Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods
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2011
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PLoS One
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Public Library of Science
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University of Cape Town
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BACKGROUND: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. METHODS: This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. RESULTS: The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. CONCLUSION: The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
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Kranzer, K., Lewis, J. J., White, R. G., Glynn, J. R., Lawn, S. D., Middelkoop, K., ... & Wood, R. (2011). Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods. PLoS One, 6(11), e27763. doi:10.1371/journal.pone.0027763