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.
Reference:
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
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, http://hdl.handle.net/11427/16235
Kranzer, Katharina, James J Lewis, Richard G White, Judith R Glynn, Stephen D Lawn, Keren Middelkoop, Linda-Gail Bekker, and Robin Wood "Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods." PLoS One (2011) http://hdl.handle.net/11427/16235
Kranzer K, Lewis JJ, White RG, Glynn JR, Lawn SD, Middelkoop K, et al. Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods. PLoS One. 2011; http://hdl.handle.net/11427/16235.
Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.