目的:疫苗的经济评估应准确反映疫苗接种的所有相关经济和健康后果,包括免疫接种后不良事件(AEFI)导致的损失。我们调查了儿科疫苗的经济评估在多大程度上解释了AEFI,使用了哪些方法,以及是否纳入AEFI与研究特征和疫苗的安全性有关。
方法:系统文献检索(MEDLINE,EMBASE,Cochrane系统评论和试验,约克大学审查和传播中心数据库,EconPapers,儿科经济数据库评估,塔夫茨新英格兰成本效益分析登记处,塔夫茨新英格兰全球健康CEA,国际卫生技术评估机构网络数据库)进行了2014年至2021年4月29日(搜索日期)之间发布的经济评估,涉及自1998年以来在欧洲和美国获得许可的五组儿科疫苗:人乳头瘤病毒(HPV)疫苗,脑膜炎球菌疫苗(MCV),麻疹-腮腺炎-风疹-水痘(MMRV)组合疫苗,肺炎球菌结合疫苗(PCV)和轮状病毒疫苗(RV)。计算了AEFI的会计比率,按研究特征分层(例如,区域,出版年份,期刊影响因子,行业参与水平)并与疫苗的安全性状况(免疫实践咨询委员会[ACIP]建议和有关安全相关产品标签更改的信息)进行三角测量。根据用于解释AEFI的成本和效果影响的方法对AEFI的研究进行了分析。
结果:我们确定了112项经济评估,其中28人(25%)占AEFI。MMRV的这一比例明显更高(80%,五分之四的评价),MCV(61%,18项评估中有11项)和RV(60%,15项评估中有9项)与HPV(6%,53次评估中有3次)和PCV(5%,21项评估中的一项)。没有其他研究特征与研究中解释AEFI的可能性相关。在ACIP建议中,AEFI更频繁的疫苗也具有更高的标签变化频率和更高的对AEFI的关注水平。九项研究说明了AEFI的成本和健康影响,18项研究仅考虑成本和一项健康结果。虽然成本影响通常是根据常规账单数据估计的,通常基于假设估计AEFI对健康的不利影响.
结论:尽管所有五种研究疫苗都证明了(轻度)AEFI,只有四分之一的审查研究占了这些,主要是以不完整和不准确的方式。我们为使用哪些方法更好地量化AEFI对成本和健康结果的影响提供指导。政策制定者应该意识到,在大多数经济评估中,AEFI对成本效益的影响可能会被低估。
Economic evaluations of vaccines should accurately represent all relevant economic and health consequences of vaccination, including losses due to adverse events following immunization (AEFI). We investigated to what extent economic evaluations of pediatric vaccines account for AEFI, which methods are used to do so and whether inclusion of AEFI is associated with study characteristics and the vaccine\'s safety profile.
A systematic literature search (MEDLINE, EMBASE, Cochrane Systematic Reviews and Trials, Database of the Centre for Reviews and Dissemination of the University of York, EconPapers, Paediatric Economic Database Evaluation, Tufts New England Cost-Effectiveness Analysis Registry, Tufts New England Global Health CEA, International Network of Agencies for Health Technology Assessment Database) was performed for economic evaluations published between 2014 and 29 April 2021 (date of search) pertaining to the five groups of pediatric vaccines licensed in Europe and the United States since 1998: the human papillomavirus (HPV) vaccines, the meningococcal vaccines (MCV), the measles-mumps-
rubella-varicella (MMRV) combination vaccines, the pneumococcal conjugate vaccines (PCV) and the rotavirus vaccines (RV). Rates of accounting for AEFI were calculated, stratified by study characteristics (e.g., region, publication year, journal impact factor, level of industry involvement) and triangulated with the vaccine\'s safety profile (Advisory Committee on Immunization Practices [ACIP] recommendations and information on safety-related product label changes). The studies accounting for AEFI were analyzed in terms of the methods used to account for both cost and effect implications of AEFI.
We identified 112 economic evaluations, of which 28 (25%) accounted for AEFI. This proportion was significantly higher for MMRV (80%, four out of five evaluations), MCV (61%, 11 out of 18 evaluations) and RV (60%, nine out of 15 evaluations) compared to HPV (6%, three out of 53 evaluations) and PCV (5%, one out of 21 evaluations). No other study characteristics were associated with a study\'s likelihood of accounting for AEFI. Vaccines for which AEFI were more frequently accounted for also had a higher frequency of label changes and a higher level of attention to AEFI in ACIP recommendations. Nine studies accounted for both the cost and health implications of AEFI, 18 studies considered only costs and one only health outcomes. While the cost impact was usually estimated based on routine billing data, the adverse health impact of AEFI was usually estimated based on assumptions.
Although (mild) AEFI were demonstrated for all five studied vaccines, only a quarter of reviewed studies accounted for these, mostly in an incomplete and inaccurate manner. We provide guidance on which methods to use to better quantify the impact of AEFI on both costs and health outcomes. Policymakers should be aware that the impact of AEFI on cost-effectiveness is likely to be underestimated in the majority of economic evaluations.