A few weeks ago, if you’d been scouring the ever-expanding mass of digitized federal paperwork, you might have noticed a contradiction.
On the one hand, the Food and Drug Administration issued a
letter stating that what
an Arizona distributor was selling as stem cell therapies were “unapproved” and posed “safety concerns.” On the other, a National Institutes of Health database —
clinicaltrials.gov — went right on listing the same merchant’s
studies, with a link to the company’s website and the word “Recruiting” displayed invitingly in green.
Similar scenarios have been popping up like fungi after rain. When a judge
ruled last week that the FDA could stop the work of U.S. Stem Cell, the firm’s trials remained on clinicaltrials.gov; the
postings were no longer actively enlisting patients, but they didn’t mention that the company’s injections had blinded at least four people, either.
Nor did a study listing sponsored by Cell Surgical Network include any indication that the FDA is
seeking an injunction against that company, too.
What worries bioethicists and biologists is not just the crossing of governmental wires. It’s also these companies’ co-opting of a taxpayer-funded database to market therapies without proof of safety or regulatory review. To let such dubious vendors post on a federal website, the critics say, is to lend them an air of legitimacy they don’t deserve.
“You can concoct this bogus appearance of science, call it a clinical study, recruit people to pay to participate in your study, and not only that: You can actually register on clinicaltrials.gov and have the federal government help you promote what you’re doing,” said University of Minnesota bioethicist Leigh Turner, a longtime critic of such rogue clinics. “That struck me as both dangerous and brilliant.”
Clinicaltrials.gov is a bit like the Wikipedia of human experiments — at once useful and dicey because of its huge, democratic breadth.
Launched in 2000, in response to a 1997 law requiring the registration of clinical trials, the website was intended for patients, doctors, and researchers alike. Its goal, in a sense, has been to lay bare the innards of biomedical research, allowing anyone and everyone to see what experimental therapies had been tried, which had worked, and — perhaps most importantly — which hadn’t.
Though every one of the 308,000 listings has, according to the NIH, undergone audits both human and automated, the quality of each post, as on Wikipedia, is highly dependent on the poster.
And, as Turner and others have
chronicled, some of the posters aren’t exactly pure as the driven snow. These critics’ concerns extend beyond the shadowy marketplace of treatments advertised as stem cells — from scientifically suspect homeopathy regimens to less-than-reputable answers to autism. But self-described stem cell clinics are among the most common, and as such, have sparked some tricky questions. At a time when lawmakers
castigate tech giants for their misinformation-spreading algorithms, what responsibility do government agencies have over the data submitted to their own online repositories? And where to draw the line between what’s allowed and what isn’t?
While there are some gray zones, Turner said, there are also some cases in which the answer is pretty clear: Namely, if a clinic’s doings are worrisome enough to trigger an FDA warning or legal action, its studies should probably be redacted from clinicaltrials.gov.
The NIH said in an email to STAT that clinicaltrials.gov includes information “about the potential risks and benefits of participating in a trial and urges people to talk to their doctors about whether to join a study.” It added that the agency “is exploring additional measures” to enhance public understanding of human research and how to use the website.
The danger posed by some trials in the database is not theoretical. In 2015,
a handful of patients went legally blind after having bits of their own fat sucked from their abdomens, modified, and injected into their eyes at a clinic operated by U.S. Stem Cell in Sunrise, Fla. Two of them had come across the company on clinicaltrials.gov.
That particular clinic did not respond to requests for comment, but the CEO of another one — also the subject of FDA actions — spoke with STAT on condition of anonymity. His company gets a few clients from postings on clinicaltrials.gov, but that’s not the main reason his staff posts there. “Most of what I get off clinicaltrials.gov is a little bit annoying … patients who expect procedures for free,” he said. “I wouldn’t say it’s a humungous patient-acquisition method at all.”
The website does help him boost his company’s credibility, though. “If the practice does a presentation or I do a presentation, and an educated consumer goes to clinicaltrials.gov, and wants to see the specifics of the study, it’s important to have it there,” he said.
That’s exactly what neuroscientist Sally Temple worries about. As the scientific director of the nonprofit Neural Stem Cell Institute, in Rensselaer, N.Y., she knows that legitimate clinical trials typically don’t involve patients paying to be treated.
Not only is it unethical to charge people for an unproven therapy; it also often means that the study won’t involve comparing the treatment to a placebo or another intervention, which is what allows researchers to say whether or not the remedy being tested actually had an effect.
Part of the issue is that there are scientifically valid uses for certain stem cells. They are, in a sense, the body’s raw materials, able to shape-shift into tissues that need repairing. Bone marrow stem cells are already used to treat leukemia, sickle cell anemia, and other diseases — and researchers are looking at myriad other potential uses.
Temple, for instance, is applying to the FDA for permission to test whether stem cells that live inside the retina might work to rejuvenate layers of eye cells that are dying off and preventing eyesight in the elderly. She worries that patients might go onto clinicaltrials.gov and confuse her own meticulous work — which involves animal studies, regulatory approvals, and carefully designed, grant-funded human trials — with those unapproved sellers of “stem cells,” some of whom may in fact not be providing stem cells at all, given that their products are often un-vetted.
“The clinics that are doing this type of surgical procedure — taking fat and putting it somewhere else without any real rationale — that is a big threat for groups like us that are trying to do it the way that is understood to form a path toward a safe and effective therapy,” she told STAT. “Patients who’ve heard about this may say, ‘Well, stem cells, if they’re injected they an cause blindness, so I’m not going to participate in a study.’ Is that going to reduce the possibility that we would be able to recruit patients?”
But simply scrubbing studies that don’t comply with FDA regulations from clinicaltrials.gov is more complicated than it seems. As Tania Bubela, dean of the faculty of health sciences at Simon Fraser University, outside of Vancouver, explained, “It has become the go-to repository for clinical trials internationally. … A lot of the international trial sites would not fall within the jurisdiction of the FDA, and so there is no ability for the FDA to want or take action against the organizations that are running trials outside of the U.S.”
She also worries that taking down studies will arouse distrust on the part of some patients. “If we simply make these things disappear, it can start to look like a big government conspiracy,” she said.
Instead, she suggested a warning that pops up when someone types in specific search terms — “stem cells,” say — that are likely to yield questionable results. While Turner would prefer to see potentially dangerous listings removed, he said that flagging them as such would be the next best thing.
For now, the warning that prospective patients are most likely to encounter as they click from trial posting to trial posting is the same every single entry: “The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.”
It’s the legal equivalent of a shrug, perhaps the defining move of the internet age, in which we’re constantly invited to post and peruse at our own peril. We know that in those mountains of data there’s both gold and pyrite to be had — and we’re suspicious of anyone telling us where we can and can’t dig. The trouble is that we often overestimate our ability to identify what we’ve found.
As historians of science and psychologists have pointed out, couching knowledge in layers of misinformation can be an effective way, willful or not, of spreading ignorance. “The paradox appears to be that the people who are most in need of advice don’t know when they need advice,” explained David Dunning, a University of Michigan psychologist who studies how well we can gauge what we don’t know.
That’s why Dennis Clegg, who studies stem cell-based eye therapies at the University of California, Santa Barbara, has stopped referring people to clinicaltrials.gov. “I used to tell people all the time, ‘Go to clinicaltrials.gov, and you can see what’s going on,’” he said. “But if they’re listing the so-called patient-funded research, where patients have to pay $5,000 or $10,000 … now the best advice I can give is, ‘Talk to your ophthalmologist.’”
