Antiretroviral Treatment Cohort Analysis Using Time-Updated CD4 Counts: Assessment of Bias with Different Analytic Methods

Katharina Kranzer, James J Lewis, Richard G White, Judith R Glynn, Stephen D Lawn, Keren Middelkoop, Linda-Gail Bekker and Robin Wood

PLOS ONE, 2011, vol. 6, issue 11, 1-7

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.

Date: 2011
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0027763

DOI: 10.1371/journal.pone.0027763

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