I have just come back from a 3-week lecture tour of South-Eastern Australia supporting the cause of the charity Mind Medicine Australia (MMA).
They have been raising money for psychedelic research for about 4 years with considerable success. Through their efforts, the Australia government last year put up $15 million for psychedelic research and seven grants have been funded covering either psilocybin or MDMA in disorders such as treatment-resistant-depression, PTSD, anorexia, addiction and OCD, several of which I am acting as an advisor to. So, it was good to catch up with these researchers as part of my tour. MMA have organised and paid for the importation of GMP supplies of both psilocybin and MDMA. Medical-grade psilocybin has now been imported into Australia with medical-grade MDMA ready for importation, so the research is good to go once all necessary approvals have been obtained.
But the main point of my visit was to raise awareness of the current research situation for both psilocybin and MDMA, putting it into context for donors (MMA is a charity), researchers, clinicians and most importantly regulators. I gave over 15 talks to a total of over two thousand members of the public, hundreds of academics and 130 members of the TGA and the Commonwealth Department of Health.
In a demanding schedule, I gave a public lecture in Byron Bay, Canberra, and several in Sydney and Melbourne as well as to the controller of the national drug regulatory system the TGA. In addition, I met with several State health ministers, Commonwealth and State policy advisers and lead psychiatrists. In these lectures [please see summary on the MMA website]. I exploded the long-standing myths of the harms of the medicines and shared the new clinical trials and brain imaging data.
A major reason for my visit was to support local psychiatrists who have been campaigning for several years for compassionate access to psilocybin and MDMA for patients who have failed to respond to conventional therapies. Australian Federal regulations allow these drugs for compassionate use but till now, for reasons that are unclear, not one State or Territory nor the Military medicine organisations have allowed this. After discussions with several of the State and National leads for psychiatry as well as representatives of the RANZCP it became clear that many of the historical myths of these drugs were still being used to defend the lack of action. Myths such as: they are very harmful, addictive and there are safer alternatives.
I learnt from the partner of one man with depression who was denied psychedelic therapy despite having failed to respond to 96 ECTs and 24 TMS treatments and over 40 different medicines who then killed himself in despair. One has to ask what purpose was served by denying compassionate access to this man? Is there anyone who could reasonably claim that 96 ECTs might be more effective and safer than a single dose of psilocybin? My sense is that professionals were preferring to defend decisions made decades ago on the basis of limited and often false evidence rather than accept that there is now sufficient evidence of efficacy and safety in resistant depression for psilocybin and in PTSD (many trials including a phase 3 one).
To overcome this impasse MMA has made available one million dollars for an open observational study of these treatments given for compassionate access in these treatment-resistant conditions — providing real-world evidence [RWE] data in treatment-resistant patients. The terms of trial entry are listed below. The outcome data will be curated in an independently managed Register hosted at Monash University. This will use the latest adaptive and Bayesian stats methods to provide regular updates on outcomes and adverse effects. This will be the first such RWE trial in psychedelic-assisted therapy in the world and will provide vital corollary data to support the ongoing RCTs, so allowing optimal clinical roll-out once they achieve marketing authorisation. And till then they will offer hope to hundreds of Australian with mental illnesses not amenable to current treatments.
The MMA RWE Research Proposal
Background: MMA has set up a world-leading training course that has trained several hundred potential therapists. They have many hundred psychiatrists ready to engage in the trial. They have also engaged Ambassadors and an Advisory Panel of top international experts and patients and relatives with lived experience.
MMA has arranged for the import into Australia of medicinal grade psilocybin and MDMA for compassionate use to be provided for the trial
The RWE protocol for treatment-resistant patients requires for each patient
a. approval of diagnosis and treatment plan
i. by the TGA
ii. and by an independent psychiatrist
b. The treatment administering psychiatrist has been trained in whichever medicine is to be used
c. Drug treatment is given to standard protocols including preparation and integration sessions
d. For the whole period of the drug treatment session there are two health care professionals present
e. The drug treatment session is filmed for safety reasons
In addition:
A Register of Patients who are given this therapy will be set up at Monash University:
i. Entering this register will be a requirement for treatment [though patients will be anonymised] –
ii. Patients will give informed consent as the treatment is off-licence
iii. The register will contain pre-and post-treatment data including standard measures of illness severity
iv. Data collection on any adverse effects
v. Patient-reported outcomes especially quality of life and other relevant outcomes e.g. sleep and wellness scores
The register will provide an independent report in a regular fashion on outcomes and safety data distributed to all stakeholders on a regular basis
Clinical efficacy will be evaluated using adaptive and Bayesian methods that have been shown within another compassionate-use clinical-register program to provide the most optimal statistical evidence of efficacy
We believe that with the above in place, psilocybin and MDMA can be administered safely to patients who have been failed by current treatments.
This compassionate use programme for treatment-resistant depression and PTSD with a Register which is constantly updated will be the first of its kind in the world. As well as helping many hundreds of patients who are currently failed by psychiatric medicines and/or conventional therapy, it will provide critical Real World Evidence (RWE) of the value of these treatments that will make a significant contribution to the growing clinical knowledge derived from commercial and other RCTs on these medicines.
RWE is now being acknowledged as a vital part of the overall evidential base for new medicines development and roll out. The former head of the UK NICE and MHRA Sir Michael Rawlins said this in his RCP Harvey Lecture in 2008: [1]
“Randomised controlled trials, long regarded at the ‘gold standard’ of evidence, have been put on an undeserved pedestal. Their appearance at the top of ‘hierarchies’ of evidence is inappropriate; and hierarchies, themselves, are illusory tools for assessing evidence. They should be replaced by a diversity of approaches that involve analysing the totality of the evidence base.” As a result, the UK NICE and MHRA are now asking for RWE as part of decision-making [2]. It seems likely other national regulatory authorities will follow suit.
References
- Rawlins, M. (2008) De testimonio: on the evidence for decisions about the use of therapeutic interventions The Lancet Dec 20;372(9656):2152–61. DOI: 10.1016/S0140–6736(08)61930–3
- https://www.nice.org.uk/corporate/ecd9/chapter/introduction-to-real-world-evidence-in-nice-decision-making