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

Background
Recently 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.
Method
A 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.
Results
The 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.
Conclusions
Vaccinating 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.

## 背景
近期一项大型临床试验表明，为65岁及以上免疫功能正常人群接种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岁及以上免疫功能正常人群接种PCV13疫苗的成本效用性。英格兰已实施全人群儿童肺炎球菌结合疫苗接种计划：2006年起采用7价肺炎球菌结合疫苗（7-valent pneumococcal conjugate vaccine，PCV7），2010年起升级为PCV13；同时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。

## 方法
本研究构建了静态队列成本效用模型，追踪2016年秋季接种PCV13的65岁人群队列直至死亡，并通过敏感性分析检验研究结果的稳健性。

## 结果
既往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，使得由PCV7血清型导致的残留疾病负担大幅降低。本研究发现，PCV13新增的6种血清型同样可产生类似的群体免疫效应，并预测2018/2019年将达到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）的发病率预测数据，以及针对65岁及以上人群的疫苗效力最新研究结果，本研究估算：为65岁免疫功能正常人群接种PCV13，可直接避免26例侵袭性肺炎球菌疾病（invasive pneumococcal disease，IPD）、69例CAP以及15例死亡。该方案的成本效用比为每获得1个质量调整寿命年（quality-adjusted life year，QALY）257771英镑（按单剂疫苗挂牌价49.10英镑、接种服务费7.51英镑计算），因此被认为不具备成本效用性；若要使该接种计划具备成本效用性，单剂疫苗价格需为负值。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，核心结论仍保持稳健。

## 结论
为65岁及以上免疫功能正常人群接种PCV13具有良好的保护效力。但由于儿童PCV13接种计划的广泛获益，疫苗型疾病的绝对发病率或将降至极低水平，因此针对老年免疫功能正常人群的单独PCV13接种计划不具备成本效用性。