Advancing Wider Implementation of Multi-regional Clinical Trials in East Asia

The ICH E17 guideline is intended to promote the effective and efficient use of multi-regional clinical trials in simultaneous global medicines development, contributing to faster patient access. However, its uptake has been slower than hoped, and some regulators often require local (national) clinical trial data for regulatory submissions. This review examines the extent of ethnic (country of origin) influences on pharmacokinetic (PK) or pharmacodynamic (PD) profile of drugs, with a focus on East Asian countries. We conclude that clinically significant ethnic differences are likely to be less common for many newer therapeutics than older drugs, especially those older small-molecule drugs with low therapeutic indices. Major source of ethnic differences in drug PK or PD are due to differences in the allelic frequencies of particular genes for metabolizing enzymes and other drug targets or receptors, respectively. The default approach for conducting clinical trials for products intended for global markets should be to assess safety and efficacy through multi-regional clinical trials and requirements for country-specific enrolment in trials infrequently justifiable only on scientific grounds.