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

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dc.contributor.authorKranzer, Katharinaen_ZA
dc.contributor.authorLewis, James Jen_ZA
dc.contributor.authorWhite, Richard Gen_ZA
dc.contributor.authorGlynn, Judith Ren_ZA
dc.contributor.authorLawn, Stephen Den_ZA
dc.contributor.authorMiddelkoop, Kerenen_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.contributor.authorWood, Robinen_ZA
dc.date.accessioned2016-01-11T06:50:47Z
dc.date.available2016-01-11T06:50:47Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: 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.en_ZA
dc.identifier.apacitationKranzer, 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. <i>PLoS One</i>, http://hdl.handle.net/11427/16235en_ZA
dc.identifier.chicagocitationKranzer, 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." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16235en_ZA
dc.identifier.citationKranzer, 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.0027763en_ZA
dc.identifier.ris TY - Journal Article AU - Kranzer, Katharina AU - Lewis, James J AU - White, Richard G AU - Glynn, Judith R AU - Lawn, Stephen D AU - Middelkoop, Keren AU - Bekker, Linda-Gail AU - Wood, Robin AB - 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. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0027763 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods TI - Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods UR - http://hdl.handle.net/11427/16235 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16235
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0027763
dc.identifier.vancouvercitationKranzer 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.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.en_ZA
dc.rights.holder© 2011 Kranzer et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherInterpolationen_ZA
dc.subject.otherAntiretroviral therapyen_ZA
dc.subject.otherBlood countsen_ZA
dc.subject.otherSimulation and modelingen_ZA
dc.subject.otherAIDSen_ZA
dc.subject.otherRegression analysisen_ZA
dc.subject.otherMorbidityen_ZA
dc.titleAntiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methodsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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