For new drug development in the pediatric population, single-arm trials assessing pharmacokinetic (PK) parameters such as volume and clearance based on a noncompartment analysis have become increasingly conducted as multi-regional clinical trials (MRCTs) to get multiple regulatory approvals for new drug development. From a statistical point of view, one of major interests in MRCTs is evaluations of regional consistency in treatment effect between the region(s) of interest and overall population, or among all regions at the trial designing stage. Although two criteria shown in the guidance of Basic principles on Global Clinical Trials [1] have often been used for regional consistency evaluations in late phase randomized two-arm parallel trials, to the best of our knowledge, no criterion for regional consistency evaluation has been proposed for single-arm MRCTs for pediatric population assessing PK parameters.
In this talk, we propose novel criteria for regional consistency evaluations for single-arm MRCTs for pediatric population assessing PK parameters. To evaluate operating characteristics of our proposed criteria, we conduct statistical simulations for various scenarios those covered practical situations.
Trends of regional consistency probabilities calculated based on our proposed criteria are same to those for late phase randomized two-arm parallel trials. Therefore, we believe that our proposed criteria for regional consistency evaluation can be used for single-arm MRCTs for pediatric population assessing PK parameters in practice.
Reference: [1]: Ministry of Health, Labour and Welfare of Japan. Basic Principles on Global Clinical Trials, September 28, 2007.