Paying research participants

Kathy Boutis and Donald J Willison say financial compensation is unavoidable, but how much should participants in clinical research get?

Clinical research would be impossible without the participation of willing human participants. But paying participants in clinical research is contested among investigators, members of research ethics boards, and ethicists. Some defend payments for participation as fair and appropriate, but others find them problematic and even offensive or unethical.¹ ² ³ ⁴

We summarise some of the ethical challenges in considering paying participants in clinical trials. We describe three models commonly proposed for compensation.⁵ And we recommend evidence based approaches for paying participants to help investigators ensure high standards of safety while maximising recruitment.

Ethical challenges

Altering risk perception

Central to the ethical challenges in financially compensating participants in research is that money may unduly induce people to take part.² ⁴ ⁶ Although most people agree that paying participants is an inducement, the amount at which it becomes an “undue inducement” is debatable. Most decisions are susceptible to multiple influences, says Grady in the American Journal of Bioethics, and therefore monetary inducements are likely to be compatible with risk assessment and voluntary choice.¹

To minimise the risk of payment creating undue inducement, Grady recommends that institutional review boards are required to review the amount, method, and timing of payment. Under these circumstances a person could be allowed the freedom to decide whether or not to participate in research after reading the purpose, risks, benefits, alternatives, and requirements of the study when asked for informed consent.¹

Empirical evidence shows that higher payment motivates participation in studies, but common payments levels do not alter research participants’ assessment of risk.⁷ ⁸ If decisions to participate represent rational trade-offs, competent people are free to decide.

Prejudicing selection of participants

Payment may bias recruitment of participants in favour of people who are more economically vulnerable. Also, people of higher socioeconomic status disproportionately benefit from research.⁹ Macklin argues that there is no way to avoid this objection on the basis of social justice, given the moral precept of equity of pay.¹⁰ On the other hand, Penz argues that lower socioeconomic groups are under-represented in research, and payment may improve the balance and yield broader representation of the socioeconomic groups that participate in research.³

In response, the Canadian guidelines for ethical conduct in research that involves human participants has issued a statement about poor participants in research as one of their guiding ethical principles.¹¹ This encourages researchers to include procedures that will protect people that may fall into this category.

Concealing risk factors

When financial compensation is high, it may lead some participants to lie about underlying conditions that might otherwise exclude them from the study.⁴ An example is the case of Bernadette Gilchrest, a 23 year old nursing student who lied about her anorexia nervosa to earn $1300 (£670; €900) in a sleep study. Gilchrest died of a cardiac arrest during the study.³ One study showed that payment increases the risk of respondents concealing information about things that may exclude them from participating, especially for low and medium risk studies.⁷

Given that participants may conceal information, investigators should not rely solely on information reported by participants themselves. Independent measures, such as screening for conditions that might put the participant at medium to high risk, are indicated. In the case of Gilchrest, this may have involved cardiac testing before being allowed to enter the sleep trial, and her lack of disclosure would then not have been the only factor in deciding her eligibility for the trial. Inability to independently check for known medium to high risk factors may be grounds for a research ethics board to reject a study.

Under-reporting of side effects

If there is a financial penalty for not completing the study, some ethicists think that participants may put themselves at risk by under-reporting side effects to avoid being removed from the study.¹² Bentley and Thacker found that payment did not seem to have a significant effect on respondents’ propensity to conceal from researchers negative effects encountered during the trial.⁷

The Council for International Organisations of Medical Sciences’ guidelines on ethical conduct for research involving humans says that participants should not be penalised financially if they discontinue the study because of toxic side effects. But a financial penalty may be reasonable if they leave the study for personal reasons.³ ¹³

How much to pay?

The question “To pay or not to pay?” has been extensively debated, but inevitably payment does and will continue to happen. The question “When and how much to pay?” has not been well defined for investigators and institutional review boards, and available evidence indicates that decisions about the circumstances of payment are currently made with minimal guidance.¹⁴ ¹⁵

Dickert and Grady have presented various payment models.⁵ In the market model, the principle of supply and demand determines whether and how much participants should be paid for participating in a given study at a specific site. The wage payment model operates on the assumption that participation in research demands little skill but demands time, effort, and potentially the endurance of undesirable procedures. Wages are set in accordance with the unskilled labour market rather than supply and demand. It assumes that all participants should be paid equally for any kind of study. Finally, there is the reimbursement model. As the name implies, payment is provided to cover only participants’ expenses. It is based on the view that participation in research should not require financial sacrifice but should not result in profit for participants either.

Guidelines on payment

The Council for International Organisations of Medical Sciences advocates that participants are reimbursed for lost earnings, travel costs, and other expenses incurred in taking part in a study. In addition, it says that people who receive no direct benefit from research be paid or otherwise compensated for inconvenience and time spent. It also says that payments should not be “so large” or the medical services so extensive as to induce prospective participants to consent to take part in the research against their better judgment—“undue inducement.”¹³

What is considered “so large” or “undue inducement” is left to the discretion of the research ethics board: what is justifiable persuasion in one case may constitute undue influence in another. For example, an unemployed person or a student may view a specific level of recompense differently from someone in employment.

Monetary and in-kind recompense must be evaluated by local ethics committees in the light of the traditions of the particular culture and population in which they are offered, therefore, to determine whether they constitute undue influence.¹³ Once a method of payment has been agreed, the specific conditions under which it will operate need to be determined. When determining these, it may be prudent for the investigator to work with the local research ethics board.

Our recommendations

The process of getting informed consent should assess how well a potential research participant has understood the goals of the research, the risks and benefits, and their ability to refuse or withdraw at any time. Particular attention should be given to the case of people who perceive that they have no other choice because they need the money or the treatment or something else available to them only through the research. In these cases extra effort to assure that they understand the nature, risks, benefits, alternatives, and requirement of the study is warranted.¹³

Potential participants in research should be independently screened for conditions that would put them at moderate to high risk if they were to participate.

The model of payment should be specific to the type of study and the target population. However, we prefer the wage payment model. It decreases the chances of exploitation because participants have other options for earning similar amounts of money while allowing people to be paid for work that is considered valuable to society.⁵ Finally, it is most in keeping with recommendations of the Council for International Organisations of Medical Sciences.¹³

More empirical evidence is necessary to help answer more objectively more challenging questions such as “At what point is a participant considered economically vulnerable?” and “What recompense is considered too large as to constitute undue influence?” Substudies should be built into clinical trials in which different payment levels are randomly offered.¹⁶ This would give the strongest evidence with which to answer questions about the amount of financial compensation.

Conclusions

Payment of participants in clinical research is likely to remain essential. Additional research is needed to further examine the many questions that arise when financial compensation is offered. In the interim, we should strive to follow the guidelines of the Council for International Organizations of Medical Sciences,¹³ with careful scrutiny by institutional review boards of the details of payment.

Competing interests: None declared.

Provenance and peer review: Not commissioned; externally peer reviewed.

See Education http://student.bmj.com/issues/08/03/education/121.php.

Kathy Boutis masters degree student, health research methodology
Donald J Willison associate professor
Email: boutis@pol.net
Student BMJ 2008;16:118-119 | 17

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