Obstacles to oncology R & D in China
By: Helena Zhang, MD | December 10, 2015
China is gaining increasing attention as a destination for the development of innovative drugs, particularly in the field of oncology. This specialty is driven in large part by the rising occurrence of cancer due to widespread tobacco use, unhealthy lifestyles, and an aging population. One-third of global lung cancer cases and approximately one-half of all diagnoses of gastric, liver, and esophageal cancer cases now occur in China, and improving outcomes for these patients is a priority for the government and for the industry.
So far much progress has been made toward achieving this goal. The Major New Drug Innovation Program (MNDIP) which launched in 2009, lead to 52 compounds and 74 new drug certifications in the ensuing five years, and roughly half of the projects funded through the program involve oncology R&D. The Chinese government has also strengthened intellectual property rights and made regulations more attractive to spur global interest and investment in the marketplace.
These are all positive developments, however the country still faces many challenges in its quest to establish itself as a global leader in innovative oncology research. These challenges fall into four key categories:
1. Early-phase development and regulatory oversight
There is a growing number of innovative new drug developers headquartered in China. However this generation of developers are all still quite young and thus have little experience navigating the development process, or dealing with the risks and complexities involved in the early and late phase clinical trial process.
To ease the learning curve, the Chinese Center for Drug Evaluation (CDE) has been allocating resources to review trial applications to help improve innovative new drug submissions and streamline the application process. This has helped handle increasing number of drug clinical trial authorization (CTA) applications being submitted in the country, especially from domestic developers, suggesting this research is moving steadily forward. The drug development knowledge of local investigators is also increasing thanks to knowledge-sharing with global pharmaceutical companies working at Chinese trial sites.
At the same time, China Food and Drug Administration (CFDA) is actively reforming the regulatory framework for conducting clinical trials and is likely to further adjust its policies in step with advances in early-phase research and oversight of increasing Investigator initiated trials (IITs).
Overall, the clinical trial environment in China has improved over the past five years as the thanks to significant efforts on the part of the government, but more work needs to be done to build the maturity and accessibility of the clinical development ecosystem.
2. Immature application of pharmacogenomic and biomarker-driven studies
In recent years, the Human Genetic Resource Administration of China (HGRAC) has begun tightening requirements of genomic samples and electronic data export in response to concerns about resources coverage, intellectual property rights, and national security in R&D activities. Currently, licensed institutions in China are the only entities that can legally collect, store, and provide human genetic resources. Because pharmacogenomics clinical research in China is still in an early stage, there isn’t sufficient data to validate their use within a clinical setting. As a result, many studies face the kinds of challenges you would expect in such a situation: immature testing methodologies inadequate sample size, poor repeatability of biomarker assay results among sites, and ethical concerns.
It will take time to develop the level of maturity in these studies with higher quality, more standardized biomarker measurement methodology. CDE could fast-track this process by partnering with its regulatory peers in the USA and Europe, and participating in events, such as the Advanced Clinical Trial Workshop China (ACT China), which provides a platform for the spread of regulatory ideas and practices by bringing representatives from the CFDA, US Food and Drug Administration (FDA), and the European Medicines Agency (EMA) together. At ACT China 2013, for example, participants discussed the way forward for biomarker-driven targeted drug development in China. The Chinese Society of Clinical Oncology (CSCO) also has a biomarker committee and exchanges ideas with its global peers.
3. Insufficient site networks
China can clear another bottleneck by developing more advanced site network-building skills, perhaps by modeling the efforts taken in other nations. The CFDA has already accredited more than 200 good clinical practice (GCP) oncology trial sites, but that is just a fraction of the oncology trial sites available in other countries. In the USA, for example, the National Cancer Institute’s Clinical Trials Cooperative Group Program includes 3,100 institutions and 14,000 investigators. If China wants to become a global engine of cancer research it needs to invest in trial site infrastructure. One example of a successful oncology site network group is the China Thoracic Oncology Group (CTONG), whose goal is design multicenter clinical trials, while promoting standardization, modernization, and improve treatment and diagnosis.
4. Inconsistent data quality
The issue of data quality has become a rate-limiting factor in drug development in China, and is negatively affecting the ability of regulators and investigators to objectively assess efficacy and safety. If China wants to establish itself as a global leader in oncology development, it must do more to regulate data management and ensure the authenticity and integrity of data.
Key to this transformation is education for clinical trial investigators on how to follow GCP principles, and record their activities in a timely manner. Independent clinical event committees (CECs) and data monitoring committee (DMCs) must also be expanded to mitigate data quality risks in the country.
Each of these issues represent significant obstacles for China, but they can be overcome through continued investment in efforts to advance the knowledge, skillsets, and infrastructure of the Chinese clinical trial environment. Strong collaborations with government, academic and industry, and a willingness to adopt best practices from the global marketplace will spur progress and help the nation achieve its long term oncology research goals.