A Single-Arm Sequental Monitoring Design for Claiming Positive or Negative Safety Signals in Patients from Multiple Baseline Risk Groups

• Activity Number: 32
• Type: Contributed
• Date/Time: Sunday, August 4, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jung Wook Park*+ and Xiaosha Sherman Zhang and Jay Yang and Stephen Eck
• Companies: Astellas Pharma Global Development, Inc. and Astellas Pharma Global Development, Inc. and Astellas Pharma Global Development Inc. and Astellas Pharma Global Development, Inc.
• Keywords: continuous monitoring ; safety signal ; multiple risk factors ; sequential probability ratio test

Abstract

During the drug development, the data available on the anticipated serious Adverse Events (AEs) associated with a new medicine may be substantially less than needed to optimally inform physicians. Furthermore, the Risk Factors (RFs) which contribute to the likelihood of any specific AE, are likely not well understood, yet equally important for the prescribing physician and patient. Ideally, the drug labeling should reflect not only the average likelihood of a patient experiencing the AE but also precisely describe how that likelihood is influenced by RFs beyond the drug. Therefore, it is of interest to design a study to monitor the AE among the subjects with multiple RFs. Here we describe an active methodology to prospectively test for AEs and their association with inter-current contributors to risk. We introduce study design which provides a continuous monitoring boundary for the positive signal using Maximized Sequential Probability Test and a group sequential boundary for the lack of signal using negative binomial distribution. Simulation study will show statistical properties of the design controlling both Type I and II errors respectively in the multi-risk factor setting.