1 Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada.
2 Costello Medical, Cambridge, United Kingdom.
J Manag Care Spec Pharm. 2019 Apr;25(4):490-498. doi: 10.18553/jmcp.2019.25.4.490.
Cost-effectiveness analyses tend not to take into account the availability of lower-priced generics following loss of exclusivity (LOE) of branded products. By not considering these generics, which are typically adopted quickly, total costs are likely to be overestimated and may be unreflective of real-world payer conditions in the United States.
To assess the impact of including future price reductions following LOE on the cost-effectiveness of fingolimod versus intramuscularly administered interferon beta-1a (IM IFNβ-1a) as treatments for multiple sclerosis.
This model was adopted from a previously published Markov model and was conducted from a U.S. payer perspective over a 10-year time horizon. Patients with relapsing-remitting multiple sclerosis entered the model and received either fingolimod (an oral therapy) or IM IFNβ-1a (an injectable). These treatments reflect the interventions studied in the TRANSFORMS randomized clinical trial. Clinical, cost, and utility inputs were based on a recent cost-effectiveness review of therapies for multiple sclerosis. To model LOE, price reductions and the proportion of patients switching to generic versions following LOE were based on published estimates. Price reductions varied to reflect the difference in product types (oral vs. large molecule injectable). Assumptions were also made around the proportion of patients switching to generic versions over time following LOE and the projected date of LOE. Outcomes included per-patient total direct costs (medication, administration and monitoring, and disease-related costs including relapses), quality-adjusted life-years, and the incremental cost per quality-adjusted life-year.
Assuming no price reductions following LOE, fingolimod was considered cost-effective versus IM IFNβ-1a ($118,434 per quality-adjusted life-year), despite having higher total direct costs over 10 years ($475,740 vs. $446,792). When including future price reductions following LOE, total direct costs were reduced with fingolimod and were lower than those accrued with IM IFNβ-1a over the model time horizon ($308,570 vs. $442,653). Cost-effectiveness results were sensitive to changes in both clinical parameters and medication costs. Scenario analyses demonstrated that an earlier date of LOE was associated with lower total costs.
Health economic models may predict higher total costs when the price reductions following LOE are not considered. Here, oral fingolimod was seen to be cost-saving versus IM IFNβ-1a over the model time horizon when such price reductions were included. The cost implications of not accounting for future price changes may determine whether an intervention is considered cost-effective and as such may influence reimbursement decisions based on cost-effectiveness thresholds. Multiple product types (e.g., oral, injectable, and infused agents) have been approved for use as treatments for multiple sclerosis in the United States, and LOE is likely to have a different effect on each of these therapies.
This study was funded by Novartis Pharmaceuticals Corporation. Hua and Hersh report consulting fees from Novartis for work on this study. Hua also reports speaking, advisory board, and consulting fees from Biogen, Genzyme, Teva, EMD Serono, Genentech, TG Therapeutics, and Novartis for activities outside of this study. Hersh also reports speaking and consulting fees from Novartis, Biogen, Genzyme, Genentech, and EMD Serono for activities outside of this study, and research grants from PCORI and Biogen. At the time of this research, Morten and Kusel were paid employees of Costello Medical, which was contracted by Novartis to undertake some of this study's work. Lin, Cave, Herrera, and Ko were paid employees of Novartis at the time of this research. Cave, Herrera, and Ko also report owning stock in Novartis Pharmaceuticals. Varga provided services to Novartis at the time of this research and has nothing further to disclose. This research was presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2017; March 27-30, 2017; Denver, CO.
在品牌产品失去专有权后（LOE），成本效益分析往往没有考虑到更便宜的仿制药的可用性。由于没有考虑到这些仿制药（通常很快被采用），总成本可能被高估，并且可能不符合美国实际支付者的情况。
评估在考虑 LOE 后未来价格降低对芬戈莫德与肌内注射干扰素β-1a（IM IFNβ-1a）治疗多发性硬化症的成本效益的影响。
该模型从之前发表的一个马尔可夫模型中采用，在美国支付者视角下进行，时间跨度为 10 年。复发缓解型多发性硬化症患者进入模型并接受芬戈莫德（口服治疗）或 IM IFNβ-1a（注射治疗）。这些治疗反映了 TRANSFORMS 随机临床试验中研究的干预措施。临床、成本和效用输入基于最近对多发性硬化症治疗的成本效益评估。为了模拟 LOE，价格降低和 LOE 后患者转向仿制药的比例是基于已发表的估计。价格降低因产品类型（口服与大分子注射）的差异而有所不同。还假设 LOE 后患者转向仿制药的比例以及 LOE 的预计日期会随着时间的推移而变化。结果包括每位患者的总直接成本（药物、管理和监测以及包括复发在内的疾病相关成本）、质量调整生命年和增量成本每质量调整生命年。
假设 LOE 后没有价格降低，芬戈莫德与 IM IFNβ-1a 相比被认为是具有成本效益的（每质量调整生命年 118434 美元），尽管在 10 年内总直接成本更高（475740 美元比 446792 美元）。当包括 LOE 后未来的价格降低时，芬戈莫德的总直接成本降低，并且在模型时间范围内低于 IM IFNβ-1a 的成本（308570 美元比 442653 美元）。成本效益结果对临床参数和药物成本的变化均敏感。情景分析表明，LOE 日期较早与总费用较低相关。
健康经济模型在不考虑 LOE 后价格降低的情况下可能会预测更高的总成本。在这里，当包括这种价格降低时，口服芬戈莫德被认为比 IM IFNβ-1a 在模型时间范围内具有成本效益。不考虑未来价格变化的成本影响可能会决定干预措施是否被认为具有成本效益，并且因此可能会影响基于成本效益阈值的报销决策。多种产品类型（例如，口服、注射和输注剂）已被批准在美国用于治疗多发性硬化症，LOE 可能对这些治疗方法中的每一种都有不同的影响。
本研究由诺华制药公司资助。Hua 和 Hersh 报告了因这项研究而从诺华制药公司获得的咨询费。Hua 还报告了因不在这项研究之外的活动而从 Biogen、Genzyme、Teva、EMD Serono、Genentech、TG Therapeutics 和 Novartis 获得的演讲、顾问委员会和咨询费。Hersh 还报告了因不在这项研究之外的活动而从 Novartis、Biogen、Genzyme、Genentech 和 EMD Serono 获得的演讲和咨询费，以及从 PCORI 和 Biogen 获得的研究赠款。在进行这项研究时，Morten 和 Kusel 是 Costello Medical 的受雇员工，该公司受诺华制药公司委托开展了这项研究的部分工作。Lin、Cave、Herrera 和 Ko 是诺华制药公司在进行这项研究时的受雇员工。Cave、Herrera 和 Ko 还报告拥有诺华制药公司的股票。Varga 在进行这项研究时为诺华制药公司提供服务，没有其他需要披露的信息。这项研究在 2017 年 3 月 27 日至 30 日举行的 AMCP 管理式医疗和专科药房年度会议上以海报形式展示。
