Danova Marco, Chiroli Silvia, Rosti Giovanni, Doan Quan V
Medical Oncology IRCCS Foundation S. Matteo, Pavia, Italy.
Tumori. 2009 Mar-Apr;95(2):219-26. doi: 10.1177/030089160909500214.
Febrile neutropenia (FN) is a major complication of chemotherapy and is associated with substantial morbidity, mortality and costs. The aim of this study was to evaluate the cost-effectiveness of primary prophylaxis with, pegfilgrastim versus six-day filgrastim in preventing FN in Italian patients with early-stage breast cancer receiving adjuvant chemotherapy associated with a > or = 20% FN risk.
The pharmacoeconomic evaluation was based on a decision-analytic model taking into account the possible consequences of FN (e.g., death and reduction/delay of chemotherapy dose). Parameters included in the model were relative risk of FN with pegfilgrastim versus six-day filgrastim; direct costs (drug purchase and FN-related hospitalizations); relative risk of relative dose intensity < 85% with pegfilgrastim versus filgrastim; impact on long-term survival due to relative dose intensity < 85%; and impact of age on FN and relative dose intensity < 85%.
Under base-case assumptions, pegfilgrastim was cost-effective compared to six-day filgrastim in Italy. The estimated cost, life expectancy and quality-adjusted life years per person for pegfilgrastim were Euro 3078, 16.47 years, and 15.32; the corresponding figures for six-day filgrastim were Euro 3033, 16.35 years, and 15.22. The corresponding incremental cost-effectiveness ratio with pegfilgrastim was Euro 409 per life-year gained and Euro 429 per quality-adjusted life year gained. One-way sensitivity analyses showed that the results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim. The results were moderately sensitive to the cost of pegfilgrastim and filgrastim, cost of drug administration, cost of FN hospitalization, and number of chemotherapy cycles. Pegfilgrastim remained cost-effective, with an incremental cost-effectiveness ratio well below the accepted limit of Euro 50,000 per life year gained in all one-way sensitivity analyses. A two-way sensitivity analysis on cost of drugs showed a range of pegfilgrastim dominance over six-day filgrastim.
At the current official price in Italy, primary prophylaxis with pegfilgrastim improved health outcomes with a very limited cost increase for the National Health Service payer. Even when very low prices of filgrastim and high prices of pegfilgrastim were considered in the model, the resulting incremental cost-effectiveness ratio remained well within the acceptable cost-effectiveness limit of Euro 50,000/quality-adjusted life year.
发热性中性粒细胞减少症（FN）是化疗的主要并发症，与较高的发病率、死亡率及成本相关。本研究旨在评估聚乙二醇化重组人粒细胞刺激因子（pegfilgrastim）与六日疗程重组人粒细胞刺激因子（filgrastim）用于意大利早期乳腺癌患者辅助化疗中预防FN的成本效益，这些患者发生FN的风险≥20%。
药物经济学评估基于一个决策分析模型，该模型考虑了FN的可能后果（如死亡以及化疗剂量的减少/延迟）。模型中纳入的参数包括pegfilgrastim与六日疗程filgrastim相比发生FN的相对风险；直接成本（药物购买及与FN相关的住院费用）；pegfilgrastim与filgrastim相比相对剂量强度<85%的相对风险；相对剂量强度<85%对长期生存的影响；以及年龄对FN和相对剂量强度<85%的影响。
在基础病例假设下，在意大利pegfilgrastim与六日疗程filgrastim相比具有成本效益。pegfilgrastim的人均估计成本、预期寿命及质量调整生命年分别为3078欧元、16.47年和15.32；六日疗程filgrastim的相应数字分别为3033欧元、16.35年和15.22。pegfilgrastim相应的增量成本效益比为每获得一个生命年409欧元，每获得一个质量调整生命年429欧元。单向敏感性分析表明，结果对六日疗程filgrastim与pegfilgrastim相比发生FN的相对风险最为敏感。结果对pegfilgrastim和filgrastim的成本、药物给药成本、FN住院成本及化疗周期数中度敏感。在所有单向敏感性分析中，pegfilgrastim均保持成本效益，其增量成本效益比远低于每获得一个生命年50000欧元的可接受限值。药物成本的双向敏感性分析显示了pegfilgrastim相对于六日疗程filgrastim的优势范围。
在意大利当前的官方价格下，使用pegfilgrastim进行一级预防可改善健康结局，而对国家医疗服务支付方而言成本增加非常有限。即使在模型中考虑filgrastim的极低价格和pegfilgrastim的高价格，所得的增量成本效益比仍远在每质量调整生命年50000欧元的可接受成本效益限值之内。
