(B-071) Uncertainty in Pre-approval and Post-approval Clinical Evidence of Drugs Granted Conditional Approval in China

Background: Conditional approval permits the regulatory agency to authorize novel therapies with clinical data that could predict their clinical benefit. Post-approval evidence should solve the remaining uncertainties among pre-approval evidence.

Objectives: To investigate the uncertainties in pre-approval pivotal studies and post-approval confirmatory studies underlying regulatory authorization of conditional approvals in China.

Methods: In this retrospective observational study, we identified all drug indications granted conditional approval in China between 2017 and 2023. The primary endpoints were the uncertainties in clinical evidence supporting conditional approvals and their conversion by 31 October 2024, as measured by the involvement of the Chinese population, consistency between approved indication and trial population, and documented overall survival benefits or quality of life improvement. We adopted descriptive analysis to compare the uncertainties in pre-approval pivotal trials and post-approval confirmatory trials.

Results: From 2017 to 2023, 127 new drug indications were granted conditional approval in China. Of them, 107 (82.3%) and 113 (89.0%) had pre-approval pivotal trials and post-approval confirmatory trials recruited Chinese population, respectively; the population in 44 (34.6%) confirmatory trials was inconsistent with that described in the conditionally approved indications and pivotal trials. By 31 October 2024, after a median follow-up of 41.4 months (range: 31.4 to 56.5 months), 45 (35.4%) indications had at least one pivotal or confirmatory trial with survival benefits or quality of life improvement over the control arm, respectively.

Conclusions: A third of drug indications had documented clinical benefits for the Chinese population at 3.5 years after conditional approval. However, uncertainties remained in other conditionally approved indications, principally on expanding population in the confirmatory trials and unverified clinical benefits. Regulators should disclose the rationale for converting conditional approvals based on extrapolation to avoid neglecting populations with limited evidence.