Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis.
OBJECTIVE
To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population.


METHODS
Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort.


METHODS
Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK.


METHODS
CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003.


RESULTS
We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins.


CONCLUSIONS
Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity.
NIHR School for Primary Care Research, Centre for Primary Care, Institute of Population Health, University of Manchester, Manchester, UK.
David
D
Reeves
David A
DA
Springate
Darren M
DM
Ashcroft
Ronan
R
Ryan
Tim
T
Doran
Richard
R
Morris
Ivan
I
Olier
Evangelos
E
Kontopantelis
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D048909:Diabetes Complications; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors; D012737:Sex Factors; D006113:United Kingdom; D055815:Young Adult
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
Primary Care; Statistics & Research Methods