Estimating the cost-effectiveness of a sequential pneumococcal vaccination program for adults in Germany

IntroductionIn Germany, a 23-valent polysaccharide pneumococcal vaccine (PPSV23) is recommended for elderly (60+) and patients 16+ with chronic diseases not associated with immune suppression. For all other patients at risk, sequential immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) first, followed by PPSV23 is recommended. Repeated vaccination with PPSV23 is recommended every 6 years after individual assessment by the physician. This was adopted into the vaccination directive with binding reimbursement and funding. However, additional voluntary services allow statutory health insurances to differentiate from each other. Aim of this study is to estimate the cost-effectiveness of voluntary service scenarios compared to the strategy in place to support informed decision making.MethodsA microsimulation framework with Markov-type process of a population susceptible to pneumococcal disease over a lifetime horizon was developed to compare effectiveness and cost-effectiveness of different vaccination strategies. We simulated 1,000 iterations for seven scenarios. Assumptions were derived from published literature and probabilistic sensitivity analysis was run to show the robustness of the model.ResultsOur study indicates that all voluntary service strategies could prevent further clinical cases compared to the existing policy. Depending on the scenario, 48–142 invasive pneumococcal disease (IPD), 24,000–45,000 hospitalized all-cause nonbacteremic pneumonia (NBP), 15,000–45,000 outpatient NBP cases, and 4,000–8,000 deaths could be avoided on average. This refers to potential savings of €115 Mio. - €187 Mio. for medical and non-medical costs. Additional costs per patient for the payer are €2.48 to €7.13 and for the society €2.20 to €6.85. The ICER per LYG ranged from €3,662 to €23,061 (payer) and €3,258 to €29,617 (societal). All but one scenario was cost-effective in ≥60% of the generated 1,000 simulations.ConclusionCompared to the vaccination strategy in place, the different hypothetical scenarios can be considered cost-effective and suitable as additional voluntary services.

在德国，23价肺炎球菌多糖疫苗（23-valent polysaccharide pneumococcal vaccine, PPSV23）被推荐用于60岁及以上的老年人群，以及16岁及以上患有非免疫抑制相关性慢性疾病的患者。对于其余所有存在肺炎球菌感染风险的人群，推荐采用先接种13价肺炎球菌结合疫苗（13-valent pneumococcal conjugate vaccine, PCV13）、后续接种PPSV23的序贯免疫方案。经医师进行个体评估后，推荐每6年复种1次PPSV23。该方案已纳入具有强制报销与资金保障的疫苗接种指令。不过，各法定健康保险机构可通过增设自愿服务项目实现服务差异化。

本研究旨在评估各类自愿服务场景相较于现行接种策略的成本效益，为临床知情决策提供依据。

本研究构建了基于马尔可夫过程的微观模拟框架，针对易感肺炎球菌疾病的人群开展终身时限模拟，以对比不同接种策略的有效性与成本效益。我们针对7种模拟场景开展了1000次迭代。模型假设均源自已发表的研究文献，并通过概率敏感性分析验证了模型的稳健性。

本研究结果显示，相较于现行接种政策，所有自愿服务策略均可减少更多临床病例的发生。按场景不同，平均可避免48~142例侵袭性肺炎球菌疾病（invasive pneumococcal disease, IPD）、24000~45000例住院全因非菌血症性肺炎（nonbacteremic pneumonia, NBP）、15000~45000例门诊NBP病例，以及4000~8000例死亡。据此可在医疗与非医疗成本方面实现1.15亿~1.87亿欧元的潜在节省。付款方视角下，每位患者的额外成本为2.48~7.13欧元；社会视角下则为2.20~6.85欧元。每获得1个生命年的增量成本效果比（incremental cost-effectiveness ratio per life year gained, ICER per LYG）范围为：付款方视角3662~23061欧元，社会视角3258~29617欧元。除1种场景外，其余所有场景在1000次模拟中≥60%的比例下均具有成本效益。

相较于现行疫苗接种策略，本研究涉及的各类假设场景均具有成本效益，可作为额外的自愿接种服务推广。