Ethnobridging for Accelerated Global Drug Development
Asian markets, particularly Japan, China, and South Korea, offer tremendous growth opportunities for the biopharmaceutical industry. Japan is the world’s second largest pharmaceutical market, and is growing at a faster rate than markets in the United States and the European Union. China is poised to become the fifth or sixth largest market, and some projections suggest it will emerge as the world’s biggest by 2050. In addition, estimates indicate that clinical research in China and South Korea for global drug development is increasing at a hefty annual pace of 25% and 30% respectively.
These are compelling statistics for pharmaceutical and biotechnology companies considering strategies for expanding market share in these Asia-Pacific countries and around the globe. However, establishing and growing a footprint in these markets comes with significant challenges that must be addressed.
• The timely conduct of clinical trials
• Collection of clinical data
• Adherence to complex regulatory issues
• The possibility that ethnic variability can influence the safety and efficacy of medicines
The fact is that risk/benefit ratios of investigational compounds can measurably differ between Asian populations and their non-Asian counterparts. PAREXEL® Early Phase has a global infrastructure with more than a decade of experience in initiating and conducting pharmacokinetic studies in healthy volunteers of Japanese, Chinese, and Korean descent. Through our practice of ethno-bridging (a term coined by PAREXEL to describe ethnic sensitivity studies), we generate clinical pharmacology data from these Asian populations, but the studies take place outside of Asia in dedicated, accredited Los Angeles and London research sites where we have access to large ethnic Asian populations.
PAREXEL offers companies looking to expand their global footprint via bridging studies of Asia-Pacific populations:
• Unmatched expertise in the diverse regulatory guidelines of various Asia-Pacific countries
• In-depth understanding of the specifics needed to submit a complete clinical data package that is acceptable to regulatory agencies in the region
• Access to the world’s largest concentrations of Asia-Pacific populations outside of their countries
This is the basis of our global clinical development strategy to expedite timelines and lower costs.
Ethno-bridging: A global clinical development strategy
In 1998, the International Conference on Harmonisation (ICH) implemented the E5 guideline, which allows for the performance of a supplemental clinical trial known as a bridging study. The purpose of the bridging study is to provide pharmacodynamic, pharmacokinetic, or clinical data that will enable extrapolation of foreign clinical data to “new” ICH regions. In other words, clinical trial data from Western countries could be extrapolated to Asian regions, and used for submission purposes, depending upon the results of bridging studies.
Ethno-bridging studies can shorten development times significantly
The limited clinical data generated by bridging studies in Asian populations are meant to accelerate development timelines by evaluating:
• Dosing regimen
In Asia-Pacific countries, particularly Japan, the intent of bridging studies is to reduce the “drug lag”—the four or five extra years it typically takes to complete clinical development in the region as compared to Western countries. The problem persists, but with ethno-bridging, our global clinical development strategy, timelines can be compressed significantly.
Our pioneering ethno-bridging approach starts in Phase I as part of the global drug development plan and is composed of two key elements:
• Studying Japanese, Chinese, and Korean populations in clinical trials taking place outside of their home countries, such as in the U.S. and Europe where clinical development is initiated but the protocols comply with regulations of the native countries and the resulting clinical trial data are acceptable to native country regulators.
• Studying all requisite global populations at once instead of waiting until the non-Asian studies are completed before starting bridging studies in Asian countries.
To implement this strategy, PAREXEL Early Phase has established operations in various locations worldwide where there are substantial populations of recently immigrated Asians. This effort is spearheaded by our research sites in Los Angeles, California and London, England, which are home to the largest populations of first generation Asians outside of Asia. Access to these populations is critical to our global clinical development strategy as several Asia-Pacific regulatory agencies have strict definitions of who is “Japanese”, “Chinese”, or “Korean”—meaning that only individuals who conform to those definitions can be recruited for ethno-bridging studies.
Start ethno-bridging in Phase I
By including Asian subjects starting in Phase I, it is possible to detect ethnic variations early on compared to Western subjects—such as differences in pharmacokinetics related to drug metabolism, absorption, distribution, elimination, safety, tolerability and pharmacodynamic profiles. Collecting this information earlier is a significant advantage. It means that sponsors can plan accordingly for later phase studies instead of taking the slower and more costly route of waiting until Phase II or Phase III to uncover the same information. This critical information adds significant value to the compound being studied, attracting potential co-development and licensing opportunities.
PAREXEL—expertise and resources
Since the mid-1990s, we have been building an infrastructure to conduct and manage clinical trials for our clients involving large-scale Asian populations in communities outside of Asia. Our most recent book on this topic is entitled Accelerating Global
Drug Development – The Science and Practice of Ethno-bridging. We have also become familiar withthe regulatory requirements for all types of submissions,including marketing applications.
Our dedicated Asian recruitment teams in London and Los Angeles are able to recruit from large Japanese, Korean and Chinese populations within the required timeframes for early phase studies. In addition, our clinical staff at both lead ethno-bridging sites are sensitive to the cultural needs of male and female volunteers of all three Asian cultures—ensuring that residential, entertainment, foods and other needs of test subjects are met.
Our leadership team has decades of experience in ethnically-sensitive clinical trial testing, and our lead sites in Los Angeles and London have successfully conducted many Phase I ethno-bridging studies for Western and Japanese/Asian pharmaceutical companies. These studies have enrolled more than 2,000 Asian subjects. We average 20 ethno-bridging clinical trials per year, and data collected by PAREXEL have consistently been accepted by Japan’s Pharmaceuticals and Medical Devices Agency.
Our research sites facilitate early phase clinical trial work by including a broad range of resources such as:
• Access to the largest populations of first generation Asians outside of Asia
• Experts who routinely consult with our biopharmaceutical clients to discuss their options for conducting
Phase I clinical trials in Asian populations in non-Asian locations, with emphasis on protocol design, regulatory issues, and data analysis
• A proprietary database that enrolls approximately 500 Japanese, Chinese, and Korean subjects annually
• A dedicated Asian enrollment team with experience in developing community outreach programs and various recruitment methods of healthy Asian subjects and Asian investigators to ensure timely enrollment
• Resources to translate informed consent forms into Asian language
PAREXEL’s extensive experience in conducting Phase I studies outside of Asia can provide you with a clear advantage. We collect data on Asian and non-Asian subjects at the same time, affording you greater opportunity to fast track clinical development because more is known about the compound sooner. This allows for better planning of Phase II and Phase III trials, globally. For more information about how PAREXEL can add value to your global clinical development program, contact us at: earlyphase@PAREXEL.com.