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Would you participate in a medical research project that required you to periodically give blood, undergo invasive diagnostic screenings and tests, and spend significant parts of each week at a local hospital undergoing these procedures? What if the results of the research project would provide no benefit to you, but could one day lead to a cure for a fatal disease?
What if researchers offered to pay you $50? Or $500?
What amount of compensation is needed to encourage people to participate in research projects? Does compensation for participation violate the principles of informed consent by "coercing" someone to participate when they would ordinarily refuse?
These are questions that many ethics committees and institutional review boards (IRBs) are struggling with as pressure from the private sector mounts to recruit more and more people to participate in medical research projects. Pharmaceutical companies, in particular, are eager to get their drugs through required clinical trials — and they have the financial capital to recruit as many people as they need.
"Concern has been expressed that the offer of money could compromise the voluntariness of someone’s decision, in essence influencing them to do something contrary to their interests or values," explains Christine Grady, RN, PhD, a researcher in the department of clinical bioethics at the National Institutes of Health in Bethesda, MD.
Grady recently published a paper examining this topic in the spring issue of the American Journal of Bioethics.1
She concludes that money is just one of many factors that might influence a person’s decision to participate in a research project. Other factors might include the availability of a medical procedure or product not otherwise available or the chance to receive free medical care.
As long as the amount of money offered is not excessive, the payment can be seen as just compensation for the time and contribution that subjects made and an indication of respect for the subject, she says.
The question is, at what point does simple compensation end and coercion begin?
"IRBs or their institutions should establish guidelines for determining when and how much should be offered to participants in a study," Grady tells Medical Ethics Advisor. "Guidelines would provide a rationale for payment, and preferably a formula or a basis for calculations. This way, decisions would be standardized within an institution (and thus fair), and IRBs have some framework for their particular decisions."
Many institutions that sponsor research, particularly those who receive federal grants, do have guidelines on payments made to research participants. These guidelines are published, along with other requirements investigators must meet, in the respective institution’s research guidelines and on their web sites.2,3
However, establishing a standard formula for paying participants would be difficult, says Ada Sue Selwitz, director of the office of research integrity (ORI) at the University of Kentucky in Lexington. The ORI oversees all research conducted at the university and supervises three medical IRBs and one nonmedical, scientific IRB.
"IRBs have to look at a number of variables in trying to decide, first of all, is it appropriate to pay subjects and, if so, how much is appropriate and when is it too much?" she says.
For example, if the study group is primarily people living in a third-world country, even a small-dollar amount of cash compensation could be coercive. Yet, a similar amount of money would not be a significant incentive to a study group drawn mostly from middle-class people living in this country, she says.
"That is the first criterion you look at: What is the study population? And in that context, is the proposed amount appropriate," she explains.
The IRB at the University of Nebraska Medical Center in Omaha tries to focus its compensation on reimbursing participants for the time they must spend participating in the various parts of the research, says Ernest Prentice, PhD, vice chancellor for academic affairs and IRB co-chair.
The amount might vary from study to study, based on what was asked of the people involved.
"We base our compensation levels on what would be a reasonable hourly rate for the time spent in preparation for, participation in, and recovery from a particular research intervention," he explains.
For example, if a participant must undergo a bronchoalveolar lavage, he or she would have to come to the hospital, undergo anesthesia, undergo the procedure, recover from the procedure at the hospital, and most likely be accompanied home by a companion, he says. "They probably wouldn’t recover from the anesthesia for a couple of hours. They probably would have a sore throat and maybe a little bit of fever. Clearly, it is inconvenient."
The researchers should come up with an amount that compensates that person for the time they must spend involved in the research from beginning to end — in this instance, the time spent going to the hospital, undergoing the procedures, recovering from the procedures, plus compensating the person who is needed to accompany them.
"We usually use the reasonable hourly rate figure of around $10 per hour," he says. "Obviously, if the person is a CEO making $300, this is not his or her normal hourly compensation, but we aren’t going to go there. This is a reasonable compensation for the time spent."
The focus, he says, is really to eliminate any disincentives to research participation rather than really "compensating" them for the service, he says. "We don’t want anyone to assume financial liabilities for taking part."
The IRB would like to move toward having a set compensation amount for every procedure that a research study might perform, Prentice adds. "We would like to have more standard, definitive guidelines in place. And, we are trying to work on what would be a reasonable dollar amount for performance of a whole series of procedures — from bronchoscopy with lavage all the way to a skin biopsy."
One benchmark that should not be used to determine the level of compensation, both Prentice and Selwitz say, is the level of risk involved.
"The level of payment must never be based on the level of risk," says Prentice. "You do not elevate the amount of compensation you deem acceptable."
In the past, some IRBs considered this an acceptable way of compensating participants, but this is now thought to be clearly coercive, Selwitz says.
"Some used to say, in approving a protocol, if it is really risky you get, say, $1,000," she says. "If there is less risk involved, $50. I don’t think anyone is doing that anymore."
You don’t want payment to be the reason that people agree to participate in, and remain in, a very risky study, she explains. "If it is a high-risk study and there is no potential benefit to the participants — no chance of a medical benefit — then the IRB is going to look very closely at the dollar amount."
Both Selwitz and Prentice also recommend that IRBs require payments to subjects to be prorated, if the project involves multiple appointments or tasks over days or weeks.
"The payment schedule can make a difference in whether the payment is coercive or not," says Selwitz. "We don’t allow there to be a lump sum at the end of the project, conditional upon the person completing the project. They must feel free to withdraw at any time."
The University of Kentucky IRBs require that subjects be paid for each portion of the project they complete, whether they remain in the study to the end or not.
Prentice encourages investigators to pay subjects a selected portion at each visit, and that the amount be tied to the amount of time involved.
"Say you have five visits. The first visit is pretty extensive, so you pay the person $50," he says. "The second visit involves significantly less time so you pay the person $25."
Under no circumstances, he says, should there be a bonus for completing the project — such as a payment schedule that lists the last visit as worth twice as much as the previous visits, he says.
A major controversy in payment of research subjects has been the question over whether children should be given compensation for participation in research, or whether their parents should receive compensation.
"What happens when the person you are enrolling is a child?" asks Selwitz. "That is a different issue. "If you offer cash compensation to the parents, you can run into situations where the parent says, My child will participate whether he wants to or not.’ Because the parent wants or needs the money."
Should you pay the children directly? Even a small amount of money could be coercive to a child, she says. "Many IRBs have chosen not to offer compensation for children involved in research at all."
Instead of cash, some investigators offer the child a small coupon to a toy store or small gift certificates, she says. "Sometimes an IRB will be OK with that and sometimes they won’t."
The University of Nebraska IRB does not compensate children at all, but will make cash reimbursements to parents for their time in taking the child to and from the medical center, says Prentice.
"We are not going to hand $10 to a child. Any-thing, whether it is money, pizza, gift certificates. We are very concerned about that," he adds.
Some IRBs, deciding that cash is inherently coercive, will allow compensation only in other forms, says Selwitz.
"Some IRBs allow payments, but not cash payments," she explains. "Particularly with vulnerable populations like children, or with [college] students. Some IRBs feel that students are already in a coercive situation. So, if you give them a free pizza or gift certificate, as opposed to $20, is that less coercive? Some IRBs say yes and some do not."
Prentice agrees with Grady that there are issues other than compensation for participation that have more potential to be coercive. And IRBs have to be sure to be aware of these, as well.
"You have to look at why people participate in research," he says. "The first reason is usually to get a particular drug or procedure that they feel may offer them some hope, but they may not have access to outside a research trial. Second, they may not have health insurance and may see the research as a way to get free medical care."
The second issue, in particular, has the potential to be very coercive and the IRB must be extremely careful to look at the planned study population and how investigators intend to recruit participants.
"We ask for a rather detailed description of the target population," he says. "In terms of demographics, we want to know what the age range is, the gender, ethnic minority status, where they are going to recruit subjects from, and how they are going to recruit them," he says.
It is important that poor people and minorities, who traditionally have less access to health care, are included in research efforts. But, it is important to ensure that these populations are not targeted because they will be less likely to refuse, or less likely, once enrolled, to leave the project.
"If the investigators say, we’re going down to the Last Chance Clinic in north Omaha, which has a high percentage of poor African-American people, and that’s where we’re going to get our people, that is a red flag to us. We need to have balance. You have balance access to the benefits of research participation without coercing people into a project and accepting risk that they would not ordinarily do so. It is a hard balance to achieve."