Proceedings: DIA China 2019
DIA China 2019
Adaptive and Patient-Centric Designs and MRCTs:
Implications for Biostatisticians in China
Susan Wang
Biostatistics & Data Science Asia
Boehringer Ingelheim, Shanghai

Harry Hua
Principal Statistician
Biostatistics & Data Science Asia
Boehringer Ingelheim, Shanghai


cientific advances often seem to raise just as many questions as they answer. The rapidly changing landscape of clinical new drug development in China is introducing innovations and challenges (often at the same time) to statisticians working in this field. These currently include multi-regional clinical trials in compliance with ICH E17, as well as adaptive designs and master protocols, patient-centric drug development, risk-based monitoring, oncology dose escalation, and biomarkers in clinical trial design and data analysis, all in accordance with ICH E9.

Key Takeaways

  • NMPA efforts to synchronize and harmonize regulatory strategies and processes with those in other, more experienced agencies include encouraging use of adaptive designs in early stage clinical development.
  • While recognition of the value of patient-centric drug development in China continues to grow, development of patient-reported outcomes tools is also at a relatively early stage in China.
  • Global data from multi-regional clinical trials remain the most important element for drug approval in China.

As the pharmaceutical industry in China undergoes transformational change and uses more complex techniques to develop innovative drugs in hard-to-treat disease areas, biostatisticians with a degree of medical background will better understand medical needs and thus will better translate medical needs into statistical questions. This will demand a change of mindset for biostatisticians: to think more strategically, to communicate more effectively, and to better understand regulations—in other words, to become a developer of new drugs with a statistical background instead of an expert in numbers.

Multi-Regional Clinical Trials in China

Recent regulatory reforms have encouraged international pharmaceutical companies to include China into their multi-regional clinical trials (MRCTs). To meet the unmet medical needs of patients in China as well as patients in other countries through these trials, it is important to understand that:

  • Global data remain the most important element of drug approval in China.
  • Chinese patient subgroup data must show consistency with global population data; if it does not, the sponsor must communicate and explore potential reasons with the NMPA.
  • Sponsor should proactively discuss the Chinese patient sample size in the MRCT before the trial begins; PMDA guidelines from Japan may provide general methodology and guidance for such discussions in China.

Master Protocols and Adaptive Design

In the global drive to make drug development more efficient, US FDA has demonstrated a more open attitude toward adaptive designs, master protocols, and other clinical trial innovations, especially by releasing their 2018 draft guidance for industry Adaptive Designs for Clinical Trials of Drugs and Biologics. Since joining ICH in 2017, the NMPA in China has encouraged use of adaptive designs in early clinical development as part of their synchronization and harmonization with other, more experienced agencies such as FDA. Adaptive designs will bring many challenges, from conduct to analysis, for biostatisticians.

Patient-Centric Clinical Development

Due to concerns about their methodological rigor and scientific robustness, patient reported outcomes (PROs) remain an evolving field in China. Most PRO assessments in local clinical trials are copied from global trials. Industry and regulatory professionals in China will keep watch on FDA’s developing series of guidance documents on this topic. As clinical and regulatory processes continue to accelerate market access in China, most experts anticipate the PROs will play an important role in supporting value-based drug development in the future.