Dave King, Senior Researcher
Despite the rescheduling of cannabis-based medicinal products (CBMPs) in November 2018, which theoretically allowed British patients access to such medications, only very limited numbers of patients have been able to benefit. While many patients and families believe that CBMPs are now available, this is simply not the case and it is worrying that this has has soured patient-clinician relationships.
Last week, Parliament’s Health and Social Care Committee (HSSC) published Drugs policy: medicinal cannabis, summarizing how the rescheduling of cannabis-based medicinal products has affected clinical practice and providing an overview of current obstacles in accessing CBMPs through the UK health system. Here we discuss those barriers.
CBMPs are not licensed and CCGs are reluctant pay for them
For a medicine to be widely prescribed on the NHS, there must be randomised, double-blinded placebo-controlled trials (RCTs) showing strong evidence of efficacy for the Medicines and Healthcare products Regulatory Agency (MHRA) to licence the drug, then further evidence of cost-effectiveness for NICE to recommend its use. No CBMPs in the UK market are yet to achieve both.
As unlicensed ‘specials,’ CBMPs have not achieved the regulatory requirements to be approved by the MHRA so can only be prescribed by specialist physicians on a named-patient basis. Unlicensed drugs are paid for by local NHS budgets managed by Clinical Commissioning Groups (CCGs). But without a clear indication of cost-effectiveness from NICE, CCGs are reluctant to approve CBMP prescriptions, which cost £25-30,000 per patient per year.
There is insufficient clinical evidence available and medicinal cannabis isn’t well suited to conventional studies
The Committee evaluated the evidence-base for CBMPs. Last year the Chief Medical Officer published a report supporting the use of CBMPs in four conditions: chronic pain in adults; chemotherapy-induced nausea and vomiting; multiple sclerosis spasticity syndromes; and intractable epilepsy. Yet a number of clinical bodies submitted testimony cautioning that the evidence is mixed or lacking.
The UK has a global reputation for clinical excellence and won’t accept the widespread introduction of a new class of medicines without demanding the same rigor of evidence for safety and efficacy that other new medicines must achieve. To do so may set a dangerous precedent and it is right that we require robust evidence and proper regulatory oversight of any new drug.
However, patients, patient advocacy groups, families and prescribing clinicians told the Inquiry that conventional RCTs do not lend well to assessing CBMPs. The RCT design attempts to control for outside factors in order to understand the specific therapeutic action of the study drug. Specific, standardised cannabinoid-based medicines (such as Sativex) are tested in this way, but plant-based cannabis products represent a staggering diversity of molecular combinations not readily reduced to a single standardised trial drug. While a single preparation can be put through the standard pharmaceutical evidence-gathering process, the results won’t necessarily provide clarity on the potential efficacy of preparations with different cannabinoid profiles. Out of countless possible combinations of 150-or-so known cannabinoids from thousands of strains of cannabis, where should research start?
There are always methodological difficulties with psychoactive medicines, not least because it is difficult to ‘blind’ them. If a study drug makes you feel high, it’s a safe bet that you didn’t get the placebo. Researchers have developed clever ways of overcoming these blinding difficulties and, despite the apparent impracticality of pushing CBMPs through traditional RCTs, there is no reason to think that new or adapted methodologies won’t emerge to address the problem. We need to see trials that permit combinations of multiple formulations, for instance. These methodologies must be rigorous enough to build the evidence base, satisfy the requirements of the MHRA and facilitate access for British patients.
The National Institute for Health Research have issued calls for funding applications for clinical trials and the Committee urges the prioritisation of resources for studies assessing CBMPs in the treatment of intractable epilepsy in children. The Committee notes that data from other countries should be used to inform guidance in the UK. Multi-centre, pan-European trials could be of great benefit and the Committee asks Government to ensure that Brexit won’t limit this opportunity.
There is an absence of comprehensive clinical education and prescription guidelines
NICE are due to release guidelines for prescribing clinicians towards the end of this year. The British Paediatric Neurology Association (BPNA), Association of British Neurologists (ABN) and the Royal College of Physicians (RCP) have released guidelines in advance. Yet patients, families and prescribing clinicians claim these initial guidelines are a barrier to prescribing. Neurologist Prof Mike Barnes criticized the guidelines as “too restrictive” and “rather negative.” The BPNA, ABN and RCP say the guidelines are based on the available evidence. Again, new methodologies better suited to assessing the evidence of cannabis-based medicines would help to break this impasse.
It is welcome that Health Education England are working on e-modules to train doctors to understand and prescribe CBMPs. NHS England are planning a process review to address bureaucratic barriers in prescribing. The report recommends issuing targeted guidance to practitioners and pharmacies following the review.
Limited UK supply of cannabis medicines means high costs while some patients resort to illegal access
There is no UK supply of CBMPs and prescriptions are made and imported on a named-patient basis. With each prescription requiring an individual importation license there is no economy of scale, significantly raising costs. The report recommends that the Department of Health and Social Care (DHSC) secure long-term international supply deals and DHSC is due to publish a review in early 2020.
The report strongly criticises industry for instances of being unwilling to supply their CBMPs for research to build the necessary evidence base and recommends “naming and shaming” such companies, calling for stronger industry involvement in medical research. In my own experience, companies producing CBMPs and looking to supply the future UK medical market are investing money and product in research. The report failed to consider incentivizing companies to further invest, which could be a more useful approach.
The lack of NHS access and high private prescription cost means some patients are illegally importing their CBMPs from abroad. The Select Committee says:
“We should not be treating patients or their families who are resorting to bringing medication here from abroad because they cannot obtain it on prescription here as if they are committing a criminal offence. Neither should patients have their medication confiscated… this cruel practice must not happen again.”
The Committee doesn’t recommend decriminalising other routes of access to cannabis products for patients unable to obtain prescriptions in the UK, such as self-cultivation. Not all patients have the physical, mental or financial ability to travel overseas to obtain prescriptions. The CDPRG recently featured the case of ‘Elizabeth’, an MS sufferer in her mid-fifties who was arrested and charged this year for cultivation and possession of 9 cannabis plants that she was growing to manage her condition. Elizabeth had attempted access of CBMPs through legal medical routes but could not sustainably afford a regular private prescription.
This omission may be due to a belief that cannabis produced by pharmaceutical companies is very different to cannabis cultivated or distributed illegally. The report is correct in saying that cannabis products on the unregulated market are of inconsistent quality, but street cannabis isn’t uniquely high in THC. The standardized medical cannabis product Bedrocan contains 22% THC and less than 1% CBD. While non-standardised cannabis products from the unregulated market, including self-cultivation, are far from the consistent, sterile products on the medical market, patients who are unable to obtain NHS prescriptions, unable to afford private prescriptions and incapacitated from traveling abroad have little other option available. No patient should be treated as a criminal for trying to be well.
Meeting the urgent needs of British patients requires priority action
Meeting the urgent needs of British patients who can benefit from medicinal cannabis requires priority action. We need immediate resources for clinical research to provide children with intractable epilepsy the medications they require. Government must assure patients with evidence-based clinical needs for CBMPs that they will not be treated as criminals for doing what they must to access medicines that work for them, however they achieve it. We need more constructive collaborations between Government, clinical science and industry. We need assurance that, as promised by Health Secretary Matt Hancock, funding won’t be an obstacle to prescriptions. This might be achieved by the development of a central subsidy fund to reduce the economic burden of prescribing unlicensed CBMPs on local NHS trusts.
The report provides a balanced, if limited, assessment of the state of play regarding cannabis-based medical products on prescription in the UK. The CDPRG will be urging movement on each of these barriers. Patients deserve a robustly evidence-based yet compassionate and pragmatic approach to medical cannabis that achieves better health outcomes for Britain.