Health technology agencies' reimbursement decisions for cancer drugs across four high-income countries.

Abstract

e23037 Background: For people with advanced cancer, alternative endpoints such as progression-free survival (PFS) often correlate poorly with meaningful outcomes including overall survival (OS) and quality of life (QOL). Health technology assessment (HTA) decisions may vary significantly between countries. As global regulators move towards convergence of drug approval decisions, it is important to understand how decisions for funding differ between jurisdictions, particularly for drugs without clear improvements in OS or QOL. Methods: We conducted a retrospective cohort study of trials used for FDA approval of cancer drugs to treat adult solid tumors from 2010 to 2021 with time-to-event endpoints. Trials were cross-referenced with HTA decisions in Canada, England, Australia, and Singapore. The unit of analysis was a drug-indication pair. The primary outcome was the HTA reimbursement decision across countries for FDA-approved drug-indication pairs, analysed according to the statistical significance of OS and PFS results. The secondary outcome was differences in time to HTA reimbursement decision across countries and by endpoint type and significance. Odds ratios (ORs) with 95% CIs were used to compare the odds of approval with Canada as the referent. Results: Of 141 FDA-approved drug-indication pairs, 66% (Canada), 69% (England and Australia), and 81% (Singapore) were given positive reimbursement decisions. Canada had the highest proportion of indications not submitted for evaluation (28%), followed by Australia (18%) and England (14%). Across all four jurisdictions, 60 indications (42%) were mutually approved, with an additional eight consistently not recommended for reimbursement or not submitted. Of 141 pairs, 79 had significant PFS and OS results, with similar recommendation rates. Singapore was significantly more likely than Canada to give a positive reimbursement decision for drugs demonstrating PFS benefit without OS improvement (OR for rejection 0.25, p=0.005). Mean decision delays versus the FDA were 16.1, 29.6, and 21.2 months in Canada, England, and Australia, respectively. Decision times did not differ by OS versus PFS benefit across countries. Conclusions: Regulatory decision-making differed substantially across the four publicly funded systems, reflecting heterogeneity in HTA priorities and governance. These findings underscore the limits to regulatory convergence, particularly in predicting downstream reimbursement outcomes. Approval timelines were not influenced by the presence of an OS benefit, suggesting that factors beyond endpoint significance and clinical benefit shape funding decisions.