Design Considerations for Medicinal Cannabis Clinical Trials in People Receiving Palliative Care

Context: Evaluating medicinal cannabis in clinical trials is important for informing its efficacy and safety in clinical care. Alongside the inherent practical challenges of conducting clinical trials in people receiving palliative care, operationalizing clinical trials with a medicinal cannabis product requires additional consideration of legal, regulatory, ethical, feasibility, pharmacological and product requirements. Objectives: This manuscript aims to explore these considerations when operationalizing medicinal cannabis clinical trials in people receiving palliative care. Methods: Our Phase I/IIb trial examined pharmacokinetic, toxicity and secondary (efficacy) outcomes of a vaporized medicinal cannabis product for anorexia in people with advanced cancer (ACTRN12616000516482). Using action research methodology, notes from trial investigator meetings served as an audit trail for the planning and execution of the trial. These data were integrated and synthesized to reveal key design considerations for operationalizing medicinal cannabis trials evaluating symptom control in people receiving palliative care. Results: Six key considerations emerged including: 1) Operating within medicinal cannabis legislation; 2) Biological plausibility of cannabinoid type(s) and impact on target symptoms; 3) Standardising cannabinoid content, mode of administration, dosage and packaging; 4) Ethical and safety considerations; 5) Optimizing trial site operationalization; and 6) Pharmacy dispensing, storage and security of product. Learnings and recommendations for future trials are also discussed. Conclusion: This study explores the learnings and challenges involved in designing and conducting medicinal cannabis trials for symptom management in people receiving palliative care. These insights gained from our experience can inform the optimal design and operationalization of future medicinal cannabis trials in cancer and other chronic conditions.