Abstract
We evaluate the probability of observing consistent results and the relationships between the required sample size and the effect size for a confirmatory multiregional trial. Three methods are evaluated, including two methods (methods 1 and 2) already proposed by the Ministry of Health, Labor and Welfare in 2007 and a new method proposed to confirm the ratio of one region to the other regions of the true treatment effect in a multiregional trial. We discuss method 1 and a new method with a survival endpoint and method 2 with a normal endpoint using numeric equations and simulations. We show that the probability of observing consistent results is not related to the effect size and the conditional probability is slightly superior to the unconditional one in both method 1 and the new method. We conclude that the probability of observing consistent results with the new method decreases according to the increase of the number of regions in method 1 previously proposed. Nonetheless, the slight difference between the new method and method 1 was observed in a small proportion of patients, which is less than 20%.
Similar content being viewed by others
References
Glickman SW. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009;360:816–823.
Ministry of Health, Labor and Welfare, Japan. Basic principles on global clinical trials. September 2007.
Li Z, Chuang-Stein C, Hoseyni C. The probability of observing negative subgroup results when the treatment effect is positive and homogeneous across all subgroups. Drug Inf J. 2007;41:47–56.
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. 2008;42:139–147.
Quan H, Zhao P-L, Zhang J, Roessner M, Aizawa K. Sample size consideration for Japanese patients in a multi-regional trial based on MHLW guidance. Pharm Stat. 2010;9(2):100–112.
Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics. 1982;38:163–170.
Schoenfeld DA. Sample size equation for the proportional hazards regression model. Biometrics. 1982;39:499–503.
PANSS Institute. Positive and negative symptoms scores, http://www.panss.org/About_Overview_the_PANSS_Institute.htm (accessed Sepember 29, 2009).
Fleiss JL. Multi-center clinical trials: Bradford Hill’s contributions and some subsequent developments. Stat Med. 1982;1:353–359.
Jones B, Teather D, Wang J, Lewis JA. A comparison of various estimators of treatment difference for multi-center clinical trials. Stat Med. 1998;17:1767–1777.
Chow SC, Shao J, Wang H. Sample Size Calculations in Clinical Research, 2nd ed. CRC Biostatistics Series. Boca Raton. FL: Chapman & Hall: 2008; 166–173.
Lachin JM, Foulkes MA. Evaluation of sample size and power for analyses of survival with allowance for non-uniform patient entry, losses to follow-up. noncompliance, and stratification. Biometrics. 1986;42:507–519.
Chung-Wang C, Anderson K, Gallo P, Collins S. Sample size estimation: a review and recommendations. Drug Inf J 2006;40:475–484.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sawa, J., Iwata, A. & Onishi, Y. Considerations on Observing Consistent Results of Treatment Effects in Multiregional Trials. Ther Innov Regul Sci 45, 65–76 (2011). https://doi.org/10.1177/009286151104500107
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1177/009286151104500107