Table 5.

Average Difference in C-Index^a Between Base Model (FRS) and Base Model + Marker, TwinGene, 2004–2009

Marker	C-Index Improvements Over the Base Model (C-Index = 0.751)
	Average Realizations, the Gold Standard	Unstratified Case-Cohort Design	Unmatched Nested Case-Control Design	Stratified Case-Cohort Design	Matched Nested Case-Control Design
BIO1b	0.028**	0.026*	0.027*	0.027*	0.044
BIO2b	0.004	0.004	0.004	0.004	0.018
HDL-Cb	0.005	0.005	0.005	0.005	0.018
BIO1c	0.028**	0.027*	0.027*	0.028*	0.045*
BIO2c	0.004	0.004	0.004	0.004	0.019
HDL-Cc	0.005	0.005	0.005	0.005	0.018

Abbreviations: BIO1, simulated biomarker 1; BIO2, simulated biomarker 2; FRS, Framingham risk score; HDL-C, high density lipoprotein cholesterol.

* P < 0.05; **P < 0.001 (for test of difference).

^aC-index is equivalent to the receiver operating characteristic area under the curve, taking censorship into account.

^bSampling ratio: 1:1; subcohort size: n = 229.

^cSampling ratio: 1:3; subcohort size: n = 632.