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Handling Missing Values in Interrupted Time Series Analysis of Longitudinal Individual-Level Data

Bazo-Alvarez, JC; Morris, TP; Pham, TM; Carpenter, JR; Petersen, I; (2020) Handling Missing Values in Interrupted Time Series Analysis of Longitudinal Individual-Level Data. Clinical Epidemiology , 12 pp. 1045-1057. 10.2147/clep.s266428. Green open access

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Abstract

Background: In the interrupted time series (ITS) approach, it is common to average the outcome of interest at each time point and then perform a segmented regression (SR) analysis. In this study, we illustrate that such ‘aggregate-level’ analysis is biased when data are missing at random (MAR) and provide alternative analysis methods. / Methods: Using electronic health records from the UK, we evaluated weight change over time induced by the initiation of antipsychotic treatment. We contrasted estimates from aggregate-level SR analysis against estimates from mixed models with and without multiple imputation of missing covariates, using individual-level data. Then, we conducted a simulation study for insight about the different results in a controlled environment. / Results: Aggregate-level SR analysis suggested a substantial weight gain after initiation of treatment (average short-term weight change: 0.799kg/week) compared to mixed models (0.412kg/week). Simulation studies confirmed that aggregate-level SR analysis was biased when data were MAR. In simulations, mixed models gave less biased estimates than SR analysis and, in combination with multilevel multiple imputation, provided unbiased estimates. Mixed models with multiple imputation can be used with other types of ITS outcomes (eg, proportions). Other standard methods applied in ITS do not help to correct this bias problem. / Conclusion: Aggregate-level SR analysis can bias the ITS estimates when individual-level data are MAR, because taking averages of individual-level data before SR means that data at the cluster level are missing not at random. Avoiding the averaging-step and using mixed models with or without multilevel multiple imputation of covariates is recommended.

Type: Article
Title: Handling Missing Values in Interrupted Time Series Analysis of Longitudinal Individual-Level Data
Open access status: An open access version is available from UCL Discovery
DOI: 10.2147/clep.s266428
Publisher version: https://doi.org/10.2147/clep.s266428
Language: English
Additional information: This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License (https://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
Keywords: interrupted time series analysis, segmented regression, missing data, multiple imputation, mixed effects models, electronic health records, big data
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 of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10112141
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