A fairly frequent topic on Science-Based Medicine is the issue of for-profit stem cell clinics selling unsupported stem cell-based treatments with little or no evidence to support them for huge amounts of money. I make no bones about it. In my estimation, every for-profit stem cell clinic is a quack clinic bilking patients with promises of the magical things they claim stem cells can do. Every. Single. One I’ve searched and searched, and I have yet to find a for-profit stem cell clinic that provides only science- and evidence-based treatments for a reasonable cost. I hope that one day I find one or more, but as of this writing, I have failed.
Unfortunately, it’s not just countries with dodgy regulation, like Mexico and countries in Central America and Asia, where you can go to get stem cells anymore. There are plenty of dodgy for-profit stem cell clinics in the US exploiting patients. These clinics like to use hard sell techniques reminiscent of unethical used car dealers or time-share hawkers. (Actually, most used car dealers and time-share sellers are more ethical than owners of stem cell clinics.) Although the FDA, FTC, and State of California have looked into regulating these clinics more closely, hundreds of them still operate relatively unencumbered, and there have even been incidents of severe harm, such as vision loss and blindness after a Florida stem cell clinic’s bogus treatment for macular degeneration. It’s not just unethical doctors, either. Non-MD quacks like chiropractors and naturopaths are getting in on the grift.
Indeed, for-profit stem cell clinics are even using celebrity endorsements to hawk their wares. Longtime readers of SBM will remember my series of posts about how a San Diego stem cell company called Stemedica enticed Gordie Howe’s family to bring him to a clinic in Mexico to receive stem cell therapies for his stroke. There’s no evidence that the octogenarian hockey legend recovered from his serious stroke any more than he would have without the stem cell treatment, but Stemedica got a whole lot of positive press just for foregoing the $30,000 or so that its affiliate normally charged for such an infusion. It was later revealed that Stemedica was run by people who had previously sold Penta Water, which (they claimed) was “structurally superior” to that run-of-the-mill water you get out of your tap or from bottles.
Then, a couple of weeks ago:
At least Shatner tagged it as an advertisement.
Of course, as I pointed out a couple of weeks ago, the stem cell therapy being advertised by William Shatner had no evidence behind it and, as stem cell scientist Paul Knoepfler pointed out, ProGenaCell, the company selling the specific product touts animal stem cells, amongst other stem cell products, leading him to ask: Are they really injecting people with animal cells? Not surprisingly, there was a fair amount of press about this as well.
Of course, celebrity endorsements, online advertising, Facebook pages, and even traditional advertisements in print, on radio and TV, and on billboards are becoming commonplace. One form of marketing, however, follows a trail originally blazed by cancer quack Stanislaw Burzynski, namely the abuse of the clinical trial process to market their stem cells. It’s something Dr. Knoepfler discussed four years ago, calling it “unapproved, for-profit human experimentation,” as did I in 2017, making the link to Dr. Burzynski’s history of charging patients to be enrolled in his scientifically-questionable clinical trials explicit.
Unfortunately, little or nothing has changed since 2017. However, it’s worth updating my post from two years ago because, although nothing has changed, it’s been noticed again that for-profit stem cell clinics are abusing ClinicalTrials.gov and to raise the alarm once again. Some of this will be familiar territory to longtime readers, but I think it’s worth reiterating every couple of years (or even a bit more often) in order to keep raising the alarm.
For-profit stem cell clinics: Imitating Stanislaw Burzynski
Anyone who is involved in human experimentation and clinical trials knows that there are two principles that are very important. (Actually, there are more than two, but for purposes of this discussion, these two are the most relevant.) First, is the idea of clinical equipoise. If you’re comparing a new treatment to an old one, for instance, there has to be genuine scientific uncertainty over which treatment is more effective and safe. If there isn’t genuine scientific uncertainty, then it is unethical to randomize patients to the treatment that we think to be inferior. In the case of a placebo-controlled trial, there must be genuine scientific uncertainty whether the treatment works; otherwise it would be unethical to randomize to a placebo group. The second principle is that human subjects should not be expected to pay for experimental treatment. There are a few, very narrow, exceptions to that rule, but in general it is considered to be one of the rules that is closer to absolute in clinical trials research. To be clear, this rule doesn’t mean that patients aren’t expected to pay for all the non-experimental components of their treatment through their insurance, Medicare, or Medicaid. It’s just that they should not be expected to pay for the experimental treatment or any additional tests or monitoring associated with the treatment that they wouldn’t have undergone if they hadn’t enrolled in the clinical trial.
This brings us to the STAT News story by Eric Boodman, “Stem cell clinics co-opt clinical-trials registry to market unproven therapies, critics say“:
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 listing of a completed study sponsored by Cell Surgical Network include any indication that the FDA is seeking an injunction against that company, too.
Does this sound familiar? It should. If you’re familiar with cancer quack Stanislaw Burzynski and his 40+-year history of administering an unproven cancer treatment while charging hundreds of thousands of dollars, a lightbulb should have gone off in your brain, and your first thought, as my first thought was, should have been: Crap! Quack for-profit stem cell clinics are copying the Burzynski model! Stanislaw Burzynski, remember, is the Polish expat doctor and researcher who in the 1970s became so enamored of something he thought he had discovered in the blood and urine, namely peptides that, according to him, were part of the body’s natural anti-cancer defense system that were deficient in cancer patients, that he became convinced that they were a superior treatment for cancer. Back in the 1970s, this was a novel concept, but unfortunately Burzynski became so sure that he had found the cure for cancer, or at least a much better treatment than what existed, that he gave up his once-promising research career, opened a private clinic, and started administering his peptides, which he had dubbed “antineoplastons,” to patients. He’s been doing it ever since, for well over four decades now, and no one’s been able to stop him, even though he has never produced anything resembling compelling evidence that his antineoplastons had significant anticancer activity (and despite the evidence they did have considerable toxicity).
Now’s not the time to rehash the entire 40 year history of Burzynski, other than that he’s still in business exploiting desperate cancer patients and to explain his abuse of the clinical trial process. Back in the late 1990s, his “innovation” in cancer quackery was, with the help of his lawyer Richard Jaffe, to realize that he could take advantage of the FDA and largely defang its efforts to shut him down by declaring his antineoplaston treatment “experimental”, and opening clinical trials, which he did. First, patients already being treated were enrolled in a wastebasket trial known as “CAN-1” a retrospective trial looking at all patients then being treated at the Burzynski Clinic. Of this trial, Jaffe wrote in his book, Galileo’s Lawyer:
…As far as clinical trials go, it [CAN-1] was a joke. Clinical trials are supposed to be designed to test the safety or efficacy of a drug for a disease. It is almost always the case that clinical trials treat one disease.
The CAN-1 protocol had almost two hundred patients in it and there were at least a dozen different types of cancers being treated. And since all the patients were already on treatment, there could not be any possibility of meaningful data coming out of the so-called clinical trial. It was all an artifice, a vehicle we and the FDA created to legally give the patients Burzynski’s treatment. The FDA wanted all of Burzynski’s patients to be on an IND, so that’s what we did.
“IND” stands for “investigational new drug.” It’s the term the FDA uses for any experimental drug being under development for approval. The FDA also permitted Burzynski to set up nearly identical phase 2 trials for every cancer that he wanted to treat. Burzynski claimed these were based on a protocol used in a trial done by the National Cancer Institute in the early 1990s when the NCI had tried to work with Burzynski. However, these trials had only one purpose, to allow Burzynski to continue treating patients with antineoplastons:
CAN-1 allowed Burzynski to treat all his existing patients. That solved the patients’ problems, but not the clinic’s. A cancer clinic cannot survive on existing patients. It needs a constant flow of new patients. So in addition to getting the CAN-1 trial approved, we had to make sure Burzynski could treat new patients. Mindful that he would likely only get one chance to get them approved, Burzynski personally put together seventy-two protocols to treat every type of cancer the clinic had treated and everything Burzynski wanted to treat in the future.
Knowing how difficult it is to write a clinical trial protocol, even one based on a previous trial, I have to give Burzynski some grudging respect here for having put together 72 of them and shepherded them through the FDA approval process in a matter of months. Sadly, it worked, and Burzynski’s business model for the 2000s was born. He would enroll whoever wanted to be treated on one of his clinical trials. Now, he didn’t charge them for the experimental drug (the antineoplastons) because charging patients on a clinical trial for the experimental drug being tested was (and still is) considered dodgy at best, highly unethical at worst. (I tend to view it as the worst; patients should not be charged to help a company test its product in order to bring it to market.) Burzynski got around this (and, to my knowledge, still does) by charging exorbitant “case management” fees and providing the antineoplastons “for free”. This is just as ethically questionable, because none of Burzynski’s fees are expenses that these patients would have been expected to bear anyway because of conventional treatment. They were only charged because these patients received antineoplastons. That’s what Burzynski’s been doing for over 20 years, and, I fear, that’s what he’ll continue to do until he retires or dies. Certainly neither the FDA nor the Texas Medical Board has been able to stop him, despite multiple attempts.
Unethically charging patients to be on scientifically worthless clinical trials
As the STAT News story notes, ClinicalTrials.gov came into being in 2000 thusly:
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.
The idea of ClinicalTrials.gov was (and is) a good one: Provide a public database of all clinical trials, along with basic information about the trials, their status (open to accrual, closed to accrual but followup still ongoing, closed, suspended, etc.), and results. Technically, since the passage of the Food and Drug Administration Amendments Act of 2007 (FDAAA), “basic results” for certain clinical trials are required to be submitted to ClinicalTrials.gov within one year of their completion date. In practice, this rule is widely ignored, which is part of why the All Trials initiative is so important, not just for stem cell trials, but for all clinical trials of all drugs and interventions.
This brings us back to for-profit stem cell clinics, which are now doing basically the same thing as Stanislaw Burzynski, setting up scientifically dodgy to worthless clinical trials and using them not only to get around FDA regulations regarding unproven stem cell therapies but as marketing tools. It is a problem that those running ClinicalTrials.gov have known about for at least two years, as it first received major publicity in 2017, when Leigh Turner published a study reported in The Washington Post. Let’s go back and take a look at that study before I come back to the STAT News story. In the introduction, Turner notes:
Numerous US businesses that engage in direct-to-consumer advertising of purported stem cell treatments recruit clients by registering clinical studies on ClinicalTrials.gov. Some studies registered by businesses selling putative ‘stem cell therapies’ disclose that study subjects are charged. The studies are explicitly described as being ‘patient-funded’, ‘patient sponsored’ or ‘self-funded’ [1,2]. However, other studies registered on ClinicalTrials.gov by businesses selling stem cell interventions do not reveal that study subjects are charged to participate in clinical research . It is only when interested individuals contact sponsors, investigators or clinic employees and inquire about enrolling in the studies that they are then informed they must pay to participate.
Listing studies on ClinicalTrials.gov is an effective way for businesses selling stem cell interventions to solicit prospective clients. One such company was recently the subject of considerable news media scrutiny after clinicians independent from the business published a study documenting that three of its patients suffered severe vision loss after paying $5000 per person for stem cell interventions that were supposed to treat their age-related macular degeneration [4–8]. At least one of the women who were blinded reportedly contacted the stem cell clinic after learning about the one of the clinical studies this business had registered on ClinicalTrials.gov .
What Turner did was simple. He searched the ClinicalTrials.gov database looking for pay-to-play stem cell clinical trials run by private clinics. He found seven studies in which the listings on ClinicalTrials.gov acknowledged that patients were charged to take part in the trials. Five of these were being conducted by the Ageless Regenerative Institute and two by the Lung Institute. He also found an additional 11 studies in which the listings by various companies didn’t mention payment but for which he was able to find other publicly available information that made it clear that patients were being charged for stem cell treatments. The studies were for all sorts of conditions, too, ranging from diabetes to osteoarthritis to chronic obstructive pulmonary disease (COPD) to critical limb ischemia (insufficient blood flow threatening to cause loss of limb) to premature ovarian failure to Parkinson’s disease and more.
As I perused the list two years ago, when I first read this study, I noticed that virtually all the studies were open-label studies, unblinded and unrandomized. In other words, they were not particularly good trials for determining whether stem cells are actually effective or not, because there were no control groups and patients and investigators were unblinded. This sort of design is generally only acceptable for phase I or early phase II trials or for surveillance trials after FDA-approval looking for adverse events that might not have been picked up in the original clinical trials used for FDA approval. Charging a patient is never appropriate, in my book, for early phase clinical trials, and, because the stem cell therapies under “trial” were not FDA-approved, a post-approval surveillance trial was not appropriate either. It was hard not to be suspicious, as Turner was, that these trials listed in ClinicalTrials.gov were nothing more than marketing tools to sell stem cell treatments far more than they were legitimate trials designed to answer an important clinical question. There isn’t even a hint of clinical equipoise in these clinical trials.
As Turner noted (and it’s worth quoting him extensively):
Critiques of ‘pay-to-participate’ clinical studies have identified serious scientific and ethical problems associated with charging individuals to participate in studies conducted on an apparent for-profit basis [54–56]. In such studies, research subjects are charged before the safety and efficacy of investigational agents have been established and the interventions in question have received premarketing authorization from the FDA. It is common to find no public record of peer-reviewed preclinical research by the investigators leading these studies. The absence of any record of peer-reviewed preclinical research generates concerns about whether the sponsors and investigators responsible for such studies have sufficient safety and efficacy data to justify making the transition from preclinical research to clinical studies involving human subjects.
‘Pay-to-participate’ studies often are open-label and, therefore, do not ‘blind’ investigators, study subjects or anyone else involved in clinical research to the intervention being tested, do not use placebos or sham procedures to control for placebo effects, and do not randomize subjects to different study arms.
Many businesses conducting ‘pay-to-participate’ studies in which stem cells are administered risk promoting the therapeutic misconception by describing investigational stem cell interventions as safe, efficacious and innovative treatments. Misrepresentations on the part of businesses conducting such studies and substantial misunderstandings on the part of research participants are particular concerns in such ‘pay-to-participate studies’. ‘Pay-to-participate’ studies also risk amplifying placebo effects as a result of the sizable fees companies often charge research participants and the hyperbole sometimes used to promote such studies.
It is common for ‘pay-to-participate’ studies in which stem cells are administered to use research methodologies and designs that are unlikely to generate meaningful evidence of safety and efficacy. For example, numerous ‘pay-to-participate’ studies that administer stem cells have expansive inclusion criteria and include study subjects with a wide range of disparate diagnoses rather than focusing on a well-defined study population of individuals suffering from a particular medical condition.
In other words, the studies that Turner found were crappy clinical studies, and patients were required to pay in order to be enrolled on them. Regular readers might recall that, over four years ago, as I was writing about Gordie Howe’s stem cell therapy for his stroke, I got in touch with Stemedica, the company that had referred Howe and his family to its partner in Mexico, Novastem, and the Clinica Santa Clarita, where Howe received his stem cell infusions. As I noted at the time, the clinical trial design was a mess, not well designed. It was basically a phase I study, unblinded, with poorly defined outcome measures and nothing resembling a rigorous design, and it, too, had pretty expansive inclusion criteria. I bet that if I were to get a hold of the “clinical trial” protocol of any of the clinical trials Turner discovered I’d find the same thing or even worse.
Yes, these clinics are following in Burzynski’s footsteps. As STAT News shows, they still are.
Stem cell clinics: Still co-opting ClinicalTrials.gov for marketing in 2019
Sadly, more than four years after scientists started sounding alarms over the way for-profit stem cell clinics have co-opted ClinicalTrials.gov and nearly two years after Leigh Turner did a significant investigation documenting how these clinics were doing it, nothing appears to have been done. As STAT News notes, in 2015 several patients went blind after adipose-derived “stem cells” were injected into their eyes at a clinic operated by U.S. Stem Cell in Sunrise, Florida. Ophthalmologist Dr. David Weinberg has written about these cases three times for us, first when they first hit the news, and then with two updates this year about the outcomes of the cases. STAT News notes that two of the blinded patients had come across the company on clinicaltrials.gov.
One part of the STAT News article is particularly telling when it comes to the attitudes of owners of these for-profit stem cell clinics, so much so that I almost laughed out loud when I read it:
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 nerve of those patients! Expecting that a clinical trial listed on ClinicalTrials.gov be free to enroll in! What entitled jerks! This CEO, however, inadvertently revealed just what Leigh Turner, Paul Knoepfler, and I have been talking about. He doesn’t view ClinicalTrial.gov as a repository for information on actual clinical trials, but rather as a marketing tool. It’s very telling that he gets annoyed when patients contact his clinic with the quite reasonable expectation that he’s running an actual clinical trial and doing what legitimate scientists and companies trying to gain FDA approval for their experimental therapy do, enrolling patients without charging them to be in the trial. His last excuse is equally telling, dismissing his use of ClinicalTrials.gov as not a large patient acquisition method. Again, to me at least, he sounds dismissive because ClinicalTrials.gov is not providing him with as many patients as he’d hoped.
But here’s the kicker:
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.
In other words, he’s using ClinicalTrials.gov as a marketing tool to boost the credibility of his clinic, exactly what Leigh Turner, Paul Knoepfler, and I have been saying all along! Certainly, the clinical trials these for-profit stem cell clinics list in the database are not high quality by any stretch of the imagination. Every time I peruse ClinicalTrials.gov for stem cell trials and look at individual trials run by clinics like this and not affiliated with a university, I fail to find any that could be considered high quality. They’re all pretty much unrandomized and unblinded, with vague primary and secondary outcomes that are usually pretty subjective and without a good scientific rationale.
Just for yucks, I did a quick search yesterday of ClinicalTrials.gov, limiting myself to stem cell trials less than two years old. I found a bunch run by universities and academic medical centers, but I also found trials like one by R3 Stem Cell being run out of a number of “integrative medicine” clinics, including Integrative Medical Center in Scottsdale, AZ; Advanced Stem Cell Institute in Encino, CA; Regenerative Medicine Research Institute, San Gabriel, CA; Frid Institute of Regenerative Medicine in New York City; and Austin Regenerative Therapy in Austin, TX. The trial, “Safety and Clinical Outcomes With Amniotic and Umbilical Cord Tissue Therapy for Numerous Medical Conditions” (NCT03899298), reminds me very much of Burzynski’s CAN-1 trial. It’s a wastebasket trial seeking to enroll 5,000 subjects in a non-randomized, unblinded, unmasked, parallell assignment trial looking at patients receiving stem cells at these clinics for “Orthopedic, Neurologic, Urologic, Autoimmune, Renal, Cardiac and Pulmonary Conditions.” Amusingly, the study is listed as being “partially patient funded”. Even more ridiculous, for all the conditions, the study states, “Outcomes will be compared to the literature results of the current gold standard for several conditions”. This is basically a useless trial, with so many conditions and outcomes that its purpose can only be to allow these clinics to use stem cell treatments for whatever the heck they want to.
R3 Stem Cell has a similar trial (NCT03390920) being run out of Stem Cell Therapy of Las Vegas, except that it’s limited only to stem cell treatments for musculoskeletal conditions. Again, it’s single arm, this time with only 200 patients, with no blinding. Meanwhile MD Stem Cells is running a single-arm, unblinded trial (NCT03724136) out of The Healing Institute in Margate, FL, for autism, dementia, encephalopathy, Lewy Body Disease, and a number of other neurologic conditions. Again, these studies, with their single arm unblinded design, panoply of conditions in their inclusion criteria, and large numbers of outcomes examined, are, from a scientific standpoint, worthless.
But what can be done? You might ask how these clinics can get away with it. Well, how did Burzynski get away with it? Part of the issue is that human subjects protections are a federal issue and don’t really have a lot of bite if the institution conducting a clinical trial is not receiving federal grant money. Normally, universities and other institutions doing clinical trials are overseen by the Department of Health and Human Services Office for Human Research Protections, which can’t do a lot if the researchers’ institution isn’t receiving federal grant money. Moreover, there’s no guarantee that the institutional review board (IRB) overseeing such studies is independent or competent. (Indeed, the Burzynski Clinic had an IRB chaired by an old crony of Burzynski’s) Another reason is that, unless a clinical trial is being done to gain FDA approval of a new drug or device, there isn’t a lot to make sure that the institution plays straight. FDA oversight of clinical trials assumes that the researchers doing them are doing them in order to produce data to use in an application for FDA approval of a new drug or device. That’s not the case for many of these stem cell studies, and often the clinics haven’t even filed an IND application.
In the STAT News article, Turner is quoted as advocating the removal entries for dubious stem cell “clinical trials” from the ClinicalTrials.gov database. While that sounds simple and reasonable, unfortunately, it’s not so easy:
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.
And alternative? Sadly, the only alternative seems to be the clinical trial equivalent of a Quack Miranda Warning:
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.
The Quack Miranda Warning, remember, is the warning many quacks tack on to websites and documents touting their products, and usually reads something like, “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.” Unfortunately, each and every entry on ClinicalTrials.gov already has an equivalent warning, “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.”
As Boodman notes:
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.
Indeed, and unscrupulous owners and operators of for-profit stem cell clinics are taking full advantage of that. Another potential strategy was suggested by Turner two years ago, namely, rigorously enforcing FDA regulations on patient-funded studies, and not allowing a clinical trial to be listed in ClinicalTrials.gov unless the charges to the clinical trial subjects have been approved by the FDA:
To improve the quality, integrity and public value of ClinicalTrials.gov, the failure of NIH officials to properly screen studies submitted to the registry needs to be addressed. In particular, screening needs to determine whether clinical studies submitted for registration in ClinicalTrials.gov have been reviewed and permitted to proceed by the FDA and IRBs, where both FDA review and IRB review are required by federal regulations. In the case of trials requiring Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications reviewed and cleared by the FDA, screening must also establish whether sponsors or investigators are authorized by the FDA to charge individuals participating in clinical studies. This legal requirement for IND studies is addressed in federal regulations and explored in detail in FDA guidance document [15–17]. 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 in the ClinicalTrials.gov registry. Regrettably, these issues were not adequately addressed in Section 801 of the Food and Drug Amendments Act and in 42 CFR Part 11, the final rule for Clinical Trials Registration and Results Information Submission [18,19].
Inded, the FDA still hasn’t provided adequate guidance. Here is a 2016 draft rule about charging for investigational drugs (FDA source here). It’s so vague as to be a mess. At the time, Paul Knopfler tried to find out how the FDA determines if a clinical trial investigator is allowed to charge patients to be in a clinical trial, and he was sorely disappointed, noting that the criteria used by the FDA to determine whether charges are allowed appear to be, for all intents and purposes, secret.
In the end, what we’re left with is the same situation as two years ago, when this problem first made the news, in which dubious for-profit stem cell clinics can abuse ClinicalTrials.gov by using it as a marketing tool. They are not the first to use set up dubious clinical trials as a strategy to be able to continue to sell their product without FDA approval. They’re just following the trail blazed by Stanislaw Burzynski 20 years ago. The FDA and Office for Human Research Protections (OHRP) need to recognize what these clinics are doing, and reevaluate and modify their regulations in order to protect patients from such abuses.