An Approach to Rationalize Partitioning Sample Size into Individual Regions in a Multiregional Trial
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Norisuke Kowoi Statistics and Clinical Programming Group, Pfizer Global Research and Development. Pfizer japan Inc. Tokyo, Japan
Christy Chuong-Stein Statistical Research and Consultinn Center. Pfizer Glob; Researchand Development. Pfizer Inc. Ann Arbor. Michigan
Osalnr Komirlmo Statistics and Clinical Programming Group, Pfizer Global Research and Development. Pfizer japan Inc. Tokyo, japan
Yoichi li Statistics and Clinical Programming Group. Pfizer Global Research and Development. Pfizer japan Inc. Tokyo, japan
Key Words Multiregional trial: Regional sample size; Consistent trend
Correspondence Address Norisuke Kawai. Statistics and Clinical Programming Group, Pfizer Global Research and Development, Pfizer japan Inc. Shinjuku Bunka Quint Bldg.. 3-22-7. Yoyogi. Shibuya-ku. Tokyo 151 -8589. japan (email: norisuke. ka wai Opfizer.com).
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An Approach to Rationalize Partitioning Sample Size Into Individual Regions in a Multiregional Trial The desire to make valuable medicines available to patients globally at approximately the same time has led many pharmaceutical sponsors to consider conducting multiregional trials. In this article, we propose an approach to mtionalize partitioning the total sample size among the constituent regions in a confirmatory multiregional trial. Our approach is tofind the minimal sample size for the smallest region so that there is a high probability of observing a consistent trend in the estimated treatment effect across
INTRODUCTION An International Conference on Harmonization (ICH) E5 guideline titled Ethnic Factors in the Acceptability of Foreign Clinical Data (1)was accepted for implementation in the United States, European Union, and Japan in 1998. This guideline gave a framework for evaluating the impact of ethnic factors on a medicine’s effect. In Japan,more than 40 medicines have been approved based on a “bridging strategy” (2) articulated in ICH E5. So far, bridging studies in a new region have traditionally been conducted after data in the original region have become available, thus leading to a drug lag. or a time lag in drug approval in the new region (see the 11th Q&A for the ICH-E5 guideline, 3). In order to minimize this time gap, an increasing momentum has been building in Japan toward global drug development to allow for simultaneous regulatory submissions for marketing authorization (4). In the West, regulatory authorities are interested in the acceptability of data from previously unfamiliar regions (5-7). The 11th Q&A for the ICH-ES guideline discusses the concept of a multiregional trial (3). A multiregional trial is a trial conducted in more than one region using a common protocol (8). h q Infonnation ~Jmounml.Vd.42. pp. 139- 147,2008 0092-8615/2008
regions if the treatment effect is positive and uniform across regions. We investigate this probability in two ways, nam*, unconditional and conditional on the overall treatment effed being statistically significant. In the case of three regions, the proportion of patients from the smallest region could be as low
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