Test Validation Phase

Analytical Validation

Detailed information regarding analytical validation for Corus CAD is not publicly available. The following preanalytical clinical and demographic variables were measured in patients used in the microarray studies: sex, age, race, body mass index, current smoker, systolic blood pressure, diastolic blood pressure, hypertension, dyslipidemia, neutrophil count, and lymphocyte count (Elashoff et al., 2011).

Statistics and Bioinformatics Validation

Discovery-phase microarray data are available in a publicly accessible database (GEO, accession number GSE20686). PCR data used in the development and validation sets are not publicly available, although Cardio Dx has indicated they would be available upon request by qualified investigators.39 Analysis of the RT-PCR results from the validation study was performed at Scripps Translational Science Institute.40

Blood samples from 640 patients were used to develop the computational model (Elashoff et al., 2011); blood samples from another 526 patients were used for validation. There was no overlap in patient samples used in each phase of the study.

Details regarding development of the computational model were published (Rosenberg et al., 2010). The model was locked down prior to the start of the validation study. CardioDx funded the study and was involved in the design and conduct of the study.

Clinical/Biological Validation

Rosenberg et al. (2010) reported statistical analyses only for the validation group. The investigators predefined the primary endpoint as the receiver-operating characteristic (ROC) curve area for prediction of disease status by the test score. In a set of 526 PREDICT patients not used for gene discovery or computational model development, the AUC for ROC was 0.70 ± 0.02 (p image 0.001). At a threshold score of 14.75, which corresponded to a 20 percent likelihood of obstructive CAD, the sensitivity and specificity were 85 percent and 43 percent, respectively. This yielded an NPV of 83 percent and a PPV of 46 percent, with 33 percent of patient scores below this threshold (Rosenberg et al., 2010).

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39 Personal communication, Steve Rosenberg, Cardio DX, October 21, 2011; December 12, 2011.

40 Personal communication, Steve Rosenberg, Cardio DX, October 21, 2011.



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