Navigating 4 key kinds of stem cell studies

Over 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!