Progress in Clinical Pharmacology in China: An Ongoing Evolution

Abstract

The landscape of clinical pharmacology research in China has continued to evolve in 2024, shown by research advancements in physiologically based pharmacokinetics (PBPK), regulatory science, and a growing emphasis on precision medicine (Figure 1). In this editorial, we reflect on the progress achieved since the Clinical Pharmacology & Therapeutics (CPT) editorial on China in early 2024,¹ showcase key research contributions, and envision a path forward for continued innovation and advancement.

The study by Xu et al. in this issue analyzes the landscape of novel drug approvals in China, analyzing 240 novel drugs approved by the National Medical Products Administration (NMPA) between 2018 and 2022.² This research reveals insights into the efficacy evidence supporting these approvals, emphasizing the regulatory flexibility granted under special programs such as conditional approvals and priority reviews. Importantly, the study highlights that innovative drugs predominantly relied on a “one pivotal trial” or “one pivotal trial plus supportive evidence” framework for efficacy demonstration. This streamlined approach underscores the impact of regulatory reforms in expediting drug development while maintaining rigorous evidence standards.

Moreover, Xu et al. identify significant differences in trial design between innovative and imported original drugs, with the latter often relying on larger datasets and multi-regional clinical trials (MRCTs).² The analysis of supportive evidence—ranging from additional studies to mechanistic and real-world evidence—further underscores the importance of integrating diverse data sources to build a robust “totality of evidence” framework. These findings are instrumental in shaping China's evolving regulatory landscape and offer a blueprint for improving drug assessment processes globally.

A recent paper by Sia and coworkers investigated aging-related changes in CYP3A function among older Chinese patients.³ The research employs amlodipine as a probe substrate and reveals that frailty—rather than chronological age—is a key determinant of CYP3A activity. Frail patients exhibited a 63% reduction in CYP3A abundance, leading to a 37% increase in plasma amlodipine exposure. These findings have important implications for dose optimization in geriatric populations, calling the attention for biologically informed approaches to drug therapy in older adults.

The integration of PBPK modeling in this study provides a powerful tool for simulating clinical scenarios and personalizing drug regimens.³ By offering actionable insights into the metabolic variability among older adults, this research advances the field of geriatric pharmacology and sets a precedent for integrating frailty metrics into clinical decision making and regulatory evaluations.

Building on the momentum of these contributions, Zhang et al. present an innovative study on the distribution and influencing factors of drug-metabolizing enzymes (DMEs) and transporters (DTs) in the gastrointestinal tract of healthy Chinese individuals.⁴ This comprehensive analysis identifies regional variations in protein expression, with CYP3A4 predominating in the small intestine and CYP2C9 in the colon. The study also highlights the role of body mass index, genotype, and microbiota composition in shaping individual variability, offering critical parameters for refining PBPK models tailored to the Chinese population.

The implications of these findings extend beyond academia, providing a foundation for more precise PK predictions for drug development. By elucidating the interplay between physiological, genetic, and microbial factors, this research paves the way for developing personalized therapies that address the unique needs of Chinese patients.

Recognizing the importance of fostering collaboration and knowledge exchange, CPT has spearheaded several initiatives to support the Chinese clinical pharmacology community. The webinar on “Publish or MedRxiv: How to Increase Success of Publishing in CPT,”⁵ conducted in 2024, attracted over 70 participants, providing practical guidance on manuscript preparation and navigating the peer-review process. These efforts have been instrumental in empowering researchers to disseminate their findings on a global stage.

Furthermore, CPT's engagement with the International Symposium in Quantitative Pharmacology (ISQP) has facilitated meaningful dialogue on research priorities and best practices.⁶ These initiatives reflect CPT's commitment to fostering a global community of clinical pharmacologists and bridging gaps in knowledge and practice.

Despite the significant progress, challenges remain. The underrepresentation of specific demographics, such as pediatric and elderly populations, in clinical trials necessitates focused research to ensure the generalizability of findings. An example is the study by Wang and coworkers from the Wuhan Children's Hospital, who determined the optimal trough concentration of tacrolimus in pediatric patients with primary nephrotic syndrome.⁷ Additionally, integrating multi-omics data, such as genomics, proteomics, and metabolomics, is crucial for unraveling the complex mechanisms underlying drug responses. Additionally, using artificial intelligence to integrate large amount of data in diversity is an inevitable future step to transform clinical pharmacology. Regulatory frameworks must evolve to incorporate these advancements, emphasizing transparency and collaboration among stakeholders.

Moreover, the establishment of systematic guidelines for evidence requirements—including the number and types of pivotal trials and the application of supportive evidence—is essential for harmonizing regulatory standards. China's commitment to the “totality of evidence” concept offers a promising framework for achieving this goal, and continued investment in education and training programs will be critical for building capacity in regulatory science and clinical pharmacology.

As the field of clinical pharmacology continues to evolve, the role of journals such as CPT in amplifying impactful research and fostering collaboration cannot be overstated. The studies highlighted in this editorial exemplify the innovative spirit and collaborative ethos driving clinical pharmacology research progress in China. By building on these achievements and addressing the challenges ahead, the global community can ensure that the advancements in clinical pharmacology continue to benefit patients worldwide.

The progress in clinical pharmacology in China, as reflected in the work presented in this and recent issues of CPT,^2-4 underscores the power of collaboration and innovation. These contributions not only enhance our understanding of drug PK and efficacy in specific populations, but also pave the way for precision medicine and regulatory excellence. As we look to the future, it is imperative to sustain this momentum, fostering a global ecosystem of clinical pharmacology that drives innovation and improves health outcomes for all.

No funding was received for this work.

The authors declared no competing interests for this work.