15 still unanswered interview questions for stem cells for vision SCOTS trial docs

What is the SCOTS Trial and why are some of its participants raising concerns?

There’s a lot going on in Florida with non-FDA approved stem cell offerings. Even just related to stem cells for vision problems alone. While US Stem Cell has drawn the most attention related to patient allegations of severe vision loss in Florida after fat stem cell injections in eyes, another group I’ll loosely call the “SCOTS Trial” has also been injecting investigational stem cells into eyes. In this case from bone marrow is used. Some patients have made allegations of harm there too in the form of vision loss.

The SCOTS Trial

I’ve covered the SCOTS Trial before including those patient allegations and open questions. One particular patient, George Gibson (see image at right below), may have been the first to raise concerns about SCOTS in 2016, and both he and others claim adverse outcomes. Reportedly, eye expert Dr. Thomas Albini examined Gibson and speculated on a link between the eye injections and some retinal scarring:

“When his vision didn’t improve, he returned to South Florida to seek help from Dr. Thomas Albini at the Bascom Palmer Eye Institute at the University of Miami. Albini said he noticed scar tissue on one of Gibson’s retinas.

The extent of the scarring, and how quickly it happened, led Albini to believe it was from the stem cell injections. “When there is a novel treatment, we assume [any problems are] related to the procedure until proven otherwise,” said Albini.”

Overall, SCOTS disputes the patient allegations.

It’s hard for those of us not directly involved to fully understand this situation.

Hoped-for SCOTS Trial interview

Early in 2018 I invited the SCOTS Trial physicians, Drs. Jeffrey Weiss and Steven Levy, to do a Q&A interview here on The Niche to try to clarify things. My impression was that they seemed generally receptive to the interview idea by email, but after sending them the 15 questions (which in one email they referred to as “reasonable” questions) in January and emailing a few polite reminders, I still don’t have any answers to the questions from them yet after about 4 months.

Maybe the answers will come, but I thought I’d post the questions now as a way to further the discussion on the SCOTS Trial and the larger issues that relate to non-FDA approved stem cell therapies for which patients must pay. Note that the SCOTS vision trials are run by an organization called MD stem cells.

Importantly, for background keep in mind that not all stem cell injections require full FDA pre-market drug approval. For example, it seems that autologous use of unmodified bone marrow stem cells for many kinds of orthopedic conditions is generally viewed as compliant even without FDA drug-level approval as it is viewed as homologous use most often. I have my doubts as to whether even such compliant offerings are reproducibly effective, but they don’t seem against FDA rules.

Other uses of bone marrow stem cells that might be or clearly are non-homologous in theory could often trigger an IND-requirement, but to me the FDA’s new guidances on this point are not entirely clear. For instance, does the SCOTS trial’s use of bone marrow stem cells injected into the eye for a variety of vision-related conditions in each case meet the homologous use standard? If not, then they would likely need an IND prior to doing this work. In my opinion as a stem cell biologist, it seems that bone marrow stem cells in most cases are not homologous to the specific cells in the eye such as photoreceptors that are lost in some of the most common eye diseases such as macular degeneration. However, SCOTS says it is FDA compliant. It would be helpful if FDA was more concrete with guidance about potential homologous vs. non-homologous use of autologous bone marrow stem cells.

The questions

Here are the questions that I sent the SCOTS Trial docs.

• 1. How did you both first get interested in and involved in stem cell research?
• 2. Do either of you have specific training in stem cells or transplantation biology?
• 3. What is the rationale for using bone marrow stem cells to treat vision loss? If, as is widely believed, hematopoietic cells cannot become cells of the eye, what specifically would the transplanted cells do that is helpful to the eye? In other words, where would the benefit/efficacy come from in terms of mechanisms?
• 4. What are the risks to injecting bone marrow cells into the eye?
• 5. Have you conducted pre-clinical studies in animals to assess safety and efficacy of your approach prior to using it in human patients? If not, why not? If yes, do you have published or unpublished data on that?
• 6. You have at times reported no adverse events in SCOTS, but some patients who participated in SCOTS have chosen to publicly self-report negative outcomes that they believe they experienced and in at least one case reported by the Sun Sentinel an independent physician Dr. Albini examined a SCOTS study subject and Albini is quoted as attributing the scarring likely to the transplanted stem cells. How should those of us in the stem cell field who are not involved in SCOTS reconcile these differences?
• 7. That Sun Sentinel article also raised questions over whether some of your patients were properly consented (http://www.sun-sentinel.com/health/fl-fea-florida-stem-cell-clinics-20171130-story.html). Can you please clarify that?
• 8. Do you have control subjects (e.g. matched, but who do not receive the stem cells) in your trials so you can rigorously assess the outcomes specifically related to the stem cell injections?
• 9. There have been some reports that you do bilateral transplantation of stem cells into both eyes. What is the rationale for that? Doesn’t that raise risk when using an investigational therapy?
• 10. It appears that to participate in SCOTS, patients must pay as much as $20,000 each to enroll. In general, there are bioethical concerns and debate over patients having to pay for enrollment in investigational trials. What’s your rationale for requiring payment? How did you determine the amount that patients pay?
• 11. In a trial that requires payment, what steps do you take to avoid that financial aspect introducing bias into the trial? For instance, do you have third parties who have no financial interest in the outcome of the trial be the ones who determine patient outcomes? Do you plan double-blinded studies in the future?
• 12. Do you have an FDA IND and/or BLA? If not, why not? Do you view your stem cell product in the manner you use it as not being a drug requiring pre-market approval by the FDA? If so, why?
• 13. Have you communicated with the FDA about your trials in the past and if so, how did that go? Are you in regular communication with the agency at this point? Has the FDA visited you and/or SCOTS locations?
• 14. How do you view recent FDA final and draft guidances on homologous use and minimal manipulation of stem cells?
• 15. What’s your view of the hundreds of “stem cell clinics” across the U.S. today selling a whole range of stem cell types for dozens of medical conditions? What makes SCOTS/SCOTS2 different in your view?