Monitoring Challenges and Maintaining Integrity of Results in Adaptive Studies

• Activity Number: 99
• Type: Invited
• Date/Time: Monday, July 30, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Pharmaceutical Research and Manufacturers of America
• Author(s): Paul Gallo*+
• Companies: Novartis
• Keywords: Data Monitoring Committee ; Adaptive trial ; interim analysis

Abstract

A main feasibility issue expected to have an important impact on the future role of adaptive trials, both in their nature and frequency, involves the monitoring processes for interim data review and adaptation decision making. Concerns about maintaining trial integrity and avoiding operational bias relate to access to information, whether direct (who sees interim data to make the adaption decision?), or indirect (what information about results can be inferred from seeing the actions taken?). We discuss whether a role in implementing adaptations is sensibly within the scope of a DMC such as might be constituted for more familiar monitoring motivations, and what changes to existing conventions, procedures, and operational models might be called for in adaptive trials. A key question involves attempting to resolve the apparent conflict between the desire to separate sponsors from knowledge of interim results, and protecting sponsor interests and bringing sponsor perspectives to bear on decisions for which they might be relevant. We illustrate with examples of how these issues were evaluated and addressed in actual adaptive trial proposals.