山东省新生儿乙肝疫苗免疫策略经济学评价研究
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摘要
研究背景
乙型病毒性肝炎(简称乙肝)是目前全球公认的重大公共卫生问题。世界范围内,76%的乙肝病毒感染者集中在亚洲：在中国,乙肝是最严重的公共卫生问题之一,据2006年全国血清流行病学调查结果估算,全国大约有9300万慢性乙肝感染者,其中慢性乙肝患者约为2000万例。乙肝具有感染率与发病率高、慢性迁延和不良转归比例高等特点,乙肝病毒(Hepatitis B Virus,HBV)感染及其不良转归包括急性乙肝、慢性乙肝、乙肝肝硬化、肝癌等,可统称为乙肝相关疾病,给病人、家庭造成沉重的经济负担(感染成本),给社会经济发展带来巨大影响。
目前世界上仍无完全治愈乙肝的特效药物,接种乙肝疫苗则成为预防和控制乙肝、降低该类疾病经济负担的最有效手段。国内外研究表明：决策树模型用于乙肝疫苗策略优化,具有简捷、直观、多元和量化等特点,辅以卫生经济学相关指标易被理解和接受。马尔可夫(Markov)模型则是模拟疾病慢性演进的复杂过程,我们可通过建立不同干预措施的Markov模型,进而估计不同干预措施下研究对象的质量调整生命年(Quality-adjusted Life Year,QALY)或费用,对所研究问题进行经济学评价研究。建立乙肝疫苗接种决策树-马尔可夫模型进行经济学评价在国外已有文献报道,但在国内,此类研究刚刚起步。
中国自1992年制定新生儿乙肝疫苗预防接种规范,2002年起,乙肝疫苗正式纳入国家免疫规划,2005年6月1日起,实现了新生儿乙肝疫苗接种免费。经过多年来的推广和实施,中国人群HBsAg携带率从1992年的9.75%下降至2006年的7.2%,乙肝疫苗接种成效显著。新近获批的新生儿用10μg重组(酿酒酵母)乙肝疫苗(简称重组乙肝疫苗)开始大批量生产,且价格略高于5μg重组乙肝疫苗,其乙肝病毒表面抗体(Antibody to HBsAg, Anti-HBs)低无应答率远远小于5μg重组乙肝疫苗,在策略政策调整前,如何合理、定量的评价新生儿乙肝疫苗接种策略的经济学效益成为决策者关注的一大问题。国内研究大多粗略而简单,笔者曾全文浏览1991年至2011年国内发表的50多篇中文文献后发现,所用模型全部为决策树模型,而此种模型无法处理乙肝及其相关疾病进展的复杂状态,方法简单,参数设置粗略,也不是世界各国乙肝疫苗免疫接种策略经济学评价研究的通用方法。
本研究从山东省乙肝相关疾病的经济负担调查入手,利用其提供的感染成本参数构建适用于山东省新生儿乙肝疫苗免疫策略的决策树-马尔可夫模型,对现有及可能的优选接种方案进行评价,进而优选、评价重要的接种方案,为卫生行政部门决策者提供政策建议,具有重要的现实意义。
研究目的
总的目的：通过较合理测算山东省HBV所有感染状态经济负担,利用其提供的感染成本参数,构建新生儿乙肝疫苗免疫策略的决策树-马尔可夫模型,定量评价不同免疫策略的成本效益,为相关政策的制定提供理论基础和数据依据。具体研究目的为：对山东省乙肝相关疾病住院病人及社区人群乙肝病毒表面抗原(Hepatitis B surface antigen, HBsAg)携带者两个角度进行调查,从直接、间接、无形经济负担三方面测算其经济负担,为山东省新生儿乙肝疫苗免疫策略经济学评价提供有效的感染成本参数；依据决策学分析基本原理和乙肝感染的慢性转归特征,结合现行乙肝疫苗预防接种的实际情况,构建山东省新生儿队列乙肝疫苗接种决策树-马尔可夫模型：定量评价山东省新生儿乙肝疫苗不同免疫策略的成本效益,对参数变化的影响进行灵敏度分析和阈值分析,从成本效益角度,回答山东省新生儿目前实施的5μg重组乙肝疫苗是否需要调整,如果是,调整至哪种策略较合理。
研究对象
研究对象为山东省2010年的新生儿出生队列。
研究方法
1.经济学评价模型及方法将新生儿队列在母亲筛检后接种、不筛检直接接种和不接种策略下,直到死亡所经历的过程(或是乙肝病毒感染,或是乙肝疫苗保护,或是自然死亡)所产生的成本和效益进行测算,建立不同免疫策略的决策树-马尔可夫模型,进行成本-效益分析。成本效益分析是计算不同免疫策略的人均全部预期成本(包括感染成本、接种成本、筛检成本等)和人均全部预期效益,根据以上两个指标计算出不同接种方案的净效益(Net Benefit, NB)和效益成本比(Benefit-Cost Ratio, BCR)两指标。为评价各参数对乙肝疫苗接种策略影响程度的大小,运用单项替代法对研究中主要参数加以变动进行灵敏度分析。通过阈值分析,找出优选策略从一种转化为另一种时某一影响较大因素的阈值。
2.资料来源及方法模型中的乙肝感染成本参数采用多阶段随机抽样方法获得慢性HBV携带者感染成本,采用和时间阶段连续病例整群抽样方法,获得急性乙肝、慢性乙肝、乙肝肝硬化、原发性肝癌等乙肝相关疾病的感染成本,其他参数为山东省数据或文献分析数据。乙肝相关疾病感染成本为病人的年例均直接、间接和无形费用。直接费用包括直接医疗和直接非医疗费用,直接医疗费用包括门诊费、住院费、治疗费、自购药费等；直接非医疗费用包括交通费、食宿费和增加的营养费等：间接费用采用人力资本法测算；无形费用测量采用表达偏好-条件估价法中支付意愿法和竞价法,对乙型肝炎病毒感染者为避免感染带来的身体上的痛苦和精神上的压力而可能愿意支付金钱的数量。
其他成本参数、疫苗相关参数、乙肝感染相关参数等主要取自山东省近期数据,个别参数为国家层面数据,或为文献分析数据。
研究结果
新生儿乙肝疫苗免疫策略成本效益分析结果显示,策略2,即母亲筛检HBsAg和HBeAg (Hepatitis B e antigen), HBsAg和HBeAg阳性者所生新生儿接种3针10μg重组乙肝疫苗合用高价免疫球蛋白(Hepatitis B immune globulin, HBIG),阴性者新生儿接种3针10μg重组乙肝疫苗,BCR为41.62,是3种策略中最高的；仅次于策略2,策略1,即直接接种3针10μg重组乙肝疫苗的BCR为2150；而策略3,即直接接种5μg重组乙肝疫苗的BCR最低,为15.06,表明接种3针5μg疫苗经济学上较10μg疫苗更不划算。若按山东省一年出生100万新生儿计算,使用3种策略均较不接种方案均可获得80亿元以上的净效益。若将现行的直接接种5μg重组乙肝疫苗调整为接种10μg重组乙肝疫苗,从社会角度讲,该出生队列将节约348亿元的资源消耗,从卫生保健支付者角度,可节约2.44亿元；若调整为母亲筛检后接种,从社会角度讲,该出生队列将节约759亿元的资源消耗,从卫生保健支付者角度,可节约530亿元。
灵敏度分析表明,乙肝病毒感染成本取直接费用和间接费用之和时,影响策略2BCR和NB的最大因素分别是乙肝疫苗接种率和贴现率,其次为HBV感染率、疫苗接种率等；影响策略1BCR和NB的最大因素分别是乙肝疫苗直接接种保护率(Vaccine Efficacy, VE,又称疫苗效力)和贴现率,其次为疫苗接种率、HBV感染率等。接种率小于50%时,策略1和策略2,其BCR和NB分别小于1和0。阈值分析结果,当10μg重组乙肝疫苗保护率降至9590%以下时,直接接种5μg重组乙肝疫苗的效益成本比要略高直接接种10μg重组乙肝疫苗：当直接接种10μg重组乙肝疫苗保护率达到99.15%时,效益成本比高于母亲筛检后接种策略：母亲未感染10μg重组乙肝疫苗保护率降至97.70%时,母亲筛检后接种策略BCR低于直接接种10μg重组乙肝疫苗策略。
结论及政策建议结论：1)基于经济负担测算结果,山东省乙肝相关疾病病人经济支出占据当年家庭收入与人均GDP的比例较大,经济负担颇为沉重。2)为切实降低乙肝病毒感染所致经济负担,山东省新生儿乙肝疫苗接种目前宜采用“母亲筛检HBsAg和HBeAg, HBsAg和HBeAg阳性者所生新生儿接种3针10μg重组乙肝疫苗+HBIG,单阳和阴性者新生儿接种3针10μg重组乙肝疫苗”,适时采用“直接接种3针10μg重组乙肝疫苗”策略。3)灵敏度分析显示,疫苗接种率是影响策略BCR和NB的最大因素,疫苗保护率是影响BCR的较大因素。4)根据现阶段山东省新生儿乙肝疫苗接种情况,直接接种10μg重组乙肝疫苗保护率的阈值分别为95.90%和99.15%,低于95.90%时,“直接接种10μg重组乙肝疫苗”策略的效益成本比略低于“直接接种5μg重组乙肝疫苗”策略,高于9915%时,“直接接种10μg重组乙肝疫苗”策略效益成本比高于母亲筛检后接种策略；母亲未感染儿童疫苗保护率阂值为97.70%,低于此值“直接接种3针10μg重组乙肝疫苗”策略效益成本比高于母亲筛检后接种策略。5)本研究注重了模型参数的权威性,尝试将上限值和下限值引入模型进行灵敏度分析,将Meta分析结果用于模型,均提高了决策分析的可靠性和证据性。
政策建议：1)针对乙肝相关疾病感染成本较高,从二级预防的角度,对携带者进行社区随访管理,防止其慢性进展和疾病转归；对慢性、重型病例及时、规范诊治,可延缓其恶性进展,进而降低经济负担。2)为根本降低乙肝相关疾病经济负担,从一级预防的角度,可优先采用母亲筛检HBeAg和HBsAg后接种策略,适时采用直接接种高剂量重组乙肝疫苗策略；灵敏度分析提示我们,执行国家扩大免疫规划的过程中,需加大监督检查力度,确保以乡镇为单位乙肝疫苗接种率达到90%以上,保持并尽力提高接种率。
创新与不足
本研究的创新之处：
1)本研究设计较新颖,与成本参数取自文献的经济学评价研究相比,本研究成本参数及主要参数取自本省。从本省乙肝病毒感染所致经济负担调查入手,测算该类疾病经济负担,基于所测算的经济负担数据确定山东省乙肝病毒相关感染成本参数,对山东省现行的新生儿5μg重组乙肝疫苗接种策略、即将实施的新生儿10gg重组乙肝疫苗策略及其他可能优选策略进行成本-效益分析。
2)本研究尝试从直接、间接和无形费用三方面测算该类疾病的感染成本,不同于以往大部分基于直接费用的经济学研究,以山东省乙肝相关疾病病人和社区HBsAg阳性者为调查对象,合理测算了乙肝病毒感染所有状态的感染成本。
3)本研究联合运用决策树和马尔可夫模型,借助计算机模拟技术为决策者提供调整现有策略的循证政策依据。
本研究的不足与展望：
1)现场调查方面：本研究在无形经济负担的调查中虽采用标准化的询问技巧,也遇到无法量化的调查对象,在计算时以量化结果的均数替代；因青岛市市北区和德州市乐陵市随访时拆迁、外出打工和拒绝调查者太多,造成社区HBsAg阳性者失访率太高,可能会影响其感染成本的测算结果；可能由于调查时间阶段较短造成个别感染成本均数不可靠,对结果会有一定程度的影响。
2)本研究建立的决策树-Markov模型是一个静态、确定、整体、封闭的模型。与动态模型相比,未考虑免疫屏障的作用,低估了免疫效益；灵敏性分析方面,参数取值未采用概率分布,与基于参数概率分布的分析相比,存在欠缺；与基于个体建立的模型相比,整体模型不能追踪个体的转归,仅采用年转归概率,因而无法反映个体转归的差异；与开放性模型相比,封闭模型忽略所模拟出生队列人群的进入和迁出,与实际情况稍有偏差。考虑免疫屏障作用并符合实际情况的动态模型的建立和评价可能是未来研究的重点。
Background
Hepatitis B is globally recognized as a major public health problem at present.76%percent of infected with the hepatitis B virus is in Asian. Hepatitis B is one of the most serious public health problems in China. According to the estimation of the national seroepidemiological survey in2006, nationwide,93million are chronically infected persons, including approximately20million cases of chronic hepatitis B patients. Hepatitis B has such characteristics as high infection rate, high incidence, a high proportion of chronic persistent and adverse outcomes and so on.HBV infection and its adverse outcomes, including acute hepatitis B, chronic hepatitis B, HBV cirrhosis, Primary liver cancer which can all be collectively referred to as hepatitis B-related diseases. Hepatitis B-related diseases cause heavy economic burden to the patient and his family and have a tremendous impact on the socio-economic development.
At present, there's still no special drug that can cure hepatitis B in the world, and therefore Vaccinating hepatitis B vaccine has been the most effective means of prevention and control of hepatitis B and decreasing the economic burden of the disease. Domestic and international research shows that decision tree model, with such characteristics as simple, intuitive, pluralistic, quantitative and so on, is used to optimize hepatitis B vaccine strategy. It is easy to be understood and accepted combined with related indicators of health economics. Through simulating the chronic progression of disease, using different Markov models to estimate research objects' QALY(Quality-adjusted Life Year) or cost under different intervention measures and implements related economics research, Markov model evaluate the research questions. Establishing a decision tree-Markov model of hepatitis B immunization Strategy for economic evaluation has been reported in foreign literature but rare in domestic literature.
Since1992,our country has laid down neonatal hepatitis B immunization rules, and since2002,the hepatitis B were formally brought into national immunization programs and since June1,2005,we achieved free newborns hepatitis B immunization. Through more than a decade's promotion and implementation, our country's HBsAg carrier rate declined from9.75%in1992to7.2%in2006and the effectiveness of hepatitis B immunization is significant. But how to reasonably and quantitatively evaluate the economics effect of newborns'hepatitis B immunization strategy has become a big problem for policymakers. Domestic researches are mostly rough and simple. After having review over50articles published domestically in between1991-2011,1find that all the models used are a decision tree model. such a model cannot handle the complexity of hepatitis B and its related diseases and its methods are simple, parameters setting roughly, rather than general methods of hepatitis B immunization strategy in economics evaluation studies of countries in the world. In this study, starting from the economic burden investigation of hepatitis B-related diseases of Shandong Province, we use its important parameters to build decision tree-Markov model for neonatal on hepatitis B immunization strategy to evaluate the existing strategy and to preferably select the important immunization programs and therefore to provide policy advice for the decision-makers of health administrative departments, which is of great practical significance.
Objectives
The overall objective of this study is to estimate the economic burden of the province hepatitis B-related diseasesh and use its scientific parameters to build decision tree-Markov model of neonatal hepatitis B immunization strategy. We make quantitative assessment for benefit of hepatitis B immunization strategy to provide data for the decision-makers.Specific research objectives include, to estimate the economic burden including direct, indirect and intangible economic burden from people HBsAg positive and inpatients,and then construct decision tree-Markov model of neonatal hepatitis B immunization strategy.Through cost-benefit analysis, sensitivity Analysis and threshold Analysis, we economically evaluate the existing immunization programs and preferably select immunization strategy. Object
2010-year neonatal birth cohort is the object
Method
1.Method for the Economic Evaluation we evaluate different immunization strategy's costs and benefits in decision tree-Markov model, including vaccinated strategy after mothers'screened, direct immunization, no immunization strategy. This cohort will experience from birth to death, or infected,protection from immunization,natural death.
Methods for different strategy's economic evaluation in decision tree-Markov model is cost-benefit analysis which calculates the expected cost and expected benefits of immunization strategy.According to the above two indicators,we calculated Net Benefit and Benefit-Cost Ratio of different immunization strategy. We use single alternative to make sensitivity analysis to select the main influencial parameters and influencing level.By Threshold Analysis, we identify threshold value of the most influential factors from one strategy to another.
2.Materials and Methods In economic burden investigation of hepatitis B-related diseases,we adopted multi-stage random sampling method and a cluster sampling for cases collected consecutively during the study period to achieve cost information for HBsAg (Hepatitis B Surface antigen)-positive,acute hepatitis B, chronic hepatitis B, hepatitis B-liver cirrhosis and primary liver cancer The other parameter is from Shandong and meta-analysis.Diseases cost are composed of direct expenses, indirect expenses and intangible expenses, respectively calculating the average cost of patients in the past year. Direct expenses are composed of direct medical costs and direct non-medical costs, direct medical costs consist of outpatient expenses, hospitalization expenses, treatment costs, prescription charge and so on. Direct non-medical costs consist of transportation costs, accommodation costs, increased nutrition cost and so on.We use human capital approach to estimate indirect expenses, using Willingness to Pay (WTP) and Auction Method of express preferences-conditions valuation to estimate the intangible expenses.
The other cost parameter,parameter related to vaccine and HBV infection are derived from Shandong Province. We gain Several parameters from our country and references.
Results
After mother screening HBsAg and HBeAg (Hepatitis B e antigen), if the result is positive then vaccinated three doses of10μg+HBIG (Hepatitis B immune globulin), if it is negative then vaccinated three doses of10μg hepatitis B vaccine.This is the second strategy,BCR is41.62.Newborns were directly vaccinated three doses of hepatitis B vaccine, and10μg per dose, BRC is21.50.And when vaccinated three doses of5μg hepatitis B vaccine, BCR of hepatitis B vaccine is15.06. It shows5μg hepatitis B vaccine is not economical than10μg hepatitis B vaccine. If there are1million newborns in Shandong province each year, Compared with one strategy of no vaccination, We obtain net benefit of8billion yuan from three kinds of strategies. If the10μg direct immunization strategy replace5μg hepatitis B vaccine.this birth cohort will save348million yuan of resource consumption from a social point of view and save244million yuan of resource consumption from the point of view of health care payer. If adjusted to vaccination after screening,this birth cohort will save 759million yuan of resource consumption from a social point of view and can save530million yuan of resource consumption from the point of view of health care payer. The results of sensitivity analysis are as follows. If we use the sum of direct and indirect economic burden of of hepatitis B-related diseases, the biggest factor that affects BCR and NB of the second strategy is hepatitis B coverage and discount rate, respectively.Followed by HBV year-infection rate and hepatitis B coverage rates, etc.The biggest factor that influence BCR and NB of the first strategy is hepatitis B vaccine efficacy of direct vaccination and discount rate,respectively. Followed by hepatitis B coverage and hepatitis B coverage,etc. When hepatitis B coverage is less than50%, BCR and NB of the first strategy and the second strategy is less than1and0, respectively.
The result of threshold analysis:the threshold value of vaccine efficacy in10μg; hepatitis B vaccine vaccinated directly is95.90%, that is to say while vaccine efficacy of10μg hepatitis B vaccine drop below95.90%, the cost-benefit ratio of5μg hepatitis B vaccine vaccinated directly is slightly higher than10μg. Compared with the second strategy,the threshold value of vaccine efficacy in10μg hepatitis B vaccine vaccinated directly is99.15%.Compared with the first strategy, the threshold value of vaccine efficacy in10μg hepatitis B vaccine efficacy when mother is not infected with hepatitis B virus is97.7%.
Conclusions and policy implications
Conclusions:1) Annual economic burden indicate the economic burden of patients related to HBV in Shandong province is very heavy.2) To cut down economic burden earnestly, the immunization strategy of vaccinating for newborns after mothers' HBsAg and HBeAg is regarded as optimal program of neonatal hepatitis B vaccine in Shandong province. We can select the immunization strategy of directly vaccinating10μg hepatitis B vaccine for newborns at the right moment.3) Sensitivity analysis shows that the biggest factor influencing BCR and NB of strategies is hepatitis B coverage. vaccine efficacy is a bigger factor influencing BCR.4)According to neonatal hepatitis B vaccination'Status quo in shandong province, When the threshold value of directly vaccinating10μg vaccine efficacy is below95.90%, its BCR is a little lower than directly vaccinating5μg recombinant hepatitis B vaccine. When its efficacy is above99.15%,its BCR is higher than the strategy after mother screening The threshold value of10μg hepatitis B vaccine efficacy for uninfected mother is lower than97.7%, direcly vaccinating10μg hepatitis B vaccine is the optimization scheme compared with the strategy after mother screening.5) We pay attention to the authority of the model parameters and attempts to introduce the upper limit and lower limit value to make sensitivity analysis model, use Meta analysis in model.The above-mentioned measures enhance the reliability of the decision analysis and evidence.
Policy recommendations:1) From the point of secondary prevention, follow-up management of carriers can prevent the chronic progress, timely diagnosis and standard treatment of chronic and severe cases can delay the malignant progression, also reduce the economic burden2) From the point of primary prevention, we adopt the immunization strategy of vaccinating for newborns after mothers'HBsAg and HBeAg of neonatal hepatitis B vaccine in Shandong province and select the strategy directly vaccinating10μg hepatitis B vaccine for newborns at the right moment.sensitivity analysis suggests that we need to increase supervision and inspection intensify to ensure that the township as a unit of HBV rate reach90%or more, and try to improve the vaccination rate on the process of the implementation of national expanded program on Immunization,
Innovation and limitation
The innovation of this study:1) on-the-spot investigation:The research design is novelty.First investigate economic burden, and then use the economic burden parameter and evaluate neonatal HBV strategy. This is different from past research which parameter is derived from literature.2) From hepatitis B-related diseases and HBsAg positive at the community in Shandong Province,we attempt to estimate the economic burden including direct,indirect, intangible economic burden.This is different from some economic researchs calculated direct cost.3) we combine decision tree and Markov model to provide evidence-based policy of adjusting the existing strategy for health decision makers of administrative department with the help of computer simulation technology.
The limitation of this research:l)This research tries to estimate economic burden of diseases Hepatitis B-related from three aspects:the direct, indirect and intangible economic burden, we encountered the data of intangible economic burden in the survey cannot be quantified and replaced this with the mean in the calculation although we used standardized questioning techniques. Because the follow-up rate is not high in Shibei county of Qingdao City and laoling county of Dezhou city, the cost of HBsAg positive at the community may be affected.The shorter study period may influence the reliability of mean of infection cost.
2) Markov model is a static,definate, whole, closed model. Compared with the dynamic model, without considering the effect of immune barrier, underestimated the immune efficiency. there is lack in sensitivity analysis without selecting parameter's probability distribution. Compared with model based on the individual, the whole model can't track the individual turnover replaced by annual transition probablities only, thus this model cannot reflect individual differences in turnover. Compared with the open model,closed model ignores into and out of the cohort,there is a slight deviation with the actual situation. The establishment of dynamic model considering immune barrier and the actual situation and evaluation may be the focus of future research.
乙型病毒性肝炎(简称乙肝)是目前全球公认的重大公共卫生问题。世界范围内,76%的乙肝病毒感染者集中在亚洲：在中国,乙肝是最严重的公共卫生问题之一,据2006年全国血清流行病学调查结果估算,全国大约有9300万慢性乙肝感染者,其中慢性乙肝患者约为2000万例。乙肝具有感染率与发病率高、慢性迁延和不良转归比例高等特点,乙肝病毒(Hepatitis B Virus,HBV)感染及其不良转归包括急性乙肝、慢性乙肝、乙肝肝硬化、肝癌等,可统称为乙肝相关疾病,给病人、家庭造成沉重的经济负担(感染成本),给社会经济发展带来巨大影响。
目前世界上仍无完全治愈乙肝的特效药物,接种乙肝疫苗则成为预防和控制乙肝、降低该类疾病经济负担的最有效手段。国内外研究表明：决策树模型用于乙肝疫苗策略优化,具有简捷、直观、多元和量化等特点,辅以卫生经济学相关指标易被理解和接受。马尔可夫(Markov)模型则是模拟疾病慢性演进的复杂过程,我们可通过建立不同干预措施的Markov模型,进而估计不同干预措施下研究对象的质量调整生命年(Quality-adjusted Life Year,QALY)或费用,对所研究问题进行经济学评价研究。建立乙肝疫苗接种决策树-马尔可夫模型进行经济学评价在国外已有文献报道,但在国内,此类研究刚刚起步。
中国自1992年制定新生儿乙肝疫苗预防接种规范,2002年起,乙肝疫苗正式纳入国家免疫规划,2005年6月1日起,实现了新生儿乙肝疫苗接种免费。经过多年来的推广和实施,中国人群HBsAg携带率从1992年的9.75%下降至2006年的7.2%,乙肝疫苗接种成效显著。新近获批的新生儿用10μg重组(酿酒酵母)乙肝疫苗(简称重组乙肝疫苗)开始大批量生产,且价格略高于5μg重组乙肝疫苗,其乙肝病毒表面抗体(Antibody to HBsAg, Anti-HBs)低无应答率远远小于5μg重组乙肝疫苗,在策略政策调整前,如何合理、定量的评价新生儿乙肝疫苗接种策略的经济学效益成为决策者关注的一大问题。国内研究大多粗略而简单,笔者曾全文浏览1991年至2011年国内发表的50多篇中文文献后发现,所用模型全部为决策树模型,而此种模型无法处理乙肝及其相关疾病进展的复杂状态,方法简单,参数设置粗略,也不是世界各国乙肝疫苗免疫接种策略经济学评价研究的通用方法。
本研究从山东省乙肝相关疾病的经济负担调查入手,利用其提供的感染成本参数构建适用于山东省新生儿乙肝疫苗免疫策略的决策树-马尔可夫模型,对现有及可能的优选接种方案进行评价,进而优选、评价重要的接种方案,为卫生行政部门决策者提供政策建议,具有重要的现实意义。
研究目的
总的目的：通过较合理测算山东省HBV所有感染状态经济负担,利用其提供的感染成本参数,构建新生儿乙肝疫苗免疫策略的决策树-马尔可夫模型,定量评价不同免疫策略的成本效益,为相关政策的制定提供理论基础和数据依据。具体研究目的为：对山东省乙肝相关疾病住院病人及社区人群乙肝病毒表面抗原(Hepatitis B surface antigen, HBsAg)携带者两个角度进行调查,从直接、间接、无形经济负担三方面测算其经济负担,为山东省新生儿乙肝疫苗免疫策略经济学评价提供有效的感染成本参数；依据决策学分析基本原理和乙肝感染的慢性转归特征,结合现行乙肝疫苗预防接种的实际情况,构建山东省新生儿队列乙肝疫苗接种决策树-马尔可夫模型：定量评价山东省新生儿乙肝疫苗不同免疫策略的成本效益,对参数变化的影响进行灵敏度分析和阈值分析,从成本效益角度,回答山东省新生儿目前实施的5μg重组乙肝疫苗是否需要调整,如果是,调整至哪种策略较合理。
研究对象
研究对象为山东省2010年的新生儿出生队列。
研究方法
1.经济学评价模型及方法将新生儿队列在母亲筛检后接种、不筛检直接接种和不接种策略下,直到死亡所经历的过程(或是乙肝病毒感染,或是乙肝疫苗保护,或是自然死亡)所产生的成本和效益进行测算,建立不同免疫策略的决策树-马尔可夫模型,进行成本-效益分析。成本效益分析是计算不同免疫策略的人均全部预期成本(包括感染成本、接种成本、筛检成本等)和人均全部预期效益,根据以上两个指标计算出不同接种方案的净效益(Net Benefit, NB)和效益成本比(Benefit-Cost Ratio, BCR)两指标。为评价各参数对乙肝疫苗接种策略影响程度的大小,运用单项替代法对研究中主要参数加以变动进行灵敏度分析。通过阈值分析,找出优选策略从一种转化为另一种时某一影响较大因素的阈值。
2.资料来源及方法模型中的乙肝感染成本参数采用多阶段随机抽样方法获得慢性HBV携带者感染成本,采用和时间阶段连续病例整群抽样方法,获得急性乙肝、慢性乙肝、乙肝肝硬化、原发性肝癌等乙肝相关疾病的感染成本,其他参数为山东省数据或文献分析数据。乙肝相关疾病感染成本为病人的年例均直接、间接和无形费用。直接费用包括直接医疗和直接非医疗费用,直接医疗费用包括门诊费、住院费、治疗费、自购药费等；直接非医疗费用包括交通费、食宿费和增加的营养费等：间接费用采用人力资本法测算；无形费用测量采用表达偏好-条件估价法中支付意愿法和竞价法,对乙型肝炎病毒感染者为避免感染带来的身体上的痛苦和精神上的压力而可能愿意支付金钱的数量。
其他成本参数、疫苗相关参数、乙肝感染相关参数等主要取自山东省近期数据,个别参数为国家层面数据,或为文献分析数据。
研究结果
新生儿乙肝疫苗免疫策略成本效益分析结果显示,策略2,即母亲筛检HBsAg和HBeAg (Hepatitis B e antigen), HBsAg和HBeAg阳性者所生新生儿接种3针10μg重组乙肝疫苗合用高价免疫球蛋白(Hepatitis B immune globulin, HBIG),阴性者新生儿接种3针10μg重组乙肝疫苗,BCR为41.62,是3种策略中最高的；仅次于策略2,策略1,即直接接种3针10μg重组乙肝疫苗的BCR为2150；而策略3,即直接接种5μg重组乙肝疫苗的BCR最低,为15.06,表明接种3针5μg疫苗经济学上较10μg疫苗更不划算。若按山东省一年出生100万新生儿计算,使用3种策略均较不接种方案均可获得80亿元以上的净效益。若将现行的直接接种5μg重组乙肝疫苗调整为接种10μg重组乙肝疫苗,从社会角度讲,该出生队列将节约348亿元的资源消耗,从卫生保健支付者角度,可节约2.44亿元；若调整为母亲筛检后接种,从社会角度讲,该出生队列将节约759亿元的资源消耗,从卫生保健支付者角度,可节约530亿元。
灵敏度分析表明,乙肝病毒感染成本取直接费用和间接费用之和时,影响策略2BCR和NB的最大因素分别是乙肝疫苗接种率和贴现率,其次为HBV感染率、疫苗接种率等；影响策略1BCR和NB的最大因素分别是乙肝疫苗直接接种保护率(Vaccine Efficacy, VE,又称疫苗效力)和贴现率,其次为疫苗接种率、HBV感染率等。接种率小于50%时,策略1和策略2,其BCR和NB分别小于1和0。阈值分析结果,当10μg重组乙肝疫苗保护率降至9590%以下时,直接接种5μg重组乙肝疫苗的效益成本比要略高直接接种10μg重组乙肝疫苗：当直接接种10μg重组乙肝疫苗保护率达到99.15%时,效益成本比高于母亲筛检后接种策略：母亲未感染10μg重组乙肝疫苗保护率降至97.70%时,母亲筛检后接种策略BCR低于直接接种10μg重组乙肝疫苗策略。
结论及政策建议结论：1)基于经济负担测算结果,山东省乙肝相关疾病病人经济支出占据当年家庭收入与人均GDP的比例较大,经济负担颇为沉重。2)为切实降低乙肝病毒感染所致经济负担,山东省新生儿乙肝疫苗接种目前宜采用“母亲筛检HBsAg和HBeAg, HBsAg和HBeAg阳性者所生新生儿接种3针10μg重组乙肝疫苗+HBIG,单阳和阴性者新生儿接种3针10μg重组乙肝疫苗”,适时采用“直接接种3针10μg重组乙肝疫苗”策略。3)灵敏度分析显示,疫苗接种率是影响策略BCR和NB的最大因素,疫苗保护率是影响BCR的较大因素。4)根据现阶段山东省新生儿乙肝疫苗接种情况,直接接种10μg重组乙肝疫苗保护率的阈值分别为95.90%和99.15%,低于95.90%时,“直接接种10μg重组乙肝疫苗”策略的效益成本比略低于“直接接种5μg重组乙肝疫苗”策略,高于9915%时,“直接接种10μg重组乙肝疫苗”策略效益成本比高于母亲筛检后接种策略；母亲未感染儿童疫苗保护率阂值为97.70%,低于此值“直接接种3针10μg重组乙肝疫苗”策略效益成本比高于母亲筛检后接种策略。5)本研究注重了模型参数的权威性,尝试将上限值和下限值引入模型进行灵敏度分析,将Meta分析结果用于模型,均提高了决策分析的可靠性和证据性。
政策建议：1)针对乙肝相关疾病感染成本较高,从二级预防的角度,对携带者进行社区随访管理,防止其慢性进展和疾病转归；对慢性、重型病例及时、规范诊治,可延缓其恶性进展,进而降低经济负担。2)为根本降低乙肝相关疾病经济负担,从一级预防的角度,可优先采用母亲筛检HBeAg和HBsAg后接种策略,适时采用直接接种高剂量重组乙肝疫苗策略；灵敏度分析提示我们,执行国家扩大免疫规划的过程中,需加大监督检查力度,确保以乡镇为单位乙肝疫苗接种率达到90%以上,保持并尽力提高接种率。
创新与不足
本研究的创新之处：
1)本研究设计较新颖,与成本参数取自文献的经济学评价研究相比,本研究成本参数及主要参数取自本省。从本省乙肝病毒感染所致经济负担调查入手,测算该类疾病经济负担,基于所测算的经济负担数据确定山东省乙肝病毒相关感染成本参数,对山东省现行的新生儿5μg重组乙肝疫苗接种策略、即将实施的新生儿10gg重组乙肝疫苗策略及其他可能优选策略进行成本-效益分析。
2)本研究尝试从直接、间接和无形费用三方面测算该类疾病的感染成本,不同于以往大部分基于直接费用的经济学研究,以山东省乙肝相关疾病病人和社区HBsAg阳性者为调查对象,合理测算了乙肝病毒感染所有状态的感染成本。
3)本研究联合运用决策树和马尔可夫模型,借助计算机模拟技术为决策者提供调整现有策略的循证政策依据。
本研究的不足与展望：
1)现场调查方面：本研究在无形经济负担的调查中虽采用标准化的询问技巧,也遇到无法量化的调查对象,在计算时以量化结果的均数替代；因青岛市市北区和德州市乐陵市随访时拆迁、外出打工和拒绝调查者太多,造成社区HBsAg阳性者失访率太高,可能会影响其感染成本的测算结果；可能由于调查时间阶段较短造成个别感染成本均数不可靠,对结果会有一定程度的影响。
2)本研究建立的决策树-Markov模型是一个静态、确定、整体、封闭的模型。与动态模型相比,未考虑免疫屏障的作用,低估了免疫效益；灵敏性分析方面,参数取值未采用概率分布,与基于参数概率分布的分析相比,存在欠缺；与基于个体建立的模型相比,整体模型不能追踪个体的转归,仅采用年转归概率,因而无法反映个体转归的差异；与开放性模型相比,封闭模型忽略所模拟出生队列人群的进入和迁出,与实际情况稍有偏差。考虑免疫屏障作用并符合实际情况的动态模型的建立和评价可能是未来研究的重点。
Background
Hepatitis B is globally recognized as a major public health problem at present.76%percent of infected with the hepatitis B virus is in Asian. Hepatitis B is one of the most serious public health problems in China. According to the estimation of the national seroepidemiological survey in2006, nationwide,93million are chronically infected persons, including approximately20million cases of chronic hepatitis B patients. Hepatitis B has such characteristics as high infection rate, high incidence, a high proportion of chronic persistent and adverse outcomes and so on.HBV infection and its adverse outcomes, including acute hepatitis B, chronic hepatitis B, HBV cirrhosis, Primary liver cancer which can all be collectively referred to as hepatitis B-related diseases. Hepatitis B-related diseases cause heavy economic burden to the patient and his family and have a tremendous impact on the socio-economic development.
At present, there's still no special drug that can cure hepatitis B in the world, and therefore Vaccinating hepatitis B vaccine has been the most effective means of prevention and control of hepatitis B and decreasing the economic burden of the disease. Domestic and international research shows that decision tree model, with such characteristics as simple, intuitive, pluralistic, quantitative and so on, is used to optimize hepatitis B vaccine strategy. It is easy to be understood and accepted combined with related indicators of health economics. Through simulating the chronic progression of disease, using different Markov models to estimate research objects' QALY(Quality-adjusted Life Year) or cost under different intervention measures and implements related economics research, Markov model evaluate the research questions. Establishing a decision tree-Markov model of hepatitis B immunization Strategy for economic evaluation has been reported in foreign literature but rare in domestic literature.
Since1992,our country has laid down neonatal hepatitis B immunization rules, and since2002,the hepatitis B were formally brought into national immunization programs and since June1,2005,we achieved free newborns hepatitis B immunization. Through more than a decade's promotion and implementation, our country's HBsAg carrier rate declined from9.75%in1992to7.2%in2006and the effectiveness of hepatitis B immunization is significant. But how to reasonably and quantitatively evaluate the economics effect of newborns'hepatitis B immunization strategy has become a big problem for policymakers. Domestic researches are mostly rough and simple. After having review over50articles published domestically in between1991-2011,1find that all the models used are a decision tree model. such a model cannot handle the complexity of hepatitis B and its related diseases and its methods are simple, parameters setting roughly, rather than general methods of hepatitis B immunization strategy in economics evaluation studies of countries in the world. In this study, starting from the economic burden investigation of hepatitis B-related diseases of Shandong Province, we use its important parameters to build decision tree-Markov model for neonatal on hepatitis B immunization strategy to evaluate the existing strategy and to preferably select the important immunization programs and therefore to provide policy advice for the decision-makers of health administrative departments, which is of great practical significance.
Objectives
The overall objective of this study is to estimate the economic burden of the province hepatitis B-related diseasesh and use its scientific parameters to build decision tree-Markov model of neonatal hepatitis B immunization strategy. We make quantitative assessment for benefit of hepatitis B immunization strategy to provide data for the decision-makers.Specific research objectives include, to estimate the economic burden including direct, indirect and intangible economic burden from people HBsAg positive and inpatients,and then construct decision tree-Markov model of neonatal hepatitis B immunization strategy.Through cost-benefit analysis, sensitivity Analysis and threshold Analysis, we economically evaluate the existing immunization programs and preferably select immunization strategy. Object
2010-year neonatal birth cohort is the object
Method
1.Method for the Economic Evaluation we evaluate different immunization strategy's costs and benefits in decision tree-Markov model, including vaccinated strategy after mothers'screened, direct immunization, no immunization strategy. This cohort will experience from birth to death, or infected,protection from immunization,natural death.
Methods for different strategy's economic evaluation in decision tree-Markov model is cost-benefit analysis which calculates the expected cost and expected benefits of immunization strategy.According to the above two indicators,we calculated Net Benefit and Benefit-Cost Ratio of different immunization strategy. We use single alternative to make sensitivity analysis to select the main influencial parameters and influencing level.By Threshold Analysis, we identify threshold value of the most influential factors from one strategy to another.
2.Materials and Methods In economic burden investigation of hepatitis B-related diseases,we adopted multi-stage random sampling method and a cluster sampling for cases collected consecutively during the study period to achieve cost information for HBsAg (Hepatitis B Surface antigen)-positive,acute hepatitis B, chronic hepatitis B, hepatitis B-liver cirrhosis and primary liver cancer The other parameter is from Shandong and meta-analysis.Diseases cost are composed of direct expenses, indirect expenses and intangible expenses, respectively calculating the average cost of patients in the past year. Direct expenses are composed of direct medical costs and direct non-medical costs, direct medical costs consist of outpatient expenses, hospitalization expenses, treatment costs, prescription charge and so on. Direct non-medical costs consist of transportation costs, accommodation costs, increased nutrition cost and so on.We use human capital approach to estimate indirect expenses, using Willingness to Pay (WTP) and Auction Method of express preferences-conditions valuation to estimate the intangible expenses.
The other cost parameter,parameter related to vaccine and HBV infection are derived from Shandong Province. We gain Several parameters from our country and references.
Results
After mother screening HBsAg and HBeAg (Hepatitis B e antigen), if the result is positive then vaccinated three doses of10μg+HBIG (Hepatitis B immune globulin), if it is negative then vaccinated three doses of10μg hepatitis B vaccine.This is the second strategy,BCR is41.62.Newborns were directly vaccinated three doses of hepatitis B vaccine, and10μg per dose, BRC is21.50.And when vaccinated three doses of5μg hepatitis B vaccine, BCR of hepatitis B vaccine is15.06. It shows5μg hepatitis B vaccine is not economical than10μg hepatitis B vaccine. If there are1million newborns in Shandong province each year, Compared with one strategy of no vaccination, We obtain net benefit of8billion yuan from three kinds of strategies. If the10μg direct immunization strategy replace5μg hepatitis B vaccine.this birth cohort will save348million yuan of resource consumption from a social point of view and save244million yuan of resource consumption from the point of view of health care payer. If adjusted to vaccination after screening,this birth cohort will save 759million yuan of resource consumption from a social point of view and can save530million yuan of resource consumption from the point of view of health care payer. The results of sensitivity analysis are as follows. If we use the sum of direct and indirect economic burden of of hepatitis B-related diseases, the biggest factor that affects BCR and NB of the second strategy is hepatitis B coverage and discount rate, respectively.Followed by HBV year-infection rate and hepatitis B coverage rates, etc.The biggest factor that influence BCR and NB of the first strategy is hepatitis B vaccine efficacy of direct vaccination and discount rate,respectively. Followed by hepatitis B coverage and hepatitis B coverage,etc. When hepatitis B coverage is less than50%, BCR and NB of the first strategy and the second strategy is less than1and0, respectively.
The result of threshold analysis:the threshold value of vaccine efficacy in10μg; hepatitis B vaccine vaccinated directly is95.90%, that is to say while vaccine efficacy of10μg hepatitis B vaccine drop below95.90%, the cost-benefit ratio of5μg hepatitis B vaccine vaccinated directly is slightly higher than10μg. Compared with the second strategy,the threshold value of vaccine efficacy in10μg hepatitis B vaccine vaccinated directly is99.15%.Compared with the first strategy, the threshold value of vaccine efficacy in10μg hepatitis B vaccine efficacy when mother is not infected with hepatitis B virus is97.7%.
Conclusions and policy implications
Conclusions:1) Annual economic burden indicate the economic burden of patients related to HBV in Shandong province is very heavy.2) To cut down economic burden earnestly, the immunization strategy of vaccinating for newborns after mothers' HBsAg and HBeAg is regarded as optimal program of neonatal hepatitis B vaccine in Shandong province. We can select the immunization strategy of directly vaccinating10μg hepatitis B vaccine for newborns at the right moment.3) Sensitivity analysis shows that the biggest factor influencing BCR and NB of strategies is hepatitis B coverage. vaccine efficacy is a bigger factor influencing BCR.4)According to neonatal hepatitis B vaccination'Status quo in shandong province, When the threshold value of directly vaccinating10μg vaccine efficacy is below95.90%, its BCR is a little lower than directly vaccinating5μg recombinant hepatitis B vaccine. When its efficacy is above99.15%,its BCR is higher than the strategy after mother screening The threshold value of10μg hepatitis B vaccine efficacy for uninfected mother is lower than97.7%, direcly vaccinating10μg hepatitis B vaccine is the optimization scheme compared with the strategy after mother screening.5) We pay attention to the authority of the model parameters and attempts to introduce the upper limit and lower limit value to make sensitivity analysis model, use Meta analysis in model.The above-mentioned measures enhance the reliability of the decision analysis and evidence.
Policy recommendations:1) From the point of secondary prevention, follow-up management of carriers can prevent the chronic progress, timely diagnosis and standard treatment of chronic and severe cases can delay the malignant progression, also reduce the economic burden2) From the point of primary prevention, we adopt the immunization strategy of vaccinating for newborns after mothers'HBsAg and HBeAg of neonatal hepatitis B vaccine in Shandong province and select the strategy directly vaccinating10μg hepatitis B vaccine for newborns at the right moment.sensitivity analysis suggests that we need to increase supervision and inspection intensify to ensure that the township as a unit of HBV rate reach90%or more, and try to improve the vaccination rate on the process of the implementation of national expanded program on Immunization,
Innovation and limitation
The innovation of this study:1) on-the-spot investigation:The research design is novelty.First investigate economic burden, and then use the economic burden parameter and evaluate neonatal HBV strategy. This is different from past research which parameter is derived from literature.2) From hepatitis B-related diseases and HBsAg positive at the community in Shandong Province,we attempt to estimate the economic burden including direct,indirect, intangible economic burden.This is different from some economic researchs calculated direct cost.3) we combine decision tree and Markov model to provide evidence-based policy of adjusting the existing strategy for health decision makers of administrative department with the help of computer simulation technology.
The limitation of this research:l)This research tries to estimate economic burden of diseases Hepatitis B-related from three aspects:the direct, indirect and intangible economic burden, we encountered the data of intangible economic burden in the survey cannot be quantified and replaced this with the mean in the calculation although we used standardized questioning techniques. Because the follow-up rate is not high in Shibei county of Qingdao City and laoling county of Dezhou city, the cost of HBsAg positive at the community may be affected.The shorter study period may influence the reliability of mean of infection cost.
2) Markov model is a static,definate, whole, closed model. Compared with the dynamic model, without considering the effect of immune barrier, underestimated the immune efficiency. there is lack in sensitivity analysis without selecting parameter's probability distribution. Compared with model based on the individual, the whole model can't track the individual turnover replaced by annual transition probablities only, thus this model cannot reflect individual differences in turnover. Compared with the open model,closed model ignores into and out of the cohort,there is a slight deviation with the actual situation. The establishment of dynamic model considering immune barrier and the actual situation and evaluation may be the focus of future research.
引文
[1]齐小秋,王宇.全国人群乙肝病毒性肝炎血清流行病学调查报告[M].北京：人民卫生出版社,2011
[2]世界卫生组织乙型肝炎第204号实况报道(2012年7月)http://www. who. int/ mediacenter/factsheets/fs204/index.htm.
[3]Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection. US Centers for Disease Control and Prevention. No. RR-8, s.1.:MMWR,2008, Vol.57.
[4]Lu FM, Zhuang H. Management of hepatitis B in China[J]. Chin Med J(Eng),2009,122(1):3-4.
[5]卫生部网站http://www.moh.gov.cn/zwgkzt/ptjnj/list.shtml.
[6]Yang BM, Kim DJ, Byun KS, et al. The Societal Burden of HBV-Related Disease: South Korea[J], Dig Dis Sci,2010,55(3):784-793.
[7]于保荣,李宁宁,张丽,等.不同医疗保障制度慢性乙肝患者住院费用及影响因素分析[J].中国卫生经济,2011,30(8)：39-41.
[8]Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B:a historical overview[J]. Vaccine,2008,26(49):6266-73.
[9]Hutton DW;Tan D;So SK, et al. Cost-effectiveness of screening and vaccinating Asian and Pacific Islander adults for hepatitis B[J]. Annals of Internal Medicine,2007,147(7):460-469.
[10]于淑丽.乙型肝炎免疫接种策略的评价.复旦大学博士论文,2003.
[11]戴志澄,祁国明中国病毒性肝炎血清流行病学调查1992-1995(上卷)[M]北京：科学技术文献出版社,1997.
[12]Liang X, Bi S, Yang W, et al. Epidemiological serosurvey of hepatitis B in China-declining HBV prevalence due to hepatitis B vaccination[J]. Vaccine,2009,27(47):6550-6557.
[13]张丽乙肝疫苗使用20年后山东省乙型病毒性肝炎血清和分子流行病学研究.山东大学博士论文,2009
[14]Hong-Anh T Tu, Herman J, Woerdenbag, Sumit Kane, Arthorn Riewpaiboon, Marinus van Hulst and Maarten J Postma.Economic evaluations of hepatitis B vaccination for developing countries[J].Vaccine,2009,8(7):907-920.
[15]张林国,编著.乙型肝炎[M].北京：科学技术文献出版社.2002.
[16]张丽,张卫,翟祥军,等.新生儿5μg和10μg重组酵母乙型肝炎疫苗初免后抗体免疫应答比较[J].中华流行病学杂志,2012,33(3)：306-309.
[17]胡善联,华庆生,应和琴,等.上海地区病毒性肝炎的费用分析[J].中国卫生经济,1988,4：52-53.
[18]唐玲,胡晓抒,扬健,等.江苏省病毒性肝炎费用分析[J].中国卫生经济,1988,12：25-27.
[19]张顺祥.病毒性肝炎病人经济负担分析[J].山西医学院学报,1990,21(2)：88-92.
[20]白亚娜成人病毒性肝炎住院费用分析[J].中国医院统计,1995,2(1)：47-49
[21]Li SC, Ong SC, Lim SG, et al. A cost comparison of management of chronic Hepatitis B and its associated complications in Hong Kong and Singapore[J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S136-S 143.
[22]Hsieh CR, Kuo CW. Cost of chronic hepatitis B virus infection in Taiwan[J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S 148-S152.
[23]Butler JR, Pianko S, Korda RJ, et al. The direct cost of managing patients with chronic hepatitis B infection in Australia [J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S187-S192.
[24]Gagnon YM, Levy AR, Iloeje UH, et al. Treatment costs in Canada of health conditions resulting from chronic hepatitis B infection [J]. J Clin Gastroenterol, 2004,38(10 Suppl 3):S179-S186.
[25]Yang BM,Kim CH,Kim JY. Cost of chronic hepatitis B infection in South korea[J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S153-S157.
[26]Lee TA, Veenstra DL, Iloeje UH, et al. Cost of chronic hepatitis B infection in the United States [J]. J Clin Gastroenterol,2004,38(Suppl 3):S144-S147.
[27]Brown RE, Cock ED, Colin X, et al. Hepatitis B management costs in France, Italy, Spain and the United Kingdom [J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S169-174.
[28]Guan ZQ, Dong ZH, Wang QH, et al. Cost of Chronic Hepatitis B Infection in China [J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S 175-S178.
[29]劳国琴,王佳良,吴勇.干扰素治疗慢性乙型肝炎病毒感染的经济效益[J].药物经济学,2006,17(16)：1223-1225
[30]Hu M, Chen W. Assessment of total economic burden of Chronic Hepatitis B (CHB)-related diseases in Beijing and Guangzhou,China [J]. Value Health,2009, 12(Suppl3):S89-S92.
[31]Ong SC, Lim SG, Li SC, et al. How big is the financial burden of hepatitis B to society? A cost-of-illness study of hepatitis B infection in Singapore[J]. J Viral Hepat,2009,16(1):53-63.
[32]杨晓玲.弱势群体的平等权保护.中国法学会行政法学研究会2010年会论文集,2010年7月.
[33]梁森,张顺祥,马起山,等深圳市乙型肝炎相关疾病经济负担及其影响国素分析[J]中华流行病学杂志,2010,31(12)：1340-1345
[34]马起山,邹宇华,张顺祥,等.广州市乙型肝炎相关疾病住院病例无形费用及其影响因素分析[J]中华流行病学杂志,2011,32(8)：660-663
[35]梁森,张顺祥,马起山,等.深圳市乙肝住院病人年直接经济负担及对家庭经济影响分析[J].中国卫生经济,2011,30(2)：56-58.
[36]伍春霞,马起山,邹玉华,等.广州市乙型病毒性肝炎住院患者经济负担分析[J].广东药学院学报,2011,27(2)：195-198.
[37]Mulley A G, Silverstein M D, Dienstag J L. Indications for use of hepatitis B vaccine, based on cost-effectiveness analysis[J]. New England Journal of Medicine,1982,307(11):644-652.
[38]Littenberg B, Ransohoff D F. Hepatitis B vaccination:Three decision strategies for the individual[J]. The American journal of medicine,1984,77(6):1023-1026.
[39]Jackiche R, Borrego ME,Raish DW,et al. The cost-effectiveness of two strategies for vaccinating US veterans with hepatitis C verus infection against hepatitis A and hepatitis B viruses[J].Am J Med Sci,2007,333(1):26-34.
[40]张顺祥,徐慧文,任延荣.运用费用效益分析和决策树法探讨中国乙肝疫苗接种策略[J].中国公共卫生,1989,5(8)：4-7.
[41]庄贵华,徐慧文,决策分析在乙型肝炎疫苗接种策略评价上的应用[J].中华预防医学杂志,1993,27(2)：69-73.
[42]张顺祥,党如波,张卫东,等.中国乙型肝炎疫苗免疫预防效果和现行策略的经济学和决策学评估[J].中华流行病学杂志,2008,29(10)：1003-1008
[43]易华云,刘爱忠,张琰.Markov模型在卫生领域中应用简介[J].循证医学,2008,8(3)：172-176.
[44]Tilson L, Thornton L, O'Flanagan D, et al. Cost effectiveness of hepatitis B vaccination strategies in Ireland:an economic evaluation[J]. Eur J Public Health,2008,18(3):275-282.
[45]Hung HF, Chen TH. Probabilistic cost-effectiveness analysis of the long-term effect of universal hepatitis B vaccination:An experience from Taiwan with high hepatitis B virus infection and Hepatitis B e Antigen positive prevalence[J]. Vaccine,2009,27(48):6770-6776.
[46]David WH,Samuel K S, and Margaret LB. Cost-Effectiveness of Nationwide Hepatitis B Catch-up Vaccination Among Children and Adolescents in China. [J].HEPATOLOGY,2009,51(2):405-414.
[47]Ruggeri M,Cicchetti A,Gasbarrini A. The cost-effectiveness or alternative strategies against HBV in Italy[J]. Health Pohcy,2011,102(1):71-80.
[48]Klinqler C,Thoumi AI,Mrithinjayam VS. Cost-effectiveness analysis of an additional birth dose of Hepatitis B vaccine to prevent perinatal transmission in a medical setting in Mozambique[J].Vaccine,2012,31(1):252-259.
[49]马福宝.经济学方法在疫苗预防传染病中的应用于评价[J].中国执业药师,2012,9(9)：25-28.
[50]Siddiqui MR,Gay WJ,Edmunds WJ,et al.Economic evaluation of infant and adolescent hepatitis B vaccination in the UK[J]. Vaccine,2011,29(3):466-475.
[51]李顺平,马东平,王健,等.中国乙肝疫苗接种策略的经济学评价系统综述[J].中国卫生经济,2011,30(3)：84-86.
[52]梁扩寰主编.肝脏病学[M]人民卫生出版社,1995
[53]迮文远主编.计划免疫学(第二版)[M].上海科学技术文献出版社.2001
[54]徐志一乙型肝炎疫苗预防乙型肝炎的效果与存在的问题[J].上海预防医学杂志,1997,9(6)：243-245.
[55]朱启镕 王建设.国产重组酵母疫苗和血源疫苗对乙型肝炎病毒母婴传播阻断效果的比较[J].中华儿科杂志,2000,38(11)：682-684.
[56]陈兴宝,陈慧芬,Alison TM,等.慢性乙型病毒性肝炎经济费用分析[J].中华医院管理杂志,2003,19(1)：58-59.
[57]庄润身,王声湧.如何评价疾病的经济负担[J].中国预防医学杂志,2001,2(4)：245-247
[58]Peabody JW,Shimkhada R,Tan C. The burden of disease, economic costs and clinical consequences of tuberculosis in the Philippines[J]. Health Policy Plan,2005,20(6):347-353.
[59]李俊华乙肝后肝硬化肝癌患者经济负担及影响因素分析,山西医科大学硕士学位论文,2011
[60]马起山.广州市乙肝相关疾病经济负担及1-14岁人群乙肝疫苗接种策略研究.广东药学院硕士学位论文,2011
[61]李晓强.乙肝相关疾病住院病人经济负担和生存质量研究.宁夏医科科大学硕士学位论文,2012.
[62]史武杰.长治地区乙肝相关疾病经济负担研究.山西医科大学硕士学位论文,2011
[63]王贵强,贾继东,王豪,等.《乙型病毒性肝炎诊断标准(WS 299-2008)》[Z]中华人民共和国卫生部,2008
[64]胡善联主编.卫生经济学[M]上海：复旦大学出版社,2003
[65]李娟,于保荣.疾病经济负担研究综述[J].中国卫生经济,2007,26(11)：72-74
[66]程晓明主编.卫生经济学[M]第2版.北京：人民卫生出版社,2007
[67]梁森,中国新生儿乙肝免疫预防策略决策分析和成本效益评价[D]郑州大学硕士论文,2011
[68]亓文婷,孙建东,徐爱强,等.山东省乙型肝炎病毒感染所致相关疾病的疾病负担研究[J].中华流行病学杂志,2009,30(7)：679-683
[69]《中国药物经济学评价指南》课题组.中国药物经济学评价指南[J].中国药物经济学杂志,2011,(3)：6-48.
[70]Leung GC,McGrath CP. Willingness to pay for implant therapy:a study of patient Preference[J].Clin Oral Implants Res,2010,21(8):789-793.
[71]王艳,张宜升,刘斌.青岛市居民减少空气污染致病的支付意愿调查[J].环境与健康杂志,2008,25(4)：326-330.
[72]吕静静,徐爱强,王健,等.关于条件价值评估法在公共卫生领域应用的综述[J].中国卫生政策研究,2011,4(3)：33-39.
[73]王舒宏,刘兴桂,李卜雪,等.疟疾病例经济负担分析[J].中国初级卫生保健,1996,10(9)：33-35.
[74]庄润森.社区居民的疾病负担研究.暨南大学硕士论文,2003.
[75]Yen ZS,Chang CJ,Chen SY, et al.How much would you be willing to pay for Preventing a new dangerous infectious disease:a willingness-to-pay in the em ergency department[J]. Am J Infect Control,2007,35(8):516-520.
[76]Fact Sheet WHO/204. Revised October 2000.
[77]Worle Health Organization.Hepatitis B(Revised August 2008) [EB/OL]. [2010-12-09].http://www.who.int/mediacentre/factsheets/fs204/en/.
[78]Coverage with primary health care services indicators.http://www.emro.who .int/index aspx
[79]Gentile A, Bhutta Z, Bravo L,et al. Pediatric disease burden and vaccination recommendations:understanding local differences [J]. International Journal of Infectious Diseases.2010,14(8):649-658.
[80]郭秀婵,陈宝珍,刘振天等.赴美国、意大利执行病毒性肝炎控制项目考察报告[R].疾病监测,2000,15(1)：30-33
[81]Review. Hepatitis B vaccination in countries with low endemicity[J]. Prescrire Int,2000,9(45):213-9.
[82]Zuckerman J, van Hattum J, Cafferkey M,et al. Should hepatitis B vaccination be introduced into childhood immunisation programmes in northern Europe? [J].Lancet Infect Dis,2007,7(6):410-19.
[83]Beutels P. Economic evaluations of hepatitis B immunization; a global review of recent studies(1994-2000)[J]. Health Econ 2001; 10(8):751-74.
[84]韩永战,陈仕珠.乙型肝炎病毒疫苗免疫接种策略及卫生经济学评价[J]世界华人消化杂志,2006,14(27)：2722-2728
[85]Sahni M,Jindal K,Abraham N,et al. Hepatitis Bimmunization:cost calculation in a community-based study in lndia[J]. Indian J GAstroenterol,2004,23(1):16-18.
[86]Xin Sun,Thomas Faunce.Decision-analytical modelling in ealth-care economic evaluations[J]. Eur J Health Econ,2008,9(4):313-323.
[87]Hutton DW, Tan D, So S K, et al. Cost-effectiveness of screening and vaccinating Asian and Pacific Islander adults for hepatitis B[J]. Ann Intern Med,2007,147(7):460-469.
[88]Wu B, Li T, Chen H, et al. Cost-Effectiveness of Nucleoside Analog Therapy for Hepatitis B in China:A Markov Analysis.[J]. Value Health,2010,13(5):592-600.
[89]张顺祥,徐慧文.决策树法预测中国乙肝疫苗接种策略[J]中华流行病学杂志,1989,10(4)：193-197.
[90]张顺祥,韩晓立,赵淑芳,等.山西乙肝疫苗接种前筛检策略初步研究[J].现代预防医学,1992,19(3)：132-135.
[91]张顺祥,韩晓立,赵淑芳.中国乙型肝炎疫苗接种前筛检策略的优化[J].中华预防医学杂志,1992,26(3)：154-158.
[92]庄贵华,徐慧文.乙肝疫苗接种策略的进一步探讨[J]西安交通大学学报(医学版),1992,13(4)：360-364.
[93]肖和卫.中国15岁以上人群乙型肝炎免疫预防的决策分析模型研究[D].中南大学硕士论文,2011
[94]李俊,孙莲英,曾雪霞,等.海南省新生儿接种乙肝疫苗成本效益分析[J]2011,11(1)：18-21.
[95]关旭静,杨超美,王进.四川省新生儿乙型肝炎疫苗接种卫生经济学评价[J].2010,16(5)：447-452.
[96]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南 (2010版)[J].中国病毒病杂志,2011,1(1)：9-23.
[97]Liaw YF.Natural history of chronic hepatitis B virus infection and long-term outcome under treatmen[J]. Liver Int,2009,29(Suppl 1)100-107.
[98]林曦敏,丁玎,张普洪,等.干扰素治疗慢性乙型肝炎患者的成本效果分析[J].中华肝病杂志,1999,7(2)：84-87.
[99]张媛媛.中国大陆人群乙型肝炎经济负担研究综述[J]中国农村卫生事业管理,2012,32(11)：1115-1118.
[100]王家良.循证医学[M].北京：人民卫生出版社,2005
[101]曹建文.临床决策分析[M].上海：复旦大学出版社,2005.
[102]TreeAge Pro 2011 User's Manual. TreeAge Software Inc 2010.
[103]Chen CJ, Yang HI. Natural History of Chronic Hepatitis B REVEALed[J]. J Gastroenterol Hepatol,2011,26(4):628-638.
[104]McMahon BJ. Natural history of chronic hepatitis B[J]. Clinics in liver disease, 2010,14(3):381-396.
[105]Zui S, Chang CJ, Chen SY, et al. How much would you be willing to pay for preventing a new dangrous infectious disease:A willingness-to-pay in the emergency department[J]. Am J Infect Control,2007,35(8):516-520.
[106]梁森,张顺祥,马起山,等.乙型病毒性肝炎病人经济负担调查问卷的信效度研究[J].中国初级卫生保健,2010,24(9)：48-49.
[107]2010年济南市国民经济和社会发展统计公报http://www.jinan.gov.cn/art/2011/2/18/art_95_272749. html.
[108]青岛市2010年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201103/18856.html.
[109]2010年聊城市国民经济和社会发展统计公报http://lcjrw.com/xinwen/bendijinrong/2011-03-30/11619.html.
[110]淄博市沂源县2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20514.html.
[111]枣庄市薛城区2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20517.html.
[112]烟台市芝罘区2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20524.html.
[113]2010年蓬莱市政府工作报告http://www.jiaodong.net/news/system/2010/01/18/010730166.html.
[114]潍坊市高密市2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201006/12085.html.
[115]济宁市邹城市2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20530.html.
[116]泰安市宁阳县2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201006/12156.html.
[117]2009年莱芜市国民经济和社会发展统计公报http://lw.sdnews.com.cn /html/59/710.htm.
[118]2009年莒南县国民经济和社会发展统计公报http://junan.stats-ly.gov.cn /junan/tjgb/55777.html.
[119]德州市2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb /201003/7960.html.
[120]Singh P, Pandey A, Aggarwal A. House-to-house survey vs. snowball technique for capturing maternal deaths in India:a search for a cost-effective method. Indian J Med Res,2007,125(4):550-6.
[121]Stanley A.Plotkin,Walter A. Orenstein,Paul A. Offit.梁晓峰,罗凤基,封多佳.疫苗学[M]北京：人民卫生出版社.2011(译著)
[122]肖和卫,张顺祥,谭红专.Meta分析对效应量率的合并方法的研究进展[J].中国预防医学杂志,2011,12(5)：445-447
[123]王华庆,随海田.甲型肝炎减毒活疫苗保护效果的Meta分析[J].中国疫苗和免疫,2008,14(1)：1-6.
[124]Gillian M. K. and Stuart N. Recombinant Hepatitis B vaccine (Engerix-B)-A Review of its Immunogenicity and Protective Efficacy Against Hepatitis B[J]. Drugs,2003,63(10):1021-1051.
[125]刘崇柏.中国病毒性肝炎人群流行病学特征及流行因素研究[J]中华肝脏 病杂志,1998,6(2)：67-70.
[126]戴志澄,祁国明.中国病毒性肝炎血清流行病学调查(下卷)[M].北京：科学技术文献出版社.1996.
[127]冀贞浩.我国新生儿乙型肝炎免疫预防策略成本效果分析.西安交通大学硕士论文.2012
[128]李文潮,赵东涛,赵清波.催化模型拟合中感染力的选择与计算[J].数理医药学杂志,2007,20(2)：135-136.
[129]李文潮,吴克坚,赵东涛.流行病学中流行率模型的应用分析[J]2008,21(1)：102-103.
[130]Liang X, Bi S, Yang W, et al. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China. [J]. J Infect Dis, 2009,200(1):39-47.
[131]梁争论,李河民.中国不同人群接种乙型肝炎疫苗的成本-效益分析[J].中国生物制品杂志,2006,19(4)：434-436.
[132]纪峰,张丽,颜丙玉,等.2006年山东省育龄期妇女乙型肝炎病毒感染状况分析[J].预防医学论坛.2006,16(9)：781-783.
[133]http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2010 /index2010.html
[134]Zhuang G H, Pan X J, Wang X L. A cost-effectiveness analysis of universal childhood hepatitis A vaccination in China[J]. Vaccine,2008,26(35):4608-4616.
[135]李士雪.卫生保健项目经济学评估方法(第3版)[M].北京：人民卫生出版社,2008(译著)
[136]沈培,张吉凯.公共卫生项目成本-效益分析中的社会贴现率研究.中国卫生经济,2010,29(6)：72-73
[137]孙利华,宗欣.对中国药物经济学评价中贴现率选择问题的思考.中国新药杂志,2010,19(9)：737-739.
[138]Tan-Torres Edejer T.,Baltussen R.,Adam T.,et al. Making choices in health car:WHO guide to cost-effectiveness analysis. World Health Organization, Geneva,2003.
[139]Zhou F,Santoli J,Messonnier ML,et al.Economic evaluation of the 7-vaccine routine childhood immunization schedule in the United States[J].Arch Pediatr Adolesc Med,2005,159(12):1136-1144.
[140]姚红玉,陈陶阳,曲春枫.我国新生儿乙肝疫苗免疫后效应概述及相关问题[J].科学通报,2012,57(20)：1911-1917.
[141]Chen HY,Lin LH,Hu FC,et al. Effects of Maternal Screening and Universal Immunization to Prevent Mother-to-Infant Transmission of HBV. Gastroenterology,2012,142(4):273-781.
[142]余文周.计划免疫工作成本和投入研究.2005年
[143]国家发展改革委办公厅关于制定重组乙型肝炎疫苗14种国家免疫规划疫苗出厂价格的通知[Z].2009年7月
[144]王富珍,崔富强,郑徽,等重组乙型肝炎疫苗(酵母)与乙型肝炎免疫球蛋白联合免疫阻断乙型肝炎病毒母婴传播的效果分析[J].中国计划免疫,2007,13(4)：293-297.
[145]王富珍,龚晓红,李辉,等.北京市乙型肝炎疫苗母婴阻断效果监测分析[J].中国计划免疫,2006,12(2)：97-98.
[146]张海艳,周艳丽,赵丽英,等.北京市原东城区乙型病毒性肝炎病毒母婴传播阻断效果评估[J].首都公共卫生,2011,5(3)：102-105
[147]张彦芳,胡玉红,等.替比夫定阻断乙型肝炎病毒母婴传播的疗效和安全性[J].药物不良反应杂志,2010,12(3)：157-159.
[148]蒋雪峰,陶志华,姚凤燕,等.乙型肝炎病毒表面抗原阳性母亲的儿童接种乙型肝炎疫苗阻断乙型肝炎病毒传播的效果分析[J].中国疫苗和免疫,2010,16(1)：89.
[149]辛崇干.临沂市新生儿接种乙型肝炎疫苗后免疫效果观察[J].职业与健康,2011,27(22)：2530-2542
[150]Liaw YF, Chu CM. Hepatitis B virus infection[J], Lancet, 2009,373(9663):582-592.
[151]Hutton DW, So SK, Brandeau ML. Cost-effectiveness of nationwide hepatitis B catch-up vaccination among children and adolescents in China[J]. Hepatology, 2010,51(2):405-414.
[152]Ni YH. Natural history of hepatitis B virus infection:pediatric perspective[J]. Journal of gastroenterology,2011,46(1):1-8.
[153]Chu CM, Liaw YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas:appreciably high rates during a long-term follow-up[J]. Hepatology,2007,45(5):1187-1192
[154]Wu Q, Zhuang G-H, Wang X-L, et al. Antibody levels and immune memory 23 years after primary plasma-derived hepatitis B vaccination:Results of a randomized placebo-controlled trial cohort from China where endemicity is high[J]. Vaccine,2011,29(12):2302-2307.
[155]Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma.epidemiological characteristics and disease burden[J]. Journal of viral hepatitis,2009,16(7):453-463.
[156]山东省统计局编.2005年山东省1%人口抽样调查资料[M].北京：中国统计出版社,2007.
[157]山东省统计年鉴-2011[M]北京：中国统计出版社
[158]李宁宁.不同医疗保障制度下乙型病毒性肝炎三种病程患者的住院治疗及费用研究.山东大学硕士论文,2012.
[159]龚红霞,刘元强,马莉,等.兰州市1996年-2006年肺癌和肝癌患者住院费用分析[J]现代预防医学,2012,39(2)：270-272.
[160]Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation[M]. Oxford, United Kingdom:Oxford University Press,2006.
[161]冯艺,颜丙玉,张丽,等.山东省法定传染病报告系统乙型病毒性肝炎报告病例临床分类复核结果分析[EB].现代预防医学,网络出版地址：http://www.cnki.net/kcms/detail/51.1365.R.20121023.1635.007.html.
[162]山东省统计局.山东省2010年国民经济和社会发展统计公报.http://www.stats-sd.gov.cn/disp/tjgb.asp?aa=1101201100.
[163]张顺祥.决策树模型在制定疾病防制策略中的应用(二)[J].中国卫生统计,1991,8(3)：60-64.
[164]张文宏.《慢性乙型肝炎防治指南》专家讨论会常见问题及解答(免疫预防部分)[J].中华传染病杂志,2006,24(4)：287-288.
[165]梁争论,李河民,庄辉.乙型肝炎疫苗免疫效果影响因素和加强免疫策略 研究[J].中华流行病学杂志,2007,28(4)：313-314.
[166]陈博,刘柳,张菊英.5μg和10μg两种剂量重组乙肝疫苗免疫效果的Meta分析[J].现代预防医学,2010,37(4)：611-614.
[167]Dave Smith, Hugn Grvelle. ThePractiee of discounting economic evaluation of health care intervention[J].Center for health economic technical paper seriesl9, university of York,2000.
[168]Vimolket T, Poovorawan Y. An economic evaluation of universal infant vaccination strategies against hepatitis B in Thailand: an analytic decision approach to cost-effectiveness[J]. Southeast Asian J Trop Med Public Health,2005,36(3):693-699.
[2]世界卫生组织乙型肝炎第204号实况报道(2012年7月)http://www. who. int/ mediacenter/factsheets/fs204/index.htm.
[3]Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection. US Centers for Disease Control and Prevention. No. RR-8, s.1.:MMWR,2008, Vol.57.
[4]Lu FM, Zhuang H. Management of hepatitis B in China[J]. Chin Med J(Eng),2009,122(1):3-4.
[5]卫生部网站http://www.moh.gov.cn/zwgkzt/ptjnj/list.shtml.
[6]Yang BM, Kim DJ, Byun KS, et al. The Societal Burden of HBV-Related Disease: South Korea[J], Dig Dis Sci,2010,55(3):784-793.
[7]于保荣,李宁宁,张丽,等.不同医疗保障制度慢性乙肝患者住院费用及影响因素分析[J].中国卫生经济,2011,30(8)：39-41.
[8]Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B:a historical overview[J]. Vaccine,2008,26(49):6266-73.
[9]Hutton DW;Tan D;So SK, et al. Cost-effectiveness of screening and vaccinating Asian and Pacific Islander adults for hepatitis B[J]. Annals of Internal Medicine,2007,147(7):460-469.
[10]于淑丽.乙型肝炎免疫接种策略的评价.复旦大学博士论文,2003.
[11]戴志澄,祁国明中国病毒性肝炎血清流行病学调查1992-1995(上卷)[M]北京：科学技术文献出版社,1997.
[12]Liang X, Bi S, Yang W, et al. Epidemiological serosurvey of hepatitis B in China-declining HBV prevalence due to hepatitis B vaccination[J]. Vaccine,2009,27(47):6550-6557.
[13]张丽乙肝疫苗使用20年后山东省乙型病毒性肝炎血清和分子流行病学研究.山东大学博士论文,2009
[14]Hong-Anh T Tu, Herman J, Woerdenbag, Sumit Kane, Arthorn Riewpaiboon, Marinus van Hulst and Maarten J Postma.Economic evaluations of hepatitis B vaccination for developing countries[J].Vaccine,2009,8(7):907-920.
[15]张林国,编著.乙型肝炎[M].北京：科学技术文献出版社.2002.
[16]张丽,张卫,翟祥军,等.新生儿5μg和10μg重组酵母乙型肝炎疫苗初免后抗体免疫应答比较[J].中华流行病学杂志,2012,33(3)：306-309.
[17]胡善联,华庆生,应和琴,等.上海地区病毒性肝炎的费用分析[J].中国卫生经济,1988,4：52-53.
[18]唐玲,胡晓抒,扬健,等.江苏省病毒性肝炎费用分析[J].中国卫生经济,1988,12：25-27.
[19]张顺祥.病毒性肝炎病人经济负担分析[J].山西医学院学报,1990,21(2)：88-92.
[20]白亚娜成人病毒性肝炎住院费用分析[J].中国医院统计,1995,2(1)：47-49
[21]Li SC, Ong SC, Lim SG, et al. A cost comparison of management of chronic Hepatitis B and its associated complications in Hong Kong and Singapore[J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S136-S 143.
[22]Hsieh CR, Kuo CW. Cost of chronic hepatitis B virus infection in Taiwan[J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S 148-S152.
[23]Butler JR, Pianko S, Korda RJ, et al. The direct cost of managing patients with chronic hepatitis B infection in Australia [J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S187-S192.
[24]Gagnon YM, Levy AR, Iloeje UH, et al. Treatment costs in Canada of health conditions resulting from chronic hepatitis B infection [J]. J Clin Gastroenterol, 2004,38(10 Suppl 3):S179-S186.
[25]Yang BM,Kim CH,Kim JY. Cost of chronic hepatitis B infection in South korea[J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S153-S157.
[26]Lee TA, Veenstra DL, Iloeje UH, et al. Cost of chronic hepatitis B infection in the United States [J]. J Clin Gastroenterol,2004,38(Suppl 3):S144-S147.
[27]Brown RE, Cock ED, Colin X, et al. Hepatitis B management costs in France, Italy, Spain and the United Kingdom [J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S169-174.
[28]Guan ZQ, Dong ZH, Wang QH, et al. Cost of Chronic Hepatitis B Infection in China [J]. J Clin Gastroenterol,2004,38(10 Suppl 3):S 175-S178.
[29]劳国琴,王佳良,吴勇.干扰素治疗慢性乙型肝炎病毒感染的经济效益[J].药物经济学,2006,17(16)：1223-1225
[30]Hu M, Chen W. Assessment of total economic burden of Chronic Hepatitis B (CHB)-related diseases in Beijing and Guangzhou,China [J]. Value Health,2009, 12(Suppl3):S89-S92.
[31]Ong SC, Lim SG, Li SC, et al. How big is the financial burden of hepatitis B to society? A cost-of-illness study of hepatitis B infection in Singapore[J]. J Viral Hepat,2009,16(1):53-63.
[32]杨晓玲.弱势群体的平等权保护.中国法学会行政法学研究会2010年会论文集,2010年7月.
[33]梁森,张顺祥,马起山,等深圳市乙型肝炎相关疾病经济负担及其影响国素分析[J]中华流行病学杂志,2010,31(12)：1340-1345
[34]马起山,邹宇华,张顺祥,等.广州市乙型肝炎相关疾病住院病例无形费用及其影响因素分析[J]中华流行病学杂志,2011,32(8)：660-663
[35]梁森,张顺祥,马起山,等.深圳市乙肝住院病人年直接经济负担及对家庭经济影响分析[J].中国卫生经济,2011,30(2)：56-58.
[36]伍春霞,马起山,邹玉华,等.广州市乙型病毒性肝炎住院患者经济负担分析[J].广东药学院学报,2011,27(2)：195-198.
[37]Mulley A G, Silverstein M D, Dienstag J L. Indications for use of hepatitis B vaccine, based on cost-effectiveness analysis[J]. New England Journal of Medicine,1982,307(11):644-652.
[38]Littenberg B, Ransohoff D F. Hepatitis B vaccination:Three decision strategies for the individual[J]. The American journal of medicine,1984,77(6):1023-1026.
[39]Jackiche R, Borrego ME,Raish DW,et al. The cost-effectiveness of two strategies for vaccinating US veterans with hepatitis C verus infection against hepatitis A and hepatitis B viruses[J].Am J Med Sci,2007,333(1):26-34.
[40]张顺祥,徐慧文,任延荣.运用费用效益分析和决策树法探讨中国乙肝疫苗接种策略[J].中国公共卫生,1989,5(8)：4-7.
[41]庄贵华,徐慧文,决策分析在乙型肝炎疫苗接种策略评价上的应用[J].中华预防医学杂志,1993,27(2)：69-73.
[42]张顺祥,党如波,张卫东,等.中国乙型肝炎疫苗免疫预防效果和现行策略的经济学和决策学评估[J].中华流行病学杂志,2008,29(10)：1003-1008
[43]易华云,刘爱忠,张琰.Markov模型在卫生领域中应用简介[J].循证医学,2008,8(3)：172-176.
[44]Tilson L, Thornton L, O'Flanagan D, et al. Cost effectiveness of hepatitis B vaccination strategies in Ireland:an economic evaluation[J]. Eur J Public Health,2008,18(3):275-282.
[45]Hung HF, Chen TH. Probabilistic cost-effectiveness analysis of the long-term effect of universal hepatitis B vaccination:An experience from Taiwan with high hepatitis B virus infection and Hepatitis B e Antigen positive prevalence[J]. Vaccine,2009,27(48):6770-6776.
[46]David WH,Samuel K S, and Margaret LB. Cost-Effectiveness of Nationwide Hepatitis B Catch-up Vaccination Among Children and Adolescents in China. [J].HEPATOLOGY,2009,51(2):405-414.
[47]Ruggeri M,Cicchetti A,Gasbarrini A. The cost-effectiveness or alternative strategies against HBV in Italy[J]. Health Pohcy,2011,102(1):71-80.
[48]Klinqler C,Thoumi AI,Mrithinjayam VS. Cost-effectiveness analysis of an additional birth dose of Hepatitis B vaccine to prevent perinatal transmission in a medical setting in Mozambique[J].Vaccine,2012,31(1):252-259.
[49]马福宝.经济学方法在疫苗预防传染病中的应用于评价[J].中国执业药师,2012,9(9)：25-28.
[50]Siddiqui MR,Gay WJ,Edmunds WJ,et al.Economic evaluation of infant and adolescent hepatitis B vaccination in the UK[J]. Vaccine,2011,29(3):466-475.
[51]李顺平,马东平,王健,等.中国乙肝疫苗接种策略的经济学评价系统综述[J].中国卫生经济,2011,30(3)：84-86.
[52]梁扩寰主编.肝脏病学[M]人民卫生出版社,1995
[53]迮文远主编.计划免疫学(第二版)[M].上海科学技术文献出版社.2001
[54]徐志一乙型肝炎疫苗预防乙型肝炎的效果与存在的问题[J].上海预防医学杂志,1997,9(6)：243-245.
[55]朱启镕 王建设.国产重组酵母疫苗和血源疫苗对乙型肝炎病毒母婴传播阻断效果的比较[J].中华儿科杂志,2000,38(11)：682-684.
[56]陈兴宝,陈慧芬,Alison TM,等.慢性乙型病毒性肝炎经济费用分析[J].中华医院管理杂志,2003,19(1)：58-59.
[57]庄润身,王声湧.如何评价疾病的经济负担[J].中国预防医学杂志,2001,2(4)：245-247
[58]Peabody JW,Shimkhada R,Tan C. The burden of disease, economic costs and clinical consequences of tuberculosis in the Philippines[J]. Health Policy Plan,2005,20(6):347-353.
[59]李俊华乙肝后肝硬化肝癌患者经济负担及影响因素分析,山西医科大学硕士学位论文,2011
[60]马起山.广州市乙肝相关疾病经济负担及1-14岁人群乙肝疫苗接种策略研究.广东药学院硕士学位论文,2011
[61]李晓强.乙肝相关疾病住院病人经济负担和生存质量研究.宁夏医科科大学硕士学位论文,2012.
[62]史武杰.长治地区乙肝相关疾病经济负担研究.山西医科大学硕士学位论文,2011
[63]王贵强,贾继东,王豪,等.《乙型病毒性肝炎诊断标准(WS 299-2008)》[Z]中华人民共和国卫生部,2008
[64]胡善联主编.卫生经济学[M]上海：复旦大学出版社,2003
[65]李娟,于保荣.疾病经济负担研究综述[J].中国卫生经济,2007,26(11)：72-74
[66]程晓明主编.卫生经济学[M]第2版.北京：人民卫生出版社,2007
[67]梁森,中国新生儿乙肝免疫预防策略决策分析和成本效益评价[D]郑州大学硕士论文,2011
[68]亓文婷,孙建东,徐爱强,等.山东省乙型肝炎病毒感染所致相关疾病的疾病负担研究[J].中华流行病学杂志,2009,30(7)：679-683
[69]《中国药物经济学评价指南》课题组.中国药物经济学评价指南[J].中国药物经济学杂志,2011,(3)：6-48.
[70]Leung GC,McGrath CP. Willingness to pay for implant therapy:a study of patient Preference[J].Clin Oral Implants Res,2010,21(8):789-793.
[71]王艳,张宜升,刘斌.青岛市居民减少空气污染致病的支付意愿调查[J].环境与健康杂志,2008,25(4)：326-330.
[72]吕静静,徐爱强,王健,等.关于条件价值评估法在公共卫生领域应用的综述[J].中国卫生政策研究,2011,4(3)：33-39.
[73]王舒宏,刘兴桂,李卜雪,等.疟疾病例经济负担分析[J].中国初级卫生保健,1996,10(9)：33-35.
[74]庄润森.社区居民的疾病负担研究.暨南大学硕士论文,2003.
[75]Yen ZS,Chang CJ,Chen SY, et al.How much would you be willing to pay for Preventing a new dangerous infectious disease:a willingness-to-pay in the em ergency department[J]. Am J Infect Control,2007,35(8):516-520.
[76]Fact Sheet WHO/204. Revised October 2000.
[77]Worle Health Organization.Hepatitis B(Revised August 2008) [EB/OL]. [2010-12-09].http://www.who.int/mediacentre/factsheets/fs204/en/.
[78]Coverage with primary health care services indicators.http://www.emro.who .int/index aspx
[79]Gentile A, Bhutta Z, Bravo L,et al. Pediatric disease burden and vaccination recommendations:understanding local differences [J]. International Journal of Infectious Diseases.2010,14(8):649-658.
[80]郭秀婵,陈宝珍,刘振天等.赴美国、意大利执行病毒性肝炎控制项目考察报告[R].疾病监测,2000,15(1)：30-33
[81]Review. Hepatitis B vaccination in countries with low endemicity[J]. Prescrire Int,2000,9(45):213-9.
[82]Zuckerman J, van Hattum J, Cafferkey M,et al. Should hepatitis B vaccination be introduced into childhood immunisation programmes in northern Europe? [J].Lancet Infect Dis,2007,7(6):410-19.
[83]Beutels P. Economic evaluations of hepatitis B immunization; a global review of recent studies(1994-2000)[J]. Health Econ 2001; 10(8):751-74.
[84]韩永战,陈仕珠.乙型肝炎病毒疫苗免疫接种策略及卫生经济学评价[J]世界华人消化杂志,2006,14(27)：2722-2728
[85]Sahni M,Jindal K,Abraham N,et al. Hepatitis Bimmunization:cost calculation in a community-based study in lndia[J]. Indian J GAstroenterol,2004,23(1):16-18.
[86]Xin Sun,Thomas Faunce.Decision-analytical modelling in ealth-care economic evaluations[J]. Eur J Health Econ,2008,9(4):313-323.
[87]Hutton DW, Tan D, So S K, et al. Cost-effectiveness of screening and vaccinating Asian and Pacific Islander adults for hepatitis B[J]. Ann Intern Med,2007,147(7):460-469.
[88]Wu B, Li T, Chen H, et al. Cost-Effectiveness of Nucleoside Analog Therapy for Hepatitis B in China:A Markov Analysis.[J]. Value Health,2010,13(5):592-600.
[89]张顺祥,徐慧文.决策树法预测中国乙肝疫苗接种策略[J]中华流行病学杂志,1989,10(4)：193-197.
[90]张顺祥,韩晓立,赵淑芳,等.山西乙肝疫苗接种前筛检策略初步研究[J].现代预防医学,1992,19(3)：132-135.
[91]张顺祥,韩晓立,赵淑芳.中国乙型肝炎疫苗接种前筛检策略的优化[J].中华预防医学杂志,1992,26(3)：154-158.
[92]庄贵华,徐慧文.乙肝疫苗接种策略的进一步探讨[J]西安交通大学学报(医学版),1992,13(4)：360-364.
[93]肖和卫.中国15岁以上人群乙型肝炎免疫预防的决策分析模型研究[D].中南大学硕士论文,2011
[94]李俊,孙莲英,曾雪霞,等.海南省新生儿接种乙肝疫苗成本效益分析[J]2011,11(1)：18-21.
[95]关旭静,杨超美,王进.四川省新生儿乙型肝炎疫苗接种卫生经济学评价[J].2010,16(5)：447-452.
[96]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南 (2010版)[J].中国病毒病杂志,2011,1(1)：9-23.
[97]Liaw YF.Natural history of chronic hepatitis B virus infection and long-term outcome under treatmen[J]. Liver Int,2009,29(Suppl 1)100-107.
[98]林曦敏,丁玎,张普洪,等.干扰素治疗慢性乙型肝炎患者的成本效果分析[J].中华肝病杂志,1999,7(2)：84-87.
[99]张媛媛.中国大陆人群乙型肝炎经济负担研究综述[J]中国农村卫生事业管理,2012,32(11)：1115-1118.
[100]王家良.循证医学[M].北京：人民卫生出版社,2005
[101]曹建文.临床决策分析[M].上海：复旦大学出版社,2005.
[102]TreeAge Pro 2011 User's Manual. TreeAge Software Inc 2010.
[103]Chen CJ, Yang HI. Natural History of Chronic Hepatitis B REVEALed[J]. J Gastroenterol Hepatol,2011,26(4):628-638.
[104]McMahon BJ. Natural history of chronic hepatitis B[J]. Clinics in liver disease, 2010,14(3):381-396.
[105]Zui S, Chang CJ, Chen SY, et al. How much would you be willing to pay for preventing a new dangrous infectious disease:A willingness-to-pay in the emergency department[J]. Am J Infect Control,2007,35(8):516-520.
[106]梁森,张顺祥,马起山,等.乙型病毒性肝炎病人经济负担调查问卷的信效度研究[J].中国初级卫生保健,2010,24(9)：48-49.
[107]2010年济南市国民经济和社会发展统计公报http://www.jinan.gov.cn/art/2011/2/18/art_95_272749. html.
[108]青岛市2010年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201103/18856.html.
[109]2010年聊城市国民经济和社会发展统计公报http://lcjrw.com/xinwen/bendijinrong/2011-03-30/11619.html.
[110]淄博市沂源县2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20514.html.
[111]枣庄市薛城区2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20517.html.
[112]烟台市芝罘区2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20524.html.
[113]2010年蓬莱市政府工作报告http://www.jiaodong.net/news/system/2010/01/18/010730166.html.
[114]潍坊市高密市2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201006/12085.html.
[115]济宁市邹城市2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201109/20530.html.
[116]泰安市宁阳县2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb/201006/12156.html.
[117]2009年莱芜市国民经济和社会发展统计公报http://lw.sdnews.com.cn /html/59/710.htm.
[118]2009年莒南县国民经济和社会发展统计公报http://junan.stats-ly.gov.cn /junan/tjgb/55777.html.
[119]德州市2009年国民经济和社会发展统计公报http://www.tjcn.org/tjgb /201003/7960.html.
[120]Singh P, Pandey A, Aggarwal A. House-to-house survey vs. snowball technique for capturing maternal deaths in India:a search for a cost-effective method. Indian J Med Res,2007,125(4):550-6.
[121]Stanley A.Plotkin,Walter A. Orenstein,Paul A. Offit.梁晓峰,罗凤基,封多佳.疫苗学[M]北京：人民卫生出版社.2011(译著)
[122]肖和卫,张顺祥,谭红专.Meta分析对效应量率的合并方法的研究进展[J].中国预防医学杂志,2011,12(5)：445-447
[123]王华庆,随海田.甲型肝炎减毒活疫苗保护效果的Meta分析[J].中国疫苗和免疫,2008,14(1)：1-6.
[124]Gillian M. K. and Stuart N. Recombinant Hepatitis B vaccine (Engerix-B)-A Review of its Immunogenicity and Protective Efficacy Against Hepatitis B[J]. Drugs,2003,63(10):1021-1051.
[125]刘崇柏.中国病毒性肝炎人群流行病学特征及流行因素研究[J]中华肝脏 病杂志,1998,6(2)：67-70.
[126]戴志澄,祁国明.中国病毒性肝炎血清流行病学调查(下卷)[M].北京：科学技术文献出版社.1996.
[127]冀贞浩.我国新生儿乙型肝炎免疫预防策略成本效果分析.西安交通大学硕士论文.2012
[128]李文潮,赵东涛,赵清波.催化模型拟合中感染力的选择与计算[J].数理医药学杂志,2007,20(2)：135-136.
[129]李文潮,吴克坚,赵东涛.流行病学中流行率模型的应用分析[J]2008,21(1)：102-103.
[130]Liang X, Bi S, Yang W, et al. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China. [J]. J Infect Dis, 2009,200(1):39-47.
[131]梁争论,李河民.中国不同人群接种乙型肝炎疫苗的成本-效益分析[J].中国生物制品杂志,2006,19(4)：434-436.
[132]纪峰,张丽,颜丙玉,等.2006年山东省育龄期妇女乙型肝炎病毒感染状况分析[J].预防医学论坛.2006,16(9)：781-783.
[133]http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2010 /index2010.html
[134]Zhuang G H, Pan X J, Wang X L. A cost-effectiveness analysis of universal childhood hepatitis A vaccination in China[J]. Vaccine,2008,26(35):4608-4616.
[135]李士雪.卫生保健项目经济学评估方法(第3版)[M].北京：人民卫生出版社,2008(译著)
[136]沈培,张吉凯.公共卫生项目成本-效益分析中的社会贴现率研究.中国卫生经济,2010,29(6)：72-73
[137]孙利华,宗欣.对中国药物经济学评价中贴现率选择问题的思考.中国新药杂志,2010,19(9)：737-739.
[138]Tan-Torres Edejer T.,Baltussen R.,Adam T.,et al. Making choices in health car:WHO guide to cost-effectiveness analysis. World Health Organization, Geneva,2003.
[139]Zhou F,Santoli J,Messonnier ML,et al.Economic evaluation of the 7-vaccine routine childhood immunization schedule in the United States[J].Arch Pediatr Adolesc Med,2005,159(12):1136-1144.
[140]姚红玉,陈陶阳,曲春枫.我国新生儿乙肝疫苗免疫后效应概述及相关问题[J].科学通报,2012,57(20)：1911-1917.
[141]Chen HY,Lin LH,Hu FC,et al. Effects of Maternal Screening and Universal Immunization to Prevent Mother-to-Infant Transmission of HBV. Gastroenterology,2012,142(4):273-781.
[142]余文周.计划免疫工作成本和投入研究.2005年
[143]国家发展改革委办公厅关于制定重组乙型肝炎疫苗14种国家免疫规划疫苗出厂价格的通知[Z].2009年7月
[144]王富珍,崔富强,郑徽,等重组乙型肝炎疫苗(酵母)与乙型肝炎免疫球蛋白联合免疫阻断乙型肝炎病毒母婴传播的效果分析[J].中国计划免疫,2007,13(4)：293-297.
[145]王富珍,龚晓红,李辉,等.北京市乙型肝炎疫苗母婴阻断效果监测分析[J].中国计划免疫,2006,12(2)：97-98.
[146]张海艳,周艳丽,赵丽英,等.北京市原东城区乙型病毒性肝炎病毒母婴传播阻断效果评估[J].首都公共卫生,2011,5(3)：102-105
[147]张彦芳,胡玉红,等.替比夫定阻断乙型肝炎病毒母婴传播的疗效和安全性[J].药物不良反应杂志,2010,12(3)：157-159.
[148]蒋雪峰,陶志华,姚凤燕,等.乙型肝炎病毒表面抗原阳性母亲的儿童接种乙型肝炎疫苗阻断乙型肝炎病毒传播的效果分析[J].中国疫苗和免疫,2010,16(1)：89.
[149]辛崇干.临沂市新生儿接种乙型肝炎疫苗后免疫效果观察[J].职业与健康,2011,27(22)：2530-2542
[150]Liaw YF, Chu CM. Hepatitis B virus infection[J], Lancet, 2009,373(9663):582-592.
[151]Hutton DW, So SK, Brandeau ML. Cost-effectiveness of nationwide hepatitis B catch-up vaccination among children and adolescents in China[J]. Hepatology, 2010,51(2):405-414.
[152]Ni YH. Natural history of hepatitis B virus infection:pediatric perspective[J]. Journal of gastroenterology,2011,46(1):1-8.
[153]Chu CM, Liaw YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas:appreciably high rates during a long-term follow-up[J]. Hepatology,2007,45(5):1187-1192
[154]Wu Q, Zhuang G-H, Wang X-L, et al. Antibody levels and immune memory 23 years after primary plasma-derived hepatitis B vaccination:Results of a randomized placebo-controlled trial cohort from China where endemicity is high[J]. Vaccine,2011,29(12):2302-2307.
[155]Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma.epidemiological characteristics and disease burden[J]. Journal of viral hepatitis,2009,16(7):453-463.
[156]山东省统计局编.2005年山东省1%人口抽样调查资料[M].北京：中国统计出版社,2007.
[157]山东省统计年鉴-2011[M]北京：中国统计出版社
[158]李宁宁.不同医疗保障制度下乙型病毒性肝炎三种病程患者的住院治疗及费用研究.山东大学硕士论文,2012.
[159]龚红霞,刘元强,马莉,等.兰州市1996年-2006年肺癌和肝癌患者住院费用分析[J]现代预防医学,2012,39(2)：270-272.
[160]Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation[M]. Oxford, United Kingdom:Oxford University Press,2006.
[161]冯艺,颜丙玉,张丽,等.山东省法定传染病报告系统乙型病毒性肝炎报告病例临床分类复核结果分析[EB].现代预防医学,网络出版地址：http://www.cnki.net/kcms/detail/51.1365.R.20121023.1635.007.html.
[162]山东省统计局.山东省2010年国民经济和社会发展统计公报.http://www.stats-sd.gov.cn/disp/tjgb.asp?aa=1101201100.
[163]张顺祥.决策树模型在制定疾病防制策略中的应用(二)[J].中国卫生统计,1991,8(3)：60-64.
[164]张文宏.《慢性乙型肝炎防治指南》专家讨论会常见问题及解答(免疫预防部分)[J].中华传染病杂志,2006,24(4)：287-288.
[165]梁争论,李河民,庄辉.乙型肝炎疫苗免疫效果影响因素和加强免疫策略 研究[J].中华流行病学杂志,2007,28(4)：313-314.
[166]陈博,刘柳,张菊英.5μg和10μg两种剂量重组乙肝疫苗免疫效果的Meta分析[J].现代预防医学,2010,37(4)：611-614.
[167]Dave Smith, Hugn Grvelle. ThePractiee of discounting economic evaluation of health care intervention[J].Center for health economic technical paper seriesl9, university of York,2000.
[168]Vimolket T, Poovorawan Y. An economic evaluation of universal infant vaccination strategies against hepatitis B in Thailand: an analytic decision approach to cost-effectiveness[J]. Southeast Asian J Trop Med Public Health,2005,36(3):693-699.