Schneider Institutes for Health Policy, Heller School, Brandeis University, 415 South Street, PO Box 549110, MS035 Waltham, MA 02454-9110, USA.
Vaccine. 2011 Sep 2;29(38):6686-94. doi: 10.1016/j.vaccine.2011.06.091. Epub 2011 Jul 13.
Although multiple studies of cost-effectiveness of pneumococcal conjugate vaccines have been conducted, no such study has examined Singapore's situation nor compared the licensed conjugate vaccines in an Asian population. This paper estimates the costs and public health impacts of pneumococcal conjugate vaccine programs, varying estimates of serotype replacement and herd immunity effects as key parameters in the analysis. Based in part on a 2008 analysis also presented here, Singapore has approved the PCV-7, PHiD-10, and PCV-13 pneumococcal conjugate vaccines as part of its National Childhood Immunisation Programme.
An economic evaluation was performed using a Markov simulation model populated with Singapore-specific population parameters, vaccine costs, treatment costs, and disease incidence data. The vaccinated infant and child cohort of 226,000 was 6% of the Singapore resident population of 3.8 million. Vaccine efficacy estimates were constructed for PCV-7, PHiD-10, and PCV-13 vaccines based on their serotype coverage in Singapore and compared to 'no vaccination'. The model estimated impacts over a five-year time horizon with 3% per year discounting of costs and health effects. Costs were presented in 2010 U.S. dollars (USD) and Singapore dollars (SGD). Sensitivity analyses included varying herd immunity, serotype replacement rates, vaccine cost, and efficacy against acute otitis media.
Under base case assumptions for the revised analysis (i.e., herd effects in the unvaccinated population equivalent to 20% of direct effects) PCV-13 prevented 834 cases and 7 deaths due to pneumonia, meningitis, and bacteremia in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 (SGD $51,854) per QALY. Without herd effects, however, the ratio was USD $204,535 (SGD $281,743) per QALY. The PCV-7 cost per QALY including herd effects was USD $43,275 (SGD $59,610) and for PHiD-10 the ratios were USD $45,100 (SGD $62,125). The original 2008 analysis, which had higher estimates of pneumonia prevention due to herd immunity and lower estimates of cost per dose, had found a cost-effectiveness ratio of USD $5562 (SGD $7661) per QALY for PCV-7.
When compared to cost-effectiveness thresholds recommended by the World Health Organization (WHO), our 2008 analysis found that vaccination of infants in Singapore with PCV-7 was very cost-effective if herd immunity effects were present. However, knowledge on herd immunity and serotype replacement that emerged subsequent to this analysis changed our expectations about indirect effects. Given these changed inputs, our current estimates of infant vaccination against pneumococcal disease in Singapore find such programs to be moderately cost-effective compared to WHO thresholds. The different findings from the 2008 and 2011 analyses suggest that the dynamic issue of serotype replacement should be monitored post-licensure and, as changes occur, vaccine effectiveness and cost-effectiveness analyses should be re-evaluated.
尽管已经进行了多项关于肺炎球菌结合疫苗成本效益的研究,但没有一项研究考察过新加坡的情况,也没有比较过亚洲人群中已批准的结合疫苗。本文旨在评估肺炎球菌结合疫苗项目的成本和公共卫生影响,将血清型替代和群体免疫效应的估计作为分析中的关键参数。基于本文中提出的 2008 年的一项分析,新加坡已批准使用 PCV-7、PHiD-10 和 PCV-13 肺炎球菌结合疫苗作为国家儿童免疫计划的一部分。
使用基于新加坡特定人口参数、疫苗成本、治疗成本和疾病发病率数据的马尔可夫模拟模型进行经济评估。22.6 万名接种婴儿和儿童占新加坡 380 万居民人口的 6%。根据疫苗在新加坡的血清型覆盖率,为 PCV-7、PHiD-10 和 PCV-13 疫苗构建了疫苗效力估计值,并将其与“无疫苗接种”进行了比较。该模型估计了五年时间内的影响,每年以 3%的贴现率折现成本和健康效果。成本以 2010 年美元(USD)和新加坡元(SGD)表示。敏感性分析包括不同的群体免疫、血清型替代率、疫苗成本和对急性中耳炎的效力。
在修订分析的基本假设下(即未接种人群的群体效应相当于直接效应的 20%),PCV-13 在接种人群中预防了 834 例肺炎、脑膜炎和菌血症病例和 7 例死亡,在未接种人群中预防了 952 例肺炎、脑膜炎和菌血症病例和 191 例死亡。包括群体效应在内,PCV-13 的成本效益比为每 QALY 37644 美元(SGD 51854 美元)。然而,没有群体效应,比值为每 QALY 204535 美元(SGD 281743 美元)。包括群体效应在内,PCV-7 的每 QALY 成本为 43275 美元(SGD 59610 美元),PHiD-10 的比值为 45100 美元(SGD 62125 美元)。2008 年的原始分析中,由于群体免疫而导致肺炎预防的估计值较高,而每剂量成本的估计值较低,发现 PCV-7 的成本效益比为每 QALY5562 美元(SGD 7661 美元)。
与世界卫生组织(WHO)推荐的成本效益阈值相比,我们 2008 年的分析发现,如果存在群体免疫效应,新加坡婴儿接种 PCV-7 非常具有成本效益。然而,随后对该分析的群体免疫和血清型替代知识的了解改变了我们对间接影响的预期。鉴于这些输入的变化,我们目前对新加坡婴儿接种肺炎球菌疾病的估计发现,与 WHO 阈值相比,此类计划具有中等的成本效益。2008 年和 2011 年分析的不同结果表明,血清型替代的动态问题应在上市后进行监测,并且随着变化的发生,应重新评估疫苗有效性和成本效益分析。