Abstract
New drug development has become globalized and the number of multi-regional clinical trials (MRCT) including Japan has increased year after year. It is well known that some ethnic factors may influence the efficacy and/or safety of drugs, and in the guideline “Basic principle on global clinical trials” the Ministry of Health, Labour and Welfare of Japan requests sponsors to evaluate effects of ethnic factors specific to individual regions on efficacy and safety of investigational drugs when conducting an MRCT. However, it may often be hard to identify what ethnic factors influence efficacy and/or safety of investigational drugs because it depends on the type of drug, the target disease, the trial design, the regions where the trial is conducted and various other factors. In our research about ethnic factors for several diseases based on the review reports published by the Pharmaceuticals and Medical Devices Agency, we found that inconsistencies in results of MRCT between regions were caused by imbalance of some ethnic factors considered to be covariates or risk factors between the regions. No ethnic factor which influenced only a specific region was found. This means that the 3-layer approach proposed by Komiyama et al is reasonable to evaluate data from an MRCT, and in addition to subgroup analyses we should use a statistical model that includes appropriate ethnic factors to estimate the efficacy and safety of investigational drugs in a specific region. We also emphasized that information about ethnic factors from MRCTs be continuously accumulated to identify what ethnic factors influence the efficacy and/or safety of drugs.
