Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England

BackgroundRecently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years.MethodA static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.ResultsThe childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.ConclusionsVaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective.

研究背景
近期一项大型临床试验表明，针对65岁及以上免疫功能正常人群使用13价肺炎球菌结合疫苗（13-valent pneumococcal conjugate vaccine, PCV13）具有良好的安全性与有效性。本研究旨在评估英格兰地区为65岁免疫功能正常人群接种PCV13疫苗的成本效益比。英格兰已推行全面的儿童肺炎球菌结合疫苗接种计划：2006年起使用7价肺炎球菌结合疫苗（7-valent pneumococcal conjugate vaccine, PCV7），2010年起更换为PCV13；同时还针对临床高危人群及65岁及以上人群开展23价肺炎球菌多糖疫苗（23-valent pneumococcal polysaccharide vaccine, PPV23）接种计划。

研究方法
本研究构建了静态队列成本效益模型，对2016年秋季接种PCV13疫苗的65岁人群队列进行随访直至其死亡，并通过敏感性分析检验研究结果的稳健性。

研究结果
PCV7儿童接种计划已在未接种的老年人群中诱导出群体免疫效应，由此导致由PCV7血清型引发的残留疾病负担较低。本研究发现，PCV13新增的6种血清型也具有类似的群体免疫保护效果，并预测2018/2019年将迎来疫苗型疾病引入后的新低水平平衡状态。结合侵袭性疾病与社区获得性肺炎（community-acquired pneumonia, CAP）的发病预测数据，以及近期针对65岁及以上人群的疫苗针对上述终点的有效性数据，本研究估算：为65岁免疫功能正常人群队列接种PCV13疫苗，可直接避免26例侵袭性肺炎球菌疾病（Invasive Pneumococcal Disease, IPD）病例、69例CAP病例以及15例死亡事件。每获得1个质量调整生命年（Quality-Adjusted Life Year, QALY）的相关成本效益比为£257,771（按单剂疫苗标价£49.10、接种服务费£7.51计算），因此该接种计划被认为不具备成本效益。若要使该计划具备成本效益，单剂疫苗的价格需为负值。研究结果对疾病发病率、疫苗保护力衰减及病例病死率较为敏感，但即便如此，整体结论依然稳健。

研究结论
为65岁及以上免疫功能正常人群接种PCV13疫苗具有有效性。但由于儿童PCV13接种计划带来的广泛获益，疫苗型疾病的绝对发病率或将降至极低水平，因此针对免疫功能正常老年人群的专属PCV13接种计划不具备成本效益。