Halloran M E, Longini I M, Struchiner C J
Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Am J Epidemiol. 1996 Jul 1;144(1):83-97. doi: 10.1093/oxfordjournals.aje.a008858.
The authors consider estimability and interpretation of vaccine efficacy based on time to event data, allowing that some of the population might have a very low probability of acquiring disease, and the rest have partial, possibly continuously distributed, susceptibility. The efficacy parameters of interest in the frailty mixing model include the fraction highly unlikely to acquire the infection or disease due to the vaccine, the degree of partial protection in those still susceptible, and the average protection or summary measure of efficacy under heterogeneity. The efficacy estimates can still be usefully interpreted when the heterogeneity results from heterogeneity in contact patterns, contact rates, or infectiousness of the contacts, as long as these are equal in the vaccinated and unvaccinated groups. A likelihood-based method allows estimation of the efficacy parameters of interest from grouped time to event data. Simulated vaccine studies assuming different levels and distributions of efficacy demonstrate that ignoring heterogeneity in susceptibility or exposure to infection generally results in underestimation of vaccine efficacy as well as incorrect interpretation of the estimates. The approach is also applicable to other covariates affecting susceptibility or exposure to infection in infectious diseases. Exploitation of the dependent happening structure of infectious diseases to obtain a shape for the baseline hazard may help identifiability. The authors recommend fitting several models to time to event data in vaccine studies.
作者基于事件发生时间数据考虑疫苗效力的可估计性和解释，假定部分人群感染疾病的概率很低，其余人群具有部分（可能呈连续分布）易感性。脆弱性混合模型中感兴趣的效力参数包括因疫苗而极不可能感染或患病的人群比例、仍易感人群中的部分保护程度，以及异质性情况下的平均保护或效力汇总指标。当异质性源于接触模式、接触率或接触者传染性的异质性时，只要接种组和未接种组中的这些因素相同，效力估计值仍可进行有益的解释。一种基于似然的方法可从分组的事件发生时间数据中估计感兴趣的效力参数。假设不同效力水平和分布的模拟疫苗研究表明，忽略易感性或感染暴露的异质性通常会导致疫苗效力估计值偏低以及对估计值的错误解释。该方法也适用于影响传染病易感性或感染暴露的其他协变量。利用传染病的相依发生结构来获得基线风险的形状可能有助于识别。作者建议在疫苗研究中对事件发生时间数据拟合多个模型。
