ScHARR, University of Sheffield, Sheffield, UK.
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Pharmacoeconomics. 2019 Jan;37(1):7-18. doi: 10.1007/s40273-018-0680-z.
As part of its Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of ibrutinib (Janssen) to submit evidence on the clinical and cost effectiveness of ibrutinib for treating Waldenström's macroglobulinaemia (WM). The School of Health and Related Research Technology Assessment Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of ibrutinib based on the company's submission to NICE. The clinical evidence was derived from one phase II, single-arm, open-label study of ibrutinib in adult patients with WM who had received at least one prior therapy (Study 1118E) and an indirect comparison using a matched cohort from a retrospective European chart review of patients receiving various treatments for WM. The indirect comparison suggested a hazard ratio for progression-free survival (PFS) of 0.25 (95% confidence interval 0.11-0.57). The ERG had concerns regarding the high risk of bias in Study 1118E, the limited generalisability of the study, and the absence of randomised controlled trial evidence. The company's Markov model assessed the cost effectiveness of ibrutinib versus rituximab/chemotherapy for patients with relapsed/refractory (R/R) WM from the perspective of the National Health Service (NHS) and Personal Social Services (PSS) over a lifetime horizon. Based on the company's original Patient Access Scheme (PAS), the company's probabilistic model generated an incremental cost-effectiveness ratio (ICER) for ibrutinib versus rituximab/chemotherapy of £58,905 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG's preferred analysis, which corrected cost errors and used the observed mortality rate from Study 1118E, generated a probabilistic ICER of £61,219 per QALY gained. Based on this amended model, additional exploratory analyses produced ICERs for ibrutinib that were > £60,000 per QALY gained. Subsequently, the company offered to provide ibrutinib at a price that resulted in ibrutinib being cost effective within the Cancer Drugs Fund (CDF). The Committee recommended ibrutinib for use in the CDF as an option for treating WM in adults who have had at least one prior therapy, only if the conditions in the managed access agreement for ibrutinib are followed.
作为其单一技术评估（STA）过程的一部分，英国国家卫生与保健优化研究所（NICE）邀请伊布替尼（杨森）的制造商提交关于伊布替尼治疗华氏巨球蛋白血症（WM）的临床和成本效益的证据。谢菲尔德大学健康与相关研究技术评估小组受委托担任独立证据审查小组（ERG）。该 ERG 根据公司向 NICE 的提交内容，对伊布替尼的临床和成本效益进行了关键评估。临床证据来自一项针对接受至少一种先前治疗的 WM 成年患者的伊布替尼的 II 期、单臂、开放标签研究（研究 1118E），以及对接受 WM 各种治疗的患者进行回顾性欧洲图表审查的匹配队列的间接比较。间接比较表明无进展生存期（PFS）的风险比为 0.25（95%置信区间 0.11-0.57）。ERG 对研究 1118E 的高偏倚风险、研究的普遍适用性有限以及缺乏随机对照试验证据表示关注。该公司的 Markov 模型从英国国家医疗服务体系（NHS）和个人社会服务（PSS）的角度评估了伊布替尼与利妥昔单抗/化疗在复发/难治性（R/R）WM 患者中的成本效益，时间范围为终身。基于公司原始的患者准入计划（PAS），公司的概率模型生成了伊布替尼与利妥昔单抗/化疗的增量成本效益比（ICER），每增加一个质量调整生命年（QALY）的成本为 58905 英镑。在对模型进行批评后，ERG 的首选分析纠正了成本错误，并使用了研究 1118E 的观察死亡率，得出了每增加一个 QALY 的成本效益比为 61219 英镑。基于此修改后的模型，进一步的探索性分析得出了伊布替尼的 ICER 超过每增加一个 QALY 60000 英镑。随后，该公司提出以一种使伊布替尼在癌症药物基金（CDF）中具有成本效益的价格提供伊布替尼。委员会建议将伊布替尼纳入 CDF 中，作为治疗至少接受过一次治疗的 WM 成年患者的一种选择，前提是遵循伊布替尼管理准入协议中的条件。
