8. Research and evaluation
8.1 Victoria’s medicinal cannabis scheme should ensure that it fosters, and responds to, clinical knowledge about cannabis as a medicine. This regulatory objective, recommended in Chapter 1, is designed to ensure that any Victorian scheme evolves in response to clinical developments and changes in the medicinal cannabis industry.
8.2 Research into cannabinoids has been described as ‘one of the fastest moving frontiers in pharmacology’. Research using cannabis is taking place around the world, in animal models, cell cultures and humans, with new cannabinoids and uses for them being discovered and evaluated.
8.3 In spite of this, as indicated in Chapter 2, there are limits on the research that has been conducted in Australia and other countries, with researchers attributing this not to a lack of scientific interest but to regulatory obstacles:
Over the past decade there has been immense international growth in this area of research as the significance of the endocannabinoid system in human health and disease becomes increasingly apparent. Despite this, we conduct our research in a tight regulatory environment that makes sourcing, holding and administering cannabinoids extremely difficult and expensive.
8.4 Such obstacles to research activity give rise to a dilemma: without the research basis, restrictions on cannabis production and administration are currently in place; because such restrictions persist, the research cannot take place. Some obstacles are not within the power of the Victorian Government to address—for example, access to cannabinoids or cannabis through importation, and approval of clinical trials, are the responsibility of the Commonwealth. Nonetheless, a Victorian scheme should seek, so far as is possible, to break down the existing constraints on research and allow inquiry and innovation in this area to flourish.
8.5 To achieve this regulatory objective, so far as is possible by way of changes to Victorian law, a number of recommendations are made in this chapter to promote research into medicinal cannabis. They are designed to enable Victorian medicinal cannabis products to be used in clinical research, and to ensure that decision making about patient eligibility and use of medicinal cannabis would be informed by a developing evidence base. It also makes recommendations regarding how the scheme could be responsive to scientific and technological change, through review and evaluation.
Enabling research and drug development
8.6 Research and development of medicinal cannabis should be a central consideration in the design of a Victorian medicinal cannabis scheme. Patient interests are much better served if research and product development continues and, indeed, is encouraged.
8.7 Developing new cannabinoid-based drugs and running the necessary trials to have them approved is a time-consuming and resource-intensive exercise. In addition, if left to the market, it relies on there being companies with a sufficient interest in the development of products for particular indications to fund research. Much is made of the success of GW Pharmaceuticals in the United Kingdom, and their revolutionary development of cannabinoids at the pharmaceutical grade. However, GW Pharmaceuticals could only have developed their refined cultivation techniques, novel extraction systems and delivery systems (over which they now hold an extensive patent portfolio) in an environment in which research and experimentation with the cannabis plant were allowed and enabled.
8.8 Australian researchers should have the same opportunity to explore new products and to test their potential, and the Victorian scheme should set out to foster technological innovation as the first step on this path, but acknowledging that this can and will occur at the same time as unrefined, unevaluated products are being supplied. Andrew Katelaris made this point, calling for the scheme to accommodate both ‘larger scale’ growing enterprises, supplying patients with products tested for potency and quality, and companies producing pharmaceutical preparations, such as GW Pharmaceuticals.
8.9 By contrast to jurisdictions with medicinal cannabis schemes, however, the United Kingdom does not allow treatment with medicinal cannabis other than Sativex and like products. There is a risk that, by allowing access to medicinal cannabis for certain groups of patient before further research takes place, the scheme could put a brake on research and drug development for those patients, because there is little incentive for patients to sign up for a clinical trial if they can already access a satisfactory product. In the Commission’s view, the best way of controlling this risk is to maintain a sharp distinction between the products accessible by eligible patients under the Victorian scheme (quality controlled but variable and untested) and products approved or intended to be approved by the TGA (standardised, characterised and evaluated).
8.10 A range of government actions could be taken to facilitate and enable research into cannabinoids and their application. Some of these, such as funding for clinical trials, participating in research, and offering research and development grants, involve non-legislative action, beyond the scope of the Commission’s reference. Likewise, other actions which would enable trials to be conducted more readily, such as the rescheduling of cannabis or a subset thereof, amending the clinical trial approval process, or relaxing restrictions on the importation of cannabinoids, are responsibilities of the Commonwealth that Victoria has no power to control. Besides these, though, there are a number of legislative reforms available to Victoria which would enable and facilitate research into cannabinoids and development of pharmaceutical-grade cannabinoid medications,
• providing for licensed cultivators to supply cannabis to researchers and manufacturers licensed by the TGA, and permitting licensed cultivators to cultivate cannabis for experimental purposes
• ensuring that medical practitioners wishing to prescribe experimental cannabinoid products within a clinical trial can access treatment permits without undue difficulty.
8.11 Importantly, by ensuring that the Victorian scheme is limited to the manufacture and distribution of quality-controlled non-pharmaceutical extracts, which are distinct from any pharmaceutical-grade products available, the standards that apply to the development and approval of pharmaceutical-grade products would remain within the control of the Therapeutic Goods Administration.
Access to cannabis by researchers
8.12 The Commission understands that a key constraint on cannabinoid research in Australia has been limited access to cannabinoid products with which to conduct research. The argument to relax these restrictions is particularly compelling in light of the number of non-psychoactive cannabinoids presently generating research interest.
8.13 A Victorian medicinal cannabis scheme should facilitate the development of new cannabis strains and the transfer of these to research institutes and pharmaceutical companies for the purpose of research and development. Clearly, research into cannabinoids cannot take place without a source of cannabinoids, such as raw cannabis.
8.14 Enabling pharmaceutical companies to access cannabis grown under a Victorian scheme would require a simple addition to the cultivator licensing scheme recommended in Chapter 6. To limit the possibility of diversion of raw cannabis, the Commission has recommended that licensed cultivators be required, through conditions on their licence, to deliver all the cannabis they produce to a manufacturer licensed under the Victorian scheme (with any remaining cannabis to be destroyed) and at all times be party to a contract with a manufacturer licensed under the Victorian scheme.
8.15 To enable research to take place, cultivators should also be permitted to deliver cannabis to TGA-licensed manufacturers, universities and research institutes. To control diversion, the scheme could require research entities to apply for and obtain licences analogous to the ‘processing licences’ available under the alkaloid poppy scheme.
8.16 It may be the case that researchers wish to cultivate cannabis themselves, to exercise greater control over the breeding and cultivation process. The Victorian Government could consider issuing researchers experimental licences to cultivate outside the scheme for supply to patients. These licences could equally be available to cultivators already licensed to produce, to enable them to test new strains and assess the impact of growing conditions. Quantities of cannabis cultivated under an experimental licence would be the subject of separate reporting to the International Narcotics Control Board.
38 Any Victorian medicinal cannabis scheme should foster research by providing for:
(e) licensed cultivators to supply cannabis to appropriately licensed manufacturers capable of producing or trialling pharmaceutical-grade cannabis-derived products
(f) researchers and those holding commercial cultivation licences to obtain experimental cultivation licences.
Treatment permits and clinical trials
8.1 Many medical practitioners urged that medicinal cannabis be made available through a clinical trial framework. The Commission agrees that clinical trials can and should continue after any Victorian scheme is introduced.
8.2 At present, a medical practitioner who wishes to administer, supply or prescribe cannabis to a patient, including under the auspices of a clinical trial, requires a permit to prescribe cannabis to that patient, due to the status of cannabis as a Schedule 9 poison. Any such permit, if granted, would be specific to the patient under treatment, in that it would authorise treatment of that person alone. In practice, however, Schedule 9 poison treatment permits are not sought in Victoria and there are no guidelines setting out when they may be issued.
8.3 Under any Victorian scheme there would be a need to ensure that people can be treated with medicinal cannabis products within a clinical trial, even if they do not fall within the eligibility criteria and/or the product has not yet been approved. For this reason, the scheme should provide for a type of experimental treatment permit, which a specialist can obtain for any person. Such a permit could also be used to facilitate the conduct of so-called ‘n of 1’ trials, recommended to the Commission as a means of testing the utility of cannabis in treating particular patients or conditions. The permit provisions could specifically apply to medicinal cannabis, or be incorporated into an existing treatment permit.
8.4 At present, treatment permits for Schedule 9 poisons are required at all times, with no exceptions. This contrasts with Schedule 8 poisons, where permits are only required if the patient is drug dependent or the treatment lasts for more than eight weeks. The government may wish to consider simplifying the process for obtaining experimental treatment permits for medicinal cannabis, or limiting them to particular situations only.
39 The Secretary of the Department of Health and Human Services should have the power to issue medical practitioners with permits to treat patients other than those who are eligible under the scheme with medicinal cannabis for trials and research.
8.5 An implementation issue for consideration by the Victorian Government is when permits to treat patients with medicinal cannabis within a clinical trial should be granted. Clinical trials in Australia are generally required to be conducted consistently with national guidelines, and are permitted to be conducted using unapproved goods if ethics committee approval is obtained. Depending on the scope of any Commonwealth action giving Victoria authority over the regulation of medicinal cannabis products, Victoria could need to establish a procedure for the approval and supervision of clinical trials using medicinal cannabis products.
Knowledge collection and information provision
8.6 The government should ensure that any Victorian medicinal cannabis scheme supports the development of knowledge and its dissemination to medical practitioners and researchers.
8.7 The scheme could achieve this in a number of ways. Education of medical practitioners would be essential, particularly as expertise is presently very limited. An important component of education is that it be continually updated and improved, so the scheme should also facilitate data collection and the distribution of results to practitioners.
8.8 In addition, as discussed in Chapter 3, medical practitioners enabling a patient to be treated with medicinal cannabis would first be required to seek a permit from the Secretary of the Department of Health and Human Services. The application for a permit would be in a prescribed form, through which the Secretary would have the ability to determine what information is collected about patients within the scheme. The collection and analysis of this information would provide practitioners and researchers with a useful source of data regarding those currently treated under the scheme.
8.9 One way in which the data could be collected and analysed is through the establishment by practitioners of a clinical registry. These registries are designed to allow practitioners in a field of medicine to compile data from their patients in order to measure the results of intervention.
8.10 In the field of chronic pain, for example, Australian practitioners have established the electronic Persistent Pain Outcomes Collaboration (ePPOC) database at the University of Wollongong. Pain practitioners and services submit data to the ePPOC about their patients’ experience of pain and the manner in which that pain was treated. The data are aggregated by the ePPOC and made publicly available.
8.11 A registry of this kind could allow practitioners to share aggregated information about how they had resolved problems around the authorisation and withdrawal of medicinal cannabis, which would inform the development of common standards. For example, Associate Professor Carolyn Arnold at Alfred Health suggested that a ‘medical cannabis chronic pain treatment’ registry should include data about:
• if cannabis use is ceased, the reason and any adverse effects observed
• details of the specific medical cannabis form and dose used.
8.12 As an alternative to condition-specific registries, Victorian health practitioners could establish a general clinical registry dedicated to the general monitoring of all patients who have been authorised to use medicinal cannabis. For example, the Québec Cannabis Registry is intended to be a database of all patients authorised to use medicinal cannabis in Québec, to enable clinical research into cannabis. This allows medical practitioners to comply with their professional obligations, as the position of the Collège des Médecins du Québec is that the prescription of cannabis is only ethically authorised ‘within a research framework’. Accordingly, the Registry will seek to:
develop and answer future questions on the medical use of cannabis, such as who uses it, for what reasons, through which methods, and at what dose. … [The Registry] will be used to compile and store clinical data collected directly from patients who use medical marijuana. The data will be gathered from sites and clinics across Quebec, and each participant will provide data for four years after recruitment. Any licensed doctor practising in the province wishing to authorise cannabis for their adult patients can enrol participants in the registry.
8.13 The patient information collected through the issuing of permits, or in creating and maintaining a clinical registry, could also be used to invite patients taking part in the scheme to be involved in clinical trials of pharmaceutical-grade cannabinoids.
40 The Secretary of the Department of Health and Human Services should collaborate with the clinical research community in developing methods and protocols for collecting and sharing information about the incidence and outcomes of treatment with medicinal cannabis products under any Victorian scheme.
Dissemination of information
8.14 Subject to privacy requirements, data collected by the government could be aggregated and disseminated to improve knowledge and understanding among practitioners. Data could also help support the production of guidelines and information documents to be circulated to practitioners, particularly where adverse effects are observed. The data would also be used in any scheme evaluation, discussed below.
41 The Secretary of the Department of Health and Human Services should:
(a) retain data collected on Permit applications and Authorities to Dispense Medicinal Cannabis in a way that enables statistical information about the operation of the scheme to be compiled and used for evaluation purposes, and for non-identifying information to be made available for the purpose of research into the efficacy of medicinal cannabis
(b) ensure that a privacy impact assessment is conducted when designing the data collection and management systems in support of the medicinal cannabis scheme, to safeguard the information privacy of patients, carers, practitioners, pharmacists and other participants in the scheme.
Responsiveness to change
8.1 The science and technology around the use of medicinal cannabis is a rapidly evolving field. Trials into the utility of cannabis are ongoing and commencing to deliver results which enable evaluations of efficacy to be made. Jurisdictions overseas with medicinal cannabis programs continue to develop innovative delivery systems.
8.2 Any Victorian scheme must therefore be sufficiently flexible to allow for legal, scientific and technical change. As Mullaways Medical Cannabis Pty Ltd observed, ‘[t]he legislation must allow for research… Limiting the scheme to current Australian knowledge would leave a Victorian Medicinal Cannabis Scheme stuck in the past based on outdated research.’
8.3 In particular, as discussed in Chapter 3, the scheme should be flexible enough to allow for new cannabis-based products to be made available to patients, and for new sets of conditions and symptoms, as new evidence emerges. In addition, changes to Australian or international law and the emergence of sources of cannabis overseas could require the Victorian scheme to respond.
8.4 There are a number of ways that laws and policies could change at the Commonwealth level or in other states, necessitating alterations to the Victorian scheme:
• medicinal cannabis schemes could be introduced in other Australian states and territories
• ‘cannabis’ or a subset thereof could be moved to another Schedule in the SUSMP
• the TGA could change its procedures to allow cannabis products to be regulated as listed (herbal) medicines.
Alternative supply options
8.5 Medicinal cannabis schemes and industries in jurisdictions around the world are in a state of flux. National policies on export and import are subject to change, meaning that in the future, the products available for import may be quite different from those available today. In addition, should other Australian states or territories begin cultivating cannabis or manufacturing cannabis products, a domestic source may become available. Likewise, cannabis-based products (like Sativex or Epidiolex) may be approved for sale in Australia through conventional TGA channels.
8.6 A Victorian scheme should accommodate the potential supply of any such products. While any importation would require the co-operation of the Commonwealth, the scheme could allow, for example, for particular overseas-made products to be designated as approved medicinal cannabis products for the purposes of Victorian law.
8.7 Research on, and the availability of, medicinal cannabis is constantly changing and will continue to do so after the commencement of the scheme. Changes could include:
• clinical trials determine whether cannabis or cannabinoids are effective in the treatment of conditions or symptoms not currently within the statutory eligibility criteria
• new technologies for manufacturing cannabis extracts or administering them to patients are developed
• international export opportunities emerge
• new cannabinoids are discovered
• new cannabis-based pharmaceuticals are approved by the TGA to be sold in Australia.
8.8 The scheme should therefore be established in such a way that it is subject to evaluation. The evaluation should consider how well the scheme is meeting its objectives. It should also consider the cost of the scheme and whether it is functioning in a sufficiently cost-effective way.
8.9 Specifically, the following matters should be taken into account in the evaluation:
• participation rates in the scheme, including for each condition
• findings of the scheme regarding the efficacy and side effects of cannabis
• the cost of the scheme
• findings of clinical trials
• the availability (if any) of cannabinoid drugs approved by the TGA and/or listed on the Pharmaceutical Benefits Scheme
• legislative and regulatory changes (if any) at the Commonwealth level and in other States or Territories since the scheme was introduced.
42 The Minister for Health should cause an independent evaluation of the scheme to take place no later than four years from its date of commencement and should be required to report to Parliament on the findings and recommendations of the evaluation.
David Allsop et al, Submission No 52 to Senate Legal and Constitutional Affairs Committee, Parliament of Australia, Inquiry into the Regulator of Medicinal Cannabis Bill 2014, 3.
Cancer Council Australia and Clinical Oncology Society of Australia, Position Statement—Medical Use of Cannabis (21 May 2015)
Ethan Russo, ‘The Solution to the Medicinal Cannabis Problem’ in Michael Schatman, Ethical Issues in Chronic Pain Management (Informa, 2007) 165.
Submission 30. See Appendix B for list of submissions.
‘The flip side of those who passionately shout for the “legalisation of cannabis” is that their call may inadvertently hamper the medical development of cannabinoids, which is a shame’: Wai Liu, ‘Why Anti-Cancer Properties in Cannabis Must be Investigated’, The Conversation (online), 26 June 2015 <http://theconversation.com/why-anti-cancer-properties-in-cannabis-must-be-investigated-42653>
Consultation 32. See Appendix C for list of consultations.
An example definition of ‘experimental purposes’ was included in cl 20(2) of the Regulator of Medicinal Cannabis Bill 2014 (Cth). It included: ‘(a) developing and testing varieties of cannabis for medicinal use; (b) improving methods of cultivating cannabis for medicinal use; (c) developing and testing cannabis products for medicinal use; (d) evaluating the efficacy or safety of cannabis products for medicinal use; (e) improving methods of using or administering cannabis products for medicinal purposes; (f) performing tests, trials and other experiments for the purposes of making or supporting an application under [the Regulator of Medicinal Cannabis Bill 2014] or the Therapeutic Goods Act 1987 [sic], or considering whether to make such an application.’
David Allsop et al, Submission No 52 to Senate Legal and Constitutional Affairs Committee, Parliament of Australia, Inquiry into the Regulator of Medicinal Cannabis Bill 2014, 3.
Governed by the Drugs, Poisons and Controlled Substances Act 1981 (Vic) Part IVB Div 3. Processing licences for alkaloid poppies are issued to the companies that are involved in converting the poppy straw into pharmaceutical opiates. These entities must hold a current manufacturing licence issued by the TGA (or a current export licence, which would enable them to export poppy straw to a manufacturer located overseas): s 69PC(8). That is, the Victorian ‘processing’ licence is held in parallel to a licence allowing them to refine or export the poppy straw.
These licences would be analogous to those available under s 69O(2), which permit a licence to cultivate alkaloid poppies to be granted for research purposes not intended for therapeutic use. The limitation regarding therapeutic use would not, however, be appropriate for the creation of experimental drugs used in human or animal trials: see definition of ‘therapeutic use’ in s 4 of the Drugs, Poisons and Controlled Substances Act 1981 (Vic).
Drugs, Poisons and Controlled Substances Act 1981 (Vic) s 33A. Unlike permits to administer, supply or prescribe Schedule 8 poisons, permits are always required for Schedule 9 poisons, not just in certain circumstances. Cf s 34 stating that Schedule 8 poison permits are only required where the person is drug-dependent or where the duration of use exceeds eight weeks, and ss 34D–34F setting out a number of exemptions.
N-of-1 or n=1 clinical trials are ‘empirical tests using a within-patient randomised, double-blind, cross-over comparison of drug and placebo (or another drug), principally to study individual patients’ responses where there is uncertainty about the effectiveness of a medication for a chronic condition’: Jane Nikles et al, ‘Stakeholders’ Views on the Routine Use of N-of-1 Trials to Improve Clinical Care and to Make Resource Allocation Decisions for Drug Use’ (2010) 34 Australian Health Review 131, 131. They involve a practitioner administering alternating placebo (or other drug) and active (drug under investigation) treatment to a patient and measuring their response, to test whether the drug induces a different response to the placebo/alternative. The alternating placebo/active doses must be produced by a third party, so that both the practitioner and the patient are unaware of what is being administered (that is, the trial is ‘double blind’): Consultation 32.
Medicinal cannabis may no longer be treated as a Schedule 9 poison, depending on the model adopted.
Drugs, Poisons and Controlled Substances Act 1981 (Vic) s 34. A range of other exceptions to the permit requirement also apply: ss 34D–34F.
For example, the Drugs, Poisons and Controlled Substances Amendment (Clinical Trials) Bill 2014 (Vic) would have simplified the process for obtaining Schedule 9 treatment permits, by enabling medical practitioners to seek a permit to treat a group of patients, not just a single individual (as is the case presently). The Cancer Council Victoria supported incorporating such a measure into a medicinal cannabis system: Submission 57.
Such as, National Health and Medical Research Council, National Statement on Ethical Conduct in Human Research (2007).
Therapeutic Goods Regulations 1990 (Cth) sch 5A, item 3.
For example, if only Victorian-approved medicinal cannabis products are able to be supplied in Victoria without attracting the provisions of the Therapeutic Goods Act 1989 (Cth), any other products would need to comply with TGA requirements for clinical trials.
Submissions 11, 22, 69, 76, 91, 99.
The education of medical practitioners is discussed in Chapter 3. See [3.226]–[3.239] above.
Cf Drugs, Poisons and Controlled Substances Regulations 2006 (Vic) Sch 2.
Several respondents to the Cancer Council Victoria’s clinician survey recommended that a program be established to monitor patient use, responses and adverse effects: Submission 99.
Enterprise One Pain Management Service, Patient Outcomes in Pain Management (31 December 2014).
Collège des Médecins du Québec, Guidelines Concerning the Prescription of Dried Cannabis for Medical Purposes (April 2014) 2.
Quebec Cannabis Registry, ‘World First: Launch of Quebec Registry for Users of Medical Cannabis’ (Press Release, 11 May 2015, Montreal) <https://registrecannabisquebec.com>.
See, eg, the Syqe dose-controlled medical cannabis inhaler, supplying a metered dose of vaporised cannabis <http://www.syqemedical.com>; Echo Pharmaceuticals’ lipophilic drug delivery technology, Alitra, used to deliver a standardised dose of THC with high bioavailability, under the name Namisol <http://www.echo-pharma.com>; and a cannabis-based CBD-rich chewing gum