REAL-WORLD DATA IN ORPHAN DRUG APPROVALS: A COMPARATIVE ANALYSIS OF THE UNITED STATES, CHINA, AND JAPAN
Author(s)
Jieying Zhang, doctor's degree, Lei Gu, master degree, Caixia Liu, master' degree, Ye Yang, master's degree, Ningying Mao, PHD, Jun Li, master's degree;
China pharmaceutical university, Nanjing, China
China pharmaceutical university, Nanjing, China
OBJECTIVES: To systematically review and compare the use of RWD in orphan drug marketing approvals across China, the US, and Japan, and to characterize jurisdiction-specific regulatory preferences and evidence trade-offs.
METHODS: Orphan drugs approved (2016-2025) were retrieved from official databases (NMPA, FDA, and PMDA) and public sources. Cases using RWD in approval reviews were included. Structured text analysis of regulatory documents (review reports, opinions, correspondence) focused on: (1) RWD sources, designs, and roles; (2) cross-national differences in the use of RWE for the same drug; (3) regulatory considerations and limitations related to RWD quality.
RESULTS: 61 orphan drug cases utilizing RWD were included: 6 (7 indications) from China, 23 (23) from the US, and 32 (33) from Japan. Regarding data sources, China relied on specific patient cohorts and overseas marketing experience (both 42.86%); The US favored natural population data (65.22%) and compassionate use/expanded access data (21.74%); Japan systematically integrated multiple RWD types, centered on active pharmacovigilance (36.36%), natural population data (30.30%), and registry studies (27.27%).For study design, China predominantly employed prospective (71.43%) or retrospective (42.86%) cohort studies; the US more frequently used external controls, particularly historical control studies (52.17%); Japan balanced both cohort and controlled studies. RWD primarily served a supplementary role (88.06%) but showed critical value in some new indication reviews. Variations in evidence combinations and regulatory requirements for the same drug submitted across different countries reflect differing priorities in data extrapolation and population representativeness. Analysis of regulatory documents identified 38 limitations related to RWD quality, primarily concerning insufficient population representativeness (17) and data integrity issues (17), followed by data accuracy (4) and timeliness (1).
CONCLUSIONS: RWD is integrated into orphan drug approval reviews in China, the US, and Japan, though notable cross-national differences in data sources, study designs, and evidence adoption. While primarily supplementary, RWD’s regulatory value is growing in specific contexts.
METHODS: Orphan drugs approved (2016-2025) were retrieved from official databases (NMPA, FDA, and PMDA) and public sources. Cases using RWD in approval reviews were included. Structured text analysis of regulatory documents (review reports, opinions, correspondence) focused on: (1) RWD sources, designs, and roles; (2) cross-national differences in the use of RWE for the same drug; (3) regulatory considerations and limitations related to RWD quality.
RESULTS: 61 orphan drug cases utilizing RWD were included: 6 (7 indications) from China, 23 (23) from the US, and 32 (33) from Japan. Regarding data sources, China relied on specific patient cohorts and overseas marketing experience (both 42.86%); The US favored natural population data (65.22%) and compassionate use/expanded access data (21.74%); Japan systematically integrated multiple RWD types, centered on active pharmacovigilance (36.36%), natural population data (30.30%), and registry studies (27.27%).For study design, China predominantly employed prospective (71.43%) or retrospective (42.86%) cohort studies; the US more frequently used external controls, particularly historical control studies (52.17%); Japan balanced both cohort and controlled studies. RWD primarily served a supplementary role (88.06%) but showed critical value in some new indication reviews. Variations in evidence combinations and regulatory requirements for the same drug submitted across different countries reflect differing priorities in data extrapolation and population representativeness. Analysis of regulatory documents identified 38 limitations related to RWD quality, primarily concerning insufficient population representativeness (17) and data integrity issues (17), followed by data accuracy (4) and timeliness (1).
CONCLUSIONS: RWD is integrated into orphan drug approval reviews in China, the US, and Japan, though notable cross-national differences in data sources, study designs, and evidence adoption. While primarily supplementary, RWD’s regulatory value is growing in specific contexts.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
RWD95
Topic
Real World Data & Information Systems
Topic Subcategory
Data Protection, Integrity, & Quality Assurance
Disease
SDC: Rare & Orphan Diseases