Clinical value and cost-effectiveness analysis of conditionally approved anticancer drugs in China from 2015 to 2023

The conditional approval (CA) process in China was established in 2015 to expedite access to urgently-needed drugs, however, the clinical benefits of CA drugs and potential gaps between pre-approval and confirmatory trials remain uncertain. Herein, we aim to compare the clinical values between CA and non-CA anticancer drugs from 2015 to 2023, and to explore the relationship between clinical benefit and average daily cost of treatment of drugs.

This retrospective study analyzed anticancer drugs first approved in China [2015-2023] using data from National Medical Products Administration (NMPA) and Center for Drug Evaluation (CDE). Daily treatment costs were derived from Pharmacodia, Yilian Pharmaceutical Procurement Database and provincial centralized pharmaceutical procurement platforms. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and complete remission/complete remission with partial hematological recovery (CR/CRh) were utilized as indicators of clinical benefit. Mann-Whitney U test was conducted to evaluate the differences among approval pathways and Pearson correlation coefficient was calculated to analyse the relationship between clinical benefit and daily cost of treatment.

There were 120 new anticancer drugs approved in China from 2015 to 2023, with 48.3% (n=58) granted CA. No significant differences in clinical benefits were observed between CA and non-CA drugs (pooled ORR: 59.3% vs. 62.7%, P=0.51; OS gains: 3.7 vs. 2.5 months, P=0.32; PFS gains: 5.3 vs. 3.3 months, P=0.33) and 23 (39.7%) drugs transitioned to routine review. For endpoints obtained in confirmatory trials, trials of 3 drugs used OS in their pivotal trials, 6 drugs used the same surrogate endpoints (ORR, CR/CRh, or PFS) in their pivotal trials, and 14 used different surrogate endpoints. Among the 3 drugs used OS in their confirmatory trial, 2 achieved clinical benefit [hazard ratio (HR) <0.75, P<0.05]; all of the 6 drugs used the same endpoints achieved clinical benefit in confirmatory trial (the ORR or CR/CRh of 3 increased ≥10%, 1 increased 0.5%, the lower limit of the PFS benefit confidence interval of 1 drug exceeded 1 month, meeting the bridging success standard, and the PFS of 1 drug was significantly extended); and among the 14 drugs used different surrogate endpoints, 10 demonstrated statistically significant clinical benefit. Economically, 62.1% (36/58) of CA drugs entered National Reimbursement Drug List (NRDL), and 34.5% (20/58) entered NRDL within 1.5 years, with NRDL-included drugs showing greater price reductions (53.22% vs. 10.64%, P<0.001). No significant correlation between drug prices and clinical benefits was found.

The CA process has facilitated innovation while addressing clinical needs. However, it is imperative for the policy to strike a balance between the urgency of clinical demands and the requirements for robust evidence. Furthermore, there is a current imbalance between the prices of drugs and their clinical value, necessitating further refinement of the pricing mechanism for innovative drugs.