Leveraging early-phase ethnobridging to reduce drug lag in China and Japan

To bring therapies to the global market as efficiently as possible, drug sponsors must recruit diverse ethnic populations beginning in phase 1. Historically, Western-based developers have conducted all necessary trials and applied for marketing approval in the United States and Europe before initiating early-phase studies in Japan and China. This approach significantly delays patient access to innovative medicines — lags that may extend several years.

By integrating major Asian markets into clinical studies as early as possible, sponsors can streamline and accelerate global drug development. And while this can be accomplished through locating studies in mainland China or Japan, sponsors are increasingly capturing critical pharmacokinetic (PK) and safety data via ethnobridging: phase 1 studies conducted in Western clinical sites using Japanese- and Chinese-born participants who are living abroad. My Parexel colleagues and I coined this term about 20 years ago as we pioneered the design and operation of bridging studies as a cost-effective way to increase ethnic diversity among participants earlier in research. Ethnobridging allows developers to concurrently gather data from Asian, North American, and European cohorts while avoiding the regulatory and logistical hurdles of setting up early-phase offshore sites.

An accepted and expanding approach

The concept of bridging as it applies to clinical research was first outlined in the International Conference on Harmonization (ICH) E5 guidelines, which were adopted in 1998 by the United States, the European Union, and Japan. Given this long history, there is abundant evidence for acceptance of ethnobridging data by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). And while there is a shorter history of Chinese-population ethnobridging, we have seen China’s National Medical Products Administration (NMPA) approve phase 2 and 3 multi-regional clinical trials based on early-phase ethnobridging data. 

Modern regulatory frameworks allow for generation of data via ethnobridging from the start of development, such as first-in-human Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies. To qualify for an ethnobridging study, a participant must have been born in the study’s country of interest and their parents and maternal and paternal grandparents must have also been born in that country. Additionally, participants must have lived outside of their country of birth for fewer than 10 years and without major changes in lifestyle, including diet — a significant factor among many extrinsic factors that can affect drug response. When focused on Chinese and Japanese participants, ethnobridging is most successful in Western cities with large Asian populations, such as London or Los Angeles.

Considerations for success

Over the last two decades, Parexel has conducted more than 300 ethnobridging studies in our early-phase clinical units (EPCUs). Data from these studies has met Japanese phase 1 requirements, earning PMDA acceptance. Regulators in China demonstrate an increasing willingness to accept ethnobridging data as well. We saw this recently when Parexel supported a sponsor’s clinical trial application (CTA) for launching a later-phase study in China without in-country phase 1 data. To satisfy NMPA requirements, we conducted a study in the U.S. with both Chinese- and U.S.-born volunteers who received varying doses of the investigational product. Using data from that study, we helped prepare the pre-CTA briefing document, justifying the safety of the product in Chinese patients. We also addressed specific questions about dose selection.

Based on this work and the resulting evidence, the NMPA’s Center for Drug Evaluation (CDE) accepted the sponsor’s pre-CTA meeting request and approved a later-phase study, saving significant cost and cutting the product’s development timeline by 6 – 12 months. 

In our experience, sponsors who want to pursue Chinese ethnobridging should engage early with the NMPA to present and discuss the scientific rationale for potential ethnic differences in the pharmacology of the investigational drug. Like the FDA in the U.S., China’s CDE offers three types of consultation meetings: 1, 2, and 3, which correspond to the FDA’s type A, B, and C consultations. NMPA guidance adopted in 2018 allows for the conditional acceptance of foreign clinical data to support Chinese registration for investigational products including but not limited to orphan drugs, drugs for unmet medical needs in China, and drugs for pediatric use. Foreign data must address the safety and efficacy of the product as it applies to Chinese patients with considerations for ethnic differences. 

When conducting an ethnobridging study, carefully consider whether inclusion/exclusion criteria will select subjects who are truly representative of China’s population. Sponsors should also consider how operational infrastructure can be designed to accommodate Chinese-born participants. This should include hiring bilingual staff, developing Chinese-language informed consent documents, and accommodating a typical Chinese diet at study sites.

By including multiple ethnic populations in phase 1 studies, sponsors can address ethnicity-specific safety risks early in research and speed delivery of critical medicines to global regions. But to maximize the value of ethnobridging, particularly to support Chinese CTAs, sponsors must collaborate closely with subject matter experts and regulators, ensuring that study designs, protocols, analytical methods, and ethnobridging strategies meet each country’s individual requirements.

For biotech companies with global ambitions, ethnobridging offers a practical way to generate the ethnic diversity data that Asian regulators require — without the cost and complexity of setting up separate phase 1 sites in China or Japan. Because we’ve long been at the forefront of ethnobridging in Asian populations, Parexel’s experts have a deep understanding of this practice and its importance within early development. Learn how we can partner with you to design and execute ethnobridging studies that meet the varied needs of all stakeholders, from regulatory authorities to study participants.

Connect with our early phase experts to explore how ethnobridging can accelerate your development timeline

Start a conversation

Explore more episodes