PMID- 37806812 OWN - NLM STAT- MEDLINE DCOM- 20231130 LR - 20240416 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 45 IP - 11 DP - 2023 Nov TI - Progress and Challenges of the New Conditional Approval Process in China: A Pooled Analysis From 2018 to 2021. PG - 1111-1118 LID - S0149-2918(23)00350-8 [pii] LID - 10.1016/j.clinthera.2023.09.006 [doi] AB - PURPOSE: To speed the review and approval of drugs and address pressing medical needs, China began to advocate for the implementation of the conditional approval process in 2017. We aimed to assess the implementation of the conditional approval process in China and further analyze its potential problems and future challenges. METHODS: This study examined the new drug approval with conditions in China between 2018 and 2021, based on an analysis of drug technical review documents from the Center for Drug Evaluation (CDE). Using publicly available information, we further analyzed the characteristics and results of pivotal clinical trials of conditionally approved drugs, postmarketing study requirements and progress. FINDINGS: Between 2018 and 2021, China conditionally approved 50 drugs, with 80% (40/50) being antineoplastic agents. Premarketing pivotal trials predominantly used single-arm clinical trials (83.7%, 41/49), while postmarketing trials mainly employed randomized controlled clinical trials (81.0%, 34/42). In oncology drugs, conditionally approved drugs with progression-free survival (PFS) and overall survival (OS) as primary endpoints achieved significant clinical value in terms of efficacy. However, there were also pivotal clinical trials with response rate (RR) as the primary endpoint that demonstrated lower clinical benefits (8.9% of drugs with RR below 20%). Safety analysis revealed substantial variations in the proportions of grade >/=3 adverse events (AEs) and serious adverse events (SAEs) across pivotal trials (Grade >/= 3 AEs: 9.0%-99.0%; SAEs: 8.0%-83.0%). For nononcology drugs, pivotal trials also demonstrated an acceptable risk-benefit ratio but exhibited methodological issues. Meanwhile, Most postmarketing studies lacked completion date restrictions (43.2%, 17/47), and no requirements were specified for the transition to full approval. Furthermore, surrogate endpoints were primarily utilized both pre- and postmarketing, but the rational selection of surrogate endpoints remains to be investigated. IMPLICATIONS: The conditional approval process expedites patient access to drugs for serious diseases. However, challenges pertaining to evidence assessment during approval and design flaws in postmarketing studies exist in China's conditional approval system, necessitating future improvements. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Li, Jinlian AU - Li J AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China. FAU - Wang, Haoyang AU - Wang H AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China. FAU - Hua, Yanzhao AU - Hua Y AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China. FAU - Liu, Yue AU - Liu Y AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China. FAU - Chen, Yi AU - Chen Y AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China. FAU - Jiang, Rong AU - Jiang R AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China; NMPA Key Laboratory for Drug Regulatory Innovation and Evaluation, Nanjing, Jiangsu Province, China. FAU - Shao, Rong AU - Shao R AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China; NMPA Key Laboratory for Drug Regulatory Innovation and Evaluation, Nanjing, Jiangsu Province, China. FAU - Xie, Jinping AU - Xie J AD - Institute of Regulatory Science for Medical Products, China Pharmaceutical University, Nanjing, Jiangsu Province, China; NMPA Key Laboratory for Drug Regulatory Innovation and Evaluation, Nanjing, Jiangsu Province, China. Electronic address: 1620214654@cpu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20231006 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Antineoplastic Agents/adverse effects MH - Biomarkers MH - China MH - Drug Approval/methods MH - United States MH - United States Food and Drug Administration MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Center for Drug Evaluation OT - Conditional approval process OT - National Medical Products Administration OT - New drug registration and review COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/10/09 00:42 MHDA- 2023/11/27 12:42 CRDT- 2023/10/08 21:59 PHST- 2023/02/05 00:00 [received] PHST- 2023/06/07 00:00 [revised] PHST- 2023/09/07 00:00 [accepted] PHST- 2023/11/27 12:42 [medline] PHST- 2023/10/09 00:42 [pubmed] PHST- 2023/10/08 21:59 [entrez] AID - S0149-2918(23)00350-8 [pii] AID - 10.1016/j.clinthera.2023.09.006 [doi] PST - ppublish SO - Clin Ther. 2023 Nov;45(11):1111-1118. doi: 10.1016/j.clinthera.2023.09.006. Epub 2023 Oct 6.