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 regions if the treatment effect is positive and uniform across regions. W e 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 as l5% to have an 80% probability that the observed treatment effects are consistent across the three regions, conditional on concluding a statistically significant overall treatment efect.

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Animal pain testing is essential for the development of new analgesic drugs, where appropriate data analyses as well as appropriate multi-factorial design of experiments are necessary to obtain meaningful results in an e‹cient fashion. The tail withdrawal experiment is one of the pain tests in which a rhesus monkey is restrained in a chair from which its tail hangs free by so it can be immersed in warm water. The monkeys consistently kept their tails in 38 40°C water for an extended period of time, and thus, the data were censored at 120 sec. The eŠect of temperature on the tail withdrawal latency was evaluated using three monkeys with a randomized block design. The eŠect of morphine on the thermal sensitivity was also evaluated. A Friedman-type two-way analysis of variance (Mack-Skillings test) demonstrated that the eŠects of both temperature and the animals were signiˆcant. The eŠect of repeated measurement in one animal was not signiˆcant using the Friedman test, indicating that the signiˆcance of the eŠect of animals could be attributed to the diŠerence in the intrinsic thermal sensitivity between animals. This method, together with a graphical approach, may prove to be valuable for assessing the sensitivity and reproducibility of an experimental condition, as well as the pharmacological eŠects of analgesic drugs.

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This article is based on the consensus of a task force of the Data Science Expert Committee, Japan Pharmaceutical Manufacturers Association. Common Technical Documents (CTDs) need to be harmonized in all of the ICH regions to enhance the scientific value and efficiency of these documents. Region-specific CTDs often require modifications for submission in different countries-an urgent issue not only for Japan but also for the countries where participation in the ICH framework will expand. CTDs themselves should be globalized, which means they should use not only a common format but also common contents, by incorporation of a 3-layer approach. In layer 1 of this approach, efficacy and safety of a study drug are evaluated through the overall study results; layer 2 entails evaluation of whether there is inconsistency in efficacy and/or safety of the study drug for a specific subgroup with overall results; and in layer 3, the results of layers 1 and 2 are used to evaluate benefits and risks in each applying country. The 3-layer approach can be used to create a globally common model using data collected in all countries in the study. This global evaluation allows benefits and risks to be evaluated in all countries and should allow globalized CTDs to be developed. Alignment between research and development sites by pharmaceutical companies and success of regulatory conventions can reduce the total amount of review time. Ultimately, these changes would lead to faster approval of new drugs.