A Doubly Randomized Delayed-Start Design for Clinical Trials in Early Intervention of Neurodegenerative Diseases

• Activity Number: 223
• Type: Topic Contributed
• Date/Time: Monday, July 30, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Qing Liu*+
• Keywords: adaptive designs ; blinded sample size adjustment ; disease-modeling ; doubly randomized delayed start design ; enrichment design ; informative differential dropouts

Abstract

Consider a clinical trial where patients with preconditions for progression to a neurodegenerative disease are randomized to receive a new test drug or standard of care. The primary objective is to assess if treatment with the new test drug can reduce the proportion of progression to the disease. This can be achieved through a randomized delayed start in which a patient who was initially randomized to receive the standard of care and who has not dropped out for any reason is re-randomized to start the new test drug or to continue on the standard of care. From the second randomization, it is possible to assess if the new test drug would modify the trajectory of the disease progression, or if patients who have missed the early treatment would still benefit from the new drug. Due to the second randomization, a fraction of patients are removed from contributing to the inference of the primary objective. Thus, it is necessary to derive a new procedure for statistical analysis of the primary endpoint as well as a method for calculating the sample size. The design is naturally adaptive because of the second randomization.