Survival biases lead to flawed conclusions in observational treatment studies of influenza patients
Survival biases lead to flawed conclusions in observational treatment studies of influenza patients
复制标题
DOI：
10.1016/j.jclinepi.2017.01.008
复制
发表时间：
2017-04-01
影响因子：
7.2
通讯作者：
Schumacher, Martin
中科院分区：
文献类型：
--
作者：
Wolkewitz, Martin;Schumacher, Martin
背景和目的：几项观察性研究报道，奥司他韦（达菲）降低了感染和住院患者的死亡率。由于观察住院时间和时间依赖性治疗分配的限制，这样的结果是容易常见类型的生存偏差（长度，时间依赖性和竞争风险偏差）。方法：英国医院的流感临床信息网络（FLU-CIN）研究组的数据，其中包括1,391例确诊的大流行性流感A/H1N1 2009年感染。我们使用了多状态模型方法，包括以下状态：入院、奥司他韦治疗、出院和死亡。时间起源是流感发作。我们显示了个体数据，风险集，风险，概率从多状态模型来研究这三个常见的生存bias.Results的影响：正确的风险比奥司他韦死亡为1.03（95%置信区间[CI]：0.64-1.66）和出院1.89（95%CI：1.65-2.16）。长度偏倚增加了两个风险比（HR）：HR（死亡）= 1.82（95% CI：1.12-2.98）和HR（放电）= 4.44（95% CI：3.90-5.05），而时间依赖性偏倚降低了它们：HR（死亡）= 0.62（95% CI：0.39-1.00）和HR（出院）= 0.85（95% CI：0.75-0.97）。长度和时间依赖性偏倚在概率方面不太明显。忽略出院作为医院死亡的竞争事件导致了显着高估的医院死亡率，并未能检测到奥司他韦对住院stay.Conclusions的减少效果：三个生存偏差的影响是显着的，它可以使神经氨酸酶抑制剂出现更有效，甚至有害。不正确和错误分类的风险集是偏倚风险率的主要来源。(C)2017爱思唯尔公司All rights reserved.
Background and Objective: Several observational studies reported that Oseltamivir (Tamiflu) reduced mortality in infected and hospitalized patients. Because of the restriction of observation to hospital stay and time-dependent treatment assignment, such findings were prone to common types of survival bias (length, time-dependent and competing risk bias).Methods: British hospital data from the Influenza Clinical Information Network (FLU-CIN) study group were used which included 1,391 patients with confirmed pandemic influenza A/H1N1 2009 infection. We used a multistate model approach with following states: hospital admission, Oseltamivir treatment, discharge, and death. Time origin is influenza onset. We displayed individual data, risk sets, hazards, and probabilities from multistate models to study the impact of these three common survival biases.Results: The correct hazard ratio of Oseltamivir for death was 1.03 (95% confidence interval [CI]: 0.64-1.66) and for discharge 1.89 (95% CI: 1.65-2.16). Length bias increased both hazard ratios (HRs): HR (death) = 1.82 (95% CI: 1.12-2.98) and HR (discharge) = 4.44 (95% CI: 3.90-5.05), whereas the time-dependent bias reduced them: HR (death) = 0.62 (95% CI: 0.39-1.00) and HR (discharge) = 0.85 (95% CI: 0.75-0.97). Length and time-dependent bias were less pronounced in terms of probabilities. Ignoring discharge as a competing event for hospital death led to a remarkable overestimation of hospital mortality and failed to detect the reducing effect of Oseltamivir on hospital stay.Conclusions: The impact of each of the three survival biases was remarkable, and it can make neuraminidase inhibitors appear more effective or even harmful. Incorrect and misclassified risk sets were the primary sources of biased hazard rates. (C) 2017 Elsevier Inc. All rights reserved.