目的:基于新型信使RNA(mRNA)的疗法,目前在发展中,正在成为广泛的威胁生命和限制生命的遗传性肝病的有希望的潜在治疗方式,包括甲基丙二酸血症(MMA)和丙酸血症(PA)。然而,部分原因是它们的复杂性,它们可能会给医疗保健系统带来相当大的财务成本。这项研究的目的是综合与MMA和PA相关的成本和临床后果的现有证据,以便从英国付款人的角度使用早期成本效用模型对基于mRNA的新型疗法进行探索性经济评估。
方法:建立了一个马尔可夫模型来模拟与新型mRNA治疗相关的成本和结果,在假设的新生MMA和PA患者队列中,与饮食管理和器官移植(护理标准)的组合进行比较。确定了关键模型驱动因素,在给定孤儿疾病支付意愿阈值的情况下,我们进行了价格阈值分析,以估计未来mRNA治疗的基于价值的价格范围.
结果:mRNA治疗与MMA和PA患者中每患者一生增加的5.7和1.3质量调整生命年(QALYs)相关,分别。成本效益的主要驱动因素是接受基于mRNA的治疗和移植的患者的效用相对改善,以及mRNA治疗的费用。假设每个QALY获得的支付范围为100,000-300,000英镑,该模型证明mRNA治疗在MMA和PA中具有成本效益,年治疗费用分别为70,452-94,575英镑和31,313-36,695英镑.
结论:尽管MMA和PA缺乏强有力的证据基础,这个模型提供了一个有用的工具来估计成本效益,并告知基于价值的定价,基于mRNA的新疗法。我们的分析还确定了研究领域,这些领域在减少此类治疗的未来健康经济评估中的不确定性方面具有最大的价值。
OBJECTIVE: Novel messenger RNA (mRNA)-based therapies, currently in development, are emerging as a promising potential treatment modality for a broad range of life-threatening and life-limiting inherited liver diseases, including methylmalonic acidemia (MMA) and propionic acidemia (PA). However, owing in part to their complexity, they are likely to come at considerable financial cost to healthcare systems. The objective of this research was to synthesize available evidence on the costs and clinical consequences associated with MMA and PA for the purpose of exploratory economic evaluation of novel mRNA-based therapies using an early cost-utility model from the United Kingdom payer perspective.
METHODS: A Markov model was constructed to simulate the costs and outcomes associated with novel mRNA therapies, compared with a combination of dietary management and organ transplantation (standard of care) among hypothetical cohorts of new-born patients with MMA and PA. Key model drivers were identified, and a price threshold analysis was performed to estimate value-based price ranges for future mRNA therapies given willingness-to-pay thresholds for orphan diseases.
RESULTS: mRNA therapy was associated with an additional 5.7 and 1.3 quality-adjusted life-years (QALYs) gained per patient lifetime among patients with MMA and PA, respectively. Key drivers of cost-effectiveness were relative improvement in utility among patients who receive mRNA-based therapy and transplantation, and the cost of mRNA therapy. Assuming a willingness to pay range of £100,000-£300,000 per QALY gained, the model demonstrated mRNA therapy to be cost-effective in MMA and PA at an annual treatment cost of £70,452-£94,575 and £31,313-£36,695, respectively.
CONCLUSIONS: Despite the lack of a strong evidence base in MMA and PA, this model provides a useful tool to estimate the cost-effectiveness, and inform value-based pricing, of new mRNA-based therapies. Our analyses also identified areas for research that will have the greatest value in reducing uncertainty in future health economic evaluations of such treatments.