【作者】 陈涛；

【导师】 吴晶；

【作者基本信息】 天津大学 ， 公共管理， 2022， 硕士

【摘要】 健康是人民群众对美好生活的重要期盼。在健康中国战略的大背景下,为实现“更高质量、更有效率、更加公平和更可持续”的全民健康目标,我国医改正在不断探索和推进以价值为导向的医药产品和医疗服务的战略性购买。在推进“基于价值的战略性购买”的过程中,药物经济学评价已被广泛用于比较分析各种医药技术的成本和健康产出,为形成决策所需的优选方案提供证据支持。癌症是严重威胁我国人民健康的重大公共卫生问题,其中乳腺癌位居所有癌症发病率第一位。虽然绝大多数早期乳腺癌患者可以接受手术治疗联合术前及术后辅助治疗,但在现有标准治疗方案(含曲妥珠单抗辅助治疗)下,患者仍存在较高的复发风险。奈拉替尼是目前唯一获批用于曲妥珠单抗辅助治疗后的强化治疗方案,但其用于中国患者的经济性尚不明确。本研究旨在评估奈拉替尼序贯曲妥珠单抗用于中国HER2阳性早期乳腺癌成年患者强化辅助治疗的经济性。本研究从中国医疗卫生体系角度出发,综合运用文献研究法、模型法和专家咨询法,构建了基于HER2阳性早期乳腺癌患者疾病自然史的马尔科夫模型。模型参数主要来源于Extel NTE临床试验、临床专家调研和已发表文献。研究通过对临床试验生存曲线的建模与外推获得了长期的疗效数据,并代入模型对患者在奈拉替尼强化辅助治疗和安慰剂治疗下终生医疗总成本及健康产出的差异进行了分析和比较,同时运用增量成本-效果比探究了奈拉替尼强化辅助治疗的经济性。此外,本研究也针对临床获益更大的HR阳性且曲妥珠单抗辅助治疗结束后≤1年亚组人群开展了分析,探究奈拉替尼在该亚组人群中是否具有更好的经济性。研究结果表明,对于HER2阳性早期乳腺癌患者而言,在接受曲妥珠单抗治疗后继续进行奈拉替尼强化辅助治疗,可以延长患者5年生存时间,并降低局部和远端复发的发生率,从而为患者带来健康获益;从成本上看,继续接受奈拉替尼强化辅助治疗虽然会增加药品费用,但可以节约患者后期的复发成本和健康管理成本。最终增量成本-效果比为103,300元/QALY,远小于3倍中国人均国内生产总值,表明奈拉替尼具有成本-效果。奈拉替尼在亚组人群中成本-效果更显著,增量成本-效果比为13,264元/QALY。不确定性分析验证了上述结果的稳健性。考虑到奈拉替尼在当前的价格下具有较好的成本-效果,建议强化乳腺癌早期治疗的重要性,以延缓病情进展,改善患者的生活质量。在奈拉替尼通过医保后,建议将其纳入“双通道”和“门诊特殊病/门诊慢病”管理机制,进一步给予政策倾斜、降低药品价格,保证药物的可及性。同时,建议进一步提高肿瘤药物经济学评价的研究质量,加强医保决策证据的可靠性。更多还原

【Abstract】 Health is an important part of people’s desire for a better life.In the context of the Healthy China Strategy,in order to achieve the goal of "higher quality,more efficient,more equitable and more sustainable",China’s government is constantly exploring and promoting the strategic purchase of value-based paying for pharmaceutical products and medical services.In this process,pharmacoeconomic evaluation has been widely used to compare and analyze the key value(including costs and health outcomes)of various medical technologies,and to provide evidence to support decision making.Cancer is a major public health problem that seriously threatens the people’s health,among which breast cancer ranks the first among all cancers in China.Although the majority of patients with early-stage breast cancer can receive surgical treatment combined with preoperative and postoperative adjuvant therapy,patients still have a high risk of recurrence under current standard treatment regiments(i.e.adjuvant trastuzumab).Neratinib is currently the only approved adjuvant regimen following trastuzumab in early-stage HER2-positive breast cancer in China,but no study has investigated the cost-effectiveness of neratinib.This study aims to evaluate the costeffectiveness of adding neratinib after adjuvant trastuzumab in Chinese patients with early-stage HER2-positive breast cancer.A Markov model based on the natural history of early-stage HER2-positive breast cancer was constructed from the health care system perspective through literature research method,model method and statistical analysis method.The model parameters were mainly derived from Extel NTE clinical trials,Chinese experts survey and published literatures.The study analyzed and compared the long-term direct medical costs and health benefits of adding neratinib after adjuvant trastuzumab in patients with early-stage HER2-positive breast cancer based on the model with the long-term efficacy data that was obtained by modeling and extrapolating survival curves in clinical trials,and the incremental cost-effectiveness ratios was also used to explore the economic implication of neratinib.In addition,this study also conducted a subgroup analysis for the population which is HR positive with less than one-year trastuzumab adjuvant treatment,to explore the cost-effectiveness of neratinib in this subgroup who had greater clinical benefit from neratinib.The results of this study showed that for patients with HER2-positive early-stage breast cancer,adding neratinib after adjuvant trastuzumab can bring health benefits to patients by extending the 5-year survival time of patients and reducing the local recurrence and distal recurrence rates.For the cost,adding neratinib could increase the drug cost,but it would save the recurrence treatment cost and health management cost especially in the later stage.In conclusion,the incremental cost-effectiveness ratio is 103,300 CNY per QALY,which is much less than3 times China’s GDP per capita,indicating that neratinib following adjuvant trastuzumab is cost-effectiveness.Moreover,for the subgroup population,neratinib was cost-effectiveness with an incremental cost-effectiveness ratio of 13,264 CNY per QALY.The uncertainty analysis verifies the robustness of the above research results.Considering that neratinib is cost-effectiveness at the current price,this study suggests to strengthen the importance of early treatment for breast cancer to prevent progression and improve the quality of life,and also suggests to include neratinib into "medical insurance dual channel" and "special outpatient formula" after it is listed in the national reimbursement drug list,so as to further give policy preference and reduce the drug price to ensure drug accessibility.At the same time,it is suggested to further improve the research quality of cancer drug economic evaluation and strengthen the reliability of medical insurance decision-making evidence.更多还原