Mapping and ranking outcomes for the evaluation of seasonal influenza vaccine efficacy and effectiveness: a delphi study

Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance. An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women. The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9). Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.

季节性流感疫苗（seasonal influenza vaccination, SIV）所提供的保护效力，可通过多种结局指标进行评估，而这些指标的异质性可能会对决策制定造成阻碍。本研究旨在探讨用于估算季节性流感疫苗效力/有效性（vaccine efficacy/effectiveness, VE）的结局指标，并就其重要性达成专家共识。首先开展了一项伞状综述（umbrella review），以收集并梳理针对季节性流感疫苗VE的系统综述中所涉及的结局指标。随后开展了德尔菲研究（Delphi study），针对主要目标人群——即儿童、劳动年龄成年人、老年人、合并基础疾病受试者以及孕妇——中的单项结局指标的重要性，通过9分李克特量表（Likert scale）进行评分以达成专家共识。本次文献综述共识别出489项结局指标。经数据精简后，共筛选出20项结局指标用于德尔菲研究流程。经过两轮德尔菲调研及一次最终共识会议，研究达成了共识。所有20项结局指标均被判定为重要或极其重要。在所有目标人群中，更为严重的结局指标（如与流感相关的住院就诊及伴/不伴实验室确认的死亡）总体排名靠前（中位数评分≥9分制中的8分）。相较于单纯关注实验室确认的感染本身，试验性与观察性VE研究应纳入更严重的流感相关结局指标，因为此类指标预计会对决策制定产生更大影响。