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Pattern mixture sensitivity analyses via multiple imputations for non-ignorable dropout in joint modeling of cognition and risk of dementia
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.ORCID iD: 0000-0003-2135-9963
London School of Hygiene and Tropical Medicine, London, UK; MRC Clinical Trials Unit at University College London, London, UK.ORCID iD: 0000-0003-3890-6206
London School of Hygiene and Tropical Medicine, London, UK.
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.ORCID iD: 0000-0002-1812-3581
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2025 (English)In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 44, no 6, article id e70040Article in journal (Refereed) Published
Abstract [en]

Motivated by the Swedish Betula study, we consider the joint modeling of longitudinal memory assessments and the hazard of dementia. In the Betula data, the time-to-dementia onset or its absence is available for all participants, while some memory measurements are missing. In longitudinal studies of aging, one cannot rule out the possibility of dropout due to health issues resulting in missing not at random longitudinal measurements. We, therefore, propose a pattern-mixture sensitivity analysis for missing not-at-random data in the joint modeling framework. The sensitivity analysis is implemented via multiple imputation as follows: (i) multiply impute missing not at random longitudinal measurements under a set of plausible pattern-mixture imputation models that allow for acceleration of memory decline after dropout, (ii) fit the joint model to each imputed longitudinal memory and time-to-dementia dataset, and (iii) combine the results of step (ii). Our work illustrates that sensitivity analyses via multiple imputations are an accessible, pragmatic method to evaluate the consequences of missing not at-random data on inference and prediction. This flexible approach can accommodate a range of models for the longitudinal and event-time processes. In particular, the pattern-mixture modeling approach provides an accessible way to frame plausible missing not at random assumptions for different missing data patterns. Applying our approach to the Betula study shows that worse memory levels and steeper memory decline were associated with a higher risk of dementia for all considered scenarios.

Place, publisher, year, edition, pages
John Wiley & Sons, 2025. Vol. 44, no 6, article id e70040
Keywords [en]
linear mixed effect model, multiple imputation, pattern mixture model, proportional hazards model, sensitivity analysis
National Category
Probability Theory and Statistics Medical Biostatistics
Identifiers
URN: urn:nbn:se:umu:diva-236554DOI: 10.1002/sim.70040ISI: 001443622400001PubMedID: 40079649OAI: oai:DiVA.org:umu-236554DiVA, id: diva2:1944711
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2019‐01064Forte, Swedish Research Council for Health, Working Life and Welfare, 2021‐00031Knut and Alice Wallenberg FoundationSwedish Research Council, 2022‐06725Swedish Research Council, K2010‐61X‐21446‐01Available from: 2025-03-14 Created: 2025-03-14 Last updated: 2025-04-24Bibliographically approved

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Gorbach, TetianaJosefsson, MariaNyberg, Lars

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Gorbach, TetianaCarpenter, James R.Josefsson, MariaNyberg, Lars
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StatisticsDepartment of Integrative Medical Biology (IMB)Umeå Centre for Functional Brain Imaging (UFBI)Department of Radiation Sciences
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Statistics in Medicine
Probability Theory and StatisticsMedical Biostatistics

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