Modeling multi-level survival data in multi-center epidemiological cohort studies: Applications from the ELAPSE project

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  • Evangelia Samoli, University of Athens
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  • Sophia Rodopoulou, University of Athens
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  • Ulla A. Hvidtfeldt, Kræftens Bekæmpelse
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  • Kathrin Wolf, Helmholtz Zentrum München - German Research Center for Environmental Health
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  • Massimo Stafoggia, Department of Epidemiology Lazio Regional Health Service, Karolinska Institutet
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  • Bert Brunekreef, Utrecht University
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  • Maciej Strak, Utrecht University, National Institute of Public Health and the Environment
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  • Jie Chen, Utrecht University
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  • Zorana J. Andersen, Københavns Universitet
  • ,
  • Richard Atkinson, St. George's University of London
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  • Mariska Bauwelinck, Vrije Universiteit Brussel
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  • Tom Bellander, Karolinska Institutet, Centre for Occupational and Environmental Medicine
  • ,
  • Jørgen Brandt
  • Giulia Cesaroni, Department of Epidemiology Lazio Regional Health Service
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  • Francesco Forastiere, King's College London
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  • Daniela Fecht, Imperial College London
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  • John Gulliver, University of Leicester
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  • Ole Hertel
  • Barbara Hoffmann, Heinrich Heine University Düsseldorf
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  • Kees de Hoogh, Swiss Tropical and Public Health Institute, University of Basel
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  • Nicole A.H. Janssen, Utrecht University
  • ,
  • Matthias Ketzel
  • Jochem O. Klompmaker, Utrecht University, National Institute of Public Health and the Environment
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  • Shuo Liu, Københavns Universitet
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  • Petter Ljungman, Karolinska Institutet
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  • Gabriele Nagel, Ulm University
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  • Bente Oftedal, Norwegian Institute of Public Health
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  • Göran Pershagen, Karolinska Institutet, Centre for Occupational and Environmental Medicine
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  • Annette Peters, Helmholtz Zentrum München - German Research Center for Environmental Health
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  • Ole Raaschou-Nielsen
  • Matteo Renzi, Department of Epidemiology Lazio Regional Health Service
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  • Doris T. Kristoffersen, Norwegian Institute of Public Health
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  • Gianluca Severi, Department of Epidemiology Lazio Regional Health Service
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  • Torben Sigsgaard
  • Danielle Vienneau, Swiss Tropical and Public Health Institute, University of Basel
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  • Gudrun Weinmayr, Ulm University
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  • Gerard Hoek, Utrecht University
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  • Klea Katsouyanni, University of Athens, King's College London

Background: We evaluated methods for the analysis of multi-level survival data using a pooled dataset of 14 cohorts participating in the ELAPSE project investigating associations between residential exposure to low levels of air pollution (PM2.5 and NO2) and health (natural-cause mortality and cerebrovascular, coronary and lung cancer incidence). Methods: We applied five approaches in a multivariable Cox model to account for the first level of clustering corresponding to cohort specification: (1) not accounting for the cohort or using (2) indicator variables, (3) strata, (4) a frailty term in frailty Cox models, (5) a random intercept under a mixed Cox, for cohort identification. We accounted for the second level of clustering due to common characteristics in the residential area by (1) a random intercept per small area or (2) applying variance correction. We assessed the stratified, frailty and mixed Cox approach through simulations under different scenarios for heterogeneity in the underlying hazards and the air pollution effects. Results: Effect estimates were stable under approaches used to adjust for cohort but substantially differed when no adjustment was applied. Further adjustment for the small area grouping increased the effect estimates’ standard errors. Simulations confirmed identical results between the stratified and frailty models. In ELAPSE we selected a stratified multivariable Cox model to account for between-cohort heterogeneity without adjustment for small area level, due to the small number of subjects and events in the latter. Conclusions: Our study supports the need to account for between-cohort heterogeneity in multi-center collaborations using pooled individual level data.

OriginalsprogEngelsk
Artikelnummer106371
TidsskriftEnvironment International
Vol/bind147
Antal sider8
ISSN0160-4120
DOI
StatusUdgivet - feb. 2021

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