The ability of stem cells to divide into different mature cell types has ignited the field of regenerative medicine. Stem cells promise to repair and regenerate damaged or diseased tissues without the need for orthodox medical or surgical interventions.
However, there is disparity between the expectations held by the general public and some medical professionals versus the reality of the emerging clinical evidence. This disconnect was highlighted recently by the case of three elderly patients who were blinded by the use of an unproven stem cell therapy at a clinic in Florida, USA (BioNews 893).
While stem cell therapies in the field of haematology are showing promise, there are still many challenges in using them in any other disease models. In some countries, medical professionals are using unproven stem cell therapies as medical procedures to treat patients in lieu of conventional treatment pathways. What is more, these practitioners are operating under the premise of a trial.
Proponents of using stem cell therapies outside the context of a true clinical trial believe that these therapies are inherently safe, particularly if the stem cells derive from the individual patient themselves. And the medical professionals offering unproven stem cell therapies are convinced that the potential benefits of undergoing the therapy far outweigh the potential risks.
These benefits are used as an argument to forge ahead with unproven therapies outside of clinical trials, as regulatory bodies are often to slow to regulate for the fast-paced field of regenerative medicine; gaining regulatory approval is usually a lengthy and costly process. And the regulation that is in place is often narrow in scope and does not account for the variety of products and manipulative techniques used in the field.
An anecdotal account of a stem cell therapy’s potential to cure a disease, however, does not make for an adequate standard of evidence. In the Florida case, three elderly patients with a progressive eye disease sought out an unproven stem cell therapy. The clinic involved was offering the therapy under the guise of a trial, however the patients had to pay for the procedure (in itself a 'red flag') that promised to 'cure' their disease. The therapy not only failed, but all three patients are now blind as described in The New England Journal of Medicine on 16 March.
Referring back to the disparity in expectations, how the word 'trial' is understood helps to clarify the basis of the disconnect between the public and clinicians, and emerging evidence. The word 'trial' in the sense of a clinical trial calls for a robust experimental framework and sets of regulations and standards that safeguard the enrolled patients' rights and overall health. Furthermore, trials are performed in a phased manner to ensure any potential risks are minimised. The results generated from a certain phase informs the researchers as to the most effective way to proceed – or indeed not proceed.
Using the word 'trial' in the sense of administering a therapy outside of the setting described above, however, only truly refers to the inherent risk of the therapy not working. Moreover, when being administered by a trusted medical professional, the harms of the therapy are often overshadowed by the promise of a 'cure' relayed by these professionals.
The differences in the interpretation of the word trial among medical professionals is reflected by the lack of strict regulation among professional bodies, such as medical councils and regulatory bodies including the Food & Drug Administration (FDA). While the FDA, for example, has published more specific guidelines in October 2015, these are unenforceable on a global scale.
Interestingly, on a regulatory level, there are opportunities afforded to medical professionals to use unproven stem cell therapies outside the context of a clinical trial as noted in the International Society for Stem Cell Research (ISSCR) 2016 guidelines:
...the ISSCR acknowledges that in some very limited cases, clinicians may be justified in attempting medically innovative stem cell-based interventions in a small number of seriously ill patients.
However the ISSCR goes on to clarify that it 'condemns' the use of unproven stem cell therapies in any other setting where clinical need is not deemed serious.
In relation to classifying unproven stem cell therapies as a medical procedure, the 2014 United States of America – v – Regenerative Sciences, LLC et al case dealt with the use of mesenchymal stem cells taken from a sample of a patient's own bone marrow to treat their own orthopaedic disorders. In this case, the court was not convinced that manipulating stem cells outside the body and reintroducing them to the patient was a matter of standard 'medical procedure', as argued by the company Regenerative Sciences LLC. Instead, the court upheld the FDA’s right to regulate the manufacturing (or manipulating) of these stem cells: however cases where there is significantly less manipulation of stem cells are yet to be tested.
Issues remain regarding how best to regulate the use of stem cell therapies, particularly in the early phases of their development. There have been calls for strict regulation through bodies such as the FDA, but others argue that strict regulation will only curtail the benefits stem cell therapies can impart. On the other hand, regulations that are too lenient, it is argued, will only harm the patient seeking the therapy, as a solid evidence base will not yet have been compiled for the therapy.
Finding a regulatory middle-ground for unproven stem cell therapies is going to be a challenge. Some believe that the most pragmatic way forward is to introduce regulations through medical professional bodies. These regulations would be broad in scope regarding unproven therapies, but would place a strong emphasis on ensuring the therapy is as beneficent as possible, and that patient autonomy is upheld throughout.