Strategic inclusion of regions in multiregional clinical trials

Abstract

Background: With the recent publication of the International Conference on Harmonisation E17 guideline and major reforms in China underway, the platform for clinical trial conduct is expected to change. This study aims to assess the strategic inclusion of regions in clinical trials and its change in trends over the past decade. Methods: The ClinicalTrials.gov registry was searched for clinical trials registered by the top 10 pharmaceutical companies between 1 January 2008 and 31 December 2017. Extracted data included phase, disease type, intervention, study start year, and region. Trial type was classified as either a local study or a multiregional clinical trial as per the International Conference on Harmonisation E17 guideline. Results: Of 2488 phase I, 1855 phase II, and 1999 phase III trials included, the majority of phase I trials were local studies (76.8%), while the majority of phase II (66.0%) and phase III (72.2%) trials were multiregional clinical trials. The proportion of multiregional clinical trials showed an increasing trend for all phases (p \ 0.01). Although North America and Europe remained the main locations, increasing trends of inclusion of other regions, such as East Asia, were noted. Conclusion: Globalization of drug development is evident with the increasing trend of multiregional clinical trial. Regulatory authorities as well as the pharmaceutical industry should prepare for the evolving setting of clinical research and problems that can arise from these changes.

Evaluation of Drug Lags in Development Initiation, New Drug Application and Approval Between Japan and the USA and the Impact of Local Versus Multi-regional Clinical Trials

“…Conducting clinical trials in large market regions simultaneously and obtaining drug approvals at the earliest time point in other countries, including Japan, would be key to avoiding a drug lag, improving efficiency in research and development, and maximizing the market exclusivity period for pharmaceutical businesses [10]. Multi-regional clinical trials (MRCTs) have been widely utilized in recent drug development strategies [11]. The key aim of MRCTs is to conduct clinical trials across the world and launch the drugs simultaneously in major countries.…”

Asia‐Inclusive Clinical Research and Development Enabled by Translational Science and Quantitative Clinical Pharmacology: Toward a Culture That Challenges the Status Quo

“…With the recent regulatory reform in China together with the country joining ICH as a full regulatory member, early participation in clinical development of novel investigational agents is now feasible due to substantial streamlining of regulatory and administrative processes. This further opens up opportunities for decreasing drug lag in China through strategic planning for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E17 8 . Furthermore, a recent FDA guidance offers valuable points to consider for enhancing eligibility criteria and enabling more inclusive enrollment practices (including, but not limited to, race, ethnicity, and location of residency) in clinical trials 9…”

“…This scientifically guided methodology would take into account recent changes in the worldwide regulatory landscape that emphasize a science‐driven, patient‐centric approach. This approach accounts for growing diversity in the Western region, core principles of the recent ICH E17 guideline for MRCTs, 13,14 recent accelerated development and approval measures in Japan, 15 and regulatory reform in China 8,16 …”

“…This further opens up opportunities for decreasing drug lag in China through strategic planning for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E17. 8 Furthermore, a recent FDA guidance offers valuable points to consider for enhancing eligibility criteria and enabling more inclusive enrollment practices (including, but not limited to, race, ethnicity, and location of residency) in clinical trials. 9 We posit that this recent evolution of the global regulatory framework for clinical development is an opportunity for clinical pharmacologists to drive progress through robust scientific positioning of Asia-inclusive development strategies leveraging the foundational principles of our scientific discipline.…”

“…This approach accounts for growing diversity in the Western region, core principles of the recent ICH E17 guideline for MRCTs, 13,14 recent accelerated development and approval measures in Japan, 15 and regulatory reform in China. 8,16 Asia is a heterogeneous continent. In the context of this tutorial, we discuss drug development considerations applicable to the eastern and northern regions of Asia (i.e., Chinese, Korean, and Japanese ethnic populations).…”