The Benefit of Stratified Clinical Trials Revisited

• Activity Number: 469
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Jitendra Ganju*+ and Kefei Zhou
• Companies: Amgen Inc. and Amgen Inc.
• Keywords: random stratum sizes ; ; interaction ; adjusted analysis

Abstract

Stratification is common in clinical trials because it reduces the variance of the estimated treatment effect. The traditional demonstration of variance reduction relies on the assumption of stratum sizes being fixed quantities. However, in practice, to speed up enrollment, the stratum sizes are allowed to vary. Under this design, the criterion changes for achieving a reduction in variance. It is demonstrated why stratification may actually increase the variance compared to no stratification even when the mean square error is reduced on account of stratification. Data from a real clinical trial will be used for illustration. The benefit attributed to stratification needs to be re-calibrated in light of findings presented, particularly given its widespread use.