CERTAINTY OF EFFECTIVENESS EVIDENCE SUPPORTING ORPHAN DRUG APPROVALS IN CHINA...
Author(s)
Jieying Zhang, Doctor's degree1, Lei Gu, master's degree1, Caixia Liu, master's degree1, Ye Yang, master's degree2, Ningying Mao, doctor's degree3, Jun Li, master's degree1.
1China pharmaceutical university, Nanjing, China, 2China Pharmaceutical University, Nanjing, China, 3China Pharmaceutical University, Nanjing, China.
1China pharmaceutical university, Nanjing, China, 2China Pharmaceutical University, Nanjing, China, 3China Pharmaceutical University, Nanjing, China.
OBJECTIVES: To assess the certainty of effectiveness evidence supporting orphan drug approvals in China and quantify the main sources of uncertainty.
METHODS: We conducted a retrospective regulatory study using review reports from China’s Center for Drug Evaluation. Drugs approved from January 1, 2016 to December 31, 2025 were screened if their approved indications were included in China’s national rare disease catalogues. For each approval, pivotal effectiveness evidence was extracted, core study design was classified, and certainty was assessed using a prespecified modified GRADE framework.
RESULTS: A total of 75 drug-indication approvals were included, covering 60 drugs and 44 rare diseases. Priority review was granted to 56 approvals (74.7%), and 16 approvals (21.3%) received conditional approval. Pivotal effectiveness evidence consisted of ≥2 randomized controlled trials (RCTs) in 42.7%, one RCT plus one single-arm study in 5.3%, single-arm evidence only in 16.0%, and one RCT only in the remaining 36.0%. Final certainty of evidence was moderate in 20.0%, low in 50.7%, and very low in 29.3%, with no approval retaining high certainty. The most frequent downgrading domains were indirectness (97.3%), imprecision (56.0%), and risk of bias (40.0%). Indirectness was mainly driven by reliance on overseas or bridging evidence (90.7%) and surrogate endpoints (22.7%), while imprecision was mainly driven by small sample sizes (48.0%). Conditionally approved indications had a higher proportion of very low certainty than non-conditionally approved indications (56.2% vs. 22.0%).
CONCLUSIONS: The certainty of effectiveness evidence supporting orphan drug approvals in China was generally limited, mainly due to evidence extrapolation, limited Chinese patient data, small samples, and surrogate endpoints. Regulatory flexibility can accelerate access in areas of high unmet need, but should be paired with clearer mechanisms for managing residual uncertainty and indication-specific post-approval evidence generation.
METHODS: We conducted a retrospective regulatory study using review reports from China’s Center for Drug Evaluation. Drugs approved from January 1, 2016 to December 31, 2025 were screened if their approved indications were included in China’s national rare disease catalogues. For each approval, pivotal effectiveness evidence was extracted, core study design was classified, and certainty was assessed using a prespecified modified GRADE framework.
RESULTS: A total of 75 drug-indication approvals were included, covering 60 drugs and 44 rare diseases. Priority review was granted to 56 approvals (74.7%), and 16 approvals (21.3%) received conditional approval. Pivotal effectiveness evidence consisted of ≥2 randomized controlled trials (RCTs) in 42.7%, one RCT plus one single-arm study in 5.3%, single-arm evidence only in 16.0%, and one RCT only in the remaining 36.0%. Final certainty of evidence was moderate in 20.0%, low in 50.7%, and very low in 29.3%, with no approval retaining high certainty. The most frequent downgrading domains were indirectness (97.3%), imprecision (56.0%), and risk of bias (40.0%). Indirectness was mainly driven by reliance on overseas or bridging evidence (90.7%) and surrogate endpoints (22.7%), while imprecision was mainly driven by small sample sizes (48.0%). Conditionally approved indications had a higher proportion of very low certainty than non-conditionally approved indications (56.2% vs. 22.0%).
CONCLUSIONS: The certainty of effectiveness evidence supporting orphan drug approvals in China was generally limited, mainly due to evidence extrapolation, limited Chinese patient data, small samples, and surrogate endpoints. Regulatory flexibility can accelerate access in areas of high unmet need, but should be paired with clearer mechanisms for managing residual uncertainty and indication-specific post-approval evidence generation.
Conference/Value in Health Info
2026-09, ISPOR Asia Pacific 2026, Bangkok, Thailand
Value in Health, Volume 55, Issue S1
Code
HPR26
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling, Coverage with Evidence Development & Adaptive Pathways
Disease
SDC: Rare & Orphan Diseases