By Gary Evans
The Secretary’s Advisory Committee on Human Research Protections (SACHRP) has finalized recommendations to assist IRBs dealing with “pay-for-participation” studies, which raise numerous ethical issues but may produce meaningful data if properly vetted.
Although still subject to some wordsmithing, SACHRP voted unanimously to approve a draft discussed and revised at an Oct. 16, 2019, committee meeting. The recommendations had not been published as this report was filed, but the text and discussion at the meeting centered on the panoply of ethical issues one might expect to arise when research subjects are asked to pay to enter a study.
“We were asked to take on this topic because we are seeing, anecdotally, that IRBs are seeing uptake in the type of trials described here,” said David Borasky, MPH, CIP, co-chair of the SACHRP Subpart A Subcommittee. “Our goal is to provide stakeholders with points to consider in assessing studies of this nature.”
The draft and discussion included frank acknowledgement of a potential profit motive rather than a research need in some pay-to-participate studies. “We know it appears that some pay-to-participate trials are not intended to generate important scientific knowledge, but rather a pretext to circumvent regulatory prohibitions against marketing investigational products,” said Borasky, who reviewed the draft and led the SACHRP discussion at the meeting.
The committee sought to find a path forward rather than simply recommend against such studies, acknowledging they could advance needed research if IRBs find sufficient answers during a rigorous inquiry. (See SACHRP’s recommendations in this issue.)
“The ethical acceptability of pay-to-participate trials is highly fact-specific,” the guidelines stated. “Therefore, SACHRP does not recommend a default presumption against pay-to-participate trials even though, in general, research subjects should not be expected to pay to contribute to socially valuable research. Instead, we recommend a careful review of each trial based on consideration of [SACHRP] questions and satisfaction for all regulatory criteria for approval.”
The pay-to-participate approach is an outlier in the research world, as most clinical trials conducted in the United States are funded by the National Institutes of Health (NIH) and other government entities, or by private drug and device companies. In contrast, pay-to-participate trials may call for participants to fully or partially fund the study.
“IRBs may face the great difficulty in review or oversight when pay-to-participate trials involve medical products that are not clearly regulated by FDA as drugs, biologics, or devices; for example, nutritional supplements, surgical procedures, autologous stem cell transplants meeting minimal manipulation and homologous use criteria, and novel applications of standard treatments,” the guidelines stated.
If researchers cannot secure funding through traditional government and industry channels, pay-to-participate may be an option to move the research forward.
“Many proposed studies will not secure government funding, sometimes because they are low quality, but often there is simply not enough money to fund all worthwhile projects,” according to the guidelines.
Similarly, industries may be reluctant to pursue research with little expectation of a return on investment. “Lastly, some pay-to-participate trials may be initiated by patient advocacy groups and ‘citizen scientists’ with reduced access to traditional funding sources or a desire to eschew them,” the guidelines stated.
The stipulation of payment to participate in a trial raises many issues for the potential subject, not the least of which is a skewed perception that paying suggests a better potential outcome. “Because asking subjects to pay to participate is unusual among clinical trials, subjects may be more likely to view participation as something valuable and payment as an exchange for some benefit,” SACHRP stated.
This “therapeutic misconception” can be overcome by ensuring subjects understand both the magnitude of potential benefit and harm. “This is true for all clinical research, but is even more critical when subjects are charged for their participation,” the guidelines stated.
Justice and Validity
A broader ethical issue that pay-to-participate research immediately raises is the aspect of social justice for those unable to afford to join, as well as scientific validity if the study is capturing only a limited population with economic resources.
“To the limited extent that pay-to-participate research offers the prospect of direct benefit to participants, the possibility of benefit as a participant should not be concentrated only in certain advantaged groups,” SACHRP stated. “The economically disadvantaged also may go to great lengths to gather the resources needed to participate; for example, through crowdfunding and perhaps undertaking debt if the potential for benefit appears sufficiently great.”
To a larger extent, pay-to-participate studies could exploit vulnerable patients who have exhausted their therapeutic options.
Regarding the issue of scientific validity, IRBs should evaluate the patient population and consider whether the research data will be broadly applicable to a diverse cohort of future subjects.
“Pay-to-participate trials also may reduce trust in science by fostering the perception that research participation is a valuable commodity made unfairly available to those individuals with more resources,” the guidelines stated.
The committee recommended IRB review, but conceded that some of this kind of research falls beyond regulatory authority. “SACHRP acknowledges that there will be proposed research that is unregulated because it is not federally funded and does not involve an FDA-regulated drug, device, or biologic,” according to the guidelines. “The committee believes that, because of the particular issues raised by trials that require participants to pay, such trials should be voluntarily submitted to an IRB, even when there is no regulatory requirement.”
In addition, the NIH asked SACHRP to list some questions that prospective subjects should ask, the answers to which should be useful to both IRBs and potential participants of pay-to-participate studies. These questions include:
- Who has reviewed and approved this research? Has there been any scientific and ethical review of the research?
- Why do researchers think what is under investigation might help people like me? What do they think it might do if it works?
- Has it been tested before? If so, how many have been tested on?
- Why am I asked to pay to join this research?
- How much will the researchers charge me to be in this research?
- What exactly will I be paying for?
- What are some reasons I might be willing to pay to join this research?
- What are some reasons I might not be willing to pay to join this research?
- If I am injured, who will pay for treatment of that injury?
- When will I be expected to pay?
- If I quit the research, will I get any of my money back? If the researchers make me leave the research, will I get any of my money back?
- Will participating in the research affect my health insurance coverage? Will my health insurance cover any part of what I am paying?