Considerations on Observing Consistent Results of Treatment Effects in Multiregional Trials
2011 Therapeutic Innovation and Regulatory Science
Sawa, J. | Iwata, A. | Onishi, Y. |
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%.