从笔者:
V.A.基里和他的同事在吸入糖皮质激素和死亡率在慢性阻塞性肺疾病的观察研究,弹出关于我最近的一篇文章的三个点上的偏差,从下落不明不朽的时间(COPD)1。事实上,不像我以前在错误分类(按作者声明没有“下落不明”)不朽纸时间2,未计不朽的时间偏差的性质,在当前文件中提出1更阴险的,我很高兴有机会澄清这些问题。
首先,V.A.基里及其同事指出的是,在他们的研究中,317名患者接受氟替卡松和沙美特罗(F + S:暴露组)具有在第一和第三的处方74之间天的持续时间,以87天为3620名患者接受短期相比效支气管扩张(SABA:参照组)。该研究使用从第一这三个药方之日起180天期间开始统计死亡之前,这一事实意味着不朽的两个时间段。第一个是在第一和第三处方,其可以通过使用第三处方作为队列条目的日期来解决之间的跨度。第二个是第三处方和180天,两组之间的这种周期不同,平均106天为F + S组和93天为SABA参考组之间的时间。这种差异意味着,如果他们在F + S暴露组,但如果SABA参照组会算谁是他们的第三个处方后的100天内身故病人将不予考虑。为了避免从差动分类这种不一致,将所得不朽时间偏差,规则是简单的:如果经常使用由三个处方限定,只要使用第三处方的日期来定义队列条目。
阶梯式护理的方法来治疗慢性阻塞性肺病,而相应的,可能会导致曝光的不适当的分层定义,它导致的“下落不明不朽时间偏差”的问题。要明白这个道理,可考虑诊断为慢性阻塞性肺病患者A在1995年谁,第一次在2001年在接受三个处方为1996年6个月内一个SABA,随后接受了第一次在1999年F + S三层处方和模具分层方法中,该患者是只的F + S暴露组包括在内。The fact that the patient survived for 3 yrs after the reference SABA is never considered under this approach. This is incorrect because the identical patient B also diagnosed with COPD in 1995, who receives for the first time three prescriptions for a SABA within 6 months in 1996 but dies in 1997 is included in the SABA group. Thus, patient A, who as patient B would have contributed to the SABA reference group had they died before receiving F+S, was not counted because they survived. Here again, the rule is straightforward: the design and analysis must use all time accumulated after any of the exposure criteria are met. Moreover, the use of a nested case-control approach within an incorrectly defined cohort will only produce incorrect results.
最后,我们一致认为,患者切换到吸入糖皮质激素(ICS)(谁应该是大多数的患者因为阶梯治疗方法上ICS)很可能是患者病情加重。因此,我们预计,死亡率原油这类患者对ICS为那些对支气管扩张剂比率高独自一人,即通过指示混杂。令人惊讶地,在索里亚诺的研究中观察到相反的等。3。与用于SABA组11.6%相比,1年死亡率F + S组的粗为3.8%。This anomalous absence of confounding by indication is simply due to the fact that the SABA group (3,620 patients) excluded a large number of patients (up to 1,045) with 1 yr of immortality, who survived to receive F+S. As a result, the rate of death in the SABA group is overestimated because its calculation is based on the person-yrs of the 3,620 patients only (the group where all the deaths occurred) instead of all 4,665 patients (that includes the 1,045 where no death could have occurred). In fact, this denominator is much larger because it should also include the contribution of immortal SABA time from patients subsequently put on ICS other than fluticasone, who were excluded from this study.
总之,药物有效性的观测数据研究是棘手。这将是如果V.A.有帮助基里和他的同事介绍它们的数据进行适当的再分析,避免不朽的时间偏差和药物有效性造成假象。
- ©ERS期刊有限公司