Presentation: Clinical evidence and access for medicinal cannabis products

TGA presentations given at: RACGP (GP17) conference, 26-28 October 2017

13 November 2017


These presentation papers are provided on the TGA's website solely for the purpose of indicating or suggesting what TGA representatives spoke about to the various conferences and seminars to which it relates. The papers are not legislative in nature and should not be taken to be statements of any law or policy in any way.

The Australian Government Department of Health (of which the TGA is a part) advises that (a) the presentation papers should not be relied upon in any way as representing a comprehensive description of regulatory requirements, and (b) cannot guarantee, and assumes no legal liability or responsibility for, the accuracy, currency or completeness of the information contained in the presentation paper.


  • Presented by: Dr Tony Gill
  • Presented at: GP17 RACGP Conference
  • Presentation date: 28 October 2017
  • Presentation summary: Overview of clinical evidence and access for medicinal cannabis products


Notifications to prescription medicines

Dr Tony Gill
Pharmacovigilance and Special Access Branch
Therapeutic Goods Administration

GP17 RACGP Conference

Slide 1 - The government’s intent

  • Treat medicinal cannabis products as medicines
  • Provide patient access to Australian-grown and manufactured medicinal cannabis outside the standard registered medicines route
  • Provision of a quality medicine through doctors prescription
  • Encourage clinical trialling for potential future TGA registration
  • The Health Products Regulation Group has oversight
    • Cultivation and manufacture (Office of Drug Control)
    • Product GMP, product scheduling and patient access through the Therapeutic Goods Administration (TGA)
  • States and Territories also have a role in regulation

Slide 2 - Evidence

Whiting et al 2015

  • There was moderate quality evidence to support the use of cannabinoids for the treatment of:
    • chronic pain and
    • spasticity
  • There was low quality evidence suggesting that cannabinoids were associated with:
    • improvements in nausea and vomiting due to chemotherapy
    • weight gain in HIV infection
    • sleep disorders, and
    • Tourette syndrome
  • Cannabinoids were associated with an increased risk of short-term AEs

Slide 3 - Evidence

National Academy of Science 2017 Report

  • In adults with chemotherapy induced nausea and vomiting, oral cannabinoids are effective anti-emetics.
  • In adults with chronic pain, patients who were treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms
  • In adults with multiple sclerosis (MS) related spasticity, short-term use of oral cannabinoids improves patient-reported spasticity symptoms.
  • For these conditions the effects of cannabinoids are modest; for all other conditions evaluated there is inadequate information to assess their effects.

Slide 4 - Clinical evidence reviews

  • Conducted by team from U NSW, U Sydney, U QLD and collaborators
  • Focus on epilepsy, MS, pain types, nausea and vomiting and palliative care
  • Systematic reviews of published reviews and findings of individual studies using Medline, Embase, PsycINFO, and EBM Reviews
  • Studies published from 1980 to early 2017
  • Priority was given to RCTs but also included observational studies, e.g. case reports, retrospective chart reviews, self-report surveys
  • Anticipated that these reviews will be published in the next few months in international journals – currently being reviewed

Slide 5 - Epilepsy

  • Five RCTs and 17 observational studies were identified - all examined CBD as adjuvant treatment (in addition to standard antiepileptic drugs)
  • Randomised controlled studies
    • In patients with paediatric-onset drug-resistant epilepsy CBD products reduced seizure frequency and achieved seizure freedom compared with placebo
    • 14% of patients withdrew because of treatment-related adverse events
    • Doses of cannabidiol required were reasonably high (20mg/kg/day) and some uncertainty around contribution of the effect of CBD on clobazam metabolism
  • Observational studies
    • In 14 of 17 studies, 56% of patients reported reductions in seizures of 50% or more.
    • In 7 paediatric studies 13% were estimated to be seizure-free
    • 10 studies reported improved quality of life in paediatric and adult groups

Slide 6 - Cancer and HIV induced nausea and vomiting

  • 11 met inclusion criteria, but were mainly against old medicines
  • In managing CINV in adults, THC/ analogues were more effective than placebo, and as effective prochlorperazine at completely controlling nausea and vomiting, and controlling /reducing nausea
  • Comparison of cannabinoids against newer anti-emetics is required
  • Research on cannabinoids for CINV in children is more limited
  • Evidence of efficacy of cannabinoids in treating nausea and vomiting in late stage AIDS and terminal cancer was equivocal

Slide 7 - Palliative care

  • 9 double blind or open label RCTs studies with a total of 1561 participants were included, but evidence was low quality
  • In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake, appetite, nausea/vomiting, pain, dizziness, mental health or sleep problems
  • In HIV patients, cannabinoids were superior to placebo for weight gain and appetite but not for nausea/vomiting
  • No convincing evidence suggesting that cannabinoids are of value for anorexia or cachexia (weakness and wasting) in cancer or HIV

Slide 8 - Multiple sclerosis

  • Nabiximols are TGA approved for the use in MS for muscle spasticity.
  • 11 systematic reviews with data from 32 studies with 3146 patients.
  • These included 10 moderate/high-quality RCTs, that examined if cannabinoids reduced pain and spasticity.
  • Five reviews concluded that there was evidence that cannabinoids may be effective for symptoms of pain and/or spasticity and positive effects on sleep and bladder symptoms
  • Mixed findings were reported on quality of life, ataxia/tremor and disability/disease progression
  • A lack of studies with non-cannabinoid comparators is a is a major evidence gap

Slide 9 - Chronic non-cancer pain

  • 102 trials of all types of study designs considered
  • Most studies with nabiximols, THC/ analogues, THC-rich preparations
  • Most evidence on cannabinoids was from studies where cannabinoids were adjuvant interventions and not first line treatments for pain
  • Patients who had cannabinoids for MS-related neuropathic pain were more likely to experience a 30% reduction in pain (low confidence) and decrease in pain scores (moderate confidence)
  • patients who had cannabinoids for non-MS related neuropathic pain were more likely to experience a 50% reduction in pain and a reduction in pain scores
  • Insufficient information to make a conclusion about cannabinoids for the treatment of pain associated with arthritis and fibromyalgia

Slide 10 - Draft clinical guidance documents

  • Draft “clinical guidance documents” for the use of cannabinoids are being developed for epilepsy, MS, pain types, nausea and vomiting and palliative care
  • Decisions on patient access to particular cannabis products will be made by the treating physician with clinical oversight from the state/territory health departments and TGA
  • Aim to produce documents by end 2017 with input by Australian clinical experts and patient

Slide 11 - Flowchart

Flowchart illustrating the TGA, states and territories pathway for Patient to access to cannabis from manufacture to cultivation and production

Slide 12 - Individual importation of medicinal cannabis

Medical practitioners can arrange patient by patient importation to fill prescriptions issued using TGA SAS A

  • Requires a licence under the Customs (Prohibited Import) Regulations 1956

Individual patients can utilise travellers’ exemption

  • to carry up to 3 months supply of medicines with them on a ship or aeroplane entering into Australia with a valid doctor’s prescription
  • Prior State Health Department approval may also be required

Slide 13 - Medicinal cannabis products are available through “unapproved products” pathways

  • No ARTG product available (SATIVEX® is approved but Australian product is not being supplied currently)
  • Authorised prescriber
  • SAS A - notification pathway for patients who are seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment
  • SAS B - application pathway for patients that do not fit SAS A

For help 1800 220 007/ 02 6232 8866,

Access to medicinal cannabis products: steps to using access schemes

Slide 14 - SAS B and Authorised Prescriber

Criteria depend upon the patients, product, prescriber

Authorised Prescribers must:

  • have training and expertise appropriate for the condition and the proposed use of the product, and
  • be able to best determine the needs of the patient and to monitor the outcome of therapy

Patient and clinical justification

  • patient information, diagnosis and indication treated
  • the seriousness of the condition
  • details of past treatment
  • expected benefits from the use of the product

Slide 15 - Product details

  • Trade name - Manufacturer/Company/Supplier
  • Dose Form i.e. tablet, extract and active ingredients
  • Shelf-life and Storage Conditions
  • Compliance with TGO 93 for composition / contamination

Administration details

  • Dosage, Route of administration, Duration of treatment

Monitoring Detail:

  • Efficacy of the treatment, adverse events/reactions
  • Human studies to demonstrate efficacy and safety data
  • Evidence levels depend on seriousness of the condition

Slide 16 - Notifications (SAS A) and Applications (SAS B and AP) 1 January 2016 to 10 October 2017

SAS A Notifications

  • 5 since June 2017 disallowance

SAS B Applications

  • Approved applications -173 (rest pending further information or withdrawn)
  • 74 for cannabidiol, rest for THC/ CBD in various ratios
  • Range of dosage forms for products

Authorised Prescriber Applications

  • Approved – 27 (and pending – 6) (101 patients to June 2017)

Slide 17 – Questions?

Print version

How to access a pdf document