An Application of Group Sequential Method for Demonstration of Efficacy in Diagnostic Imaging Development

• Activity Number: 423
• Type: Contributed
• Date/Time: Tuesday, August 2, 2011 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Gajanan Bhat*+ and Jeffrey Joseph and Dana Washburn
• Companies: Lantheus Medical Imaging, Inc. and Omnicare Clinical Research, Inc. and Lantheus Medical Imaging, Inc.
• Keywords: Sensitivity ; Specificity ; diagnostic efficacy ; interim analysis ; adaptive design ; imaging trial

Abstract

A joint hypothesis of sensitivity and specificity in a pivotal new diagnostic imaging product development is used to demonstrate efficacy. A new diagnostic imaging product (PET myocardial perfusion) is compared to an FDA-approved comparator imaging modality (SPECT) as well as both modalities being compared to an acceptable truth standard (coronary angiography (CA)). Where clinically the sensitivity is more important than specificity, the test can be one of superiority with regards to sensitivity, but one of non-inferiority with regards to specificity. Adaptive design approach (maximize statistical power and an interim analysis) in order to provide flexibility to Phase 3 will be critical to the success of the clinical program. A GSM for a joint hypothesis of superiority in sensitivity and non-inferiority in specificity incorporating O'Brien-Fleming function will be used. The total power is the combination of powers attributed to individual hypothesis with the two parameters being interrelated and dependent on disease prevalence in trial population as determined by the CA. The proposed methodology provides an approach to control overall Type I error from multiple analyses.