ICH E17 Guideline were required (e.g., cardiovascular outcome studies, vaccine efficacy studies). More re- cently, global regulatory strategies are also used to plan and conduct studies more effi- ciently to facilitate more rapid availability of drugs to patients worldwide. MRCTs allow for an examination of the applicability of a treatment to diverse popula- tions. The intrinsic and/or extrinsic factors that are believed or suspected to impact upon responses to the drug can be further evaluated based on data from various regions using a single protocol.
For example, the impact on the treatment effect of genetic differences or different distribution of gene polymorphisms in drug metabolising enzymes or the mo- lecular target of a drug can be examined in exploratory and/or confirmatory MRCTs that include subjects with different intrinsic factors across regions. Accumulated knowledge of the impact of intrinsic and extrinsic factors and global sharing of experiences in various regions may promote inclusion of additional regions in MRCTs. The primary reason for performing MRCTs is to evaluate the overall treatment effect based on data from subjects in all regions.
However, intrinsic and/or extrinsic factors may be expected to impact subjects’ responses to drugs differently across regions and should be considered when planning MRCTs. If major differences in treatment effects are expected, available data should be assessed to decide, whether it is appropriate and feasible to conduct the MRCT. Even in the case of expected major differences in treat- ment effects, it may still be possible, to conduct MRCTs by excluding some regions or a defined subgroup within a region, after careful consideration. Additional strategies to study a disease and/or drug in the excluded regions should be considered (see ICH E5).
If MRCTs are the source of data in the bridging strategy based on the ICH E5 guideline, MRCTs could provide more robust evidence than single regional trials for extrapolation of study results. In some cases, single-region studies may be appropriate, such as in the evaluation of drugs to treat or prevent a disease that is prevalent in a single region (e.g., anti-malarial drugs, vaccines specific to local epidemics, or antibiotics for region-specific strains). MRCTs can facilitate simultaneous global development of a drug and reduce the number of clinical studies conducted separately in each region, thereby minimising unnecessary duplication of studies.
Although MRCTs require more coordination during the planning stage and possibly increase start-up time, their use may provide a pathway for earlier 4