Compensation and Reimbursement

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.

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.

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.

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:

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.

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

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.