中国女性乳腺癌筛查策略优化研究及卫生经济学评价

发布时间：2018-08-09 15:16

【摘要】：目的筛查方法、筛查起止年龄以及筛查间期是构成乳腺癌筛查策略的重要因素。实施不同的乳腺癌筛查策略,会有不同的筛查收益。因此,在合理有效利用国家有限的卫生资源条件下,针对我国女性乳腺癌发病特点,本研究分析了临床乳腺检查、乳腺超声检查及乳腺钼靶X线摄影检查三种方法单独或组合(串联或并联)的灵敏度和特异度及其影响因素,探索构建多种不同组合的乳腺癌筛查策略并对其进行成本效果分析,从而优化我国女性乳腺癌筛查策略,为提高乳腺癌防治的卫生资源配置提供政策性建议。方法1.2008-2010年参与“中国女性乳腺癌筛查优化方案多中心研究”的33234名女性,采用χ2检验计算临床乳腺检查、乳腺超声检查、乳腺钼靶X线摄影检查单独、串联或并联的灵敏度、特异度及其基于二项分布的95%可信区间和影响因素。分别以35岁或40岁作为筛查开始年龄,59岁、64岁或69岁作为筛查截止年龄,三种方法的单独或组合作为筛查方法,每2年或每3年一次的筛查间期构建乳腺癌筛查策略。2.筛查的主要目的是早期发现,也即筛查的直接效果表现为筛查发现的乳腺癌患者相对于临床就诊的乳腺癌,病理分期存在一定的前移。因此,本研究分别收集“中国女性乳腺癌筛查优化方案多中心研究”中筛查发现的182名乳腺癌患者及中国7地区(北京、沈阳、长沙、广州、上海、西安、成都)1998-2008年乳腺癌回顾性调查研究中同期临床就诊的435例乳腺癌患者的病理分期构成信息,并采用Markov模型分析筛查的长期效果。根据乳腺癌发病规律及筛查干预进展规律,采用Treeage Pro 2011软件分别构建乳腺癌自然史进展Markov模型和乳腺癌筛查诊断Markov决策模型。模型循环周期为1年,采用队列模拟的方法评估10万人群未来50年不同筛查策略下所获得的筛查效果,如寿命损失年、质量调整寿命损失年,以及额外的成本花费,从而计算筛查相对于不筛查综合的成本效果比。同时根据不同筛查年龄,比较22种策略相互间以及相对于不筛查的增量成本效果比,从而确定最佳的筛查起止年龄。3.对影响乳腺癌筛查卫生经济学效果的因素进行评价,包括多因素的飓风图敏感性分析,不同人群全因死亡率、人群乳腺癌发病率、贴现率等进行单因素敏感性分析及基于筛查数据进行我国女性乳腺癌临床前期逗留时间评估。结果1.单独乳腺钼靶筛查的灵敏度为86.0%(95%CI:79.2%-92.8%),特异度为94.3%(95%CI:94.0%-94.5%)。在钼靶基础上补充CBE或BUS,即与之并联,能提高筛查方法的灵敏度和特异度,其中CBE、MAM并联的灵敏度和特异度分别为92.2%(95%CI:86.9%-97.4%)和93.7%(95%CI:93.4%-94.0%);BUS、MAM并联的灵敏度和特异度分别为95.0%(95%CI:90.7%-99.3%)和93.2%(95%CI:93.0%-93.5%),而三种方法并联时灵敏度最高,为97.0%(95%CI:93.7%-100.0%),特异度为92.8%(95%CI:92.5%-93.1%)。根据不同筛查起止年龄、筛查方法及筛查间期,共构建132种适合中国女性的乳腺癌筛查策略。2.分别对这132种筛查策略进行成本效果分析,结果显示优势可选策略有4种,即为35-59岁每3年一次的BUS、MAM串联筛查方法、35-59岁每2年一次的BUS、MAM串联筛查方法、35-59岁每2年一次的CBE、BUS、MAM并联筛查方法和35-69岁每2年一次的CBE、BUS、MAM并联筛查方法。以3倍人均GDP作为评价标准,则最优策略为35-69岁每2年一次的CBE、BUS、MAM并联筛查,与不筛查时相比,10万女性每增加一个寿命年(或质量调整寿命年)的增量成本为36774元(90706元)。对不同筛查年龄成本效果分析结果显示,每2年一次的筛查间期要优于每3年一次;并联筛查优于串联。所有的优势筛查策略中均包含BUS的筛查方法,提示在我国当前的乳腺癌发病水平以及经济条件下,BUS筛查具有一定的指导价值。3.对35-69岁每2年一次CBE、BUS、MAM并联筛查优势策略进行飓风图敏感性分析发现,女性乳腺癌发病率的年增长率对筛查策略的成本影响最大,其次是筛查截止年龄、乳腺癌诊断费用等。采用不同人群的年龄别全因死亡率、乳腺癌年龄别发病率、贴现率对模型进行单因素敏感性分析结果不变,模型较稳定。同时结合中国女性乳腺癌筛查方法多中心研究数据,计算得到我国女性乳腺癌临床前期的平均逗留时间为10.46年(95%CI:8.10-13.51),50岁以下女性的平均逗留时间为9.37年(95%CI:5.71-15.38),50岁及以上女性的平均逗留时间为10.84年(95%CI:8.04-14.61)。目前尚没有发现对临床前期逗留时间及进展概率有影响的协变量。结论在单独MAM筛查基础上补充CBE或BUS,能有效提高筛查方法的准确性,三者并联时灵敏度最高,具有较好的提前发现乳腺癌的效果。35-69岁每2年一次的CBE、BUS、MAM并联筛查是最适合我国国情及女性生理特点的乳腺癌筛查优势策略,与不筛查时相比,10万女性每增加一个寿命年(或质量调整寿命年)的成本为36774元(90706元)。研究结果提供了适合我国女性乳腺癌筛查的科学依据,可以考虑在我国乳腺癌高发且经济较发达地区的适龄女性中进行筛查应用。中国年轻女性(50岁)的逗留时间更短,乳腺癌临床前期的进展概率更快,因此也提醒我们在逗留时间内尽早筛选乳腺癌高危人群,更好的提前发现乳腺癌,筛查效果会更加明显。
[Abstract]:Objective screening methods, screening age and interval are important factors to form a screening strategy for breast cancer. The implementation of different screening strategies for breast cancer will have different screening benefits. Therefore, the clinical milk is analyzed in this study under the reasonable and effective utilization of the limited health resources of the country. Glandular examination, breast ultrasound examination and mammographic mammography examination of three methods alone or in combination (series or parallel) sensitivity and specificity and its influence factors, explore and construct a variety of different combinations of breast cancer screening strategies and analysis of its cost effectiveness, thus optimizing the screening strategy for female breast cancer in China, in order to improve breast cancer The prevention and treatment of health resources allocation provided policy recommendations. Methods 33234 women who participated in the "multi center study of the Chinese women's breast cancer screening and optimization program" in 1.2008-2010 were used to calculate the clinical breast examination, breast ultrasonography, mammography and mammography, the sensitivity, the specificity and the two based on the x 2 test. The 95% confidence interval and influencing factors of the item distribution were screened at the age of 35 or 40 years as screening age, 59, 64 or 69 years as screening cut-off age, and the three methods of screening were used as screening methods, and the main purpose of screening.2. screening for breast cancer screening every 2 or 3 year screening interval was early detection, that is, screening The direct results showed that there was a certain shift in the pathological staging of breast cancer patients found by screening for breast cancer. Therefore, 182 breast cancer patients and 7 regions of China (Beijing, Shenyang, Changsha, Guangzhou) were collected and found in the multi center study on the screening and optimization of women's breast cancer in China. Shanghai, Xi'an, Chengdu) 1998-2008 years of retrospective investigation of breast cancer in the period of 435 cases of breast cancer in the same period of the pathological staging information, and using the Markov model to analyze the long-term results of screening. According to the law of breast cancer and the regulation of screening intervention, the natural history of breast cancer was constructed by using Treeage Pro 2011 software. Progress Markov model and breast cancer screening and diagnosis Markov decision model. The model cycle cycle is 1 years. The cohort simulation method is used to evaluate the screening effect of 100 thousand people under different screening strategies for the next 50 years, such as life loss year, quality adjusted life loss year, and additional cost cost, so as to calculate screening relative to non screening. At the same time, the overall cost effectiveness ratio, according to the different screening age, compared the 22 strategies to each other and relative to the non screening incremental cost effectiveness ratio, thus determined the best screening and stop age.3. for the effects of breast cancer screening health economics, including the multi factor hurricane map sensitivity analysis, the different population whole A single factor sensitivity analysis for the mortality, the incidence of breast cancer, the rate of discounting, and the evaluation of the pre clinical stay time for women's breast cancer in China based on screening data. Results the sensitivity of 1. single mammography screening was 86% (95%CI:79.2%-92.8%), and the specificity was 94.3% (95%CI:94.0%-94.5%). CBE or B was supplemented on the molybdenum target basis. US, in parallel with it, can improve the sensitivity and specificity of the screening method, in which the sensitivity and specificity of CBE and MAM parallel are 92.2% (95%CI:86.9%-97.4%) and 93.7% (95%CI:93.4%-94.0%) respectively; BUS, MAM parallel sensitivity and specificity are 95% (95%CI:90.7% -99.3%) and 93.2% (95%CI:93.0%-93.5%) respectively, while the three methods are sensitive in parallel. The highest degree was 97% (95%CI:93.7%-100.0%), and the specificity was 92.8% (95%CI:92.5%-93.1%). According to the different screening age, screening method and interval, a total of 132 kinds of breast cancer screening strategies suitable for Chinese women were constructed,.2., respectively, on the cost-effectiveness analysis of the 132 screening strategies. The results showed that there were 4 dominant alternative strategies, that is 35-59. Once every 3 years, BUS, MAM series screening, 35-59 year old BUS, MAM series screening, 35-59 year old CBE, BUS, MAM parallel screening method and 35-69 year CBE, BUS, MAM parallel screening method. The optimal strategy is 3 times per capita GDP as the evaluation criterion, and the optimal strategy is 2 years, 2 years, 2 years parallel CBE The incremental cost of 100 thousand women per life year (or the quality adjusted life year) was 36774 yuan (90706 yuan) compared to the non screening screening. The results of the different screening age cost results showed that the screening interval of every 2 years was better than every 3 years; the parallel screening was superior to the series. All the dominant screening strategies included BUS. The screening method suggests that under the current level of breast cancer and economic conditions in China, BUS screening has a certain guiding value for.3.. The sensitivity analysis of CBE, BUS, MAM parallel screening advantage strategy for 35-69 year old, BUS and MAM, found that the annual growth rate of female breast cancer incidence has the greatest impact on the cost of screening strategy. The second is the age of screening, the cost of diagnosis of breast cancer, and the age specific mortality rate of the different population, the age of breast cancer, the rate of discounting, the result of the single factor sensitivity analysis and the stability of the model. Meanwhile, the female breast cancer screening method in China is combined with the multi center research data to calculate the female breast in China. The average stay time of preclinical cancer was 10.46 years (95%CI:8.10-13.51), the average stay of women under 50 years of age was 9.37 years (95%CI:5.71-15.38), and the average time of stay of 50 years old and above was 10.84 years (95%CI:8.04-14.61). Supplementation of CBE or BUS on the basis of single MAM screening can effectively improve the accuracy of screening methods. The three cases have the highest sensitivity in parallel, with a better effect of early detection of breast cancer, CBE, BUS, MAM parallel screening is the most suitable strategy for breast cancer screening, which is the most suitable for China's national conditions and women's physiological characteristics. It is the same as that of non screening. The cost of 100 thousand women per life year (or the quality adjusted life year) is 36774 yuan (90706 yuan). The results provide a scientific basis for the screening of women's breast cancer in China, which can be considered for screening and application among women of high incidence of breast cancer in the more developed areas of China. The stay of young women (50 years old) in China. Shorter time, the early stage of breast cancer progress is faster, so it is also a reminder of the early screening of breast cancer high-risk groups in the stay, better early detection of breast cancer, screening results will be more obvious.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.9

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