Michele Russell-Einhorn has spent 23 years working in the world of institutional review boards, which decide whether to green-light clinical trials. In all that time, she’s never seen quite so many proposals as she has in the past year that rely on an unusual — and controversial — funding mechanism.
Some plan to ask participants to pay $7,000 or so to enroll. Another wanted to ask for upward of $250,000.
In each case, there were “serious concerns about how ethical it was to charge people to participate in the research — and whether it was absolutely necessary,” said Russell-Einhorn, chief compliance officer for Advarra, the second-largest commercial IRB.
These studies have caught the attention of federal regulators. The Food and Drug Administration recently asked a federal advisory committee to consider how the research community should think about such trials, an agency spokesperson confirmed. Members of that panel are now drafting recommendations on the issue. And the National Institutes of Health asked the committee to consider whether its existing resources to guide patients considering a clinical trial are adequate for scenarios in which they are being asked to pay, a spokesperson for that agency confirmed.
The new scrutiny reflects mounting concern about these trials at a time when they’re perceived to be increasing in volume — and when several have attracted media attention.
Last year, STAT reported on a plan in Florida to charge seniors a fee proposed as high as $285,000 to enroll in a clinical trial in which they would get young-blood transfusions to try to forestall aging. That proposal was part of the reason that the Health and Human Services Secretary’s Advisory Committee on Human Research Protections — or SACHRP — decided to take up the issue, according to Holly Fernandez Lynch, a University of Pennsylvania bioethicist who sits on a subcommittee that’s helping draft the recommendations.
In the same field, the startup Ambrosia recently ran a clinical trial that charged about 80 people $8,000 each to get an infusion of blood plasma from a young donor — before halting its business in response to a warning from the FDA. Meanwhile, a clinic in Panama enrolled 20 autistic children in a stem cell trial that charged parents $7,200, the science news site Spectrum reported last month.
FDA regulations permit such trials in “extraordinary circumstances,” such as when the drug being tested has a price tag so high that the trial couldn’t otherwise be run. (Asked why FDA recommended that SACHRP take up the issue of pay-to-participate trials, an FDA spokesperson said the agency suggests topics that its believes “may be of interest to a wide range of stakeholders.”)
But experts say these trials are ethically fraught for a number of reasons: At worst, they run the risk of being a guise for an enterprise looking to profit from desperate patients. But even when intentions are sound, the trials are likely to only enroll those patients who can afford to participate, thereby skewing the results. There could also be a weak study design, without blinding or a control group, because patients would likely be reluctant to pay for a placebo. And they may reinforce the common misconception among patients that clinical trials are a route to accessing treatments that are guaranteed to help them.
Still, SACHRP doesn’t want to rule out the possibility that such trials can in rare cases be valuable, Fernandez Lynch said.
“The examples that we have, that get this kind of media attention, it’s obvious that people shouldn’t be asked to pay to participate in those trials,” Fernandez Lynch said. “But there are some where we think we don’t want to have a hard-line stance that says no, never, this could never be appropriate, because sometimes, we think, in rare circumstances, it could be ethically acceptable to ask for this kind of cost-sharing.”
Fernandez Lynch pointed to research around medical uses of illicit drugs, like medical marijuana and psychedelics, that might have a hard time getting funded through traditional channels, though she acknowledged that that field has increasingly been finding mainstream funding.
But Dr. Steven Joffe, a pediatric oncologist and bioethicist at the University of Pennsylvania, worries about making exceptions for even a few trials.
“If you open the door to these trials, you inevitably are going to get … exploitative trials, and bad trials, and trials that don’t lead to any useful information,” Joffe said.
Sure, Joffe said, a blanket policy against pay-to-participate trials would mean foregoing a few potentially valuable trials. “But you are also closing the door to a lot of potential abuse that is very likely to happen — and overall the harms of opening the door outweigh the benefits,” he said.
A draft of the recommendations discussed at a SACHRP meeting last week offers a hint of the balancing act that the panel is trying to strike. The recommendations urge IRBs to consider questions like, “Does the study meet relevant thresholds of scientific quality?” and “Is the risk-benefit balance acceptable?”
SACHRP doesn’t expect to finalize its recommendations on the subject until its next meeting in December or its subsequent one next March, said SACHRP committee member Nancy King, who’s also a bioethicist at Wake Forest School of Medicine. When finalized, SACHRP’s recommendations will be delivered to HHS Secretary Alex Azar, and they’ll be meant to offer general guidance for researchers, patients, IRBs, and regulatory agencies.
Good data are lacking on the volume of pay-to-participate trials, in part because the researchers running them don’t always disclose that information when they announce their results or list their studies on the government’s human study registry, clinicaltrials.gov.
“Whether it’s just that we are seeing more of it — there’s more attention, there’s more press, there’s more academic study of the phenomenon — or whether there’s actually truly growth in the phenomenon, I think is hard to say,” Joffe said.
The largest commercial institutional review board, WIRB-Copernicus Group, didn’t return STAT’s requests for comment on how many of these study protocols it’s seeing.
At Advarra, they’re still relatively rare. Russell-Einhorn estimated that, even with the surge this past year, they represent just a handful of the thousands of protocols that she and her team review annually.