Correlation between clinical trial endpoints of marketed cancer drugs and reimbursement decisions in China

Abstract

ObjectiveThis study aimed to assess whether different clinical trial endpoints in pivotal trials of cancer drugs were associated with reimbursement decisions in China.Materials and methodsCancer drugs marketed before June 30th, 2021 with publicly available technical review reports for application of drug registration on Center for Drug Evaluation (CDE) website were reviewed. The trial design characteristics and relevant clinical outcomes [e.g., overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)] were extracted from the technical review reports, while the reimbursement decisions were reviewed from National Healthcare Security Administration (NHSA) website. The differences in trial characteristics and clinical outcomes between drugs with positive reimbursement decisions and negative ones were compared by hypothesis test (Pearson's chi-squared test, Fisher's exact test, independent samples t-test and Mann-Whitney U test). The correlation between different clinical trial endpoints and reimbursement decisions was analyzed by multivariate logistic regression.ResultsThere were 112 cancer drug indications included in this study. Among these indications, 76 received a positive reimbursement decision, and the most common primary endpoints of them were PFS (42.1%) and ORR (30.3%). Taking PFS (OR = 7.333) and ORR (OR = 5.271) as the primary endpoints were more likely to receive a positive reimbursement decision compared with OS (P = 0.003). The proportion of drugs marketed with phase I (75.0%) and phase II (85.7%) clinical trials receiving positive reimbursement decisions are significantly higher than those marketed with phase III clinical trials (61.3%, P = 0.043). The magnitude of clinical benefit only had subtle influences (Prisk benefit − OS = 0.627, Prisk benefit − PFS = 0.087, Psurvival benefit − OS = 0.545, Psurvival benefit − PFS = 0.189) on the drug reimbursement decisions, however, the drug prices and clinical needs also made a difference on that.ConclusionThis study found that, in Chinese drug price negotiations from 2017 to 2021, policymakers have focused more on meeting clinical needs and filling therapeutical gaps in National Reimbursement Drug List (NRDL), while requirements for the selection of primary endpoints, clinical trial phases, and clinical benefits have been reduced. In the future, emphasis should be put on the use of surrogate endpoints and clinical benefits.

Price negotiation and pricing of anticancer drugs in China: An observational study

“…Indeed, most of the indications supported by single-arm clinical trials were approved through conditional approval, which was specialized for the approval of health technology treating serious and life-threatening diseases without available effective treatments. This finding was consistent with the previous study, which concluded that Chinese health authorities have placed a high priority on meeting clinical needs and addressing therapeutic gaps in the NRDL while reducing the requirements for clinical trials [ 33 ]. Nevertheless, extra attention could be paid to addressing the uncertainty of clinical evidence or accounting for the strength of clinical evidence when setting pricing strategies in China.…”

Integrating China in the International Consortium for Personalized Medicine: A Position Paper on Personalized Medicine in Sustainable Healthcare

“…Because complex patients are simultaneously affected by different conditions, they require multiple diagnostic tests and clinical examinations by various specialists, taking care of the person as a whole rather than just as a sum of different conditions [60]. Policymakers will need to address this when dealing with reimbursement forms, elaborating new schemes that keep this into account, building up a solid and personalized network revolving around each patient, fostering collaborations of medical and nonmedical professionals toward common goals, crossing the borders of academic institutions and national countries, to access the largest amount of information and competencies available [61,62].…”

The correlation between the costs and clinical benefits of national price-negotiated anticancer drugs for specific cancers in China

“…We can observe that, concerning the magnitude of OS and PFS gains, high prices might not explicitly yield the equivalent benefit regardless of the implementation of negotiation policy. In fact, to accelerate the launch and access to drugs of treatment shortage in the reimbursement list, policymakers put an increasing emphasis on the clinical consequences or cost-effectiveness of drugs rather than the quality of evidence [ 35 ], resulting in almost a quarter of launched drugs to be approved based on surrogate endpoints rather than the most reliable OS outcome [ 14 ]. Other countries were confronted with the same dilemma [ 36 , 37 ].…”