Implementation of Promising Zone Methodology in a Ph 3 Trial in AML (VALOR)

• Activity Number: 398 - Different Approaches to the Increase of a Sample Size When the Unblinded Interim Estimate of the Treatment Effect Looks Promising
• Type: Topic Contributed
• Date/Time: Tuesday, August 1, 2017 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jennifer Smith*
• Companies: Sunesis
• Keywords: promising zone ; VALOR ; adaptive designs ; interim analysis ; sample size re-estimation

Abstract

A ''promising zone'' design of a clinical trial allows the increase of study's sample size when the unblinded interim estimate of the treatment effect looks promising. This promising zone methodology was used successfully in the VALOR study, a recent randomized double-blind controlled study of vosaroxin +cytarabine vs. cytarabine alone in 711 relapsed or refractory AML patients. The interim analysis results were deemed "promising" and the sample size was increased accordingly. Practical considerations around the implementation of the methodology, including sensitivity analyses, communication, blinding, and timing and specification of the final analysis will be discussed with reference to the 2010 draft Guidance for Industry: "Adaptive Design Clinical Trials for Drugs and Biologics".