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Combined models for pre- and post-treatment longitudinal biomarker data: an application to CD4 counts in HIV-patients.

Stirrup, OT; Babiker, AG; Copas, AJ; (2016) Combined models for pre- and post-treatment longitudinal biomarker data: an application to CD4 counts in HIV-patients. BMC Medical Research Methodology , 16 , Article 121. 10.1186/s12874-016-0187-2. Green open access

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Abstract

BACKGROUND: There has been some debate in the literature as to whether baseline values of a measurement of interest at treatment initiation should be treated as an outcome variable as part of a model for longitudinal change or instead used as a predictive variable with respect to the response to treatment. We develop a new approach that involves a combined statistical model for all pre- and post-treatment observations of the biomarker of interest, in which the characteristics of response to treatment are treated as a function of the 'true' value of the biomarker at treatment initiation. METHODS: The modelling strategy developed is applied to a dataset of CD4 counts from patients in the UK Register of HIV Seroconverters (UKR) cohort who initiated highly active antiretroviral therapy (HAART). The post-HAART recovery in CD4 counts for each individual is modelled as following an asymptotic curve in which the speed of response to treatment and long-term maximum are functions of the 'true' underlying CD4 count at initiation of HAART and the time elapsed since seroconversion. Following previous research in this field, the models developed incorporate non-stationary stochastic process components, and the possibility of between-patient differences in variability over time was also considered. RESULTS: A variety of novel models were successfully fitted to the UKR dataset. These provide reinforcing evidence for findings that have previously been reported in the literature, in particular that there is a strong positive relationship between CD4 count at initiation of HAART and the long-term maximum in each patient, but also reveal potentially important features of the data that would not have been easily identified by other methods of analysis. CONCLUSION: Our proposed methodology provides a unified framework for the analysis of pre- and post-treatment longitudinal biomarker data that will be useful for epidemiological investigations and simulations in this context. The approach developed allows use of all relevant data from observational cohorts in which many patients are missing pre-treatment measurements and in which the timing and number of observations vary widely between patients.

Type: Article
Title: Combined models for pre- and post-treatment longitudinal biomarker data: an application to CD4 counts in HIV-patients.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12874-016-0187-2
Publisher version: http://dx.doi.org/10.1186/s12874-016-0187-2
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: CD4, HAART, HIV, Longitudinal data, Mixed effects models, Statistical methodology
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/1516612
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