1. Background
This guidance was originally developed by the National Research Ethics Advisors’ Panel (NREAP) and has subsequently been updated by the UK Research Ethics Development Group (UKREDG).
2. Coercion and Undue Inducements
2.1 The terms ‘coercion’ and ‘undue inducement’ are routinely used by Research Ethics Committees (RECs) during the course of their ethics review but there is a tendency for these to be applied inconsistently and interchangeably with insufficient regard for the subtly different ethical concerns that underlie each term. The following are considered to be useful definitions and have been used in this guidance:
Coercion: ‘…is paradigmatically a case of the denial of autonomy, since it consists in the deliberate imposition of one person’s will on another. However, coercion usually takes the form of threats, which restrict people’s options. Inducements are offers, not threats and they expand people’s options'[1]
Undue inducements: ‘…are excessively attractive offers that lead people to do something to which they would normally have real objections based on risk or other fundamental values.’ [2]
3. Payments, Risks and Burdens
3.1 There are differences of opinion amongst some academics and RECs over whether it is ever acceptable to pay research participants in relation to the level of risk involved in research. Whilst NREAP has previously endorsed the position taken by the HRA’s Phase I Advisory Group that ‘payments made to participants in phase I trials must never be related to risk’ the panel sympathises with the view that not to allow payments on the basis of risk would be unduly paternalistic in the absence of evidence that the participants’ ability to provide valid consent would be compromised.[3],[4]
3.2 The Governance Arrangements for NHS Research Ethics Committees (GAfREC) require RECs 'to be assured that any anticipated risks, burdens or intrusions will be minimised for the people taking part in the research and are justified by the expected benefits for the participants or for science and society'.5.
3.3 In the context of ethically approved research, normally involving only minimal anticipated risks or risks justified by the expected benefits, discussion of payment for 'risk' may be considered largely irrelevant.
3.4 Where payment is proposed, the REC should consider whether the payment is proportionate to the 'burden' imposed by the research. Such burdens may often be significant without involving excessive risk e.g., number of hospital visits, tissue samples taken, lifestyle restrictions, diaries, questionnaires, use of technology such as electronic patient reported outcomes, interaction with apps etc.
3.5 RECs should only approve research projects where they are assured that any anticipated risks, burdens or intrusions will be minimised and are justified by the expected benefits (other than the benefit of payment) for the participants or for science and society. Such risks, burdens and benefits should be clearly described in the participant information sheet.
3.6 RECs should always consider the acceptability or otherwise of the payments proposed but should not suggest or insist upon an increase in the level of payments offered unless this is to remedy an unjustifiable difference in payment to participants within the same study.
3.7 Where the risk and burdens of the research are considered by a REC to be justified by the potential benefits then it will normally be acceptable for competent adults to participate in the research study without being paid (including reimbursement of expenses).
3.8 Where it is considered ethically acceptable for individuals to take part in a study for no payment, it would also be acceptable to pay individuals for participation in that study proportionate to the level of burdens involved and/or (justified) risk.
3.9 Financial or other incentives, of themselves, are not considered coercive nor present an undue inducement to a potential participant where the risks and burdens involved are those that a competent, adult participant might reasonably accept for no payment.
4. Payment to Patients: Non-therapeutic Research
4.1 Where patients are invited to take part in non-therapeutic research as 'patient volunteers' (i.e. they do not have the disease that is a target of the research) they should be treated as ‘healthy volunteers’ with regards to payment.
5. Payment to Patients: Therapeutic Research
5.1 The ethical argument against the payment of patients to take part in research is generally thought to derive from the assertion that patients are particularly vulnerable, susceptible to therapeutic misconception, and subject to an imbalance of power that can exist between the patient and those providing their care, particularly if the healthcare professional is also involved in the research. In addition, patients often derive medical benefit in a way that healthy volunteers/patient volunteers do not.[5]
5.2 Payments to patients, in addition to reimbursement, for taking part in therapeutic research are permissible. Such payments may serve to reduce the possibility of therapeutic misconception by highlighting that patients are being asked to take part in a research project rather than receive clinical treatment.[6]
5.3 Payment may also serve to reduce the imbalance of power by making the patient’s participation seem less like a ‘favour’ that is being asked of them by the healthcare professional/researcher. [7]
5.4 The pragmatic argument that offering payment, as an incentive, is simply unnecessary as patients are already well disposed to participate does not necessarily make payment unethical. Indeed, given that healthy volunteers and patient volunteers may be paid to take part in research it would seem unfair not to pay patients asked to make a similar research contribution. Furthermore, the possibility that patients might benefit from the research intervention itself does not necessitate that they be barred from receiving actual, additional benefits such as payment, or that these additional benefits would be coercive or constitute an undue inducement.
6. Payment to People Who Use Drugs (PWUDs) To Take Part in Research
6.1 RECs often have understandable concerns that cash payments to people who use drugs to reimburse research participation will facilitate their drug purchases. This has led many RECs to prefer vouchers as an alternative to cash payments in this group. However, such approaches have been denounced by drug user advocacy groups as discriminatory [8]. In addition, there is evidence that payment for participation in research does not promote the purchase of drugs nor lead to relapse [9], [10], [11], [12], [13] and can enhance recruitment.
6.2 In the absence of evidence to the contrary, people who use drugs (PWUDs) should be assumed to be autonomous individuals able to make their own decisions about taking part in research and should not be treated differently to other participants in terms of payment for their participation.
6.3 Where payment is deemed to be acceptable for taking part in research it is acceptable for that payment to be made in cash. Whilst vouchers (or other non- cash payments) may also be used, a REC should not normally insist upon the use of vouchers (or other non-cash payments) for participants who use drugs where cash payments are proposed by researchers.
7. Payments to Children and Incapacitated Adults
7.1 The Medicines for Human Use (Clinical Trials) Regulations (2004) explicitly prohibit the giving of incentives or financial inducements (except provision for compensation in the event of injury or loss [14]) to children (under 16 years of age), incapacitated adults, or their parents/legal representatives to participate in clinical trials of investigational medicinal products (CTIMPS).
7.2 For other (non-CTIMP) research involving children, the Royal College of Paediatrics, Child Health: Ethics Advisory Committee 'Guidelines for the ethical conduct of medical research involving children' (2000) similarly state that researchers must ‘offer families no financial inducement, although expenses should be paid’.
7.3 A report by the NIHR Medicines for Children Research Network concluded that it was acceptable and reasonable to give a small reimbursement or appreciation for participation, but under no circumstances should any sort of incentive or compensation payment be provided.
7.4 The MRC ethics guide ‘Medical research involving adults who cannot consent’ (2007) notes that, whilst incentives or financial inducements should not be used, ‘MRC policy is that, as in other research, payment of legitimate expenses of participants or representatives directly related to participation in the trial is generally considered acceptable.’
8. Presentation of Precedents to RECs
Where it is acceptable to pay participants in excess of expenses, then where similar ethically approved studies have been conducted previously it is recommended that applicants clearly indicate this along with the amounts paid to the participants in these studies. Applicants should also present a justification for the proposed payments.
8.1 RECs should consider both the justification and the stated precedents presented to them. If the committee requests any changes to the proposed payments, as part of their opinion, they should give clear reasons and, where appropriate, references to any published guidance used to reach this decision.
9. Pro Rata Payments/Completion Bonuses
9.1 Completion bonuses or full payment only upon successful completion of the study procedures should not normally be permitted. Pro rata payments should always be offered to participants based on the amount of time completed or number of research procedures undertaken unless robust justification (e.g., methodological reasons) can be provided for not doing so. Such payments should be detailed in the participant information sheet. Where participants who choose to withdraw from the study will not be paid pro-rata, this must be made explicit in the participant information sheet and justification must be provided to the REC.
10. Referring to payments in advertisements
10.1 Generic advertisements:
Payments made to participants in phase I trials must never be related to risk.
Payment amounts can be detailed in generic advertisements in the form of a daily rate (in this context the term "daily" refers to a 24-hour period). A minimum daily rate should be used in all generic advertisements and stated as being "from £X". The group recommends that the minimum amount to be stated is from £200 per day. Therefore, generic advertisements should not normally give a range but instead solely state that the payment amount would be "from £200 per day”. The minimum daily rate will be regularly reviewed to ensure its continuing relevance. Lower amounts may also be acceptable in some cases depending on the level of inconvenience. The suitability of the amount stated will be considered as part of the ethics review of documentation submitted to the Generic Review Committee.
10.2 Study specific advertisements:
The group agreed that specific payment amounts could be used in the context of study specific advertising. Such specific amounts should be backed up with clear reasons in any submission to an ethics committee clearly explaining how the amount had been calculated.
Payment amount should be discreet and not prominent within the advertisement. For example, the payment amount should not be the headline or very first line of the advert.
References
[1] Wilkinson M., Moore A. Inducement in research. Bioethics 1997;11: 373–89
[2] Dickert, Neal (2004) 'Payment, Coercion, and Undue Inducement' PowerPoint presentation: http://www.bioethics.nih.gov/primr/dickert.ppt.ppt
[3] Jones, E. & Liddell, K. Should healthy volunteers be paid according to risk Yes. BMJ 2009;339:b4142
[4] Wilkinson & Moore op. cit.
[5] Dickert, Neal, and Christine Grady (1999): 'What’s the price of a research subject? Approaches to payment for research participation.' New England Journal of Medicine, 341(3):198.
[6] This statement is in line with The Royal College of Physicians’ 'Guidelines on the practice of ethics committees in medical research with human participants (Fourth edition)': '10.17 …Payment may help patients distinguish procedures that are done purely for research purposes from those done for their benefit, thus minimising vulnerability due to ‘therapeutic misconception'
[7] Dickert & Grady, op. cit.
[8] Australian Injecting and Illicit Drug Users League (AIVL). National Statement on ethical issues for research involving injecting/illicit drug users. Canberra: Australian Injecting and Illicit Drug Users League (AIVL), 2003.
[9] Festinger DS, Marlowe DB, Croft JR, et al. Do research payments precipitate drug use or coerce participation? Drug Alcohol Depend 2005;78:275–81.
[10] Festinger DS, Marlowe DB, Dugosh KL, et al. Higher magnitude cash payments improve research follow-up rates without increasing drug use or perceived coercion. Drug Alcohol Depend 2008;98:128–35.
[11] Slomka J, McCurdy S, Ratliff EA, et al. Perceptions of financial payment for research participation among African-American drug users in HIV studies. J Gen Intern Med 2007;22:403–1409.
[12] Dempsey JP, Back SE, Waldrop AE, et al. The influence of monetary compensation on relapse among addicted participants: empirical versus anecdotal evidence. Am J Addict 2008;17:488–90.
[13] Topp L, Islam MM, Day CA. Relative efficacy of cash versus vouchers in engaging opioid substitution treatment clients in survey-based research. Journal of Medical Ethics. 2012 Dec; http://dx.doi.org/10.1136/medethics-2012-100884
[14] Compensation in the event of loss includes expenses and loss of earnings related to the participation in the clinical trial.