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Consideration of regional difference in design and analysis of multi-regional trials


  • This article is a US Government work and is in the public domain in the USA.

  • This article is published in Pharmaceutical Statistics as a special issue on Multi-regional Clinical Trials–What are the challenges?, edited by Sue Jane Wang, Office of Biostatistics, Office of Translational Sciences, CDER, U.S. Food and Drug Administration, MD, USA


Clinical trial strategy, particularly in developing pharmaceutical products, has recently expanded to a global level in the sense that multiple geographical regions participate in the trial simultaneously under the same study protocol. The possible benefits of this strategy are obvious, at least from the cost and efficiency considerations. The challenges with this strategy are many, ranging from trial or data quality assurance to statistical methods for design and analysis of such trials. In many regulatory submissions, the presence of regional differences in the estimated treatment effect, whether they are different only in magnitude or in direction, often presents great difficulty in interpretation of the global trial results, particularly for the acceptability by the local regulatory authorities. This article presents a number of useful statistical analysis tools for exploration of regional differences and a method that may be worth consideration in designing a multi-regional clinical trial. Published in 2010 by John Wiley & Sons, Ltd.