Disparities in the access to immune checkpoint inhibitors approved in the United States, the European Union and mainland China: a serial cross-sectional study

Jia-Xin Cai; Shi-Yu Wang; Hao Hu; Carolina Oi Lam Ung; Fu-Xiao Li; Teng-Fei Lin; Shi-Fu Luo; Hai-Bo Song; Zhi-Rong Yang; Jin-Ling Tang; Wei-Hua Meng

doi:10.1136/bmjph-2024-001995

Disparities in the access to immune checkpoint inhibitors approved in the United States, the European Union and mainland China: a serial cross-sectional study

BMJ Public Health. 2025 Mar 13;3(1):e001995. doi: 10.1136/bmjph-2024-001995. eCollection 2025.

Authors

Jia-Xin Cai^#^{1

2}, Shi-Yu Wang^#^{3

4}, Hao Hu^{5

6

7}, Carolina Oi Lam Ung^{5

6

7}, Fu-Xiao Li², Teng-Fei Lin³, Shi-Fu Luo^{2

8}, Hai-Bo Song^{9

10}, Zhi-Rong Yang^{2

3}, Jin-Ling Tang^{2

3}, Wei-Hua Meng^{1

11

12}

Affiliations

¹ Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, China.
² Department of Computational Biology and Medical Big Data, Shenzhen University of Advanced Technology, Shenzhen, China.
³ Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
⁴ Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁵ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China.
⁶ Centre for Pharmaceutical Regulatory Sciences, University of Macau, Taipa, Macao SAR, Macao.
⁷ Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China.
⁸ Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China.
⁹ National Center for ADR Monitoring, Beijing, China.
¹⁰ NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China.
¹¹ Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Dundee, UK.
¹² Center for Public Health, Faculty of Medicine, Health and Life Sciences, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.

^# Contributed equally.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionised antitumour therapy. However, regional differences in ICI labels, including the impact of the review process and supporting trial evidence, remain unclear.

Methods: We conducted a serial cross-sectional study to examine trends and differences in indication approvals and associated clinical trials for ICIs across different regulatory agencies. We searched ICI labels approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and National Medical Products Administration (NMPA) in Mainland China before 31 December 2022 and assessed the indications and clinical trials in labels. Relative lags of indication approvals were compared using the Mann-Whitney U test. The review time and interval between trial completion and indication submission were compared using the Kruskal-Wallis test.

Results: We collected 10 ICIs with 90 indications from the FDA, 10 ICIs with 70 indications from EMA and 16 ICIs with 65 indications from NMPA. Relative lags of ICI indication approval in China (median 344.0 (IQR 220.0, 688.0) days) were longer than in the European Union (118.5 (55.0, 189.0) days) (p<0.0001). Both the European Union (243.0 (191.0, 298.0) days) and China (283.0 (248.0, 339.5) days) demonstrated significantly longer review durations for ICI indications than the United States (181.0 (148.8, 191.8) days) (p<0.0001). While indication submissions to NMPA were significantly more delayed than those to the FDA (p<0.001), the former relied more on trial evidence of OS (84.0%) than the latter (58.0%).

Conclusion: ICIs approved in the United States, the European Union and mainland China differed in indications, approval time, review duration and evidence base, which may impact access to life-saving treatments. Future studies should investigate the impact of these differences and the underlying reasons beyond the evidence supporting the label approvals.

Keywords: Health Services Accessibility; Pharmacoepidemiology; Public Health.