Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

TY - JOUR

T1 - Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

AU - Thompson, Simon

AU - Kaptoge, Stephen

AU - White, Ian

AU - Wood, Angela

AU - Perry, Philip

AU - Danesh, John

AU - Jørgensen, Torben

AU - Emerging Risk Factors Collaboration

AU - Tybjærg-Hansen, Anne

AU - Frikke-Schmidt, Ruth

AU - Nordestgaard, Børge G.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within-and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.

AB - Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within-and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.

KW - Age Factors

KW - Coronary Disease

KW - Data Interpretation, Statistical

KW - Epidemiologic Methods

KW - Fibrinogen

KW - Humans

KW - Proportional Hazards Models

KW - Risk Factors

KW - Sex Factors

KW - Smoking

KW - Time Factors

U2 - 10.1093/ije/dyq063

DO - 10.1093/ije/dyq063

M3 - Journal article

C2 - 20439481

SN - 0300-5771

VL - 39

SP - 1345

EP - 1359

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 5

ER -