Abstract
The Japanese regulatory agency, the Ministry of Health, Labour and Welfare, requires sponsors to enroll a specific number or proportion of Japanese patients in multiregional clinical trials (MRCTs) in order to allow for the appropriate statistical evaluation of the efficacy and safety of an investigational drug in the Japanese population. This means the actual proportion of Japanese patients to the total sample size would need to be determined by taking into account the proportion of patients in other regions as well as the appropriate statistical considerations. Determining the proportion of Japanese patients that satisfies the regulatory agency’s statistical requirement, along with taking into account the practical limitations of patient enrollment, would be difficult for sponsors. We believe that recent studies about the proportion of Japanese patients enrolled in MRCTs provides sponsors with useful information about partitioning sample size into individual regions for MRCTs in oncology. In this study, we investigated the proportion of Japanese patients in MRCTs and further compared the efficacy results from the overall population to that of the Japanese population. The proportion of Japanese patients averaged approximately 10.9%, but the proportion varied depending on the drug type. The results of the primary endpoints in Japanese patients were similar to those of the overall population, regardless of the proportion of Japanese patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ministry of Health, Labour, and Welfare (MHLW) of Japan. Guidelines for Clinical Evaluation Methods of Anti-Cancer Drugs. Notification No. 9. Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, Tokyo, Japan, 1991.
International Conference on Harmonization. E5 Guideline: Ethnic Factors in the Acceptability of Foreign Clinical Data (R1). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E5_R1/Step4/E5_R1__Guideline.pdf. Published 1998. Accessed June 6, 2016.
Ministry of Health, Labour, and Welfare (MHLW) of Japan. Guidelines for Clinical Evaluation Methods of Anti-Cancer Drugs. Notification No. 1101001. Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, Tokyo, Japan, 2005.
Ministry of Health, Labour, and Welfare (MHLW) of Japan. Basic principles on Global Clinical Trials. Notification No. 0928010. Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, Tokyo, Japan, 2007.
Kawai N, Chuang-Stein C, Komiyama O, Li Y. An Approach to rationalize partitioning sample size into individual regions in a multiregional trial. Drug Inf J. 2007;42:139–147.
Quan H, Zhao PL, Zhang J, Roessner M, Aizawa K. Sample size considerations for Japanese patients in a multi-regional trial based on MHLW guidance. Pharm Stat. 2010;9:100–112.
Ikeda K, Bretz F. Sample size and proportion of Japanese patients in multi-regional trials. Pharm Stat. 2010;9:207–216.
Luo X, Shih WJ, Ouyang SP, Delap RJ. An optimal adaptive design to address local regulations in global clinical trials. Pharm Stat. 2010;9:179–189.
Tsou HH, Chow SC, Lan KK, et al. Proposals of statistical consideration to evaluation of results for a specific region in multi-regional trials—Asian perspective. Pharm Stat. 2010;9:201–206.
Ando Y, Hamasaki T. Practical issues and lessons learned from multi-regional clinical trials via case examples: a Japanese perspective. Pharm Stat. 2010;9:190–200.
Ando Y, Uyama Y. Multiregional clinical trials: Japanese perspective on drug development strategy and sample size for Japanese subjects. J Biopharm Stat. 2012;22:977–987.
Chen CT, Hung HM, Hsiao CF. Design and evaluation of multiregional trials with heterogeneous treatment effect across regions. J Biopharm Stat. 2012;22:1037–1050.
Chen X, Lu N, Nair R, et al. Decision rules and associated sample size planning for regional approval utilizing multiregional clinical trials. J Biopharm Stat. 2012;22:1001–1018.
Chen J, Quan H, Gallo P, Ouyang SP, Binkowitz B. An adaptive strategy for assessing regional consistency in multiregional clinical trials. Clin Trials. 2012;9:330–339.
Huang Y, Chang WJ, Hsiao CF. An empirical Bayes approach to evaluation of results for a specific region in multiregional clinical trials. Pharm Stat. 2013;12:59–64.
Wu YJ, Tan TS, Chow SC, Hsiao CF. Sample size estimation of multiregional clinical trials with heterogeneous variability across regions. J Biopharm Stat. 2014;24:254–271.
Liu JT, Tsou HH, Gordon Lan KK, et al. Assessing the consistency of the treatment effect under the discrete random effects model in multiregional clinical trials. Stat Med. 2016;35:2301–2314.
Yuan Z, Chen G, Huang Q. Adaptive strategies in designing the simultaneous global drug development program. J Biopharm Stat. 2016;26:590–597.
Khin NA, Yang P, Hung HM, et al. Regulatory and scientific issues regarding use of foreign data in support of new drug applications in the United States: an FDA perspective. Clin Pharmacol Ther. 2013;94:230–242.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. General principle on planning/designing Multi-Regional Clinical Trials E17. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E17/E17_Final_Concept_Paper_July_2014.pdf. Published 2014. Accessed June 6, 2016.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Hirakawa, A., Kinoshita, F. An Analysis of Japanese Patients Enrolled in Multiregional Clinical Trials in Oncology. Ther Innov Regul Sci 51, 207–211 (2017). https://doi.org/10.1177/2168479016672702
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1177/2168479016672702