Drug or Procedure? Does It Matter As Long As It Works?

A recent article in NPR resurrects an important, controversial issue for the FDA - stem cell treatments.

Often considered the body's "master cells", stem cells help form and repair damaged tissue in the body. The most potent, embryonic stem cells, can essentially differentiate into any other kind of cell - potentially allowing them to regenerate tissue in the brain, the spine, or anywhere else. As the name implies, however, embryonic stem cells only exist in embryos, raising ethical concerns. Also, stem cells derived from embryos face the prospect of tissue rejection when placed in a new host, potentially requiring recipients to take dangerous immunosuppressive drugs for life. 

Adult stem cells, however, exist in tissue across the body. These cells, however, are more specialized and can only repair specific types of tissue. In 2011, Celltex Therapeutics was formed - the company offered a process that would genetically alter adult cells to have certain properties of embryonic cells. These cells would then be re-injected into the patient from whom they came. The thought was that this could help patients with a variety of chronic diseases - Multiple Sclerosis, Alzheimer's, Amyotrophic lateral sclerosis (Lou Gehrig's Disease) - if not curing the diseases, at least offering a potentially effective treatment where often none exist.

In 2012 the FDA identified over 30 violations at the Celltex facility, most of which pointed in one direction - that Celltex was marketing an unapproved drug. Under traditional FDA regulations, medical procedures (referred to as the "practice of medicine") are largely unregulated beyond basic sanitary standards, along with any regulations the FDA imposes specifically on the associated laboratory tools or devices involved in the transplant. This stance covered the gamut from bone marrow transplants to in-vitro fertilization.

However, the FDA has taken an increasingly aggressive regulatory stance towards physician offered stem cell therapies, based on the more than "minimal manipulation" standards (and indeed, FDA's very broad statutory authority) that would allow regulation of the process under CFR 1271.3(f)(1) (the section of FDA's regulations that deal with the use of human tissue). Under this statue, the FDA determined that Celltex fell short, and thus their process could be regulated as a drug.

While the FDA has shown promise lately by working to develop more adaptive standards for clinical trials, their position on stem cell treatments is rather worrisome. The fact is that stem cell treatments similar to the process that Celltex was offering have already shown promise; proving the efficacy in double-blind randomized clinical trials, however, is extremely difficult.

Many of the diseases that stem cells would help treat are orphan diseases (those with fewer than 200,000 patients in the U.S.), making recruitment for large-scale trials very difficult. And for people suffering from diseases like Alzheimer's, the risk-benefit often falls on the side of taking a chance with what may be unproven treatment.

Instead of forcing companies like Celltex (which is now moving their operations to Mexico!) to comply with narrowly defined trial guidelines, the FDA should make it easier for such treatments to receive approval through an alternative pathway that recognizes the difference between Celltex's process and a cancer drug.

This would require a pathway that is more conducive to Bayesian analysis - for instance, multiple "N=1" trials (where one person decides to try an unproven treatment - like Ms. Wilkinson from NPR's piece) could be used to gather data on fairly simple clinical or surrogate endpoints (in the case of Ms. Wilkinson, 11 out of 25 of her MS symptoms improved!). This data could be used to both validate new surrogate endpoints for future use, and to offer additional data to the FDA as approval is pending. Certainly, shutting down a lab without recognizing that physicians have been traditional innovators in the medical field - and still invent new surgeries without FDA regulation - seems like an extreme step. Surely there was a middle of the road approach that would have recognized the value of the procedure while warning patients that they were highly experimental and collecting additional data that could be validated through other means.

But more importantly, when it comes to dealing with a part of your own body (remember, Celltex was taking stem cells out of person A and putting them back into person A) it seems rather draconian to classify the product in question as a drug.

While the long-term efficacy of stem cell treatments may not be certain, there is much evidence showing at least some short improvements in patients that receive them. For those with otherwise untreatable diseases, this is undoubtedly a gamble worth taking.

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