ICH E17 Guideline mation about them should also be collected during the confirmatory trial for eval- uation of their impact on treatment effects. 3. MRCTs are planned under the assumption that the treatment effect applies to the entire target population, particularly to the regions included in the trial. Strategic allocation of the sample size to regions allows an evaluation of the extent to which this assumption holds. 4.
Pre-specified pooling of regions or subpopulations, based on established knowledge about similarities, may help provide flexibility in sample size alloca- tion to regions, facilitate the assessment of consistency in treatment effects across regions, and support regulatory decision-making. 5. A single primary analysis approach for hypothesis testing and estimation of the overall treatment effect should be planned so that it will be acceptable to all con- cerned regulatory authorities. A structured exploration to examine the consistency of treatment effects across regions and subpopulations should be planned. 6.
In light of diverse regional practices, ensuring high quality of study design and conduct in accordance with ICH E6 in all regions is of paramount importance to ensure the study results are interpretable. Careful attention to quality during trial planning, investigator training, and trial monitoring will help achieve consistently high trial quality required for a successful MRCT. 7. Efficient communication among sponsors and regulatory authorities is encour- aged at the planning stage of MRCTs, with the goal of obtaining acceptance of a global approach to study design across the different regulatory regions. 2.
GENERAL RECOMMENDATIONS IN THE PLANNING AND DESIGN OF MRCT S 2.1 Strategy-related Issues 2.1.1 The Value of MRCTs in Drug Development Historically, drug development focused on regulatory strategies designed for specific reg- ulatory regions. In that context, MRCTs had been recognised as an efficient way to enable recruitment of the planned number of trial subjects within a reasonable timeframe when either the disease and/or condition was rare (e.g., an enzyme deficiency disorder), for special (e.g., elderly, paediatric) populations, or when very large numbers of subjects 3