Flexible Sample Size Considerations Using Information Based Interim Monitoring

• Activity Number: 129
• Type: Invited
• Date/Time: Monday, August 12, 2002 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section*
• Author(s): Cyrus Mehta*+ and Anastasios Tsiatis
• Affiliation(s): Cytel Software Corporation and North Carolina State University
• Keywords: sample size re-estimation ; adaptive design ; information based monitoring ; group sequwntial ; interim monitoring

Abstract

At the design phase of a clinical trial the total number of participants needed to detect a clinically important treatment difference with sufficient precision depends frequently on nuisance parameters like variance, baseline response rate, or regression coefficients other than the main effect. In practical applications, nuisance parameter values are often unreliable guesses founded on little or no available past history. Sample size calculations based on these initial guesses may therefore lead to over- or underpowered studies. It is, however, possible to be flexible on sample size but rather continue collecting data until we have achieved the desired information. Such a strategy is well-suited to being adopted in conjunction with a group sequential clinical trial where the data are monitored routinely anyway. We contrast our approach with adaptive designs, which allow the sample size to be modified based on sequentially computed observed treatment differences