Supplementary Material for: Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation

<b><i>Introduction:</i></b> Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS). <b><i>Objectives:</i></b> We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain. <b><i>Methods:</i></b> A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time. <b><i>Results:</i></b> More than half (<i>n</i> = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (<i>p</i> = 0.034), and pain intensity scores verged on significance (<i>p</i> = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%). <b><i>Conclusion:</i></b> This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids.

<b><i>引言：</i></b> 澳大利亚已为慢性难治性疼痛患者开具药用大麻处方，但目前尚缺乏不同大麻素的安全性与有效性相关数据。本研究设计了一项观察性研究，旨在通过大麻接入诊所观察性研究（CACOS），收录在大麻接入诊所接受口服药用大麻制剂处方的患者的有效性、不良事件（adverse events, AEs）及健康相关生活质量（health-related quality of life, HRQoL）相关数据。
<b><i>研究目的：</i></b> 本研究旨在评估接受大麻素油制剂处方以治疗慢性疼痛的个体的有效性、报告的不良事件情况，以及患者报告结局指标（patient-reported outcomes）的变化。
<b><i>研究方法：</i></b> 本研究针对处方了Δ9-四氢大麻酚（Δ9-tetrahydrocannabinol）与大麻二酚（cannabidiol）油制剂、且疼痛症状持续至少3个月的患者开展横断面分析。由临床医师报告的不良事件按系统、器官、类别及发生频率进行分类整理。基于已发表的最小临床重要差异（minimal clinically important differences）分析患者问卷应答结果，以评估随时间推移健康相关生活质量的具有临床意义的变化。
<b><i>研究结果：</i></b> 超过半数受试者（<i>n</i> = 91/151, 60.3%）在观察期内发生至少1例不良事件，平均随访时长为133 ± 116天。本研究未报告严重不良事件。队列整体的患者报告疼痛影响评分显著降低（<i>p</i> = 0.034），疼痛强度评分接近统计学显著性（<i>p</i> = 0.053）。多数患者的睡眠（49.3%）与疲劳（35.6%）情况获得具有临床意义的改善。
<b><i>结论：</i></b> 本分析呈现了作为临床诊疗常规一部分所收集的真实世界数据。超过三分之一的患者从口服药用大麻中获益，鉴于其疼痛的难治性特征，这一结果具有重要临床价值。疼痛影响的缓解证实了该制剂的持续处方合理性，同时验证了本观察性方法作为评估药用大麻素治疗效力工具的有效性。