Abstract：
BACKGROUND: Vaccine regulatory decision-making is based on vaccine efficacy against etiologically confirmed outcomes; however, these outcomes may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes to radiologically/etiologically confirmed outcomes.
METHODS: We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines [CRD42019145268]. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).
RESULTS: Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 [95%CI not calculable], 2.1 [95%CI: 1.5;3.0], and 3.7 [95%CI: 1.0;10.2]; the VPDI ratios comparing clinically defined to radiologically confirmed pneumonia ranged from not calculable to 2.7 [95%CI: 1.2;10.4]; the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) to laboratory confirmed IPD was 3.8 [95%CI not calculable]. Among adults, the ratio comparing clinically defined to radiologically confirmed pneumonia was 1.9 [95%CI: -6.0;9.1] and to vaccine serotype confirmed pneumonia was 2.9 [95%CI: 0.5;7.8].
CONCLUSIONS: While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine\'s public health value.
METHODS: We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines [CRD42019145268]. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).
RESULTS: Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 [95%CI not calculable], 2.1 [95%CI: 1.5;3.0], and 3.7 [95%CI: 1.0;10.2]; the VPDI ratios comparing clinically defined to radiologically confirmed pneumonia ranged from not calculable to 2.7 [95%CI: 1.2;10.4]; the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) to laboratory confirmed IPD was 3.8 [95%CI not calculable]. Among adults, the ratio comparing clinically defined to radiologically confirmed pneumonia was 1.9 [95%CI: -6.0;9.1] and to vaccine serotype confirmed pneumonia was 2.9 [95%CI: 0.5;7.8].
CONCLUSIONS: While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine\'s public health value.
摘要：
背景：疫苗监管决策是基于针对病因学证实的结果的疫苗效力；然而，这些结果可能低估了可预防的疾病负担.为了量化这种低估，我们将临床确定结局的疫苗可预防疾病发生率(VPDI)与放射学/病因学证实的结局进行了比较.
方法：我们对几种疫苗（1997-2019年）的疗效试验进行了系统评价，并报告了肺炎球菌结合疫苗的结果[CRD42019145268]。数据被提取为临床综合征中的结果，从最敏感到最具体的组织。确定每个结果的VPDI，并计算了VPDI比率，具有临床定义的结果（分子）和放射学/病因学证实的结果（分母）。
结果：在9项研究中，我们计算了27个VPDI比率；24的值>1。在儿童中，临床定义与疫苗血清型中耳炎的VPDI比率为0.6[95CI不可计算]，2.1[95CI:1.5;3.0]，和3.7[95CI:1.0;10.2];将临床定义的VPDI比率与放射学确诊的肺炎进行比较,范围从无法计算到2.7[95CI:1.2;10.4];将临床疑似侵袭性肺炎球菌病(IPD)与实验室确诊IPD进行比较的VPDI比率为3.8[95CI无法计算].在成年人中，临床诊断与放射学确诊肺炎的比率为1.9[95CI:-6.0;9.1],与疫苗血清型确诊肺炎的比率为2.9[95CI:0.5;7.8].
结论：虽然个别点估计存在很大的不确定性，VPDI比率有一致的趋势，最常见的是1.5到4倍的不确定性，这表明使用临床定义的结局可能会更准确地估计肺炎球菌结合疫苗的公共卫生价值。
方法：我们对几种疫苗（1997-2019年）的疗效试验进行了系统评价，并报告了肺炎球菌结合疫苗的结果[CRD42019145268]。数据被提取为临床综合征中的结果，从最敏感到最具体的组织。确定每个结果的VPDI，并计算了VPDI比率，具有临床定义的结果（分子）和放射学/病因学证实的结果（分母）。
结果：在9项研究中，我们计算了27个VPDI比率；24的值>1。在儿童中，临床定义与疫苗血清型中耳炎的VPDI比率为0.6[95CI不可计算]，2.1[95CI:1.5;3.0]，和3.7[95CI:1.0;10.2];将临床定义的VPDI比率与放射学确诊的肺炎进行比较,范围从无法计算到2.7[95CI:1.2;10.4];将临床疑似侵袭性肺炎球菌病(IPD)与实验室确诊IPD进行比较的VPDI比率为3.8[95CI无法计算].在成年人中，临床诊断与放射学确诊肺炎的比率为1.9[95CI:-6.0;9.1],与疫苗血清型确诊肺炎的比率为2.9[95CI:0.5;7.8].
结论：虽然个别点估计存在很大的不确定性，VPDI比率有一致的趋势，最常见的是1.5到4倍的不确定性，这表明使用临床定义的结局可能会更准确地估计肺炎球菌结合疫苗的公共卫生价值。
