Background

Recommendations by countries’ health technology assessment (HTA) agencies are used to decide which new therapies warrant the allocation of limited health-care resources to make them available through publicly funded health systems. This process is of public health importance for balancing the dual aims of optimising patient outcomes while ensuring financial sustainability. We evaluated which factors affect HTA outcomes and the time to positive HTA outcome, focussing on the role of clinical benefit evaluated with the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).

Methods

In this retrospective analysis, data were extracted from publicly available HTA reports and related sources from six country settings and their respective HTA agencies (Australia, Canada, England, France, the Canadian province of Quebec, and Scotland). We evaluated new cancer medicines for treating solid tumours in a non-curative setting with published ESMO-MCBS scores and that had been assessed by at least three HTA agencies between Jan 1, 2011, and Dec 31, 2020. Using ESMO-MCBS score as an independent variable, we did descriptive and multivariable regression analyses to evaluate: (1) factors associated with the time between marketing authorisation and positive (unrestricted [List] and restricted [List with Constraints]) HTA outcome; and (2) factors associated with HTA outcomes.

Findings

67 medicine–indication pairs used in non-curative settings were identified, totalling 360 HTA submissions (medicine–indication–country triplets) reviewed by the six HTA agencies. Factors significantly associated with a reduced interval between marketing authorisation and a positive (unrestricted or restricted) HTA outcome included a high ESMO-MCBS score (ie, 4 or 5, vs a low or average score of 1–3; hazard ratio [HR] per 1 month increment 1·42 [95% CI 1·11–1·81], p=0·0055), parallel review (vs standard marketing authorisation process; HR 1·69 [1·13–2·54], p=0·011), having a risk-sharing agreement or special funding arrangements (vs no funding agreement, HR 4·62 [95% CI 2·51–8·51], p<0·0001, and HR 4·16 [2·03–8·50], p=0·0001, respectively), and assessment by particular HTA agencies (pan-Canadian Oncology Drug Review vs National Institute for Health and Care Excellence [NICE], HR 2·82 [1·68–4·75], p=0·0001; and Haute Autorité de Santé vs NICE, HR 5·70 [2·87–11·33], p<0·0001). Accelerated marketing authorisation was significantly associated with a longer time to positive HTA outcome (vs standard authorisation process; HR 0·70 [95% CI 0·51–0·95], p=0·024). Positive HTA outcomes (both unrestricted and restricted) were significantly associated with a high ESMO-MCBS score (vs low or average ESMO-MCBS score; relative risk ratio [RRR] 14·10 [95% CI 3·54–56·20], p=0·0002, and RRR 4·52 [1·90–10·75], p=0·0006, respectively) and acknowledgment of unmet medical need (vs unmet need not recorded, RRR 22·73 [5·51–93·73], p<0·0001, and RRR 1·87 [1·18–2·97], p=0·0075, respectively). By contrast, positive HTA outcomes (unrestricted and restricted) were inversely associated with uncertainties regarding inputs to economic models informing HTA submissions (vs uncertainties not recorded, RRR 0·28 [0·10–0·78], p=0·014, and RRR 0·45 [0·25–0·82], p=0·010, respectively). Regarding country-relevant effects, inverse associations with positive HTA outcomes (both unrestricted and restricted) were observed for assessment in Quebec (vs England; RRR 1·15×10⁻⁶ [1·44×10⁻⁷–9·09×10⁻⁶], p<0·0001, and RRR 0·33 (0·24–0·46), p<0·0001, respectively) and for assessment in Australia (vs England; RRR 1·78×10⁻⁶ [1·04×10⁻⁸–3·00×10⁻⁴], p<0·0001, and RRR 0·30 [0·15–0·61], p=0·0008, respectively).

Interpretation

Several factors informed HTA outcomes for new cancer medicines. A high ESMO-MCBS score, defined as indicating substantial clinical benefit, increased the likelihood of a positive HTA outcome and shortened the interval between marketing authorisation and HTA outcome, and this association was not affected by other variables. Additional factors informing HTA outcomes include evidence uncertainties and unmet medical need. Country-relevant differences exist in the time-to-HTA outcome and the propensity of some countries to achieve positive (restricted or unrestricted) outcomes compared with others.

Funding

None.

中文翻译：

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使用 ESMO-Magnitude of Clinical Benefit Scale 指导 HTA 关于癌症药物承保范围和报销的建议：回顾性分析

 背景

各国卫生技术评估 （HTA） 机构的建议用于决定哪些新疗法需要分配有限的医疗保健资源，以便通过公共资助的卫生系统提供。这个过程对于平衡优化患者结果和确保财务可持续性的双重目标具有公共卫生重要性。我们评估了哪些因素会影响 HTA 结局和达到阳性 HTA 结局的时间，重点关注使用欧洲肿瘤内科学会临床益处量表 （ESMO-MCBS） 评估的临床益处的作用。

 方法

在这项回顾性分析中，数据是从 6 个国家/地区及其各自的 HTA 机构（澳大利亚、加拿大、英格兰、法国、加拿大魁北克省和苏格兰）的公开可用的 HTA 报告和相关来源中提取的。我们通过已发布的 ESMO-MCBS 评分评估了在非治愈性环境中治疗实体瘤的新癌症药物，并且在 2011 年 1 月 1 日至 2020 年 12 月 31 日期间已由至少三个 HTA 机构评估。使用 ESMO-MCBS 评分作为自变量，我们进行了描述性和多变量回归分析以评估： （1） 与上市许可与阳性 （非限制性 [列表] 和限制性 [有限制] 列表] HTA 结果之间的时间相关的因素;（2） 与 HTA 结局相关的因素。

 发现

确定了 67 个用于非治愈性的药物-适应症对，总共有 360 个 HTA 提交（药物-适应症-国家三元组），由 6 个 HTA 机构审查。与上市许可与阳性（不受限制或受限）HTA 结局之间间隔缩短显著相关的因素包括高 ESMO-MCBS 评分（即 4 或 5，与低评分或平均评分 1-3;每 1 个月增加风险比 [HR] 1·42 [95% CI 1·11–1·81]，p=0·0055），平行评价（与标准上市许可流程相比;HR 1·69 [1·13–2·54]，p=0·011），具有风险分担协议或特殊资助安排（与无资助协议相比，HR 4·62 [95% CI 2·51–8·51]，分别为 p<0·0001 和 HR 4·16 [2·03–8·50]，p=0·0001），以及特定 HTA 机构的评估（泛加拿大肿瘤药物审查与国家卫生与临床优化研究所 [NICE]，以及 HR 2·82 [1·68–4·75]，p=0·0001;和 Haute Autorité de Santé vs NICE，HR 5·70 [2·87–11·33]，p<0·0001）。加速上市许可与较长的 HTA 阳性结局时间显著相关（与标准授权流程相比;HR 0·70 [95% CI 0·51–0·95]，p=0·024）。阳性 HTA 结局（不受限制和限制）与高 ESMO-MCBS 评分（与低或平均 ESMO-MCBS 评分相比;相对风险比 [RRR] 14·10 [95% CI 3·54–56·20]，p=0·0002 和 RRR 4·52 [1·90–10·75]，p=0·0006）和承认未满足的医疗需求（与未满足的需求相比，未记录、 分别为 RRR 22·73 [5·51–93·73]，p<0·0001 和 RRR 1·87 [1·18–2·97]，p=0·0075）。 相比之下，积极的 HTA 结果（不受限制和受限）与为 HTA 提交提供信息的经济模型输入的不确定性呈负相关（与未记录的不确定性相比，RRR 分别为 0·28 [0·10–0·78]、p=0·014 和 RRR 0·45 [0·25–0·82]，p=0·010）。关于国家相关效应，在魁北克省观察到与阳性 HTA 结果（不受限制和受限）呈负相关（与英格兰相比;RRR 1·15×10⁻⁶ [1·44×10⁻⁷–9·09×10⁻⁶]，p<0·0001 和 RRR 0·33（分别为 0·24–0·46），p<0·0001）和澳大利亚评估（与英格兰相比;RRR 1·78×10⁻⁶ [1·04×10⁻⁸–3·00×10⁻⁴]，p<0·0001 和 RRR 0·30 [0·15–0·61]，p=0·0008）。

 解释

几个因素影响了新癌症药物的 HTA 结果。高 ESMO-MCBS 评分（定义为表明显著的临床益处）增加了 HTA 阳性结局的可能性，并缩短了上市许可和 HTA 结局之间的间隔，并且这种关联不受其他变量的影响。影响 HTA 结局的其他因素包括证据不确定性和未满足的医疗需求。与其他国家相比，一些国家/地区在 HTA 结局的时间和实现积极（限制性或非限制性）结局的倾向方面存在国家相关性差异。

 资金

 没有。