The Application of Group Sequential Stopping Boundaries to Evaluate the Treatment Effect of an Experimental Agent Across a Range of Marker Expression

• Activity Number: 330
• Type: Topic Contributed
• Date/Time: Tuesday, August 5, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Eric Holmgren*+
• Companies: Oncomed
• Keywords: Biomarker ; Cutpoint ; Phase 2 ; Clinical Development

Abstract

Using stopping boundaries developed for group sequential trials, we control the overall type 1 error for a series of tests that evaluate the treatment effect of an experimental agent in each of several predefined marker subgroups. We then go on to present a procedure based on these group sequential stopping boundaries that provides strong control of type 1 error for testing a series of hypotheses regarding the treatment effect over a range of marker expression. To provide some context for this procedure we will also discuss the role of a biomarker in Phase 2 from the perspective of the clinical development plan as a whole and compare the strategy where the Phase 2 statistical plan controls the type 1 error for assessing whether there is a treatment effect in a marker defined subgroup with the strategy where the Phase 2 statistical plan controls the type 1 error for the determination of the presence of a cut point above which there is a large treatment effect and below which there is a minimal treatment effect.