On Evaluation of Consistency in Multi-Regional Clinical Trials

• Activity Number: 673 - Clinical Trial Design- 8
• Type: Contributed
• Date/Time: Thursday, August 2, 2018 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Lisa Ying* and Fuyu Song and Shein-Chung Chow and Na Zeng and Jiayin Zheng and Xiaodong Li and David Henry and Venkat Sethuraman
• Companies: and Center for Food and Drug Inspection, cFDA and Food and Drug Administration and National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital and Fred Hutchinson Cancer Research Center and Bristol-Myers Squibb Company and Bristol-Myers Squibb Company and ZS Associates
• Keywords: Test for consistency; Consistency index; Similarity; Non-inferiority&Superiority; Sensitivity index

Abstract

Multi-regional clinical trials have become very popular for global pharmaceutical development. However, clinical results observed from some regions may not be consistent with the results from other regions and/or all regions combined. The inconsistency observed may be due to ethnic differences in different regions, differences in medical practice, or by random chance due to small sample size for the region. Some regional regulatory agencies require consistency evaluation between local country results and overall results. The challenge is there is no detailed guidance on the definition of 'consistency' and methodology to evaluate it. In this presentation, several statistical tests for consistency between clinical results observed from a specific sub-population and the entire population are proposed. These methods are compared through extensive simulation. As most published articles discussed consistency evaluation for superiority situations, we have discussed consistency evaluation for non-inferiority situation through a simulated example concerning consistency in some countries. Recommendations of the statistical methods to be used for consistency evaluation are given.