Navigating 4 key kinds of stem cell studies

kinds of stem cell studiesOver the years and in particular after Dr. Oz’s show a couple weeks ago, I’ve heard from many patients who are absolutely convinced that stem cell therapies do in fact work and are safe. They have been focused particularly on hematopoietic stem cell therapy (HSCT) for MS but also other investigational applications using a variety of stem cell types including adipose stem cells.

Almost without exception the kind of stem cell therapy that patients are referring to in these cases are not conclusively proven to work and be safe. In certain instances the type of stem cell therapy some patients mention are not the same kinds of stem cell therapies as what Dr. Oz and his guests were criticizing. We all need to keep in mind that there are different stages to or kinds of stem cell therapy studies.

What are the main different types of stem cell therapeutic studies? How do we tell the differences and what benefits/risks are possible with each type to patients?

First, there are preclinical studies, which can range from work done in a test tube to cells in a dish to transplants in rodents or other research animals. This kind of research can be exciting and lay the foundation for clinical work. On the flip side, some times it can be hyped as being very close to leading to a human therapy. For instance, just because a paper shows that a certain type of stem cell may have benefit in cells in a dish or in rats doesn’t mean it will do the same in people. Often it won’t. But this kind of research is an important first step even it doesn’t mean a human therapy of the same kind is near on the horizon. So for most patients, this kind of stem cell work is not the basis alone for a therapy you will get any time soon or at least it shouldn’t be, but it is worth paying attention to as part of one’s ongoing stem cell “homework”. The risk at this level is giving patients too much unsupported hope. Yes, this category could probably be subdivided into many categories (e.g. in vitro vs. in vivo, etc.), but hopefully you get the point that this is foundational work overall.

Early phase clinical trials are designed to learn more about the drug in question (yes, stem cells can be drugs) such as its pharmacological properties in vivo and especially its safety. The main question at issue here is in fact whether a therapy has adequate safety.  These studies generally will not use placebo control. When most people refer to early “clinical trials” in the US, they mean FDA-approved trials with INDs in place before even one patient gets involved. I believe this is the most appropriate definition of an early clinical trial. Patients who enroll in early trials are taking risks for the benefit of others and to advance knowledge so I think of it as somewhat of a heroic act.

A concern is whether in some instances those who will be administering the investigational therapy will conduct proper consent. Sometimes there could be, perhaps even unconsciously, some indication given to the patient that they derive some medical benefit from an early trial even though these trials aren’t designed to test efficacy and often use sub-clinical doses. Open-label studies can lead to placebo effects or other confounding outcomes. Patients should not have to pay to enroll in these.

Later phase clinical trials further test safety and now start to tell us as a community about efficacy too. The gold standard is the RCT or randomized controlled trial. In these trials, patients can be in control groups (placebo or standard of care) or receive the therapy being tested such as an investigational stem cell drug. Patients are not typically charged for these also, except under what are supposed to be very rare instances pre-approved by the FDA. If conducted rigorously and yielding successful results, in the end these trials can fairly definitively demonstrate that something is safe and effective. Even then, sometimes safety issues can arise later with more widespread marketing and use as we’ve seen with various non-biological drugs, but that’s fairly rare.

Now moving outside the FDA-approved clinical trials process for the fourth kind of experiment….

Stem cell clinic’s “trials” are a different kettle of fish stem cells. In my opinion these are designed in many cases primarily to generate income taken from patients for the benefit of the for-profit businesses running them. Sometimes those running them truly believe the offerings work. Only very rarely (I would estimate ~1% of the time) here in this domain is data ever published.

Patients have to pay to get the experimental offerings from clinics. Also, these experiments usually do not have preclinical data to strongly support them, they lack control groups, they in some cases enroll large numbers of patients for no defined scientific/medical reason, most often they are not FDA-approved, and usually do not have data released publicly or subject to objective peer review by the wider stem cell community.

Now if a stem cell clinic publishes their study data in a legit peer-reviewed journal, even if it is not data from a RCT and even if it isn’t in some fancy top-tier journal, this can be useful for the community and some credit is due. Publishing in a peer-reviewed journal is not only a valuable step scientifically and medically, but also it means that the patients taking risks by being involved in this (and paying for it) are given an additional level of respect in that the information from their participation can help others.

Bottom line

Taking a probing, critical look at the different kinds of stem cell offerings out there such as those falling into one of the four above sections discussed above, is just practicing good science and medicine. Science is all about asking tough questions.

I understand that for some individual patients it may be only human nature to want to defend that “thing” such as an experimental stem cell offering that they believe helped them, but these things have to be rigorously proven and those administering (and in some cases profiting from) as yet unproven stem cell clinical offerings should be open to answering a range of questions. This goes across the board from stem cell clinics to those running FDA-approved clinical trials with INDs — so there’s no double standard!

Kudos to Dr. Oz for stellar stem cell clinic show: time for more action

For me it’s been a wild week of grant and paper writing, grant review, going over data, and more, but finally I had a chance to watch this week’s Dr. Oz show on stem cell clinics in full last night and I give it an A+ grade.

dr-oz-stem-cells

A show producer went undercover with an MS patient to a number of stem cell clinics and let the clinic people’s words do the talking about what’s most important to the clinics: money and not patients’ well-being.

The guests on the show included actor and MS patient Montel Williams and stem cell scientist Dr. Sally Temple, the President of ISSCR. They and Dr. Oz all did great on covering this issue. A special shout-out to Sally Temple for doing the show. Not many leading scientists are willing to put themselves out there to make a difference like that.

The show combined science, medicine, and compelling personal stories together with the undercover videos to expose the stem cell clinic industry for what it actually is: an endeavor almost solely focused on making money taken from vulnerable patients. It’s an industry that collects tens of millions of dollars from patients for experimental offerings that have little-to-no data behind them. No FDA approval.

And there have been bad outcomes ranging from deaths to blindness. Tumors.

If certain stem cells work and are safe for specific medical conditions, you must prove it scientifically and medically, and you have to do that first before you start marketing it. This means putting patients before profits.

Many biotech companies are doing exactly that and there are a host of promising investigational stem cell therapies in various clinical trials. Some will be proven safe and effective, which is so exciting! Others won’t work out. We can’t know the difference in advance of getting the data, but stem cell clinics are pretending they know their stuff works and is safe.

What do I say to patients who believe that the offerings of stem cell clinics do work?

Each of us understandably place great weight on our own individual patient experiences, but the experiences of one, ten, or even many more patients don’t prove things if they aren’t studied carefully with controls and in an unbiased manner. In biomedical science we learn that often, even if we are excited about an idea/hypothesis, once we carefully study our data collected from enough properly controlled experiments and it all gets examined critically by qualified colleagues, we end up being proven wrong. Sometimes we are right. The key thing is you have to let data tell the difference rather than hope or belief.

I appreciated how Dr. Oz issued a call to action at the end for his wide audience to tackle the major problem of stem cell clinics. We all need to work together on this. There’s going to be major positive impact from the show as a starting point to more action that involves the FDA, the FTC, and other governmental agencies such as state attorney generals and medical boards.

Dr. Oz Explosive Exposé on Stem Cell Clinics Airs Tomorrow

American stem cell clinics put thousands of patients at risk each year through hawking expensive, unproven and unapproved medical interventions, and now Dr. Oz is reportedly taking them on in a new show set to air tomorrow. dr-oz

Those running the clinics have affixed the buzz phrase “stem cells” onto a whole range of stuff ranging from A (actual stem cells, but unproven) to Z (zombie cells; aka not really living cells of the stem cell variety.)

While at times in the past the Dr. Oz Show has been criticized for how it discussed unproven health interventions, from what I can tell on the stem cell front now, they are very serious about exposing how risky the stem cell clinic industry has become.

A clip of the Dr. Oz show I was able to see in last week was striking. Another clip above from the show of Montel Williams is quite intense.

I was able to get this quote from Dr. Oz himself about this situation and the show:

“These stem cell clinics are using the potential of legitimate research to take advantage of patients desperate for help. These physicians are violating not only the trust of their patients but also the law and hopefully our show will push the FDA to use its authority to shut them down.”

I’ve set my DVR to record it. If you have any interest at all in stem cells as a patient, scientist, physician, student, grant funder, science writer, FDA person, FTC person, etc., you should check this out.

Dr. Sally Temple, President of ISSCR, is also on the show. I’m told that the stem cell clinic segment will be the second half of the show.

Doctors call for Dr. Oz to be booted from Columbia

DrOZControversial TV physician Dr. Mehmet Oz hasn’t had a great year what with his disastrous testimony before Congress.

Now Dr. Oz has been slammed by a group doctors from across the country. Update: Orac points out that these doctors have some of their own baggage when it comes to science.

They reportedly want him removed from Columbia because of alleged quackery.

These other doctors who want Oz’s neck don’t mince words according to the NY Daily News:

“He’s a quack and a fake and a charlatan,” said Dr. Henry Miller of Stanford, the first person to sign the poison-pen letter.

No pulling of the punches there by Miller (pic below).

That’s got to hurt for Oz, especially with other events this year including the green coffee bean scandal, a story broken by Ivan Oransky.
henry miller stanford

His Congressional testimony performance was a far cry from his bombastic circus-like persona in his TV show.

Before Congress, he was rather meek and couldn’t really defend himself from charges that on his show he sells hype and could be misleading his audience. This contrast was reminiscent of the scene in The Wizard of Oz when the wizard is revealed for what he really is behind the curtain.

I haven’t been an Oz fan myself to put it mildly, in part because he did a terrible performance on stem cells with Michael J. Fox on Oprah.

Miller of Stanford Med School explained his thinking on why Columbia has chosen to keep Oz:

“I think I know the motivation at Columbia,” he continued. “They’re star-struck, and like having on their faculty the best-known doctor in the country. But the fact is that his advice endangers patients, and this doesn’t seem to faze them. Whether they’re hoping Oprah will come and endow a center for homeopathic medicine, I don’t know.”

It seems like Oz has sort of had his cake and eaten it too over the years. Being a real doctor at Columbia and then playing this wizard-like showman on his TV show. Will that dual life end? Maybe not any time soon.

Columbia continues to defend him:

“Columbia is committed to the principle of academic freedom and to upholding faculty members’ freedom of expression for statements they make in public discussions,” said Columbia University Medical Center spokesman Doug Levy.”

Here is the full text of the letter as posted on the Washington Post website:

Lee Goldman, M.D.
Dean of the Faculties of Health Sciences and Medicine
Columbia University

Dear Dr. Goldman:

I am writing to you on behalf of myself and the undersigned colleagues below, all of whom are distinguished physicians.

We are surprised and dismayed that Columbia University’s College of Physicians and Surgeons would permit Dr. Mehmet Oz to occupy a faculty appointment, let alone a senior administrative position in the Department of Surgery.

As described here and here, as well as in other publications, Dr. Oz has repeatedly shown disdain for science and for evidence-based medicine, as well as baseless and relentless opposition to the genetic engineering of food crops. Worst of all, he has manifested an egregious lack of integrity by promoting quack treatments and cures in the interest of personal financial gain.

Thus, Dr. Oz is guilty of either outrageous conflicts of interest or flawed judgments [sic] about what constitutes appropriate medical treatments, or both. Whatever the nature of his pathology, members of the public are being misled and endangered, which makes Dr. Oz’s presence on the faculty of a prestigious medical institution unacceptable.

Sincerely yours,

Henry I. Miller, M.D.
Robert Wesson Fellow in Scientific Philosophy
& Public Policy
Hoover Institution
Stanford University
Stanford, CA

Scott W. Atlas, M.D.
David and Joan Traitel Senior Fellow
Hoover Institution
Stanford University
Stanford, CA

Jack Fisher, M.D.
Professor of Surgery (emeritus)
University of California, San Diego
La Jolla, CA

Shelley Fleet, M.D.
Anesthesiologist
Longwood, FL

Gordon N. Gill, M.D.
Dean (emeritus) of Translational Medicine
University of California, San Diego
La Jolla, CA

Michael H. Mellon, M.D.
Pediatric Allergist
San Diego, CA

GIlbert Ross, M.D.
President (Acting) and Executive Director
American Council on Science and Health
New York, NY

Samuel Schneider, M.D.
Psychiatrist
Princeton, NJ

Glenn Swogger Jr. M.D.
Director of the Will Menninger Center for Applied Behavioral Sciences (retired)
The Menninger Foundation
Topeka, KS

Joel E. Tepper, M.D.
Hector MacLean Distinguished Professor of Cancer Research
Dept of Radiation Oncology
University of North Carolina School of Medicine
Chapel Hill, NC

Ear-itating: Awesome Oliver Invokes Vacanti Mouse While Blistering Dr. Oz

Comedian John Oliver has an absolutely blistering segment (see below) on Dr. Oz in which he skewers the physician huckster.

The video includes incredibly telling Oz testimony before Congress in which the celebrity doctor seems frankly pretty pathetic and cannot answer even simple questions about his selling of arguably snake oil on his show.

Oz likes to use words like “magic” when grossly hyping alternative medicine on his show as though he were the Wizard of Oz or something, but before Congress you could say he wasn’t in Kansas (the safe environment of his show) anymore.

How did a smart, caring physician get so far removed from evidence-based medicine that he is leading millions of his viewers astray? It’s hard to say. Also Dr. Oz claims that he makes no money from the products that he pitches on his show so one has to wonder what the heck is his motivation for being so extreme on his show? Given his talents and his audience he has the power to do so much good via education, but mostly this doesn’t happen. Is there any hope he’ll turn it around to be more positive? I doubt it.

Making it all the more interesting from our stem cell-centric universal view is that while revealing Dr. Oz for what he really is, Oliver refers to the famous “Vacanti mouse” (which had a sort of engineered human ear-like thingy grown on its back) created some years ago in the lab of Charles Vacanti, of more recent STAP cell fame.

At least that was my interpretation of what Oliver said.

Mouse support groupWatch starting right around the 3:00 time point in the video for this reference when Oliver invokes the concept of a mouse support group (see video screenshot image at left) in which one of the mice says:

“I have an ear growing out of my F’ing back!”

Sounds like the Vacanti Mouse to me. I don’t know of a whole lot of mice with ears growing on their backs.

Who knew that there would be some link, no matter how indirect, between STAP cells and Dr. Oz?

You can read about how Dr. Oz has been completely wrong about stem cells in the past in a rather dramatic way on Oprah’s old show and my thoughts on that here.