A version of this article was previously published in Health Europa Quarterly issue 10.
Access to medicinal cannabis for patients was legalised in Australia in 2016, allowing doctors to request permission to prescribe from the Australian government.
Prescription occurs mostly on a case-by-case basis involving evidence that patients have failed to benefit from available conventional prescription medications. Since legalisation, a few thousand Australians have been prescribed a medicinal cannabis product.
Despite this, many tens of thousands of Australians continue to self-medicate with illicit medicinal cannabis due to the difficulty and cost involved in accessing a legal prescription. Additionally, doctors generally do not feel well-educated around the use of these products, with specialists often feeling that there is inadequate evidence to support their use in specific conditions.
The Therapeutic Goods Administration (TGA), Australia's medicines regulatory body (akin to the FDA in the USA and EMA in Europe), is currently collecting some potentially useful information from doctors prescribing medicinal cannabis. However, the TGA is not analysing or disseminating this information for use by health professionals or the patient community.
Here we explore how the Australian government might be missing a key opportunity for research into medicinal cannabis and what might be done to address this.
Patient access pathways
First we will explain how Australians obtain a medicinal cannabis prescription. Australia has chosen to incorporate medicinal cannabis into our existing health regulatory framework governing unregistered medicines. In Australia, drugs that doctors prescribe conventionally have obtained 'registration' with the TGA.
To obtain registration, a drug sponsor is generally required to run large-scale clinical trials proving safety and efficacy and provide the resulting evidence to the TGA. With one exception (Nabiximols, aka "Sativex"), this process has not been completed for any medicinal cannabis products in Australia. This means that the more than 50 other medicinal cannabis products available – including oils, capsules, sprays and botanical material – are 'unregistered' medicines.
There are two main ways Australian patients gain access to unregistered medicines: the Authorised Prescriber Scheme and the Special Access Scheme Category B (SAS-B). So far, around 60 doctors have been granted Authorised Prescriber status for a cannabis medicine, meaning they can freely prescribe to a specific class of patients directly under their care. Becoming an Authorised Prescriber is an onerous, time-consuming process and restricts the prescriber to one medicinal cannabis product and one patient class.
Authorised Prescribers are only required to notify the TGA within 6 months of prescribing an unregistered medicine to a patient. So accurately determining how many people are currently accessing medicinal cannabis through this scheme is difficult to ascertain, although it has been estimated to be between 20% and 30% of medicinal cannabis patients.
The bulk of patients receive access to products via the SAS-B pathway, which allows doctors to request a prescription for an unregistered medicine for a specific patient on a case-by-case basis. Approval is granted by the TGA, but may sometimes require additional State/Territory approvals depending upon patient location and product choice.
The number of individual approvals through the SAS-B pathway has increased from a handful per month in early 2018 to over 1,500 per month as of June 2019 (see Figure 1). Each approval represents a prescription authorisation for an individual patient, usually for an amount of medication that will last 6 months.
Clinical evidence gaps
Despite the substantial rise in monthly approvals, overall patient numbers are small. This is at least partly due to the unresolved questions about the efficacy of medicinal cannabis in treating many conditions.
Recently published reviews indicate modest-to-good quality evidence to support cannabis use in chronic non-cancer pain; multiple sclerosis spasticity; paediatric epilepsy; palliative care; and chemotherapy-induced nausea and vomiting (CINV). Summarised critical reviews of the existing clinical evidence for medicinal cannabis use in each of these five areas has been compiled by the TGA and comprises their 'clinical guidance' documents, which are publicly available.
Unsurprisingly, the indications with the highest quality of positive published evidence, and most supported by the TGA guidance documents, account for the majority of SAS-B approvals.
Figure 2 shows a breakdown of the SAS-B approvals from January 2018 to May 2019 showing a general upwards trend heavily skewed toward prescriptions for chronic non-cancer pain. (We should note that we were granted access to these data only after a formal Freedom of Information Request was approved in June 2019).
Additionally, there are a range of conditions where the clinical evidence for medicinal cannabis efficacy is minimal to non-existent (shows as 'Other' in Figure 2), yet doctors are using the SAS-B scheme to prescribe for these conditions, presumably based on their own research, patient demand, or trial and error (see Table 1).
Table 1. Breakdown of "Other" SAS-B approved conditions in total from November 2016 to the 31st of May 2019.
|Number of SAS-B approvals|
|Post-traumatic Stress disorder (PTSD)||111|
|Sleep disorders including insomnia||56|
|Autism Spectrum Disorder||25|
|Gastrointestinal Disorders (Ulcerative colitis, Crohn's disease, Irritable bowel syndrome)||23|
|Mood Disorder – Unspecified||19|
|Movement disorder – Unspecified||14|
|Rare neuromuscular disorders (Issacs, Kearns-Sayre, Motor Neuron, Stiff persons, PSP)||13|
|Behavioural problems (including aggression & agitation)||11|
|Restless Legs Syndrome||5|
|Panic disorder – Unspecified||2|
|Blood glucose management||1|
|Neurological disorder – Unspecified||1|
What data is being collected?
To prescribe via the SAS-B route, clinicians submit a standard application justifying the need for an unregistered medicinal cannabis product for an individual patient. The information provided to the TGA on all applications includes:
- The age and sex of the patient
- The primary medical indication justifying the application
- Details about their diagnosis and other co-morbid medical conditions, including the severity of their primary indication
- Details of previously attempted and failed treatments, and justification as to why no other TGA-registered medicines are appropriate
- Any prior SAS approval number (for renewals)
This information alone is quite informative and would provide a platform to better understand the types of patients receiving medicinal cannabis. Another key piece of information that could be extracted from the existing data is the number of renewals, or lack thereof, across indications.
A renewal could be taken as a proxy for the effectiveness of a medicinal cannabis intervention. Similarly, if there is an absence of renewals, then this might indicate a low level of success, or highlight other issues with the medicinal cannabis framework such as the cost of these products to patients.
Some SAS-B data, such as that shown in Figures 1 and 2, are being made available to researchers (such as our team) but only through Freedom of Information (FOI) requests. There is very limited information that the TGA proactively releases. We believe it would be most suitable for the TGA, as a trusted and well-respected regulator, to publish this information and a summary analysis on its website for the use of health professionals and researchers.
Who is monitoring patients?
Companies that have newly registered drugs are required to monitor patients for drug safety and efficacy ('pharmacovigilance'). The unregistered nature of Australia's medicinal cannabis products means this requirement is absent. And the TGA does not, and has no intention of initiating, its own pharmacovigilance program.
The TGA's stance on this issue is not surprising and is in line with their responsibilities as a regulator and not a drug sponsor.
Most medicinal cannabis companies are unlikely to register their products with the TGA anytime soon. Such registrations will likely be years from now, meaning data arising from tens of thousands of approvals and renewals will go unexamined in the meantime. This is the point at which unusual and unique circumstances require exceptional duties to be performed; something we hope the TGA will recognise.
The TGA is acutely aware of the fragile state of evidence for medicinal cannabis in many conditions, having commissioned clinical guidance documents for several of these. In the TGA clinical guidance document on chronic non-cancer pain, they state that the evidence is still lacking for many pain conditions and as such,
'There is a need for larger trials of sufficient quality, size and duration to examine the safety and efficacy of medicinal cannabis use in [chronic non-cancer pain]'.
We are now in a situation where over 1,000 Australians are prescribed a medicinal cannabis product for pain every month (see Figure 2.) Systematic monitoring of these patients would assist in building this evidence base, even potentially informing future updates to the TGA's guidance documents. In fact, the TGA have found analogous pharmacovigilance programs, in the form of registries, to be effective tools for assessing clinical safety in other therapeutic areas.
One Australian state is attempting to fill the data gap
As of January 2019, researchers from the Office of Medicinal Cannabis in the Australian State of Victoria partnered with several Australian universities to initiate The Australian Medicinal Cannabis Safety and Effectiveness Study. Every patient prescribed Schedule 8 medicinal cannabis (which includes all medicinal cannabis products except for 98%-pure cannabidiol or 'CBD' products) in Victoria can enrol, alongside their prescribing doctor, to provide data about the patient's concomitant medications, the condition they are treating, and how cannabis is affecting the progression of their disease and symptoms.
This State-driven approach faces its own problems. It requires doctors and patients to opt-in, and the State is not notified by the TGA to provide authorisation for Schedule 4 cannabis medicines (containing 98% cannabidiol or 'CBD'), so these approvals are lost. It is also limited to doctors and patients in a single State, missing out on the majority of Australian prescriptions.
Aside from this single State project there are several observational cohort studies emerging from newly-established medicinal cannabis access clinics. Such studies are either being sponsored by the clinic or the cannabis companies supplying the products.
This is helpful market research but potentially distorted by commercial conflicts of interest. And these organisations are not required to publish or make the source data publicly available for use in clinical guidance.
A missed opportunity
We reached out to the TGA for comment and they clarified their position;
'Reflecting the TGA's decision under the Therapeutic Goods Act 1989, whether to give SAS B approval to a medical practitioner for medicinal cannabis products for a particular patient, the TGA asks the practitioner to confirm that the benefits outweigh the risks for that patient. It does not collect historical observations of the efficacy of that product. It is also not authorised to require an applicant medical practitioner to report to it the efficacy, in the patient for whom the approval is sought, of the approved use. Subject to the Therapeutic Goods Act, the TGA may not separately use that information for an altogether different purpose. This 'SAS B data' is also separate to data collected under the adverse event reporting regime. The TGA is also not authorised to carry out clinical trials or prepare risk management plans.'
To put such a system in place would admittedly not be free and this is made even more difficult by the fact that the TGA is mandated to operate on a cost-recovery basis. Although much useful information is already being captured by the TGA, to extend this into a more rigorous data capture process, such as a registry, would require additional resources and legislative amendments to the Therapeutic Goods Act.
Australian governments do however seem willing to fund other medicinal cannabis-related projects and amend legislation where necessary. The TGA created and implemented an online portal to streamline SAS-B requests in mid-2018 which has improved access significantly, likely at considerable expense. And various State Health Departments have directly funded several medicinal cannabis clinical trials, not to mention the significant AUD$6 million investment by the New South Wales Department of Health to establish a call centre to answer people's questions about medicinal cannabis.
With the resources and infrastructure Australia has at its disposal, there is no reason that a highly informative system of data capture around medicinal cannabis patients cannot be achieved at a national level.