Head To Head

Should healthy volunteers in clinical trials be paid according to risk? Yes

BMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b4142 (Published 22 October 2009) Cite this as: BMJ 2009;339:b4142
  1. Eleri Jones, barrister1,
  2. Kathleen Liddell, lecturer2
  1. 1Middle Temple, London, EC4Y 9AT
  2. 2Faculty of Law, University of Cambridge, Cambridge CB3 9DZ
  1. Correspondence to: E Jones eleri.jones{at}cantab.net

    Eleri Jones and Kathleen Liddell argue that objections to paying according to risk are paternalistic, but John Saunders (doi:10.1136/bmj.b4145) thinks that it would lead to people being exposed to unacceptable danger

    The severe reactions experienced by healthy volunteers in the TGN1412 (Northwick Park) trial have led to questions about payment for participation.1 Currently, the dominant view is that only time and expenses should be remunerated. By this logic a healthy volunteer participating in a half day trial at risk of immunological storm is paid the same as a volunteer participating in a half day observational study. This is objectionable for two reasons: firstly, because there should be recognition of a volunteer’s gift to society2 for the higher risks in some trials and, secondly, because it is inconsistent with other practices in society.

    The law and current guidelines

    The law allows volunteers to be paid subject to approval by a research ethics committee.3 In addition, the volunteer must give free and informed consent, yet there has been little judicial guidance on the influences, such as money, that render a competent person’s decision involuntary. In medical treatment cases, the influence must be more than just persuasive.4 5 In financial cases, independent advice is a central consideration.6 Neither line of authority necessarily applies to medical research.

    Guidelines for clinical trials are often vague, stating that proposed payments should not be so high as to cause coercion or undue influence. The Association of the British Pharmaceutical Industry states that “Payment must never be related to risk,”7 whereas the Royal College of Physicians notes that “Payments may be variably made for time, inconvenience, travel, or incurring risk.”8Importantly, payment according to risk does not mean the riskiness of the trial is open-ended. In addition to the individual’s agreement, the level of risk must comply with the limits in the clinical trial directive and be approved by an ethics committee.

    Why pay more?

    Healthy volunteers who agree to participate in a clinical trial do so on the understanding that there is no personal benefit but a risk of adverse reactions. Some agree to undertake the more risky trials—for example, first human testing of new drugs (phase I trials). These are generous decisions for the good of science and society and should be recognised in some way. Money is a pragmatic choice because it can be exchanged for something reflecting the individual’s preferences. Paying a supplement recognises the added risk that some volunteers undertake, commending them more highly than others.

    Opponents object that higher payment for participation in risky trials is an irresistible inducement. However, in a society where autonomy is highly valued this view is paternalistic. The law fiercely upholds people’s fundamental right to choose what to do with their own body, even if that choice may not seem sensible to others.4 In other areas of life where money is associated with risk, this paternalistic approach is not found. A person is free to make high risk financial investments, even if he stakes his entire savings and property. No one suggests that these decisions are coerced or irresistible. Workers employed in dangerous industries, such as firefighting and mining, are paid a wage premium (colloquially known as danger money), recognising that there is a high risk of serious injury or death. These practices are permitted on the grounds that such services are important to society, that those who do them deserve to be rewarded for contributing in special ways, and that adults should be free to choose the activities they undertake. Subject to the following caveats, payment of volunteers should be viewed in the same way.

    Volunteers’ understanding is key

    The crux of the issue lies not in esoteric views about money being an undue influence but in volunteers’ abilities to appreciate risk. It is well known that money motivates individuals;9 this in itself is not objectionable. It is also well known that volunteers often fail to appreciate the true risks that a trial poses.10 However, the most important question is whether individuals’ understanding of risk is affected by larger sums of money. Little research has been done on this issue, but the few studies carried out indicate that money does not affect understanding of risk.11 Indeed, a payment element based on risk would serve as a signalling device alerting individuals to the riskier trials.

    To further improve healthy volunteers’ understanding of research proposals, specialist independent advisers and recall tests could be introduced for phase I clinical trials. This should be supplemented by better regulation of advertising,12 some of which has been shown to be misleading and confusing. To ensure that public sector research is not financially out-gunned by private sector money, it would be sensible to adopt some sort of standardised scale for risk payments and to make supplementary risk payments optional or substitutable with appropriate non-monetary benefits.

    It has not been shown that an additional risk based payment would reduce individuals’ abilities to understand the risks of research and thereby invalidate the consent given. Unless this is shown, it is too paternalistic to prohibit payment according to risk. With the above proposed improvements to research regulation, volunteers’ understanding of risks would be improved. The choice to participate could then properly be left to volunteers and their special contribution recognised.

    Notes

    Cite this as: BMJ 2009;339:b4142

    Footnotes

    • Competing interests: None declared.

    References