Time-dependent bias was common in survival analyses published in leading clinical journals

Objective: In survival analysis, "baseline immeasurable" time-dependent factors cannot be recorded at baseline, and change value after patient observation starts. Time-dependent bias can occur if such variables are not analyzed appropriately. This study sought to determine the prevalence of such time-dependent bias in highly-cited medical journals. Study Design and Setting: We searched Medline databases to identify all observational studies that used a survival analysis in American Journal of Medicine, Annals of Internal Medicine, Archives of Internal Medicine, British Medical Journal, Chest, Circulation, Journal of the American Medical Association, Lancet, and New England Journal of Medicine between 1998 and 2002. Studies with "baseline immeasurable" time-dependent factors were susceptible to time-dependent bias if a time-dependent covariate analysis was not used. Results: Of 682 eligible studies, 127 (18.6%, 95% CI 15.8-21.8%) contained a "baseline immeasurable" time-dependent factor and 52 (7.6% [5.8-9.9%] of all survival analyses/40.9% [32.3-50.0%] of studies with a time-dependent factor) were susceptible to time-dependent bias. In 35 studies (5.1% [3.7-7.1%]/27.6% [20.5-35.9%]), the bias affected a variable highlighted in the study abstract and correction of the bias could have qualitatively changed the study's conclusion in over half of studies. Conclusion: In medical journals, time-dependent bias is concerningly common and frequently affects key factors and the study's conclusion. (C) 2004 Elsevier Inc. All rights reserved.