What is the role of the ethics committee in protecting a human subject from himself – or herself? An IRB must ask itself this question when reviewing the amount of compensation offered to healthy subjects in a Phase I trial. Websites such as GPGP.net (“Get Paid, Guinea Pig”) and thepennyhoarder.com offer advice on clinical trials as a source of income for would-be trial participants, and a variety of blog postings describe participating in Phase I trials as a path to easy money. Even though no precise formula is available, a variety of guidelines can help ethics committees assess whether proposed compensation may be too low or too high.
“Phase I” trials are the earliest studies conducted in humans when a new drug is being developed. Some Phase I studies (such as oncology trials) are conducted in patients, while many are conducted using healthy participants. Some Phase I studies are “first-in-human” and involve the first administration of a new investigational drug in a human being. Phase I studies are largely nontherapeutic; as described by the FDA, they should be designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness (21 CFR 312.21).
The total number of subjects and patients included in Phase 1 studies varies with the drug, but is generally in the range of 20 to 80. Many trials require participants to report to a research center multiples times a day, week, or month for blood draws and physical examinations. Some trials require participants to keep records of their nutritional intake, exercise levels, or lifestyle habits. Depending on the length and type of the trial, participants may be required to stay overnight—or several nights—for around-the-clock observation.
Phase I trials using healthy subjects typically pay the participants to participate, and at times the payments can appear quite high. Some participants have claimed they can make up to $40,000 a year by participating in clinical trials, and websites have promoted clinical trial participation in articles such as “8 Weird Ways to Make Extra Money.” A website maintained by Drugwatch.com lists the following examples of compensation available for participation in clinical trials:
- $50 for going through the screening process
- $500-$700 for some three-day trials
- An antidepressant trial paid participants around $2,000 per week
- Participants in a study of malaria vaccines received between $2,000 to $4,000
Another website, brokelyn.com/human-guinea-pig, outlines typical pay rates for typical procedures, such as $50 for a typical MRI and $600 for a typical PET scan.
International guidelines direct the ethics committee to review the amount and method of payment to subjects “to assure that neither presents problems of coercion or undue influence.” (ICH E6 Sec. 3.1.8). An offer of money could constitute undue influence if it were so high that it would cause someone to act against his or her better judgment and take risks that are inconsistent with their values or typical behavior.
On the other hand, ethics committees also are encouraged to consider whether payments are so low that they are exploitative. Some commentators believe that “[w]hat usually matters most when it comes to offering subjects money is not coercion or undue influence, but exploitation.” (Shamoo and Resnick, 2006). Exploitation is a concern, especially for research conducted in the developing world and for studies that might attract poor, uneducated subjects.
So how high is too high, and how low is too low? Several different approaches have been proposed: the market model, the wage model, and the reimbursement model. (Dickert and Grady 1999)
- According to the market-based approach, the value of the labor is whatever the study sponsors will pay
- According to the wage model, subjects should be paid a wage equivalent to the wage paid to unskilled laborers
- According to the reimbursement model, subjects should be compensated for lost wages, travel, and other expenses
Another suggestion is to blend the market-based approach with the wage model, in a “free wage model.” (Shamoo and Resnick, 2006). Under this model, subjects should be paid at least a minimum wage equivalent to the wage paid to unskilled laborers, but no upper limits would be placed on payments, reasoning that “[i]f companies are willing to pay subjects more than minimum wage, then they should be able to do so.”
Even though it is doubtful that ethics committees will refrain from reviewing the upper limits of proposed compensation altogether, this model provides another set of yardsticks for measuring proposed subject compensation.
Ethics committees also will consider a number of other factors when reviewing compensation for Phase I studies involving healthy subjects. The ICH guidelines dictate that payments to a subject should be prorated and not wholly contingent on completion of the trial by the subject. Most ethics committees will allow completion bonuses to be offered to participants, but according to the FDA, the amount to be paid should not be so large as to unduly induce subjects to stay in the study when they would otherwise have withdrawn. Ethics committees also should consider whether the study sponsor plans to provide compensation for research-related injuries. Finally, the ethics committee must ensure that the informed consent document clearly addresses these issues.
No precise formula is available to determine whether proposed compensation for a Phase I study involving healthy individuals is too high or too low. A variety of payment models can help an ethics committee as it balances concerns of exploitation against concerns of undue influence, and hopefully with the aid of these models a committee can focus its attention on all the issues important to Phase I trials.