(035) Study Design Considerations for Real-world Observational Studies Supporting Pre-Approval Regulatory Decision-making in China

Background: Both industry and regulatory authorities in China are exploring the potential of using real-world evidence (RWE) to support regulatory decision-making. This interest was sparked by the launch of the Boao Lecheng International Medical Tourism Pilot Area in 2019 (which permits the use of innovative drugs that have been approved abroad but not yet in China, paid by patients, allowing for real-world data on those pre-approved drugs) and the release of the first RWE technical guideline by the Chinese National Medical Products Administration (NMPA) in 2020. Although previous literature has provided an overview of using RWE for drug regulatory decisions, there is limited information on how those real-world studies were designed.

Objectives: To summarize the key study design characteristics of real-world studies considered by regulatory authorities in China in the new drug or indication approval.

Methods: We began by searching for approved drug products, in which RWE was considered during the approval process, from publicly available sources released by regulatory authorities as of the end of 2023, including government documents and official government news. We then extracted study design characteristics from relevant publications found through PubMed or Google Scholar and product assessment reports from The Center for Drug Evaluation of NMPA through a manual review.

Results: As of 2023, 9 drug products were approved with the support of RWE (new drug approval: n=7; new indication approval: n=2). These products covered seven therapeutic areas, the most common one being oncology (n=3).
Three products used historical cohorts: 2 using medical charts to assess off-label use in hospitals for new indication approval and 1 using secondary databases from Taiwan national insurance claims and Hong Kong electronic medical records for new drug approval in mainland China. All these retrospective studies were comparative by including untreated patients or patients treated with standard of care, except for 1 chart review study, which described the safety profile for pediatric label expansion.
The real-world studies for the other 6 products used a prospective cohort study design and were all conducted in the Boao Lecheng pilot area. The sample sizes ranged from 9 to 46 patients and no hypothesis testing was conducted.
The primary outcomes for the real-world studies of 8 products were effectiveness measures, whereas the primary outcome for the pediatric label expansion study was safety.

Conclusions: The regulatory authorities in China could consider RWE to support the pre-approval decision-making for drug products, given that data come from reliable sources that represent the Chinese population. However, case-by-case discussion with the regulatory authorities is encouraged.