Statistical Considerations on Randomization Strategy, Drug Supply Strategy, and Other Trial Operational Factors

• Activity Number: 390
• Type: Topic Contributed
• Date/Time: Tuesday, July 31, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Xiaohong Huang*+ and Lixia Jiao and Lynn Wei and Hui Quan
• Companies: Sanofi Aventis and Sanofi Aventis and Sanofi and Sanofi
• Keywords: Randomization ; clinical supply ; recruitment ; center stratified ; central stratified

Abstract

Appropriate randomization strategy and clinical supply strategy in clinical trials will help achieve treatment balance while reduce selection bias and efficiently manage the clinical supplies. Patient recruitments are typically very challenging in rheumatoid arthritis (RA) trials. In order to achieve fast recruitment RA trials usually end up with many small centers with limited number of patients per center. The center-stratified randomization strategy will ensure more predictable clinical supply and can reduce costs through minimizing drug waste. However, limited patients at center level will cause many open blocks which may result in significant treatment imbalance, especially when adopting more than one strata. The central-stratified randomization guarantees treatment balance. However, it is difficult to predict clinical supply need. Excessive clinical supply will cause more drug waste and insufficient clinical supply will delay patient recruitment. A cost function considering various factors is developed. A simulation study closely mimic an RA study was conducted to compare the cost function under various randomization strategies and clinical supply strategies.