Bioethics is an area of deep personal interest to me, and it is something that has challenged me many times in my entrepreneurial career. There are always opportunities to cut corners, to be “selective” with information, to be biased in decision making. Biomedical research and product development is tough because the dollars at stake are huge and the barriers to success are vast. This means that sometimes even good people can make bad decisions.
I have previously written about my position on Australia’s regenerative medicine industry. It is surprising how we really do lead the way in terms of “quackery”, both in private clinics and through fairly dubious public companies like Regeneus, Cynata and, even to an extent, Orthocell. Given the clear importance of regenerative medicine, tissue engineering and stem cells to the future of human health, I believe we absolutely do need to get this right. The impact of getting it wrong is not only disastrous for our economy, but it can set the whole field back by a decade if we are not careful. Either investors will simply get turned off by the idea that this is something worth putting money behind, or at the more nefarious end of the spectrum, patients get hurt. Remember what happened with TeGenero? It arguably set us back by 10 years on the immuno-oncology front. The remarkable hubris of gene therapy pioneers and the death of Jesse Gelsinger is the reason why gene therapy has been slow to take off, despite the obvious need.
In Australia, we have a unique “peril” at the moment. It relates to the misconception that an “ethics approval” means good science and good clinical practice. I wish it did, and it should, but in reality – it doesn’t. There have been two recent examples of where an ethics approval from an independent NMHRC-accredited firm has been effectively commercially touted as an endorsement of good science. I have previously reported on Regeneus’ RGSH4K ACTIVATE study (ACTRN12615000516583) and the company’s positioning that this ethics approval was somehow a major commercial inflection point. Despite several attempts to obtain a copy of the patient information and consent form (PICF) from the HREC (Bellberry), the principle investigator (Prof. Stephen Clarke) and the company itself, I was unsuccessful.
Why did I want the PICF?
Because I wanted to understand how the company explained to patients the nature of the study, the risks of the study, and the management of any potential conflicts of interest between the institution running the study and the sponsor (Regeneus). There is plenty of confidential information around a clinical trial that rightly – in the interest of the trial, patient confidentiality and commercial sensitivity – must be kept utterly confidential. But the PICF is not really a confidential document, it is a public-domain document, because patients don’t sign a confidentiality agreement to look at a PICF. Patients do enter into patient-physician confidentiality to discuss the relevance of the PICF to their individual circumstances, but the document itself is not bound by this confidentiality. In my opinion, a PICF is a discoverable document and any organisation that is overly cagey about sharing this document has something to hide*.
More recently, another firm, “The MasterCell Stem Cell Centre” and “Australian Custom Pharmaceuticals Pty Ltd” received ethics approval (also from Bellberry*) for an adipose-derived stem cell trial in multiple sclerosis (MS). You can see the details on ANZCTR (ACTRN12615000687594). Frankly, if I managed to convince you that the Regeneus study was shocking in its complete and utter lack of scientific merit, this study will blow your mind. In this study, an “all comers” cohort of MS patients are eligible to have their disease treated by an adipose-derived (fat) stem cell “extraction” mixed with a bunch of “peptides” (not disclosed) and some platelet-rich plasma. The whole shooting match is then irradiated, filtered and intravenously injected. All of this is done in a shopping centre in Broadbeach (Gold Coast) and – most disturbing of all – “patients are required to contribute to the trial cost”.
This is not a “clinical trial”, this is nothing more than an ethics-approved money-making scam.
Now, you don’t have to be an expert in MS to understand that this is pure bullshit and quackery. This treatment doesn’t even expand the pool of cells to make sure there are enough of those little stem cell doodads to have any “immunomodulatory” value (“non-expanded”). There is no segmentation of the patient population whatsoever, a major issue for a serious disease such as MS where severity fluctuates constantly. As such, without careful patient selection, a number of patients are of course going to “improve” in the course of taking the therapy. Imagine what a few good testimonials is going to do for business? Especially since the “MasterDerm” clinic offers so many other treatments. Maaaate, I reckon if you can patch up someone’s MS, fixing someone’s boner or bald-spot is going to be a no-brainer, right? Moreover, the summary on ANZCTR actually includes factually incorrect information regarding treatment safety, “recent research and clinical evidence has demonstrated that human adipose-derived stem cells are safe for use in humans and can regulate the operation of the immune system and ameliorate degenerative activity”. This statement helps you to understand why I care deeply about reading the PICF for these studies. It is likely that this same garbage is regurgitated to a patient on the consent form, when the whole purpose of the consent process is to inform the patient of the risks.
How on earth can an ANZCTR entry or a consent form inform a patient of the safety of an unproven, untested experimental drug?
Both Regeneus and the MasterCell Stem Cell Centre have done something clever – but also intrinsically unethical. It doesn’t matter that one company is private (with some non-profit “foundations” on the side) and the other is public, the same principle applies. What these commercial organisations have done, is use a 3rd party HREC to legitimise their highly questionable business activities. I must confess I have always had a weakness for Brazilian women, but Dr. Sorya Felix is completely and utterly unqualified to treat MS patients. Regeneus also has no evidence whatsoever that RGSH4K has any clinical merit. Safe? Perhaps. Efficacious, no. But because both organisations managed to get Bellberry to grant them an ethics approval, they are – in the eyes of the patient – legit.
I want to say one last thing for the avoidance of doubt. I reached out to Bellberry several times and I found them to be professional, diligent and highly-responsive. They are also clearly protecting their client’s interests, which is appropriate. I found Bellberry’s CEO, Kylie Sproston, to be extremely professional. I don’t believe that Bellberry has any fundamental flaw in its HREC process or protocols/SOPs. I do think Bellberry probably suffers from a lack of depth in its medical advisory and a lack of experience in dealing with regenerative medicine / stem cell ethics reviews, especially in specific disease areas like MS. If it did have a depth of clinical domain knowledge in regenerative medicine, there is no way these studies would have been approved.
Additional note (06/08/15) : I have had a follow-up from Kylie Sproston at Bellberry who clarified that the MasterDerm HREC approval has, in fact, not yet been granted (Regeneus has) but is pending review. She also noted that the ANZCTR entry is somewhat challenging for patients to interpret and she has provided feedback as such to ANZCTR. I wish to express my appreciation to Bellberry for the clarification, and hope that we may see the right outcome for this study (i.e. it should, under no circumstances, proceed).
*I had several interactions with Regeneus management team about this issue and, as I have said, was not successful in obtaining a copy of the PICF. I was assured that any possible commercial conflict of interest between Regeneus, the investigators, and the institutes involved in both the origination of the intellectual property and the conduct of the study was appropriately managed. In fact, I was informed that there was no conflict of interest.
I accept this at face value.