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

Publication

Author(s):

Kranzer K, Lewis JJ, White RG, Glynn JR, Lawn SD, Middelkoop K, Bekker LG, Wood R.

Pub Title:

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

Pub Date:

Nov 30 2011

Pub Region(s):

Southern Africa

Journal Issue:

11

Page Number:
e27763

Journal:

Title: 
PLoS One
Link: 
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027763

PubMed: 22114687
Pub PDF: PDF icon 22114687.pdf

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.

PMID: 22114687 [PubMed - indexed for MEDLINE]

PMCID: PMC3219676

 
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Citation:

Kranzer K, Lewis JJ, White RG, Glynn JR, Lawn SD, Middelkoop K, Bekker LG, Wood R. Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods. PLoS One. 2011;6(11):e27763. doi: 10.1371/journal.pone.0027763. Epub 2011 Nov 17. PubMed PMID: 22114687; PubMed Central PMCID: PMC3219676.