Genomic Classifier for Patient Enrichment: Misclassification and Type I Error Issues in Pharmacogenomics Noninferiority Trial

• Activity Number: 485
• Type: Invited
• Date/Time: Wednesday, August 3, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Statistics in Biopharmaceutical Research Journal
• Author(s): Sue-Jane Wang*+
• Companies: U.S. Food and Drug Administration/CDER
• Keywords: Biomarker Qualification ; Disease prevalence ; False positive classification ; Nondifferential misclassification ; noninferiority ; positive predictive value

Abstract

Unlike the phenotypic characteristics, a genomic diagnostic assay is needed to assess whether a patient truly has the genomic characteristics of interest for therapeutic investigation. However, in reality, the diagnostic assay is not perfect without misclassification error. We consider a targeted or enrichment pharmacogenomics clinical trial with a non-inferiority objective. In this paper presentation, we assess the maximum type I error rate associated with falsely concluding non-inferiority in the presence of misclassification of subject's genomic status. To achieve a prescribed level of positive predictive value, the feasibility of a genomic biomarker for enrichment in a non-inferiority study is a function of disease prevalence. If the evidential standard of much less inflation of type I error rate can be achieved, a genomic biomarker, if qualified, may be useful as an adjunct tool for patient selection.