Does stem cell clinic IRB approval mean much? Insights from blinding cases

Could the blinding of three women at a stem cell clinic have been prevented by better oversight or was the clinic acting outside of the scope of oversight by its institutional review board (IRB)?

More broadly, when is an IRB conducting proper oversight and how do we know? When on the other hand is it not being careful enough or even outright enabling risky behavior by those selling non-FDA-approved, experimental stem cell “treatments”?

It can be hard to really be sure. What makes this area particularly muddled is that most of what IRBs do is confidential. We in the stem cell community are as a result left with a bunch of questions in general and about specific cases such as the blinding of these women.

When things go wrong and patients have bad outcomes how much is the responsibility of an IRB versus the stem cell clinics doing the actual experiments? Stem cell clinics often point to their IRB-approved status as some kind of merit badge, but how much does that approval mean? My goal in today’s post is to tackle that last question.

stem cells eyes

Kuriyan, et al. 2017 NEJM Figure 2A showing patient with severely damaged eyes leading to loss of sight

Over at BuzzFeed reporter Peter Aldhous has been following the story of the three women who were blinded by experimental offerings of US Stem Cell, Inc. In Aldhous’ new article he focuses more on US Stem Cell’s IRB. This IRB was run by an organization called the International Cellular Medicine Society (ICMS), which in theory was responsible for overseeing work of US Stem Cell.

There are a host of questions about what happened leading to the women losing their vision and what if any role the ICMS IRB had in overseeing the experiments on these patients. Did US Stem Cell wander outside the scope of ICMS IRB oversight in this case? Could the ICMS IRB have done a better job? If the ICMS IRB did its job well here, I still wonder how they can help to prevent more bad outcomes like this from happening? Presumably the ICMS IRB is overseeing work by many other stem cell clinics as well. How much risk is there at those places? If a business doesn’t follow its IRB’s rules, what happens then? It’s hard to find answers to questions like these. Continue reading

NEJM paper links 3 blinded patients to publicly-traded stem cell clinic

Do 3 blinded stem cell clinic patients with major or complete vision loss constitute a significant adverse outcome?

I would say so and a new paper details how this happened apparently at a particular publically-traded South Florida stem cell clinic business.

You can see the damaged retinas of one such patient below in an image from a new NEJM paper reporting the severe adverse outcomes. The red areas are hemorrhaging with other substantial damage to the retina as well.

How did this all happen?

stem cells eyes

Kuriyan, et al. 2017 NEJM Figure 2A

Last year the story began to break of multiple patients alleging they had been blinded by different businesses in South Florida. Dr. Thomas Albini presented on some information on this at the FDA meeting last fall, but things weren’t entirely clear. Back then there were also indications of lawsuits by patients related to alleged vision loss due to experimental stem cell offerings against various parties involved.

Now we have more details on some of the cases in this new NEJM article (Kuriyan, et al.) in which the authors attribute these patients’ experiences to a withdrawn “trial”, NCT02024269, which lists Bioheart (now known as US Stem Cell, Inc.) as the sponsor. I put “trial” in quotes because it was withdrawn and also because as best as I can tell this wasn’t a traditional FDA-approved trial of the kind normally based on pre-clinical data and an IND. US Stem Cell, Inc. is a publicly-traded company ($USRM) and its stock has been all over the place this year. I’m not aware of US Stem Cell having FDA approval for what it is doing.

The NEJM article oddly does not mention Bioheart or US Stem Cell, Inc. by name as the place where the patients were given the stem cells, but the authors do clearly link them together and other information further supports this connection. Continue reading

SCOTS Study on Stem Cells for Vision: Still Questions as Patient Alleges Harm

Eye injection

Eye surgery image from Wikipedia. Is clinics injecting stem cells into an eye a good idea? OK with FDA?

I’m hearing more questions from the community about alleged harm from stem cell clinics selling stem cells for a number of vision-related conditions and some concerns include the so-called SCOTS study.

I first blogged about SCOTS early this year and back then I myself had questions too. Some commenters then raised concerns or questions about SCOTS in weighing in on that post.

In my opinion SCOTS is almost certainly not a traditional FDA phased clinical trial, which raises issues right from the get go. I’m not aware of the trial having, for instance, an IND. Patients must pay $20,000 to participate and that brings additional questions.

The clinicaltrials.gov listing is here (reminder in general that a listing on that website does not equal FDA approval or some kind of NIH approval of the actual clinical science). The company mentioned as the responsible party is Retinal Associates of South Florida in collaboration with another business, MD Stem Cells.

A self-reported SCOTS study patient, George Gibson, made allegations to Scientific American that he lost vision after participating in the study:

“But not every story of stem cell therapy has such a rosy outcome. George Gibson was in his late 60s when he partially lost his vision during heart surgery. He says he paid $20,000 to get stem cells injected into his eye with the guarantee that he would be able to read a few more lines on an eye chart. Gibson claims that instead, he lost vision in that eye completely, but his assertions could not be verified. There have been other reports of vision loss in stem cell procedures performed elsewhere. Gibson didn’t get one of the first-come-first-serve slots to speak at the hearing; instead, he and his wife stood outside the meeting room during breaks with big signs that read, “I lost my sight to the SCOTS stem cell procedure!!!”

To be clear, this outcome has not been independently verified and the SCOTS investigators dispute the allegation.

Another SCOTS patient, Doug Oliver, who has also commented on this blog, has apparently had the opposite kind of experience. He self-reported a very striking positive outcome after receiving the stem cells in SCOTS and this has gotten a lot of media attention.

Two case report publications are listed as associated with the SCOTS study:

So what is going on here?

The short answer is that we as a community don’t know yet.

In a number of different stem cell studies over the years we’ve heard about individual patients having striking outcomes. Anecdotal reports of alleged potential harm or benefit should definitely be paid attention to and given consideration, but what we really need is comprehensive data from properly controlled studies to have confidence that an investigational stem cell therapy is (or is not) safe and effective.

Related to this specific study, I’m very happy for Doug, but the SCOTS study needs to show/publish all the data including any potential adverse outcomes before we can know what is going on with this investigational treatment. Last week I emailed Dr. Steven Levy, MD who is running the study asking if I could do a brief email Q&A with him for the blog, but so far no reply. Dr. Jeffrey Weiss is listed as the Principal Investigator so I may reach out to him as well if I don’t hear from Dr. Levy.

Study that injects marrow cells into eye, charges $20K raises many questions

Eye injection

Eye surgery image from Wikipedia. Is injecting stem cells into an eye a good idea? OK with FDA?

Whenever I see a stem cell headline like this one from a recent Baltimore Sun piece, it raises many questions: Stem cells apparently reverse woman’s blindness.

First of all, is the reporter, Meredith Cohn in this case, being cautious enough with that “apparently” in the headline? Part of the reason for this question is that the “treatment” in question is unproven, so far there’s no public data beyond 1 patient, and I wasn’t able to find evidence of an IND for this so it’s unclear if the FDA is OK with it.

Second, I immediately wonder what kind of stem cells are being used. In this case, the physician who is doing the study, Dr. Jeffrey Weiss in Margate, Fla, is injecting bone marrow stem cells into the patients’ eyes.

Third, does it make any sense to inject bone marrow cells into a person’s eyeball to treat a vision condition? I’m not a vision or bone marrow scientist, but there’s no obvious rationale to me. Even the doctor doesn’t claim to know for sure how it might work. Anti-inflammatory? Mobilization of or enhanced survival of endogenous cells? Other?

Fourth, is it safe? Who knows. There would definitely be some risks associated with transplanting these stem cells into the eye. Update: a mouse study from right here at UC Davis a few years ago suggests more broadly that this kind of approach might be safe for one particular type of retinal injury ( HT to @SurgeonRetina on Twitter), but that’s a long way away from being sure that what the human study that we are focusing on here is doing is safe.

Fifth, is there a charge? In this case, yes, it costs patients $20,000. This makes me even more concerned. Does 100% of this money go to running the trial? Or is there some profit (i.e. total funds generated exceed total costs of the trial)?

Sixth, will this newspaper article encourage other patients to take the same risk? I think it probably will. The article includes some caveats, but enough?

Digging more into the article, there’s some confusing text about FDA regulations and how they apply to this trial:

“The U.S Food and Drug Administration must permit the use of “investigational” drugs, and the NIH requires that researchers attest they have such permission to register a trial. While the FDA continues to tweak regulations, there are exceptions when stem cells aren’t considered drugs, such as when they are minimally processed and taken from and used in the same person.”

I’m not clear what this means.

The FDA “must permit” investigational drugs she writes, but the way it is written is confusing and again I’m not aware that this study has that permission. Does it? If so, I hope to hear about that. Cohn leaves this issue up in the air.

She also doesn’t touch on the crucial homologous use issue. Cells must be used in a clinically homologous manner or they are automatically drugs requiring pre-approval. Does bone marrow seem similar to the eye?

The clinicaltrials.gov listing is here and the business doing the study is Retinal Associates of South Florida in collaboration with MD Stem Cells. So far I haven’t been able to find evidence that this is a traditional phased FDA-approved clinical trial.

Unfortunately we are seeing more and more of these kinds of unusual listings at clinicaltrials.gov. The listings are called “clinical trials” by those doing them and the media, and patients have to pay.

This kind of human stem cell clinical experiment is exactly the type of thing that we need more clarity about from the FDA.