Of special concern, said Jeffrey Goldberg, professor of ophthalmology at the Stanford University School of Medicine and one of the authors of the report, was the clinic's ability to list its study on a comprehensive database of clinical trials called ClinicalTrials.gov, which is run by the National Institutes of Health. At least one of the patients — and maybe more — believed that she was taking part in a government-sanctioned study, he said.
Goldberg called the incident a “wake-up call across the spectrum” — for patients, physicians and government regulators. “Surely,” he said, “it's an opportunity for the FDA to increase patient safety for these unapproved clinical trials.”
Thomas Albini, a University of Miami ophthalmologist and another one of the authors, said that he and his colleagues at the Bascom Palmer Eye Institute had treated two of the patients for severe complications in 2015, shortly after they had undergone the stem-cell procedures at a clinic in Sunrise, Fla. The severe complications included detached retinas, hemorrhages and vision loss.
“It's a disaster,” Albini said, noting that the patients, before the stem-cell treatments, had only moderate vision loss. “Buyer beware: These stem-cell clinics that function in this very unregulated way are doing procedures that are not approved … and they can be quite dangerous.”
The NEJM article did not identify the clinic or the patients, but its listing on the ClinicalTrials.gov website shows the sponsor as Bioheart Inc., also known as U.S. Stem Cell Inc., and says that the study was “withdrawn” before patients were enrolled. The clinic still has other stem-cell studies listed on the site, including for chronic obstructive pulmonary disease and degenerative disc disease.
Repeated calls to U.S. Stem Cell and to Kristin Comella, who is listed as the chief scientific officer, have not been returned. In a NPR story last year, Comella said that two of the clinic's patients had suffered detached retinas following treatments, prompting the clinic to stop doing eye procedures.
According to Florida court filings, two of the patients involved, ages 72 and 78 at the time, sued the clinic and some individuals involved in the procedures. Their attorney, Andrew Yaffa of Coral Gables, said that the case “was resolved to the mutual satisfaction of the parties” but that neither he nor his clients could comment beyond that. The third patient was an 88-year-old Oklahoma resident who sought medical help a week after the stem-cell procedure at the Dean McGee Eye Institute in Oklahoma City.
Albini said the eye damage could have been the result of contamination during preparation of the stem cells. He also said it was possible that the stem cells could have changed into cells that are associated with scarring. Even if the solution had been prepared correctly, he said, there's no evidence that it could have helped restore the patients' vision.
Albini said the three patients paid $5,000 each for the stem-cell procedure, which involved conducting mini-liposuction procedures to remove fat from the abdominal area, isolating the stem cells from the fat and injecting those cells directly into eyes. Charging the patients was a “red flag,” he said, that this was not a traditional clinical trial. A second was treating both eyes at the same time, rather than seeing how one eye responded before treating the other.
Age-related macular degeneration is the leading cause of vision loss in people older than 75 in the United States. While researchers are making “tremendous” progress using stem cells to treat the disease, the field requires careful study with meticulously designed trials, the authors of the paper said. The FDA has approved only a few stem-cell therapies, mostly for blood disorders.
The proliferation of stem-cell clinics — there are more than 570 of them, according to a study published last year — has ignited a fierce debate among physicians, patients and scientists about how they should be regulated. FDA rules allow the use of patients' own stem cells for treatments, without agency approval, but only if the procedures meet stringent conditions. The stem cells, for example, cannot be more than “minimally manipulated” and must be intended for the original function. That would not typically include using stem cells from fat to repair eye cells.
Albini said that the FDA had started an investigation into the case but a spokeswoman said the agency does not discuss potential or ongoing investigations. She added that consumers are encouraged to contact the FDA and state authorities to report any potentially illegal or harmful activity related to stem-cell-based products. The FDA has issued several drafts of guidance for the stem-cell industry to try to outline its thinking on the matter, but the documents have not been finalized, and many clinic operators oppose FDA regulation.
Paul Knoepfler, a stem-cell scientist at the University of California at Davis who is a frequent critic of the clinics, said he didn't understand why the FDA and the NIH have not moved more aggressively to ensure patient safety.
“It's puzzling and concerning,” he said. He said that allowing the clinics to list their trials on ClinicalTrials.gov is “almost like a form of advertising for products that don't have FDA approval. That's really problematic.”
In a statement, the NIH said that the information on ClinicalTrials.gov is provided by study sponsors and that posting on the site doesn't reflect endorsement by the NIH, which doesn't independently verify the scientific validity of the trial. It also said that every study includes links to an NIH disclaimer. “However, we agree that such caveats need to be clearer to all users and we will be adding a more prominent disclaimer in the future.”