背景:由于长期结果不确定,在报销决策期间对一次性治疗进行经济学评估具有挑战性。ELIANA试验提供的5年结果数据和tisagenlecleucel的真实世界证据,第一个嵌合抗原受体T细胞(CAR-T)治疗,提供了重新评估先前成本效益分析(CEA)预测的机会。
目的:对tisagenlecleucel治疗儿童/青年复发性或难治性急性淋巴细胞白血病(r/rALL)的既往CEA进行系统的文献综述(SLR),并评估最近获得的影响ELIANA的5年疗效数据和更新的CEA模型中CAR-T制造的进展。
方法:搜索OVIDMEDLINE/Embase和健康技术评估(HTA)数据库,以英文报告tisagenlecleucelforr/rALL的成本效益结果。SLR中包括了公开报告的增量成本效益比(ICER)的评估。按照PRISMA指南进行研究筛选和数据抽象。提取的数据包括国家/货币,透视,临床试验证据,模型结构,长期疗效外推方法(即,总生存期[OS]),时间地平线,贴现率,和结果(即,生命年[LY],质量调整的LY[QALY],和ICER)。Wakase等人报道的CEA模型。使用ELIANA的5年OS数据和实际实践中告知的CAR-T输注率进行了更新。
结果:SLR中包含了与15项独特研究相对应的16条记录(11篇出版物和5篇HTA报告);所有记录都是从各自国家的医疗保健系统角度进行的。大多数研究发现tisagenlecleucel具有成本效益,但所有研究预计tisagenlecleucel的3年和5年OS率低于观察到的3年和5年OS率,分别,来自5年ELIANA数据。当应用来自最新ELIANA数据切割的更新的OS预测和更高的输注率92.5%(根据现实世界的输注率)-96.0%(根据制造商的成功率)到Wakase等人的CEA时。,tisagenlecleucel的相关QALY从11.6增加到14.6-15.0,LYs从13.3增加到17.0-17.5。因此,在更新的CEA模型中,tisagenlecleucel的ICER从¥2,035,071降至¥1,787,988-¥1,789,048与blinatumab相比,从¥2,644,702降至¥2,257,837-¥2,275,181与氯法拉滨联合治疗相比。
结论:考虑到最近的试验和实际数据,在发布tisagenlecleucel可能的成本效益时的预测似乎低估了其最终的经济价值。为了平衡初始评估的不确定性与提供新型肿瘤治疗的需要,随着新数据的出现,付款人可以考虑灵活的报销政策以及正在进行的评估。
BACKGROUND: Economic evaluation of one-time therapies during reimbursement decision-making is challenging due to uncertain long-term outcomes. The availability of 5-year outcome data from the ELIANA trial and real-world evidence of tisagenlecleucel, the first chimeric antigen receptor T-cell (CAR-T) therapy, presents an opportunity to re-evaluate the predictions of prior cost-effectiveness analyses (CEAs).
OBJECTIVE: To conduct a systematic literature review (SLR) of prior CEAs of tisagenlecleucel for pediatric/young adult relapsed or refractory acute lymphoblastic leukemia (r/r ALL) and evaluate the impact of recently available 5-year efficacy data from ELIANA and advances in CAR-T manufacturing in an updated CEA model.
METHODS: OVID MEDLINE/Embase and health technology assessment (HTA) databases were searched for full-text economic evaluations in English reporting cost-effectiveness results for tisagenlecleucel for r/r ALL. Evaluations with publicly reported incremental cost-effectiveness ratios (ICERs) were included in the SLR. Study screening and data abstraction were conducted following PRISMA guidelines. Data extracted included the country/currency, perspective, clinical trial evidence, model structures, long-term efficacy extrapolation approaches (i.e., overall survival [OS]), time horizon, discount rates, and outcomes (i.e., life years [LY], quality-adjusted LY [QALY], and ICERs). The CEA model reported in Wakase et al. was updated using 5-year OS data from ELIANA and the CAR-T infusion rate informed by real-world practice.
RESULTS: Sixteen records corresponding to 15 unique studies were included in the SLR (11 publications and 5 HTA reports); all were conducted from the health care system perspective of the respective countries. Most studies found tisagenlecleucel to be cost effective, but all studies\' projected 3- and 5-year OS rates for tisagenlecleucel were lower than the observed 3- and 5-year rates, respectively, derived from 5-year ELIANA data. When applying updated OS projections from the most recent ELIANA data cut and higher infusion rates of 92.5% (per the real-world infusion rate)-96.0% (per the manufacturer success rate) to the CEA of Wakase et al., the associated QALYs for tisagenlecleucel increased from 11.6 to 14.6-15.0, and LYs increased from 13.3 to 17.0-17.5. Accordingly, the ICERs for tisagenlecleucel decreased from ¥2,035,071 to ¥1,787,988-¥1,789,048 versus blinatumomab and from ¥2,644,702 to ¥2,257,837-¥2,275,181 versus clofarabine combination therapy in the updated CEA model.
CONCLUSIONS: Projections at launch of the likely cost effectiveness of tisagenlecleucel appear to have underestimated its ultimate economic value given more recent trial and real-world data. To balance uncertainty in initial valuation with the need to provide access to novel oncology therapies, payers can consider flexible reimbursement policies alongside ongoing assessments as new data emerge.