Dewilde Sarah, Carroll Kevin, Nivelle Emilia, Sawyer James
Services in Health Economics, Brussels, Belgium.
KJC Statistics, Wilmslow, UK.
Cost Eff Resour Alloc. 2020 Feb 10;18:7. doi: 10.1186/s12962-020-0205-4. eCollection 2020.
Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established.
A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain.
Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany.
Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m are included in the model.
接受蒽环类药物治疗的儿童癌症幸存者发生心脏毒性的风险较高，尤其是累积剂量超过250mg/m时。随机试验支持右丙亚胺是高危患者预防心脏毒性的唯一推荐药物，但尚未确定其在儿科癌症患者中的成本效益。
建立一个适用于不同国家医疗保健系统视角的成本效益模型，该模型基于包括性别、诊断时年龄、蒽环类药物累积剂量和胸部放疗暴露等基线特征，模拟10000例患有肉瘤或血液系统恶性肿瘤的患者。从已发表的文献中得出发生充血性心力衰竭以及因原发癌症复发、继发性恶性肿瘤、心源性死亡、肺源性死亡和其他原因导致死亡的风险方程。将这些方程应用于各个模拟患者，并确定直至发生这些事件的时间。右丙亚胺对CHF或死亡风险的治疗效果基于对每种肿瘤类型的右丙亚胺随机和非随机研究的荟萃分析。该模型包括五个国家（法国、德国、英国、意大利和西班牙）特定的药物和给药成本数据、心力衰竭诊断和管理的各个方面以及因不同原因导致的死亡情况。
在五个国家中，接受右丙亚胺治疗的患者平均每例获得的质量调整生命年（QALY）效益在0.530至0.683之间。对于接受蒽环类药物治疗的肉瘤和血液系统恶性肿瘤儿科患者，无论蒽环类药物的累积剂量如何，右丙亚胺都具有成本效益。无论肉瘤和血液系统恶性肿瘤的蒽环类药物剂量如何，所有国家的增量成本效益比（ICER）都很可观（范围：从占优到2196欧元）。各国的个体ICER差异很大，在西班牙和意大利右丙亚胺表现为占优，而在英国和德国，该比例约为欧洲平均水平的两倍。
在欧洲，右丙亚胺是预防患有肉瘤或血液系统恶性肿瘤的儿科患者蒽环类药物心脏毒性的一种极具成本效益的治疗方法，无论他们接受治疗的医疗保健系统如何。当模型纳入接受蒽环类药物剂量>250mg/m的患者时，这些益处依然存在。
