Addressing Ethical Concerns Regarding Offers of Payment to Research Participants
Background
In January 2018, FDA updated its Information Sheet regarding payments to participants to clarify that “[i]n contrast to payment for participation, FDA does not consider reimbursement for travel expenses to and from the clinical trial site and associated costs such as airfare, parking, and lodging to raise issues regarding undue influence.” The document continues: “Other than reimbursement for reasonable travel and lodging expenses, IRBs should be sensitive to whether other aspects of proposed payment for participation could present an undue influence, thus interfering with the potential subjects’ ability to give voluntary informed consent.”
SACHRP has been asked to consider whether there is a need for additional updates to guidance related to payments that go beyond reimbursement of participant expenses. Specifically, recommendations are sought as to whether and when payments to study participants may constitute an undue influence as described in the FDA regulations 21 CFR Part 50.20 and the corresponding HHS regulations 45 CFR Part 46.116.
Current OHRP and FDA Guidance
OHRP FAQs currently define undue influence as potentially occurring “through an offer of an excessive or inappropriate reward or other overture in order to obtain compliance.” They do not, however, explicitly define what would make a reward excessive or inappropriate. Instead, the FAQs go on to say:
Because influence is contextual, and undue influence is likely to depend on an individual’s situation, it is often difficult for IRBs to draw a bright line delimiting undue influence. It is up to the IRB to use its discretion in determining which circumstances give rise to undue influence. . . . Because of their relative nature and lack of clear-cut standards on the boundaries of inappropriate and appropriate forms of influence, investigators and IRBs must be vigilant about minimizing the possibility for coercion and undue influence. Reasonable assessments can be made to minimize the likelihood of undue influence or coercion occurring. For example, IRBs may restrict levels of financial or nonfinancial incentives for participation and should carefully review the information to be disclosed to potential subjects to ensure that the incentives and how they will be provided are clearly described. Known benefits should be stated accurately but not exaggerated, and potential or uncertain benefits should be stated as such, with clear language indicating how much is known about the uncertainty or likelihood of these potential benefits.
Like the FDA Information Sheet, OHRP FAQs recognize that “[p]aying research subjects in exchange for their participation is a common and, in general, acceptable practice.” However, IRBs are instructed to be sensitive to whether “any aspect of the proposed remuneration will be an undue influence, thus interfering with the potential subjects’ ability to give informed consent.” Both OHRP and FDA indicate that “[r]emuneration for participation in research should be just and fair,” but OHRP warns IRBs to make sure that payments are not so high that they “could compromise a prospective subject’s examination and evaluation of the risks or affect the voluntariness of his or her choices.” This is the closest the FAQs come to defining outcomes that would make payment excessive or inappropriate.
OHRP also recommends that the consent process include “a detailed account of the terms of payment, including a description of the conditions under which a subject would receive partial or no payment (e.g., what will happen if he or she withdraws part way through the research or the investigator removes a subject from the study for medical or noncompliance reasons),” and FDA provides similar guidance. OHRP recommends that “payment be prorated for the time of participation in the study rather than delayed until study completion, because the latter could unduly influence a subject’s decision to exercise his or her right to withdraw at any time.” Similarly, the FDA Information sheet indicates that the IRB should review both the amount , proposed method, and timing of payment, and encourages prorating. FDA also explicitly permits “payment of a small proportion as an incentive for completion of the study . . . [so long as] such incentive is not coercive. The IRB should determine that the amount paid as a bonus for completion is reasonable and not so large as to unduly induce subjects to stay in the study when they would otherwise have withdrawn.”
Finally, OHRP asserts that “IRBs should not consider remuneration as a way of offsetting risks” when deciding whether research should be approved. However, “remuneration to subjects may include compensation for risks associated with their participation in research and that compensation may be an acceptable motive for agreeing to participate in research.” On this issue, the FDA Information Sheet states that “[p]ayment to research subjects for participation in studies is not considered a benefit that would be part of the weighing of benefits and risks; it is a recruitment incentive.” Even though IRBs are directed not to consider payment in their approval decisions, they should be aware that potential participants are likely to include payment in their weighing of potential benefits and risks of harm.
SACHRP’s Goals
IRBs are granted considerable discretion, but few tools, to help them determine when payment (or other benefits) may unduly influence an individual’s decision-making about whether to enroll or remain in a research study. Combined with the directive from regulators to “be vigilant,” some IRBs may take a “better safe than sorry” approach that prioritizes avoiding undue influence but fails to give adequate consideration to other important goals.
SACHRP believes that this approach is problematic. Most payments to participants do not pose concerns about undue influence and are often ethically important, assisting in recruitment and completion of trials, facilitating diverse participation, and acknowledging the value of participants’ contributions to research. Therefore, the aim of these recommendations is to provide guidance to help IRBs evaluate what sorts of payment are likely to raise ethical concerns and which are not – and in the former case, what efforts can be taken to minimize the possibility of undue influence.
In this guidance, we seek to:
• Explicate the concept of undue influence in a way that can practically guide IRB and investigator decisions regarding acceptable offers of payment for research participation;
• Clarify that several types of payment (namely, reimbursement of reasonable costs incurred as a result of participation; fair compensation for participants’ time and effort; and token payments of appreciation) do not raise concerns regarding undue influence;
• Describe the limited circumstances in which incentive payments may raise concerns regarding undue influence; and
• Provide mechanisms to minimize the possibility of undue influence when incentive payments are offered.
Scope
Although undue influence and coercion are often discussed together, this document focuses primarily on undue influence because genuine offers of payment do not satisfy the definition of coercion. Coercion entails a threat to violate someone’s rights or fail to fulfill an obligation to him or her in order to obtain compliance, creating a circumstance in which the person has no reasonable alternative but to comply. Thus, a threat to withhold payment that has been promised would be coercive (and not really an offer of payment), whereas a genuine offer of payment to which an individual is not otherwise entitled cannot coerce.
SACHRP has also focused herein on payment to decisionally capable adults offered in IRB-approved research at all risk levels, including research with and without potential direct benefit to participants. Although some of the principles discussed may be useful when considering payment for studies in which individuals are unable to consent to their own research participation, those contexts raise further ethical concerns associated with influencing those (e.g., parents or legally authorized representatives) who make study participation decisions on behalf of others.
Payments that are part of the study’s scientific design, e.g., as an intervention to evaluate whether they change behavior, should be reviewed by the IRB like any other study intervention and are not considered within the scope of this document. Also outside the scope of this document are payments intended to reimburse or compensate study participants in the event of study-related injury. Lotteries for payments to subjects are not included.
Finally, although we have focused on financial payments, similar issues may be relevant for other types of non-financial benefits offered to all research participants.
When Payment May Constitute Undue Influence
Undue influence has been defined by some scholars in the research ethics literature as occurring when there is an (1) excessive offer of something valuable or desirable that leads to (2) poor judgment or a compromised decision-making process, which in turn leads to (3) a decision to engage in harmful activity that seriously contravenes the decision-maker’s interests or obligations. We use this definition as a jumping off point only. As explained below, SACHRP remains concerned about compromising the decision-making process, regardless of whether the outcome for any individual research participant is likely to be harmful.
IRB approval of research should play an important role in minimizing the likelihood of adverse outcomes and promoting effective consent processes. Thus, the IRB’s involvement should make offers of payment in research less concerning than payment offers might be outside the research context, where there may be no independent assessment of an activity’s acceptability or support for the decision-making process.
For every study, the IRB’s first responsibility is to determine whether the risks of harm and potential benefits are appropriately balanced for the study’s target population (i.e., those satisfying inclusion criteria and not meeting exclusion criteria). The IRB should consider whether payment is acceptable only after it is satisfied that the study is acceptable.
With this approach, IRBs can protect typical participants in the target population from research that would be objectively harmful. Nonetheless, IRBs cannot necessarily ensure that study participation would acceptably align with the interests of every individual participant, because IRBs approve research on a population basis, rather than for each individual who might enroll. Moreover, protecting the autonomy of individual participants is fundamental, even in IRB-approved research. Therefore, IRBs must also determine whether the informed consent process will provide clear and complete information about the study and support adequate consideration and comprehension of that information. An adequate consent process enables participants to decline participation in research that would be subjectively harmful according to their own judgment of their interests, values, and obligations.
Thus, SACHRP takes the position that payment raises concerns about undue influence when it appears likely to inhibit potential participants’ adequate consideration of and reflection about important study features, such as risks, burdens, and discomforts, and impair their understanding of the research and their participation in it.
Payments other than incentive payments are unlikely to have this effect. The mere fact that payment influences a decision to participate in research does not make that decision involuntary or that influence undue, even if an individual would not have chosen to participate without payment – and even if the individual might have preferred not to participate if no payment was offered. Decision-making is always influenced by many factors, and only factors that infringe on decision-making processes are problematic. When people adequately consider and understand what they are being asked to do and when what they are being asked to do is acceptable, there is no reason for ethical concern.
Next, we will apply these definitional factors to different types of payment offers for study participation.
Payments Not Raising Concern About Undue Influence
Reimbursement
1. SACHRP agrees with and recommends that OHRP adopt the stance on reimbursement payments described in the May 2018 FDA Information Sheet “Payment and Reimbursement to Research Subjects.”
Reimbursing participants (or their caregivers) for out-of-pocket costs incurred as a result of study participation, such as transportation, lodging, childcare, additional medical expenses, and meals outside the home, is intended to minimize the financial impact of study participation. Reimbursement may therefore encourage individuals to participate who would not otherwise enroll due to financial constraints, making such payments influential, but not unduly influential. Because participants are not offered a net benefit via reimbursement (i.e., they are at best “breaking even”), it will not make research participation more attractive than alternatives. Thus there is no reason to be concerned that reimbursement payment would compromise decision-making.
Reimbursement is ethically acceptable and may vary among participants based on the costs they individually incur. Although lost wages are probably better viewed as a matter for compensation rather than an out-of-pocket cost suitable for reimbursement, SACHRP otherwise recommends a broad interpretation of costs that should be deemed reimbursable. For example, although reimbursing for meals outside the home may appear to go beyond restoring baseline financial status, since individuals would pay to eat regardless of study participation, failure to reimburse these costs would ignore the likelihood of higher costs and inconvenience faced by participants who must eat outside the home as a consequence of participation.
Some participants may be willing to enroll even without reimbursement, for example because they have altruistic motivations or expectations of direct benefit that would, in their estimation, outweigh the costs of participation. Nevertheless, participants contributing to socially valuable knowledge generally should not be required to bear financial burdens in order to do so. Moreover, offering reimbursement can make participation more widely accessible, and therefore more diverse. Therefore, reimbursement should be considered the ethical default, offered whenever it is feasible to do so, recognizing that sometimes study budgets may not be sufficient to cover reimbursement. In the event a participant is motivated to enroll by altruism, he or she is free to decline reimbursement payments (or payment of any type).
Compensation
2. SACHRP recommends that OHRP and FDA clarify that compensating participants for their time and effort is not an undue influence.
Compensation addresses the participant’s contribution of time and acceptance of research-related burdens and inconvenience, as distinguished from the out-of-pocket costs addressed through reimbursement.
Like reimbursement, compensation may influence an individual’s decision to participate in research; in particular, he or she may decline participation if no compensation is offered because of the “opportunity costs” associated with research participation. That is, some individuals may have to forgo other sources of income as a consequence of spending time in research. Compensation therefore does not make participation more attractive than alternatives, but rather helps to make it as attractive as other similarly burdensome ways of spending one’s time, by at least making up for some of the financial difference between research participation and other activities. Thus, in these cases there is no reason to be concerned that compensation payment would compromise decision-making. In a circumstance in which an individual has no income, however, an offer of payment for research participation may function as an incentive and should be analyzed according to the approach described in sections 4 and 5 below.
To the extent that participants make different contributions of time and undertake different burdens – for example, by virtue of attending more extensive or uncomfortable study visits – compensation may be adjusted accordingly. Because participants in research with the possibility of direct medical benefit are also contributing to research and making important sacrifices, it is appropriate to offer compensation to them as well, rather than limiting compensation to participants in research without the possibility of direct medical benefit.
IRBs need not determine dollar amounts for acceptable compensation payments in the abstract, but should instead rely on investigators to justify the amounts they propose to offer as compensation in particular studies along these terms. Benchmarks that have been used include the average working wage and purchasing parity ratio in the community where the research is being done. SACHRP believes this is reasonable, recognizing that amounts may therefore differ to some extent across sites in multicenter trials.
As noted above, one of the justifications for this kind of payment is to offset participants’ opportunity costs. Participants all have different capacities to generate income outside of research, which means that their actual opportunity costs could vary substantially. Thus, an approach to compensation that truly sought to “make participants whole” could lead to the conclusion that compensation payments should be calibrated to lost income. Such an approach creates problems of equity, however, because participants who experience the same research procedures would not be equally compensated. SACHRP believes that these conflicting ethical principles – full compensation v. equitable compensation – are best resolved in favor of equity. On this approach, then, compensation is not necessarily intended to match a participant’s true “hourly rate” or the earnings that particular individuals could expect outside a study, but rather to acknowledge the importance of their contributions to research and the sacrifices associated with participation. Therefore, all participants in a given study should be compensated equally, with appropriate adjustments for local monetary value across sites and to account for circumstances in which participants may be asked to take on different activities within the study, as noted above.
Appreciation
3. SACHRP recommends that OHRP and FDA acknowledge that appreciation payments to research participants do not raise concerns about undue influence.
Small payments or gifts are not intended to meaningfully reimburse or compensate study participants. Rather, they are intended to thank them for their contribution. Because of their minimal nature, these payments are unlikely to influence decisions about study participation, and therefore raise no concern about undue influence. Appreciation payments may be particularly important when budgets do not allow full reimbursement or compensation, or when all participants are hospital inpatients for whom reimbursement and compensation are not pressing needs.
Avoiding Undue Influence in the Context of Incentive Payments
4. SACHRP recommends that OHRP and FDA clarify that incentive payments may raise concerns regarding undue influence in some cases.
In contrast to reimbursement and compensation, incentive payments go beyond what participants might be owed as a matter of fairness. Instead, they seek to encourage speedy and complete study recruitment and retention by making research participation potentially more attractive than alternatives. Because incentives entail a net benefit to participants, they do have the potential to compromise the informed consent process, raising concerns of undue influence. The greater the net benefit, or the more contingent the benefit is on completing study participation, the greater the concern that consideration of payment might overwhelm consideration of other reasons, besides payment, for joining or not joining the study or continuing with it. However, this does not mean that incentive payments are inherently impermissible.
Imagine Prospective Participant 1, whose reasoning about enrolling in an IRB-approved study goes as follows: “If the payment were not so high, I probably wouldn’t do this. I’ve thought carefully about the risks and benefits, asked questions about them, and understand them. Still, the risks worry me. But I need the money, so I’m going to say yes.” This participant has been influenced by payment, but not unduly influenced because she has not been asked to join an unreasonable study (assuming adequate IRB review) and because she is making an informed, understanding, and voluntary choice under the circumstances. Her conclusion that study participation is her best available alternative to make money does not make it involuntary; if the total avoidance of pressure was a requirement for voluntary decision-making, the standard could rarely be satisfied.
Now consider Prospective Participant 2, who reasons about the same study: “I am desperate for money. I don’t care about the risks, I don’t even want to know what they are. Just sign me up so I can get paid.” Unlike Prospective Participant 1, this individual has been unduly influenced by the offer of payment. He too would be enrolling in a reasonable study, but payment has inhibited his adequate consideration of reasons for or against participation. This is important because IRBs and investigators have an ethical and regulatory duty to support, promote, and enhance reasoned decision-making by potential research participants. Although individuals are free to make “rash” or “snap” decisions outside the research setting (for example, when accepting a job offer or making a purchase), IRBs and investigators must fulfill their responsibilities for research participant protection, including assurance of adequate informed consent. IRBs need not monitor the enrollment process of each individual participant or account for their unique characteristics. They discharge their duty through their evaluation of the appropriateness of the incentive, the completeness and clarity of the consent form, and the circumstances in which consent is sought and obtained.
5. SACHRP recommends that OHRP and FDA acknowledge that concerns about incentive payments that may be unduly influential can be managed without necessarily lowering or eliminating them, and provide guidance regarding how to minimize the possibility of undue influence.
Given the possibility that a study may recruit people like Prospective Participant 2, should IRBs err on the “safe side,” prohibiting incentive payments or ensuring that only low incentive payments are offered?
This approach is problematic, for several reasons. First, failure to provide adequate incentives can have a detrimental effect on research and research participants (note that the same is true for inadequate reimbursement and compensation payments). For example, it may lead to difficulty reaching enrollment targets necessary to answer the scientific questions of interest. Under-enrollment risks wasting resources and exposing participants to risks and burdens without adequate social value, which are both important ethical considerations. Moreover, higher incentive payments may help encourage a wider variety of participants to enroll, helping to avoid unjust imposition of risks and burdens on economically vulnerable populations. These considerations suggest that reducing incentive payment to address concerns about undue influence is not necessarily ethically preferable and may be inappropriately one-sided.
Second, it is important to recognize that although the limited available empirical evidence about the effects of payment on research participants is inconclusive, it suggests that payment may not in fact blind participants to risk or impair their comprehension, but rather may increase their levels of caution and perception of risk. Payment may also help draw attention to distinctions between research and clinical care.
Finally, it is important to note that IRBs should not assume that incentive payments are likely to compromise participants’ decision-making simply because the population of potential participant is economically disadvantaged. If IRBs bar high incentives out of concern that they will encourage enrollment by individuals of lower socioeconomic status, they should be aware that such individuals may still be encouraged by lower payments – and in fact may be the only participants so encouraged, leading to justice concerns. In that case, participant protection has not been increased. Instead, some potential participants may have been discouraged from enrollment, and those who enroll may have been disadvantaged, as the result of unfairly paternalistic overprotection by a well-meaning but mistaken IRB.
The better approach is to acknowledge that, in addition to the role IRBs play in minimizing undue influence by refusing to approve research that would unreasonably contravene participant interests, IRBs must also protect and promote autonomous decision-making by prospective participants through their oversight of informed consent disclosures and the consent process.
To help any potential participant avoid an impulsive or superficial decision that fails to fully consider or understand the risks and benefits of study participation, IRBs should encourage investigators to adopt approaches that will support high-quality decision-making. These may include some well-recognized approaches, such as:
• Setting aside sufficient time for knowledgeable study staff to review the entire consent form with potential participants and answer any questions, rather than permitting a passive consent process in which potential participants are expected to review materials on their own.
• Including tests of comprehension or “teach-back” methods that will provide an indication that potential participants are aware of and understand key information about the study.
• Incorporating a waiting period for potential participants to reflect on their desire to participate and potentially discuss the study with trusted others.
• Facilitating explicit consideration of how a prospective participants’ current interests may conflict with their future interests (for example, asking for reflection about the value to the individual of trading payment now for risks that may materialize into harms later).
• Providing further support for any individual who expresses that he or she “has no choice” but to enroll, whether due to pressure from medical or financial needs.
SACHRP notes that the “key information” requirement in the revised Common Rule may also promote these goals. Most important is the recognition that IRBs and investigators have a variety of mechanisms to help transform anyone like Potential Participant 2 at least into someone like Potential Participant 1, avoiding concern about undue influence while still allowing incentive payments. In other words, cogent consent forms and processes aimed at supporting and promoting informed decision-making can help minimize the likelihood that participants will be motivated to ignore or misunderstand key information because of the attractiveness of incentive payments.
Importantly, the regulations do not require elimination of influence, but rather that investigators minimize the possibility of undue influence. From a practical perspective, the total elimination of any possibility of undue influence is likely to be infeasible or substantially overprotective, or to make research difficult or impossible to carry out. Therefore, it should be neither the expectation nor the goal. Moreover, IRBs should make sure that any discomfort they have with incentive payments is not serving as a proxy for discomfort with the risks inherent in the study protocol. Concern about incentive payments should not mask concern about allowing a research study to proceed at all.
In summary, IRBs should consider a number of factors when evaluating the acceptability of incentive payments:
• Their responsibility to approve research only when risks are reasonable in relation to benefits to participants and/or society;
• The possibility that incentive payments will compromise the informed consent process;
• Steps that can be taken to support autonomous decision-making in those contexts;
• Tradeoffs that may be associated with restricting incentive payments and how that may affect achieving adequate recruitment; and
• How similar payment might be viewed outside the research setting.
6. In light of all these considerations, SACHRP recommends that OHRP and FDA encourage IRBs to analyze offers of payment to research participants based on the purpose of the offer: reimbursement, compensation, appreciation, or incentive. Investigators should also be encouraged to specify the purpose of payment offers in IRB submissions and justify amounts according to this framework.
We acknowledge that in many instances, the distinction between compensation for subjects’ time and effort and incentive payments might not be straightforward. We anticipate that investigators’ attempts to explain and justify payments will nonetheless be helpful to the IRB.
Additional Considerations
Timing of payment
In addition to payment offers themselves, it is also important to consider whether the timing of payment will interfere with participants’ regulatory right to withdraw their consent to research participation at any time and for any reason without penalty.
7. SACHRP recommends that reimbursement and compensation payments be prorated, in line with existing OHRP and FDA guidance.
As noted above, both OHRP and FDA guidance recommend prorating payment to participants in line with the proportion of study participation an individual has completed, rather than withholding all payment unless participation is complete. SACHRP agrees that this is the right approach for reimbursement and compensation, but as discussed below, recommends that proration not be required for incentive payments.
Making accrual of reimbursement and compensation payments contingent on study completion is inappropriate because it conflates such payments with incentives, using them to encourage completion rather than as intended – that is, to reimburse a participant’s costs or compensate for a participant’s time and burden. Those expenses have all been incurred in proportion to the extent of an individual’s participation even if it is ultimately incomplete, and therefore should accrue on a prorated basis. Proration in this context will not lead to undue influence because participants have no reason to continue participation to secure reimbursement or compensation of costs not yet incurred or contributions not yet made. Ideally, prorated payment should be paid at periodic intervals, but prorated amounts may sometimes be held until study end, for example when a study is short and administrative constraints make paying all participants at once most efficient.
With regard to incentives, proration would help encourage participants to continue participating until each scheduled “checkpoint,” which can avoid undue influence so long as the conditions for study approval and adequate participant decision-making remain satisfied, as discussed below. However, unlike reimbursement or compensation, which are intended to essentially “repay” participants for their costs and contributions, incentives are not necessarily tied to costs and contributions that accrue over time. Instead, their function may be to encourage participants not only to complete specified “checkpoints,” but rather to cross the study “finish line,” as the data may only be valuable (or may be most valuable) if the participant completes the entire study. Proration may not achieve that goal; instead, a completion bonus may be necessary and should be permissible with certain safeguards.
8. SACHRP recommends that OHRP and FDA guidance clarify that incentives paid as completion bonuses can be appropriate and are not necessarily unduly influential.
When incentive payment is contingent on a participant’s study completion (i.e., a completion bonus), its purpose is specifically to encourage participants who might otherwise withdraw not to do so. Importantly, this does not mean that the right to withdraw necessarily has been compromised.
To determine whether a completion bonus constitutes an undue influence, it should be analyzed according to the criteria for assessing and minimizing undue influence that would apply to incentive payments made at any time. Importantly, the IRB’s responsibilities extend beyond initial study approval and require that research be allowed to continue only when the risks and benefits continue to be acceptable. IRBs must require study termination if the risks become too great for participants in general, and must require removal from the study of any individual experiencing risks that are too great. In both cases, participants should be deemed to have completed participation and receive any promised completion bonus, as they have fulfilled their responsibility not to drop out early.
When an IRB allows research to continue because it determines that the risks and benefits remain acceptably balanced, the primary consideration is whether the completion bonus will compromise participants’ subjective decision-making about whether to remain enrolled when it is objectively reasonable for them to do so. Avoiding compromised decision-making requires that IRBs ensure that the consent process continues throughout the duration of study participation, with continual discussion of new information about the individual or participants as a group that may bear on a decision about whether to remain enrolled. If participants understand and consider this information, there is little reason to be concerned that their decision to remain enrolled has been compromised by the completion bonus or that their right to withdraw has been infringed.
However, SACHRP acknowledges that the right to withdraw offers an important check on both IRB and individual participant decision-making; if either party “got things wrong” about the acceptability of research participation, the participant can drop out. In order to maximally preserve this safeguard, when research is especially risky, it may be appropriate to limit the completion bonus amount in proportion to the total study payment so that it will be less likely to influence participant behavior, unduly or otherwise.
Note that, in general, providing an incentive payment in the form of a completion bonus is least likely to be of ethical concern if the study also compensates and reimburses participants on a prorated schedule. Absent reasonable reimbursement and prorated compensation, a completion bonus might be called an incentive, but could be functioning for the participant as reimbursement or compensation. Therefore, SACHRP recommends that completion bonuses be permitted only when a study provides reimbursement (as needed) and compensation payments.
In all cases, SACHRP agrees with current guidance that timing and conditions of payment should be clearly specified in informed consent materials.
Deception by participants
9. SACHRP recommends that OHRP and FDA guidance advise IRBs to encourage investigators to take steps to avoid deception by participants regarding eligibility or other aspects of participation in order to secure payment.
When reimbursement and compensation payments are offered, the lack of net benefit suggests there is little reason for individuals to engage in deceptive behavior in order to secure them. In contrast, participants highly motivated by incentive payments, which do offer net benefit, could potentially make false statements to investigators or omit important information to overcome eligibility criteria or to continue participation in a study. This is problematic from the perspective of participant safety and as a matter of research integrity. Therefore, IRBs should encourage researchers to take reasonable and appropriate measures to minimize the risks of deception by participants in circumstances in which the amount of incentive payments (including completion bonuses) makes deception seem likely. In some studies, it may be possible to add objective measures to self-reported criteria used for enrollment, continuing participation and assessment of safety.. ) Paying completion bonuses even to individuals who are involuntarily terminated from study participation due to unreasonable risk, as described above, will also help make sure that participants are not encouraged to withhold information about any adverse events they experience. Because risks of participant deception can be minimized, these concerns should not prevent use of otherwise appropriate incentive payments.
Advertising payment
10. SACHRP recommends that OHRP and FDA guidance acknowledge the permissibility of advertising study payment.
Payment of any type is intended to facilitate enrollment, which it cannot do if participants are not made aware of the offer. If an IRB has approved payment, there is no reason it should be treated as a secret or surprise; advertising payment may motivate individuals to enroll on that basis, but if the payment is acceptable, so is that motivation. Because advertising is the first step in the consent process, payment information on advertisements should be truthful, clear, and appropriately contextualized with regard to study risks and burdens. This means that the availability and amount(s) of payment should not be highlighted to a greater extent than other relevant information about a study or in a way that obscures such information. However, it also need not be excluded from advertising materials.
Conclusion
The 2018 FDA revised guidance regarding participant payment is a step forward in its explicit recognition that reimbursement payments do not raise concerns about undue influence. However, as articulated in this document, SACHRP believes that this guidance does not go far enough in easing concerns about offers of payments to research participants. For the reasons stated above, SACHRP recommends that FDA and OHRP issue guidance that recognizes that, in addition to reimbursement payments, compensation and token appreciation payments do not raise concerns about undue influence. SACHRP further recommends that FDA and OHRP issue guidance that recognizes the concerns about unduly influential incentive payments can be managed without necessarily lowering or eliminating the payments, and outlines ways to minimize the possibility of undue influence. SACHRP believes such guidance could support IRB decision-making regarding participant payments and encourage appropriate use of payments to facilitate the conduct and completion of research.
