Correcting hazard ratio estimates for outcome misclassification using multiple imputation with internal validation data

Objective Outcome misclassification may occur in observational studies using administrative databases. We evaluated a two-step multiple imputation approach based on complementary internal validation data obtained from two subsamples of study participants to reduce bias in hazard ratio (HR) estimates in Cox regressions. Methods We illustrated this approach using data from a surveyed sample of 6247 individuals in a study of statin-diabetes association in Quebec. We corrected diabetes status and onset assessed from health administrative data against self-reported diabetes and/or elevated fasting blood glucose (FBG) assessed in subsamples. The association between statin use and new onset diabetes was evaluated using administrative data and the corrected data. By simulation, we assessed the performance of this method varying the true HR, sensitivity, specificity, and the size of validation subsamples. Results The adjusted HR of new onset diabetes among statin users versus non-users was 1.61 (95% confidence interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when diabetes status and onset were corrected based on self-report and undiagnosed diabetes (FBG >= 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report and undiagnosed diabetes/impaired FBG (>= 6 mmol/L). In simulations, the multiple imputation approach yielded less biased HR estimates and appropriate coverage for both non-differential and differential misclassification. Large variations in the corrected HR estimates were observed using validation subsamples with low participation proportion. The bias correction was sometimes outweighed by the uncertainty introduced by the unknown time of event occurrence. Conclusion Multiple imputation is useful to correct for outcome misclassification in time-to-event analyses if complementary validation data are available from subsamples. Copyright (C) 2017 John Wiley & Sons, Ltd.