Springate David A, Ashcroft Darren M, Kontopantelis Evangelos, Doran Tim, Ryan Ronan, Reeves David
NIHR School for Primary Care Research, Centre for Primary Care, Institute of Population, Health, University of Manchester, Manchester, UK Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK.
Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, UK.
BMJ Open. 2015 Apr 13;5(4):e007299. doi: 10.1136/bmjopen-2014-007299.
To conduct a fully independent, external validation of a research study based on one electronic health record database using a different database sampling from the same population.
Retrospective cohort analysis of β-blocker therapy and all-cause mortality in patients with cancer.
Two UK national primary care databases (PCDs): the Clinical Practice Research Datalink (CPRD) and Doctors' Independent Network (DIN).
CPRD data for 11,302 patients with cancer compared with published results from DIN for 3462 patients; study period January 1997 to December 2006.
All-cause mortality: overall; by treatment subgroup (β-blockers only, β-blockers plus other blood pressure lowering medicines (BPLM), other BPLMs only); and by cancer site.
Using CPRD, β-blocker use was not associated with mortality (HR=1.03, 95% CI 0.93 to 1.14, vs patients prescribed other BPLMs only), but DIN β-blocker users had significantly higher mortality (HR=1.18, 95% CI 1.04 to 1.33). However, these HRs were not statistically different (p=0.063), but did differ for patients on β-blockers alone (CPRD=0.94, 95% CI 0.82 to 1.07; DIN=1.37, 95% CI 1.16 to 1.61; p<0.001). Results for individual cancer sites differed by study, but only significantly for prostate and pancreas cancers. Results were robust under sensitivity analyses, but we could not be certain that mortality was identically defined in both databases.
We found a complex pattern of similarities and differences between databases. Overall treatment effect estimates were not statistically different, adding to a growing body of evidence that different UK PCDs produce comparable effect estimates. However, individually the two studies lead to different conclusions regarding the safety of β-blockers and some subgroup effects differed significantly. Single studies using even internally well-validated databases do not guarantee generalisable results, especially for subgroups, and confirmatory studies using at least one other independent data source are strongly recommended.
基于一个电子健康记录数据库，使用来自同一人群的不同数据库样本，对一项研究进行完全独立的外部验证。
对癌症患者β受体阻滞剂治疗与全因死亡率的回顾性队列分析。
两个英国国家初级保健数据库（PCD）：临床实践研究数据链（CPRD）和医生独立网络（DIN）。
11302例癌症患者的CPRD数据与DIN中3462例患者的已发表结果进行比较；研究期为1997年1月至2006年12月。
全因死亡率：总体；按治疗亚组（仅β受体阻滞剂、β受体阻滞剂加其他降压药物（BPLM）、仅其他BPLM）；以及按癌症部位。
使用CPRD时，β受体阻滞剂的使用与死亡率无关（HR = 1.03，95%CI 0.93至1.14，与仅开具其他BPLM的患者相比），但DIN中使用β受体阻滞剂的患者死亡率显著更高（HR = 1.18，95%CI 1.04至1.33）。然而，这些HR在统计学上无差异（p = 0.063），但仅使用β受体阻滞剂的患者存在差异（CPRD = 0.94，95%CI 0.82至1.07；DIN = 1.37，95%CI 1.16至1.61；p < 0.001）。不同研究中个别癌症部位的结果存在差异，但仅前列腺癌和胰腺癌差异显著。敏感性分析结果稳健，但我们不能确定两个数据库中死亡率的定义完全相同。
我们发现数据库之间存在相似和差异的复杂模式。总体治疗效果估计在统计学上无差异，这增加了越来越多的证据表明不同的英国PCD产生可比的效果估计。然而，两项研究单独得出了关于β受体阻滞剂安全性的不同结论，且一些亚组效应差异显著。即使是使用内部验证良好的数据库进行的单一研究也不能保证结果具有普遍性，尤其是对于亚组，强烈建议使用至少一个其他独立数据源进行验证性研究。
