Leigh Turner, who authored the study and is an associate professor at the University of Minnesota's Center for Bioethics and School of Public Health, said NIH should use much tougher screening tools to scrutinize, and in many cases exclude, such listings. The problem, he said, is that the clinics are not getting clearance from the Food and Drug Administration to conduct the studies and charge the participants.
In addition, he said, the clinics are marketing their products to the public without FDA approval, sometimes in direct-to-consumer ads, even as the purported studies are occurring.
“Do we really want ClinicalTrials.gov to be 'caveat emptor,' where no one is paying attention to the substance of studies being listed?” said Turner. “A lot of these studies are just marketing pitches designed to appeal to people with COPD, multiple sclerosis and Parkinson's disease.”
In recent years, hundreds of stem-cell clinics have proliferated in the United States; only a very few stem-cell treatments have been cleared by the Food and Drug Administration.
The clinics, for the most part, insist that they do not need FDA approval -- either to test or market their products -- because they are practicing medicine, which is outside the agency's purview. They also say they are exempted from agency guidance on stem cells because they don't alter the stem cells much, a claim that is in dispute.
In response, critics of the clinics, including Turner, say that FDA guidance indicates that many of the procedures do indeed required FDA approval for both the testing and marketing phases. But the FDA's apparent reluctance to crack down on the businesses has created confusion — and opportunity.
ClinicalTrials.gov, which was created by a 1997 federal law and made available to the public in February 2000, is a searchable database of clinical trials in the United States and elsewhere. The trials are testing experimental treatments funded by public and private organizations around the world. Usually, the goal of the trials is to see if the treatments are safe and effective and ready to be reviewed by the FDA for approval.
The NIH clinical trials website operates to a large extent on an honor system in which the government relies on the companies and researchers listing their studies to answer accurately whether a product requires FDA oversight. Turner says the system isn't working. “Absent evidence that the FDA has reviewed such studies, approved all charges to research subjects and permitted clinical research to proceed, such studies should not be accepted for inclusion and public listing,” he wrote in the article.
Most legitimate trials do not charge patients to participate, although patients might face incidental costs, such as travel. By contrast, participants in “pay to participate” studies often are charged thousands of dollars, Turner said.
In a statement, NIH said it “agrees that it is of paramount importance for potential research participants to know about the potential benefits and risks of participating in clinical research studies.”
The agency noted that it added a prominent disclaimer to the ClinicalTrials.gov home page in March 2017 stating: “Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted health care professional before volunteering for a study.” The agency said it continues to evaluate ways to improve the site.
The posting of the disclaimer followed the publication of a New England Journal of Medicine article earlier this year that reported three women suffered significant vision loss or were blinded after receiving stem cells from fat in a procedure touted as part of a clinical trial at a South Florida clinic. The women had paid $5,000 per person for the therapies that were supposed to treat macular degeneration. At least one of them heard about the procedure through ClinicalTrials.gov and thought she was taking part in a government-sanctioned study, the authors of the article said.
In many of the clinics, the stem-cell procedures involve liposuction, in which fat cells are extracted, processed and then injected into other parts of the body.
“This is an important problem that needs to be addressed,” said Timothy Caulfield, a law professor at the University of Alberta who wasn't involved in the study but has called for tighter regulation of unproven stem-cell treatments. “Many of us have noticed that ClinicalTrials.gov is being used as a marketing ploy to give a veneer of scientific legitimacy to these clinics, but this is the first paper to provide concrete evidence on how it plays out.”
Yet Caulfield added that it isn't easy to come up with a solution to the problem.
Turner looked for businesses and clinics in the United States that offer unregulated stem-cell treatments that advertise directly to consumers and charge patients to take part. He found seven studies in which the listings on ClinicalTrials.gov acknowledged that patients are charged to take part in the trials — five by the Ageless Regenerative Institute and two by the Lung Institute. He found an additional 11 studies in which the listings by various companies don't mention payment but other publicly available information makes it clear patients are charged. He said there are other listings from clinics throughout the world on the site.
Ageless Regenerative Institute is using stem cells in people with diabetes, erectile dysfunction and other problems, according to the database listing. The Lung Institute is focusing on COPD and other ailments. Neither company provided answers to inquiries about their trials.
Turner was the co-author of a study published last summer in the journal Cell Stem Cell that showed that unregulated stem-cell clinics are proliferating across the United States. According to that study, at least 351 companies with 570 clinics are marketing unapproved treatments for conditions such as osteoarthritis, Alzheimer's, autism and injured spinal cords, as well as for cosmetic enhancements. And the number is probably higher now, he said.