Desperate times ask for…medical innovation.

On 26 October 2014 Gordie Howe (86), better known as “Mr Hockey” in Canadian ice hockey circles, suffered a debilitating stroke that left him bedridden and barely able to talk or eat, before suffering another stroke early in November 2014. But within days after receiving stem cell treatment he miraculously recovered to the extent that he could mobilise independently, recognise speech forms such as proverbs and idioms, interacted more and was less difficult to understand.

This is the kind of hope and hype desperately ill patients cling to when it comes to the translation of stem cell treatments. However, the treatment Howe received, the processes he followed and the availability thereof to the general population must be clarified to prevent false hope and disillusioned patients.

Howe was entered into a federally licensed and Institutionally Review Board approved clinical stem cell trial at Novastem in Mexico. Novastem is approved for conducting clinical trials for several medical conditions, including stroke, by using allogeneic stem cells manufactured by Stemedica Cell Technologies (San Diego, Califoria) as licensed distributor thereof. As part of this clinical trial Howe was injected with neural stem cells into his spinal cord to help his brain to repair damage and received mesenchymal stem cells via intravenous infusion to improve blood circulation in the brain.

It is important to note that Howe received this stem cell treatment as a participant in a clinical trial and never bought any services or products as these specific stem cell treatments are not yet FDA approved and allowed to be commercialised. In South Africa, stem cell based treatments qualify as biological medicine in terms of the Medicine Control Council’s (MCC) Guidelines for the Registration of Medicines, because the active ingredient or key excipients have been derived from living organisms or tissues, or manufactured using a biological process. Government Notice R510, Government Gazette 24727, issued in terms of Section 14(1) of the Medicines and Related Substances Control Act 101 of 1965, also requires the registration of all biological medicines before it may be sold to the public.

However, very few stem cell based treatments have been registered and authorised for sale. Reason being that due to their relative novelty in science and the difficulty in controlling their self-renewal and differentiation, stem cells and their derivatives can behave very unpredictable and has not yet proved to be safe. Animal models of many diseases do not accurately reflect human diseases and is sometimes poor predictors of immune or biological responses in humans. The safety and efficacy of stem cell treatments in humans can only be proved through long, complex and rigorous preclinical and clinical studies which often include many setbacks and failures.

But upon considering the services offered on the website of Novastem (http://www.novastem.mx) it creates the impression that they provide proven stem cell treatments for a wide range of diseases. And here is where we find the devil in the detail. Stem cell treatments can only be offered for sale when its safety and efficacy has been demonstrated after thorough clinical trials in humans and approved by the applicable regulatory body, such as the Medicines Control Council in South Africa, the US Food and Drug Administration (FDA) or the European Medicines Agency (EMEA), for treatment of specific diseases.

In the absence of proven and registered stem cell treatments offered for sale, patients are left with one of two options to undergo regulated treatments.

The first option is to take part in a clinical trial, like Howe, if the patient complies with all the inclusion criteria of the specific clinical trial. In a interview with ESPN’s Keith Olbermann, Dr Maynard Howe (no relation to Gordie Howe), CEO and vice chair of Stemedica explained that Howe underwent stem cell treatment in Mexico as opposed to the USA due to the fact that the inclusion criteria for the clinical trial in Mexico allowed Howe immediate participation, where the inclusion criteria for the USA trail required a 6 months waiting period, leaving Howe with running the risk of not surviving until then.

The International Society for Stem Cell Research’s (ISSCR) Guidelines for the Clinical Translation of Stem Cells (2008) as well as the World Medical Association’s Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects (Brazil, October 2013) allow for a second option in the form of medical innovation. These guidelines recommend that only in exceptional and very limited cases, clinicians may be justified in attempting unproven stem cell based interventions in a small number of their patients facing some of the most intractable diseases confronting clinicians if it, according to the clinician’s judgement, offers hope of saving life, re-establishing health or alleviating suffering.

However, where clinical trials exclusively aim to produce generalizable knowledge, medical innovations primarily aim to provide new experimental forms, which safety has not yet been proven, of clinical care that have a reasonable chance of success for individual patients with few or no acceptable medical alternatives. Thus the mere fact that a procedure is medically innovative does not qualify it as clinical research, and vice versa.

But having regard to the current unpredictability of stem cell treatments, as discussed herein above, these treatments may inadvertently violate a physician’s ethical obligation to “do no harm” by producing more injury than benefit and is medical innovation therefore subject to even stricter scientific and ethical review. The ISSCR guidelines specifically recommends that innovative stem cell based treatments may only be undertaken if a peer reviewed written plan of the treatment exists which explains the chances of success, why the proposed intervention should be attempted, the types of cells being transplanted, how the cells will be administered and a plan for clinical follow-up data collection to assess the effectiveness and adverse effects of the cell treatment. Further considering that cellular transplants will persist for many years in patients with irreversible actions, South Africa’s HPCSA’s Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa (2006) stipulates that provision must also be made for the long term monitoring and care of patients undergoing innovative treatments.

Before consenting to such risky treatments and to ascertain the legitimacy of the purported attempts at medical innovation the ISSCR brought out a Patient Handbook on Stem Cell Therapies (2008) which briefly explains in layman’s terms what stem cells and stem cell therapy are, the whole clinical trial process and reasons for it, what information must be provided to consider giving informed consent and most importantly, what needs to be considered carefully to satisfy oneself that any proposed stem cell treatment, albeit via clinical trial or medical innovation is safe and legal. Such considerations include, amongst others, claims based on patient testimonials, multiple diseases treated with the same cells, the source of the cells and how the treatments will be administered, whether it is clearly documented and alleged claims of no risks.

It is thus advisable to consult both a stem cell specialist and biotechnology law expert before embarking on medical innovative treatments to ensure that the purported treatments are safe and legal and not founded on hype alone.

By Marietjie Botes
marietjie@dyason.co.za