Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods

Kranzer, Katharina, Lewis, James J. ORCID: https://orcid.org/0000-0002-8603-2761, White, Richard G., Glynn, Judith R., Lawn, Stephen D., Middelkoop, Keren, Bekker, Linda-Gail and Wood, Robin 2011. Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods. PLoS ONE 6 (11) , e27763. 10.1371/journal.pone.0027763

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Social Sciences (Includes Criminology and Education)
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of Acceptance:	24 October 2011
Last Modified:	27 Jun 2024 13:30
URI:	https://orca.cardiff.ac.uk/id/eprint/169538

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