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A method making fewer assumptions gave the most reliable estimates of exposure-outcome associations in stratified case-cohort studies.

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Jones, Edmund 
Sweeting, Michael J 
Sharp, Stephen J 
Thompson, Simon G 
EPIC-InterAct Consortium 


OBJECTIVE: A case-cohort study is an efficient epidemiological study design for estimating exposure-outcome associations. When sampling of the subcohort is stratified, several methods of analysis are possible, but it is unclear how they compare. Our objective was to compare five analysis methods using Cox regression for this type of data, ranging from a crude model that ignores the stratification to a flexible one that allows nonproportional hazards and varying covariate effects across the strata. STUDY DESIGN AND SETTING: We applied the five methods to estimate the association between physical activity and incident type 2 diabetes using data from a stratified case-cohort study and also used artificial data sets to exemplify circumstances in which they can give different results. RESULTS: In the diabetes study, all methods except the method that ignores the stratification gave similar results for the hazard ratio associated with physical activity. In the artificial data sets, the more flexible methods were shown to be necessary when certain assumptions of the simpler models failed. The most flexible method gave reliable results for all the artificial data sets. CONCLUSION: The most flexible method is computationally straightforward, and appropriate whether or not key assumptions made by the simpler models are valid.



Case–cohort study, Cox model, Hazard ratio, Meta-analysis, Stratification, Subcohort selection, Case-Control Studies, Data Collection, Diabetes Mellitus, Type 2, Humans, Incidence, Motor Activity, Proportional Hazards Models, Reproducibility of Results, Statistics as Topic

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J Clin Epidemiol

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Elsevier BV
Medical Research Council (MR/L003120/1)
Medical Research Council (G0800270)
Medical Research Council (MC_UU_12015/1)
British Heart Foundation (None)
Medical Research Council (G0800270/1)
EJ, MJS and SGT were supported in part by the UK Medical Research Council and the British Heart Foundation. SJS was supported by the UK Medical Research Council [Unit Programme number MC_UU_12015/1]. The EPIC-InterAct study was funded by the EU FP6 programme (LSHM_CT_2006_037197).