Kanavos Panos, Visintin Erica, Angelis Aris
Department of Health Policy and LSE Health-Medical Technology Research Group, London School of Economics and Political Science, London, UK.
Department of Health Policy and LSE Health-Medical Technology Research Group, London School of Economics and Political Science, London, UK.
Lancet Oncol. 2024 Dec;25(12):1644-1654. doi: 10.1016/S1470-2045(24)00505-9.
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).
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.
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 [1·44×10-9·09×10], 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 [1·04×10-3·00×10], p<0·0001, and RRR 0·30 [0·15-0·61], p=0·0008, respectively).
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.
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各国卫生技术评估（HTA）机构的建议用于决定哪些新疗法值得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些疗法。这一过程对于平衡优化患者治疗效果和确保财务可持续性这两个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结果以及获得积极HTA结果所需的时间，重点关注使用欧洲医学肿瘤学会临床获益程度量表（ESMO-MCBS）评估临床获益的作用。
在这项回顾性分析中，数据从六个国家及其各自的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）公开的HTA报告及相关来源中提取。我们评估了用于非治愈性环境中治疗实体瘤的新型癌症药物，这些药物具有已公布的ESMO-MCBS评分，并且在2011年1月1日至2020年12月31日期间至少经过了三个HTA机构的评估。以ESMO-MCBS评分为自变量，我们进行了描述性和多变量回归分析，以评估：（1）与上市许可和积极（无限制[列入清单]和有限制[有约束条件列入清单]）HTA结果之间的时间相关的因素；以及（2）与HTA结果相关的因素。
确定了67个在非治愈性环境中使用的药物-适应症对，六个HTA机构共审查了360份HTA提交材料（药物-适应症-国家三元组）。与上市许可和积极（无限制或有限制）HTA结果之间的间隔缩短显著相关的因素包括高ESMO-MCBS评分（即4或5，与低或平均评分1-3相比；每增加1个月的风险比[HR]为1.42[95%CI 1.11-1.81]，p=0.0055）、平行审查（与标准上市许可程序相比；HR 1.69[1.13-2.54]，p=0.011）、有风险分担协议或特殊资助安排（与无资助协议相比，HR分别为4.62[95%CI 2.51-8.51]，p<0.0001和HR 4.16[2.03-8.50]，p=0.0001），以及由特定HTA机构进行评估（泛加拿大肿瘤药物审查与英国国家卫生与临床优化研究所[NICE]相比，HR 2.82[1.68-4.75]，p=0.0001；法国卫生高级管理局与NICE相比，HR 5.70[2.87-11.33]，p<0.0001）。加速上市许可与获得积极HTA结果的时间延长显著相关（与标准许可程序相比；HR 0.70[95 %CI 0.51-0.95]，p=0.024）。积极的HTA结果（无限制和有限制）与高ESMO-MCBS评分显著相关（与低或平均ESMO-MCBS评分相比；相对风险比[RRR]分别为14.10[95%CI 3.54-56.20]，p=0.0002和RRR 4.52[1.90-10.75]，p=0.0006）以及对未满足医疗需求的认可（与未记录未满足需求相比，RRR分别为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（无限制和有限制）与为HTA提交材料提供信息的经济模型输入的不确定性呈负相关（与未记录不确定性相比，RRR分别为0.28[0.10-0.78]，p=0.014和RRR 0.45[0.25-0.82]，p=0.010）。关于与国家相关的影响，在魁北克进行评估（与英格兰相比）时观察到与积极的HTA结果（无限制和有限制）呈负相关（RRR分别为1.15×10[1.44×10-9.09×10]，p<0.0001和RRR 0.33[0.24-0.46]，p<0.0001），在澳大利亚进行评估（与英格兰相比）时也观察到与积极的HTA结果呈负相关（RRR分别为1.78×10[1.04×10-3.00×10]，p<0.0001和RRR 0.30[0.15-0.61]，p=0.0008）。
有几个因素影响了新型癌症药物的HTA结果。高ESMO-MCBS评分（定义为表明有实质性临床获益）增加了获得积极HTA结果的可能性，并缩短了上市许可和HTA结果之间的间隔，且这种关联不受其他变量影响。影响HTA结果的其他因素包括证据不确定性和未满足的医疗需求。与国家相关的差异存在于获得HTA结果的时间以及一些国家与其他国家相比获得积极（有限制或无限制）结果的倾向方面。
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