Groenwold R H H, Hoes A W, Hak E
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Eur Respir J. 2009 Jul;34(1):56-62. doi: 10.1183/09031936.00190008. Epub 2009 Feb 12.
Estimates of influenza vaccine effectiveness have mostly been derived from nonrandomized studies and therefore are potentially confounded. The aim of the current study was to estimate influenza vaccine effectiveness in preventing mortality among the elderly, taking both measured and unmeasured confounding into account. Information on patients aged >or=65 yrs from the computerised Utrecht General Practitioner database on eight influenza epidemic periods and summer periods was pooled to estimate influenza vaccine effectiveness in preventing mortality. Summer periods (during which no effect of vaccination was expected) were used as a reference to control for unmeasured confounding in epidemic periods. After adjustment for measured confounders using multivariable regression analysis, propensity score matching and propensity score regression analysis, influenza vaccination reduced mortality risk (odds ratios (ORs) 0.58 (95% confidence interval (CI) 0.46-0.72), 0.56 (95% CI 0.44-0.71) and 0.56 (95% CI 0.45-0.69), respectively). After additional adjustment for unmeasured confounding (as observed during summer periods), the association between influenza vaccination and mortality risk decreased (OR 0.69 (95% CI 0.52-0.92)). We conclude that after state-of-the-art adjustment for typical confounders such as age, sex and comorbidity status, unmeasured confounding still biased estimates of influenza vaccine effectiveness. After taking unmeasured confounding into account, influenza vaccination is still associated with substantial reduction in mortality risk.
流感疫苗效力的估计大多来自非随机研究，因此可能存在混杂因素。本研究的目的是在考虑已测量和未测量的混杂因素的情况下，评估流感疫苗在预防老年人死亡方面的效力。汇总了来自乌得勒支全科医生计算机数据库中8个流感流行期和夏季的65岁及以上患者的信息，以评估流感疫苗在预防死亡方面的效力。将夏季（预计无疫苗接种效果）作为对照，以控制流行期未测量的混杂因素。在使用多变量回归分析、倾向评分匹配和倾向评分回归分析对已测量的混杂因素进行调整后，流感疫苗接种降低了死亡风险（比值比分别为0.58（95%置信区间0.46 - 0.72）、0.56（95%置信区间0.44 - 0.71）和0.56（95%置信区间0.45 - 0.69））。在对未测量的混杂因素进行额外调整后（如在夏季观察到的），流感疫苗接种与死亡风险之间的关联降低（比值比0.69（95%置信区间0.52 - 0.92））。我们得出结论，在对年龄、性别和合并症状态等典型混杂因素进行先进的调整后，未测量的混杂因素仍然会使流感疫苗效力的估计产生偏差。在考虑未测量的混杂因素后，流感疫苗接种仍与死亡风险的大幅降低相关。
