Compensation and Reimbursement

Site: EUPATI Open Classroom
Course: Trial Participants' Rights & Obligations
Book: Compensation and Reimbursement
Printed by: Guest user
Date: Saturday, 22 January 2022, 4:09 AM

1. What is Compensation?

Compensation can mean two distinct things:
  1. When participants receive money or other benefits for their participation in the clinical trial, or

  2. When they receive a payment or other services if they suffer any harm from a clinical trial (insurance/indemnity).
Both are called compensation and described in this lesson.

The practice of compensating participants for taking part in a clinical trial has been in place for more than 200 years. However, as one study points out (1), this has always remained a matter of debate with no universally accepted standards – mainly for ethical and moral reasons. So, why then is compensation paid in research? Compensation can be useful to recruit the required number of trial participants in the given time frame. It can be paid for relieving participants of financial burden or recognising time sacrifice or as appreciation of their contribution to science; it can also be useful to motivate healthy volunteers to take part in Phase I clinical trials.

1.1. Compensation for Participation

It depends on the sponsor and the given study whether or not compensation is paid to participants. Compensation schemes are more common in Phase I clinical trials. According to one report by the European Forum for Good Clinical Practice (EFGCP) (2), legislation and practice in Europe vary widely from country to country. Some countries exclude compensation entirely, but the most common practice requires that any compensation is reviewed and approved by the ethics committee associated with the given study. The EU Clinical Trial Directive (2001/20/EC) and Regulation 536/2014 (3) specifically prohibit the payment of any compensation for participation - other than the reimbursement of expenses or income lost - to participants who are incapacitated and cannot sign an informed consent form (ICF), or who are pregnant, or minors. Otherwise this EU legislation only provides that ‘no undue influence, including that of a financial nature, [must be] exerted on subjects to participate in the clinical trial.

For example, one clinical research centre in the UK provides detailed guidelines for healthy volunteers who want to participate in clinical trials (4). This assures that a small payment is ensured alongside the reimbursement of travel expenses.

Some research suggests that the amount of money received by participants influences their decision to participate.

1.2. Compensation for Damage Suffered (Insurance/Indemnity)

The EU Clinical Trials Directive introduced an 'obligatory insurance/indemnity' which has substantially increased the costs and administrative burden of conducting clinical trials. The new regulation recognises that clinical trials do not always pose additional risk to the participants over normal clinical treatment. Therefore, in cases where there is no additional risk, or such risk is negligible, no specific damage compensation (insurance or indemnity) will be required. With respect to trials where there is additional risk and the sponsor is obliged to ensure adequate insurance coverage, the new regulation puts EU member states under an obligation to set up a national indemnification mechanism on a not-for-profit basis. This should be of particular value to non-commercial sponsors, for whom it has been difficult to obtain insurance coverage. (5) The EU also requires all sponsors and CRO’s to be completely transparent about financial transactions made with participants or trial sites.

The informed consent signed by the participant must contain specific references to any compensation schemes, and the insurance coverage offered to the participants should they suffer any injury or harm. The informed consent should also be specific about how the insurer can be contacted, so that participants are not necessarily required to arrange their claims through the study personnel or the CRO.

2. Ethical Considerations

Payments in clinical trials have raised ethical concerns for many years. In 2005 Christine Grady (6) from the National Institutes of Health summarised the problem:

‘Several ethical concerns arise regarding the payment of research participants. The most commonly expressed concern is that payment could be coercive or serve as undue inducement to research participants. By definition, coercion is understood to involve a threat of physical, psychological, or social harm in order to compel an individual to do something, such as participate in research. However, money for research participation is an offer or an opportunity and not a threat and therefore cannot be perceived as coercion. But can money be considered an undue inducement? Existing guidelines warn against undue inducement and its potential to compromise informed consent, although there is disagreement about what exactly constitutes undue inducement and consequently disagreement about the extent to which it is a valid problem in research.’

2.1. Vulnerable Populations

Compensation is always a special concern in case of vulnerable populations. It is a particularly difficult issue in case of children and the mentally challenged. They do not or cannot make their own decisions but their parents/legal guardians will decide for them, while the risk is not divided the same way: the member of the vulnerable group carries the risk, but the parent or guardian gets the compensation. This is one of the reasons why the EU does not allow compensation to such vulnerable groups beyond the reimbursement of their expenses. ‘For the poor, illiterate and the unaware, monetary inducements can easily be enticing’, state Pandya and Desai (1).

It may happen that the participant does not understand completely what the implications of participation may be. Patient advocates and patient organisations may play a key role in mediating in these situations, and in flagging any irregular practices in this field to the authorities.

3. How Much Compensation?

Pandya and Desai give an accurate description of the currently existing models for setting the amount of compensation (1):

‘There are several proposed models of making payment to subjects for trial participation. Some of the ways are more ethically acceptable than the others. The common models are:

The market model is based on the principle of supply and demand, which decides when and what is to be paid to the research subjects for a particular study in a particular location. This means that compensation is paid to the subjects for the studies that offer little or no benefits or the studies for which the target population is difficult to reach. Also, this implies that in case of studies that offer benefits or have a huge target population, little or no compensation is paid. This model has advantages like targeted number of subject recruitment achieved in the required time frame, decreased financial sacrifice by the subjects and high completion bonus ensures protocol compliance. However, on the flip side, this model leads to very high compensation in few of the hard-to-find-subject studies, which could serve as undue inducement and could unnecessarily commercialize the research participation. High payment can lead to subjects not paying attention to the risks involved in the study, as well as leading them to hide important data that could deem them ineligible for the study. It could also create situations where the investigators are competing for subjects by paying higher amounts.

The wage model is based on the concept that research participation requires little or no skill, but it does involve consideration of the time and effort of the subject and also discomfort that is faced by subjects. The model is in alignment with egalitarianism. This model suggests that the subjects engaged in similar activities be paid similarly. Thus, here, the subjects are paid on a scale parallel with that of the unskilled but essential jobs. The advantages of this model could include minimization of the issue of undue inducement, reduced inter-study competition as seen in the market model that would also encourage investigators to minimize the risks involved, decreased financial sacrifice by the subjects and prevention of discrimination between high-income and low-income groups (like the reimbursement model described below) as subjects of the same study receive equal compensation. However, it creates difficulty in achieving the targeted number of subject recruitment in the required time frame and it usually attracts the low-income population. It views subject's research participation as an unskilled job and many believe it to be inappropriate commercialization of the research participation.

The reimbursement model is also in alignment with the egalitarianism principle. This model suggests that compensation should only recover the costs incurred by the subject for participating in the trial. Also, the time spent away from work can be reimbursed proportional to their earning capacity. This model helps in resolving the issue of undue inducement to a certain extent. Subjects are less likely to hide information or overlook the risks involved in the study. The model also decreases the financial sacrifice by the subjects. On the other hand, the issues with this model could be difficulty in achieving the targeted number of subject recruitment in the required time span. Also, different subjects have different earning capacities based on their qualifications, which leads to either preference for the low-income group or high cost of study if subjects from the high-income group are selected.

The appreciation model suggests compensation at the time of study completion as a token of gratitude or appreciation. This has no impact on the study recruitment as it is given at the end of the study. However, this model could have an impact on subject retention and may act as an inducement to prevent a patient from discontinuing. It needs to be used along with one of the above-mentioned models. The researcher needs to carefully weigh the pros and cons of each of the above models and decide which one is best suited for the study on hand. It is also best to decide and document the mode of compensation before the trial is initiated, taking the stakeholders and the Ethics Committee in confidence and with the mandatory approval obtained from these.’

4. Summary

There are no clear, standard guidelines to follow for CRO’s or sponsors regarding compensation to research participants for taking part in a trial. Compensation is not always monetary, it can also take the form of health services, food, or other benefits.

There are different models of compensation that studies apply, and often no compensation is given for participation alone, except to healthy volunteers in Phase I studies. Patient activists and advocates should be prepared to know more about the different regulatory frameworks in order to judge compensation related issues. In the European Union, it is mandatory to include explicit references to insurance coverage for study-related injuries in the informed consent documentation. Patient advocates should always be aware of the special needs and issues of vulnerable populations.