Authors' objectives: The overall aim of this HTA report was to investigate the efficacy, effectiveness, safety, cost-effectiveness, and budget impact of medical cannabis use in chronic pain and spasticity in Switzerland.

Authors' results and conclusions: Heterogeneity between studies in outcomes and outcome measures, data skewness, and incompleteness of study results precluded the calculation of pooled estimates for efficacy data for the stratified pain and spasticity populations. Overall, the efficacy data on medical cannabis use for chronic pain and spasticity was inconsistent (i.e. studies with comparable patient populations and similar type of medical cannabis did not show consistent results pointing in the same direction) and inconclusive (i.e. none of the studies was able to draw a definitive conclusion on the efficacy of medical cannabis). Furthermore, multiple factors increase the risk of bias in studies on medical cannabis, however the extent as well as the direction of the potential bias are difficult to comprehend. Although it was possible to calculate pooled estimates for part of the safety outcomes and some patient populations, the issues highlighted for efficacy also apply to safety, resulting in an incomplete safety profile of medical cannabis. For cost-effectiveness modelling, the absolute change in numeric rating scale (NRS) score was the preferred efficacy outcome measure in the chronic pain models, and the proportion of responders at ≥30% reduction in NRS score was the preferred efficacy outcome in the spasticity models. Resulting from this, usable efficacy evidence for cost-effectiveness modelling was available for two chronic pain populations (neuropathic pain and musculoskeletal pain) and two spasticity populations (MS and motor neuron disease). These studies reported the efficacy of THC:CBD spray (Sativex®). Using a healthcare perspective, lifetime horizon, and 3% discounting of costs and effects, THC:CBD spray in addition to SOC resulted in a minimal loss in quality-adjusted life years (QALYs) for neuropathic pain compared to SOC alone, and only small QALY gains for the other populations. In all models, the costs of THC:CBD spray in addition to SOC were higher than SOC alone. Sensitivity analyses showed that treatment effect, utility values, and baseline pain or spasticity scores were the most influential parameters. The budget impact estimates were surrounded by substantial uncertainty. Websites and documents from HTA agencies pointed out several relevant legal, social, ethical, and organisational issues related to the use and reimbursement of medical cannabis. While the research question encompassed all chronic pain and all spasticity populations, there was only sufficient evidence to assess the efficacy and safety of the use of medical cannabis for people with neuropathic pain, musculoskeletal pain, cancer pain, spasticity in MS and spasticity in motor neuron disease. However, due to incomplete, inconclusive, and inconsistent study findings, no conclusions could be drawn on the efficacy and safety of medical cannabis in these patient populations. In studies on medical cannabis, an unpredictable bias and uncertainty in the evidence base arises caused by the risk of unblinding of patients to their treatment allocation in combination with the patient-reported outcomes for the symptoms chronic pain and spasticity. Given these considerations it is neither possible to conclude that medical cannabis is an efficacious and safe treatment option for chronic pain and spasticity, nor to conclude that medical cannabis is not efficacious and safe for the treatment of chronic pain and spasticity. Future studies on medical cannabis to treat these symptoms will likely be exposed to similar challenges and limitations, of which only part can be solved with improved study designs and complete reporting of results. Modelling was performed to provide indicative cost-effectiveness estimates, and showed that THC:CBD spray in addition to SOC was associated with minimal changes in QALYs against additional costs compared to SOC alone. The generalisability of the cost-effectiveness and budget impact estimates to other populations, other medical cannabis products or other routes of administration is unknown. When considering reimbursement of medical cannabis for certain populations, relevant legal, social, ethical, and organisational issues should also be considered. For example, reimbursement of medical cannabis will be subject to different and interconnected Swiss laws with regard to cultivation, consumption, distribution, and prescription. In addition, reimbursement of medical cannabis may have social and ethical consequences, for example as a result of a gap between patient expectations and scientific evidence. Other concerns include accessibility restrictions, vulnerable populations at risk of unintended consequences, and illicit use. Furthermore, organisational challenges may arise in the supply and quality control of medical cannabis products.

Authors' methods: Systematic reviews were conducted adhering to international methodological standards. Systematic literature searches were performed in PubMed (MEDLINE), Embase.com, and other complementary databases to identify relevant efficacy, effectiveness, safety, and cost-effectiveness evidence. Only RCTs and economic evaluations were included in the corresponding searches. Data were extracted from the included studies in evidence tables, and the outcomes of the quality assessment were reported. The data on medical cannabis use for chronic pain was stratified in three subpopulations: cancer pain, neuropathic pain, and musculoskeletal pain. Data on medical cannabis use for spasticity was stratified in two subpopulations: multiple sclerosis (MS) and motor neuron disease. During the scoping phase, the systematic literature search on the cost-effectiveness of medical cannabis use in chronic pain and spasticity did not provide evidence for Switzerland. Therefore, cost-effectiveness models were developed, characterising the natural history of the disease in a patient’s lifetime in the Swiss clinical practice. The models were used to determine the cost-effectiveness of medical cannabis in addition to standard of care (SOC) to SOC alone for all subpopulations for which usable efficacy evidence was available. Non-systematic searches were performed to identify cost and health-related quality of life (expressed in utilities on a scale from 0 to 1) input for cost-effectiveness modelling. The uncertainty around input parameters was explored in sensitivity and scenario analyses. In addition, the projected budget impact was calculated, using input for the budget impact calculations were derived via a survey among clinical experts. Websites of HTA agencies were searched for information on social, legal, ethical, and organisational aspects related to pre-scribing medical cannabis. For these HTA domains, the evidence was described narratively.

Project Status: Completed

URL for project: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-projekte/medizinalcannabis.html

Year Published: 2021

URL for published report: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0049mcan-hta-report.pdf.download.pdf/h0049mcan-hta-report.pdf

URL for additional information: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-programm.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Switzerland

Organisation Name: Swiss Federal Office of Public Health (FOPH)

Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland

Contact Name: Stephanie Vollenweider

Contact Email: hta@bag.admin.ch

Copyright: Swiss Federal Office of Public Health