| Objective(s):Immunogenicity,safety and cost effectiveness of 60μg hepatitis B vaccines were estimated while it was used with a 2-dose and 1,2months vaccination schedule among the susceptible persons aged≥16 years.The more information would be provided for improving the strategy of hepatitis B vaccination for the adults in China.Methods:This study had been divided two parts,the first was related to the immunogenicity and safety,and the second was about the cost effectiveness.1.A single-center,randomized,parallel-group,open label,non-inferiority clinical trial design was employed.A total of 800 subjects aged≥16 years in Da Yao county were enrolled and random Ly assigned to the test and control groups in a 1:1 ratio.The subjects in the test group were vaccinated with 2 doses of 60μg hepatitis B vaccines using 0,2 months vaccination schedule,the subjects in the control group had 3 doses of20μg hepatitis B vaccines with 0,1,6 months vaccination schedule.The blood samples were taken from the subjects before immunization and 30 days after full-dose vaccination for HBs Ab testing.Adverse events occurred within 30 days after each dose inoculated were recorded from the subjects.Finally,the serum HBs Ab positive seroconversion rates,geometric mean concentration(GMC),the proportion of HBs Ab response level and the incidence of adverse reactions were compared between the two groups.The x~2 test or Fisher’s exact probability test was used for statistical analysis of HBs Ab seroconversion rate and the proportion of HBs Ab response levels.The original value of HBs Ab concentration≥10m IU/m L was included in the GMC calculation.If the data was in normal distribution,t-test or ANOVA will be used,and Wilcoxon or Kruskal Wallis H-rank sum test will be employed for non normal distribution;Non-inferiority means that the lower limit of two-side 95%CI for the difference in HBs Ab seroconversion rate between the test group and the control group was greater than threshold of-10%.The difference in the total incidence of adverse events and symptoms between the two groups was compared using a 95%CI(if there is no overlap in the 95%CI between the two groups,it is considered a statistical difference).In this study,the hypothesis testing was conducted usingα=0.05 with a 95%CI(two-sides).P<0.05 is statistically significant.2.Based on estimating the total cost and total benefit of hepatitis B vaccination at different doses,the cost-benefit analysis was conducted with net present value and benefit cost ratio as indicators.(1)The data will be collected,such as vaccination cost and transportation cost of 20μg and 60μg hepatitis B vaccine,HBs Ag carrier rate;probability of outcomes for transforming into chronic infection,liver cirrhosis and liver cancer associated with hepatitis B;the protection rate of the vaccine;the full-dose coverage rate;discount rate;direct,indirect and intangible costs of hepatitis B-related diseases.(2)The cost estimation:the costs include the fee of vaccination and transportation.(3)Benefits estimation:It is the cost saved by people who should have been infected by HBV and suffered from hepatitis B related diseases because they were protected by Hep B vaccination.(4)Cost benefit analysis:a.Net present value=total benefits of immunization strategies-total cost.If the difference is greater than 0(the difference>0),it indicates that the strategy is economically feasible;b.Benefit Cost Ratio(BCR)=Benefit of Immunization Strategy/Cost of the Strategy.If the BCR is greater than 1,it means that the strategy generates positive benefits.(5)Sensitivity analysis:When the full-dose coverage rate of 20μg and 60μg hepatitis B vaccines is changed,there will be an impact on the cost-effectiveness ratio.The BCR is greater than 1,it means that the strategy have positive benefits.Results 1.Immunogenicity and safety of the 60μg hepatitis B vaccine rapid immunization schedule in the susceptible individuals aged≥16 years:(1)The seroconversion rates of HBs Ab after the full-dose vaccination schedule completed was 93.09%and 97.94%in the test group and the control group,respectively.425.48m IU/m L and 790.32m IU/m L of GMC got from the test group and the control group.There was a statistical difference in the seroconversion rates of HBs Ab and GMC between the two groups(x~2=9.28,P=0.002;Z=-4.13,P<0.001).The difference in the seroconversion rates of HBs Ab between the two groups was-4.85%(95%CI:-7.96%～-1.73%),with a lower limit of 95%CI>-10%.The seroconversion rate of HBs Ab in the test group was not inferior to that in the control group.(2)The seroconversion rate of HBs Ab of subjects with aged 40-49 years,female,BMI24-26.9kg/m~2group,non hepatitis B vaccination history,HBc Ab negative in the control group after whole course immunization completed was higher than those in the test group;The GMC of HBs Ab of subjects with aged 50-49,female,male,BMI<18.5kg/m~2,18.5-23.9 kg/m~2,24-26.9 kg/m~2,no history of Hep B vaccination,and HBc Ab negative in the control group after whole course immunization completed was higher than those in the experimental group;There was no statistically significant difference in the seroconversion rate of HBs Ab and GMC of HBs Ab between the two groups among other subjects with different characteristics(P>0.05).(3)There was no statistically significant difference in the seroconversion rate of HBs Ab and GMC among subjects of different ages,BMI,gender,and HBc Ab status before immunization within the test and control groups(P>0.05).There was a statistical difference in the GMC of HBs Ab between subjects of two groups with different Hep B vaccination histories(H=6.47,P=0.039;H=6.90,P=0.032).(4)The total incidence of adverse events in the test group and control group was24.36%(95%CI:21.35%-27.37%)and 20.93%(95%CI:8.59%-23.26%),respectively,and the solicited adverse reactions are all grade 1 and grade 2 adverse reactions.The total incidence of solicited local adverse reactions and local grade 1 adverse reactions in the test group was higher than that in the control group,while there was no difference in the incidence of adverse reactions among other doses.2.Cost benefit analysis of 0,2 vaccination schedule of 60μg hepatitis B vaccine applied in susceptible persons≥16 years:(1)Cost analysis:The total cost of vaccination of 60μg hepatitis B vaccine was 5.481million yuan(vaccination cost 5.423 million yuan,transportation cost 58000 yuan),the total cost of vaccination of 20μg hepatitis B vaccine is 3.4055 million yuan(vaccine vaccination cost 3.3075 million yuan,transportation cost 98000 yuan).(2)The total annual benefits of vaccination of 60μg and 20μg hepatitis B vaccine were5.1946 million yuan and 5.4652 million yuan,respectively.The annual benefits preventing acute hepatitis B infection,chronic hepatitis B infection,liver cirrhosis and liver cancer related to hepatitis B were 137800 yuan vs 145000 yuan,4437300 yuan vs4668400 yuan,559300 yuan vs 588500 yuan,respectively.The total benefit of vaccination of 60μg hepatitis B vaccine was less than those of 20μg hepatitis B vaccine.(3)Cost benefit analysis:The net present value after inoculating 60μg and 20μg hepatitis B vaccine was-286400 yuan and 2059700 yuan,the cost-effectiveness ratios are 0.95 and 1.60,respectively.If the full-dose vaccination coverage was 45%,vaccination of 20μg hepatitis B vaccine was better than 60μg hepatitis B vaccine in terms of health economics.(4)Sensitivity analysis:When the full-dose vaccination coverage was 49%,60%and90%,the BCR of both groups is greater than 1.Conclusion(s):The seroconversion rates of 60μg hepatitis B vaccine with a two-dose and 0,2 months vaccination schedule using among susceptible persons≥16 years is not inferior to those of 20μg hepatitis B vaccine with routine vaccination schedule,the incidence of adverse reactions using two different immune schedules is equivalent.It has good immunogenicity and safety.From an economic standpoint,when comparing the full-dose coverage of the two vaccines,it can be concluded that the seroconversion rates of the 60μg hepatitis B vaccine with a two-dose and 0,2 months vaccination schedule are not superior to those of the 20μg hepatitis B vaccine with the routine vaccination schedule.The positive benefits can be generated,when the full-dose vaccination coverage is greater than 49%,and the higher the full-dose vaccination coverage,the greater the positive benefits.Due to 0,2 months vaccination schedule having fewer doses and shorter vaccination interval,the overall vaccination coverage will be increased,and has highly feasible in terms of health economics.This schedule is highly feasible in terms of health economics.In summary,the feasibility of 60μg hepatitis B vaccine with 0,2 months vaccination schedule using among the susceptible persons aged≥16 years is relatively high. |
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