Institute for Medical Technology Assessment (iMTA), Erasmus University Rotterdam, Rotterdam, The Netherlands.
Novartis Pharma B.V., Amsterdam, The Netherlands.
Pharmacoeconomics. 2021 Apr;39(4):383-397. doi: 10.1007/s40273-021-01003-y. Epub 2021 Feb 19.
The emergence of gene therapies challenge health economists to evaluate interventions that are often provided to a small patient population with a specific gene mutation in a single dose with high upfront costs and uncertain long-term benefits. The objective of this study was to illustrate the methodological challenges of evaluating gene therapies and their implications by discussing four economic evaluations of voretigene neparvovec (VN) for the treatment of RPE65-mediated inherited retinal disease. The checklist for economic evaluations of gene therapies of Drummond et al. was applied to the economic evaluations of VN performed by US Institute for Clinical and Economic Review, two country adaptations of the company model in the UK and the Netherlands, and another US publication. The main differences in methodological choices and their impact on cost-effectiveness results were assessed and further explored with sensitivity analyses using the Dutch model. To enable comparison between the economic evaluations, costs were converted to US dollars. Different methodological choices were made in the economic evaluations of VN resulting in large differences in the incremental cost-effectiveness ratio varying from US$79,618 to US$643,813 per QALY. The chosen duration of treatment effect, source of utility values, discount rate and model structure had the largest impact on the cost-effectiveness. This study underlines the findings from Drummond et al. that standard methods can be used to evaluate gene therapies. However, given uncertainty about (particularly long-term) outcomes of gene therapies, guidance is required on the acceptable extrapolation of treatment effect of gene therapies and on how to handle the uncertainty around this extrapolation in scenario and sensitivity analyses to aid health technology assessment research and align submissions of future gene therapies.
基因疗法的出现给卫生经济学家带来了挑战，他们需要评估这些疗法，这些疗法通常针对具有特定基因突变的小部分患者群体，单次给予一剂高成本药物，且长期效益不确定。本研究的目的是通过讨论四种针对 RPE65 介导的遗传性视网膜疾病的 voretigene neparvovec（VN）治疗的经济评估，来说明评估基因疗法的方法学挑战及其意义。我们应用了 Drummond 等人的基因疗法经济评估清单，对美国临床和经济评论学会、英国和荷兰对公司模型的两次国家改编，以及另一个美国出版物对 VN 进行的经济评估进行评估。评估了方法选择的主要差异及其对成本效益结果的影响，并使用荷兰模型进行敏感性分析进一步探讨了这些差异。为了能够在经济评估之间进行比较，我们将成本转换为美元。VN 的经济评估中做出了不同的方法选择，导致增量成本效益比的差异很大，从每 QALY 的 79618 美元到 643813 美元不等。所选择的治疗效果持续时间、效用值来源、贴现率和模型结构对成本效益影响最大。本研究强调了 Drummond 等人的研究结果，即可以使用标准方法来评估基因疗法。然而，鉴于基因疗法的结果（特别是长期结果）存在不确定性，需要指导意见，说明基因疗法治疗效果的可接受外推，以及如何在情景分析和敏感性分析中处理这种外推的不确定性，以帮助卫生技术评估研究，并使未来基因疗法的提交保持一致。
