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Assessing risk prediction models using individual participant data from multiple studies.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pennells, Lisa 
White, Ian R 
Thompson, Simon G 
Wood, Angela M 

Abstract

Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous.

Description

Keywords

C index, D measure, coronary heart disease, individual participant data, inverse variance, meta-analysis, risk prediction, weighting, C-Reactive Protein, Coronary Disease, Data Interpretation, Statistical, Female, Humans, Male, Meta-Analysis as Topic, Middle Aged, Models, Statistical, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors

Journal Title

Am J Epidemiol

Conference Name

Journal ISSN

0002-9262
1476-6256

Volume Title

179

Publisher

Oxford University Press (OUP)
Sponsorship
Medical Research Council (G0701619)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
Medical Research Council (G0800270)
National Institute for Health Research (NIHR) (NF-SI-0512-10165)
Medical Research Council (MC_U106179471)
Medical Research Council (G0800270/1)