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Improved Correction of Misclassification Bias With Bootstrap Imputation

van Walraven, Carl

doi: 10.1097/MLR.0000000000000787
Applied Methods: PDF Only

Objective: Diagnostic codes used in administrative database research can create bias due to misclassification. Quantitative bias analysis (QBA) can correct for this bias, requires only code sensitivity and specificity, but may return invalid results. Bootstrap imputation (BI) can also address misclassification bias but traditionally requires multivariate models to accurately estimate disease probability. This study compared misclassification bias correction using QBA and BI.

Study Design: Serum creatinine measures were used to determine severe renal failure status in 100,000 hospitalized patients. Prevalence of severe renal failure in 86 patient strata and its association with 43 covariates was determined and compared with results in which renal failure status was determined using diagnostic codes (sensitivity 71.3%, specificity 96.2%). Differences in results (misclassification bias) were then corrected with QBA or BI (using progressively more complex methods to estimate disease probability).

Results: In total, 7.4% of patients had severe renal failure. Imputing disease status with diagnostic codes exaggerated prevalence estimates [median relative change (range), 16.6% (0.8%–74.5%)] and its association with covariates [median (range) exponentiated absolute parameter estimate difference, 1.16 (1.01–2.04)]. QBA produced invalid results 9.3% of the time and increased bias in estimates of both disease prevalence and covariate associations. BI decreased misclassification bias with increasingly accurate disease probability estimates.

Conclusions: QBA can produce invalid results and increase misclassification bias. BI avoids invalid results and can importantly decrease misclassification bias when accurate disease probability estimates are used.

Department of Medicine and Epidemiology and Community Medicine, Ottawa Hospital Research Institute and Institute for Clinical Evaluative Sciences, University of Ottawa, Ottawa, ON, Canada

C.v.W. is supported by a University of Ottawa, Department of Medicine Clinician Scientist Chair.

The author declares no conflict of interest.

Reprints: Carl van Walraven, MSc, MD, Department of Medicine and Epidemiology and Community Medicine, University of Ottawa, ASB1-003 1053, Carling Avenue, Ottawa, ON, Canada K1Y 4E9. E-mail:

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