical progress or the health of others, scientific curiosity, interest in the goals of the study, the prospect of making friends or having new experiences (Stunkel and Grady 2011; Grady et al. 2017; Fisher et al. 2018; Manton et al. 2019). Additionally, the obligation to pay research participants may be overridden by justified research budget constraints. If investigators have no money to pay for participation in a socially valuable research project, it is better to allow them to proceed without payment, than obliging them to pay, thereby forcing them to resign from conducting the study (Gelinas et al. 2018).

To sum-up, the payment for research subjects is an incentive or inducement for participation grounded in the principle of social beneficence. This is expressive verbis acknowledged by the U.S. Food and Drug Administration (2018) guidance which argues that payment to research subjects is “a recruitment incentive” and by the European Union’s Clinical Trial Regulation (2014) which refers to any payment offered to trial participants as “incentives or financial inducements” (art. 31.1(d); art. 32.1(d), 33(d)). Thus, payment is not, as some scholars and guidelines suggest, a demand of justice or fairness (Gelinas et al. 2018, 2020; Persad et al. 2019; Lynch et al. 2021) or requirement of non-maleficence and beneficence for an individual subject (Bierer et al. 2021). These principles, supplemented by the principle of respect for autonomy and other considerations regarding non-exploitation, are nevertheless very important. While they do not provide an ethical rationale for offering payment for research participations by themselves, they set contours for an ethically sound payment practice.

The paper argues that the ethical anatomy of paying research participants is built upon four basic principles of research ethics (and bioethics in general). The ethical “spine” of the practice is the principle of social beneficence, which requires the maximization of the common good—in the case of research practice—socially valuable scientific knowledge. This principle grounds a general prima facie moral obligation of offering payment to research subjects. The remaining ethical principles constitute a “skeleton” of morally sound payment practices by providing additional moral reasons for offering or not offering certain types of payments to research participants. As discussed above and presented in Table 1, the principles argue for offering research participants:

Obviously, a proper application of this ethical “skeleton” into research practice requires investigators and RECs/IRBs to take into account “the nature of the study, the nature of participants contributions and vulnerabilities, institutional and organizational guidelines, and local and cultural norms” (Grady 2005, p. 1686). Moreover, to make the proposed scheme fully helpful in determining whether any particular offer of payment is not overtly attractive and whether it meets standards of not equality, adequacy and non-exploitation, further detailed analyses of these standards are needed. The proposed scheme should also be tested against and enriched by further empirical studies about payment, especially about how money impacts subjects’ decision-making processes and behaviors.