Economic Evaluation Of Hepatitis B Immunization Strategy Among Newborns In Shandong

BackgroundHepatitis 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.ObjectivesThe 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. Object2010-year neonatal birth cohort is the objectMethod1.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.ResultsAfter 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 implicationsConclusions: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 limitationThe 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.