Institute of Pharmaceutical Medicine (ECPM), University of Basel, Klingelbergstrasse 61, CH-4056, Basel, Switzerland.
Novartis Pharma Schweiz AG, Rotkreuz, ZG, Switzerland.
BMC Health Serv Res. 2022 Jun 28;22(1):837. doi: 10.1186/s12913-022-08211-y.
We aimed to evaluate the cost-effectiveness of voretigene neparvovec (VN) compared with standard of care (SoC) for patients with inherited retinal disease (IRD) caused by a biallelic RPE65-mutation. VN is a live, non-replicating adeno-associated virus serotype 2 (AAV2). SoC is best supportive care provided to patients with visual impairment. Patients under SoC may experience progressive vision loss leading to complete blindness.
We adapted a previously published Markov cohort model for IRD. An annual cycle length, life-long time horizon, discount rate of 3% for cost and health outcomes, and Swiss health system perspective were used. Data from a randomised controlled phase III trial of VN versus SoC (ClinicalTrials.gov: NCT00999609) were used to estimate transitions between health states in the first year, after which VN patients were assumed to remain for 39 subsequent years in the health state they were in at the end of the first year. After the 40 year for VN patients and 1 year for SoC patients, visual decline was modelled based on observational data on the natural progression of the disease. Quality-adjusted life years (QALYs) were calculated based on an external study which elicited clinicians' EQ-5D-5L-based utility estimates for IRD patients with a RPE65-mutation. Costs (Swiss Francs (CHF), year 2018-2019) included drug acquisition/ administration, adverse events, testing for sufficient viable retinal cells, and healthcare-related costs of blindness. Societal costs of blindness were added in a complementary analysis. Robustness of the model results were tested in sensitivity and scenario analyses.
For the base-case, VN resulted in incremental costs per patient of CHF 764'402 (VN: CHF 901'654, SoC: CHF 137'252), incremental blindness-free years of 7.67 (VN: 28.32, SoC: 20.65) and incremental QALYs of 6.73 (VN: 18.35, SoC: 11.62), leading to an incremental cost-effectiveness ratio of CHF 113'526 per QALY gained. In probabilistic sensitivity analysis, the cost-effectiveness of VN was better than CHF 100,000 per QALY gained in 41% of iterations. For the scenario analysis in which a societal perspective was adopted and for which a 50% work-related productivity loss from blindness was assumed, incremental costs of CHF 423,837 and an ICER of CHF 62'947 per QALY gained were produced. The scenario assuming VN treatment effect lasts for 20 years produced an ICER of CHF 156'171 per QALY gained, whereas assuming a life-long VN treatment effect resulted in an ICER of CHF 96'384 per QALY gained.
The incremental cost-effectiveness ratio of VN compared to the SoC was estimated to be CHF 113'526 and CHF 62'947 per QALY gained, respectively, from a Swiss healthcare system, and societal perspective assuming a 50% productivity loss.
我们旨在评估 voretigene neparvovec（VN）与标准护理（SoC）相比，用于治疗由双等位基因 RPE65 突变引起的遗传性视网膜疾病（IRD）患者的成本效益。VN 是一种活的、非复制的腺相关病毒血清型 2（AAV2）。SoC 是为视力受损患者提供的最佳支持性护理。接受 SoC 的患者可能会经历视力逐渐下降，导致完全失明。
我们改编了先前发表的用于 IRD 的马尔可夫队列模型。采用年度周期长度、终生时间范围、3%的成本和健康结果贴现率以及瑞士卫生系统视角。使用来自 VN 与 SoC 随机对照 III 期试验（ClinicalTrials.gov：NCT00999609）的数据来估计第一年中健康状态之间的转换，此后，VN 患者假设在第一年结束时处于的健康状态下再持续 39 年。对于 VN 患者的 40 年和 SoC 患者的 1 年后，根据对疾病自然进展的观察性数据来模拟视力下降。质量调整生命年（QALY）是基于一项外部研究计算的，该研究征求了临床医生对具有 RPE65 突变的 IRD 患者基于 EQ-5D-5L 的效用估计。成本（瑞士法郎（CHF），2018-2019 年）包括药物获取/管理、不良事件、检测足够存活的视网膜细胞以及与失明相关的医疗保健成本。在补充分析中加入了失明的社会成本。通过敏感性和情景分析测试了模型结果的稳健性。
对于基本情况，VN 导致每位患者的增量成本为 CHF 764'402（VN：CHF 901'654，SoC：CHF 137'252），增加的无失明年数为 7.67（VN：28.32，SoC：20.65）和增加的 QALY 为 6.73（VN：18.35，SoC：11.62），导致每增加一个 QALY 的增量成本效益比为 CHF 113'526。在概率敏感性分析中，VN 的成本效益在 41%的迭代中优于每 QALY 增加 CHF 100,000 的标准。在采用社会视角并假设失明导致 50%工作相关生产力损失的情景分析中，产生了 CHF 423,837 的增量成本和 CHF 62'947 的增量成本效益比。假设 VN 治疗效果持续 20 年的情景产生了每 QALY 增加 CHF 156'171 的增量成本效益比，而假设终身 VN 治疗效果则产生了每 QALY 增加 CHF 96'384 的增量成本效益比。
从瑞士医疗保健系统和社会角度（假设失明导致 50%的生产力损失）来看，VN 与 SoC 相比的增量成本效益比分别估计为 CHF 113'526 和 CHF 62'947，每 QALY 增加。
