Can analyses of electronic patient records be independently and externally validated? Study 2: the Effect of Beta-Adrenoceptor Blocker Therapy on Cancer Survival; a Retrospective Cohort Study
David a Springate, Darren M Ashcroft, Evangelos Kontopantelis, Tim Doran, Ronan Ryan, David Reeves(2015)
Can analyses of electronic patient records be independently and externally validated? Study 2: the Effect of Beta-Adrenoceptor Blocker Therapy on Cancer Survival; a Retrospective Cohort Study.
BMJ Open, doi: 10.1136/bmjopen-2014-007299
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To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different database sampling the same population.
Retrospective cohort analysis of beta-blocker therapy and all-cause mortality in cancer patients.
Two UK national primary care databases (PCDs): the Clinical Practice Research Datalink (CPRD) and Doctors’ Independent Network (DIN).
CPRD data for 11302 cancer patients compared to published results from DIN for 3462 patients.
January 1997 to December 2006.
Primary and secondary outcome measures
All-cause mortality: overall; by treatment subgroup (betablockers only, beta-blockers plus other blood pressure lowering medicines (BPLM), other BPLMs only); and by cancer-site.
Using CPRD, beta-blocker use was not associated with mortality (HR=1.03, 95%CI 0.93-1.14, vs patients prescribed other BPLMs only), but in DIN beta-blocker users had significantly higher mortality (HR=1.18, 95%CI 1.04 to 1.33). However, these hazard ratios were not statistically different (p=0.063), but did differ for patients on beta-blockers alone (CPRD=0.94, 95%CI 0.82-1.07; DIN=1.37, 95%CI 1.16-1.61;
p<0.001). Results for nine 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. Our finding that overall treatment effect estimates were not statistically different, adds to a growing body of evidence that different UK PCDs produce effect estimates comparable within statistical tolerance. However, some subgroup effects differed significantly and individually the two studies lead to different conclusions
regarding the safety of beta-blockers for cancer patients. Single studies based on internally well-validated databases therefore do not guarantee generalisable results, especially for subgroups. In all cases, confirmatory studies using at least one other independent data source are strongly recommended.
- Author for correspondence
- David Reeves
- Email for correspondence
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