Challenges with integrating early-stage cancer trial endpoints into economic models: review of health technology recommendations for adjuvant or neoadjuvant therapies in Canada.

Abstract

Objectives: Adjuvant and neoadjuvant therapies for early-stage cancers demonstrate early clinical benefit in delaying disease recurrence. Health technology assessments require economic evaluations modeling lifetime disease trajectories. We examined modeling approaches used in Canadian health technology reviews to understand relevant challenges and identify opportunities for methodological improvements.

Methods: From CDA-AMC reimbursement recommendations for adjuvant/neo-adjuvant treatment of solid tumors, we collected outcomes and details of submitted clinical and economic evidence. We classified issues raised during economic review related to data maturity, surrogacy, treatment pathways, and assumptions surrounding extrapolation, duration of benefit and cure.

Results: Reviews from Jul/2015-Mar/2023 were identified. Reimbursement was recommended in 14/18 (78%) reviews. All assessments described OS as immature. Most (9/10, 90%) reviews with interim comparative OS data recommended reimbursement, while several (3/8, 38%) without OS data were not recommended. CDA-AMC revisions changed implications for cost-effectiveness ($50,000/QALY threshold) in 10/18 (56%) reviews. Duration of benefit assumptions was inconsistent among both submitters and reviewers. Cure-time was consistently revised to ≥5 years from initiation.

Conclusions: Despite surrogate endpoints and immature survival data, positive reimbursement recommendations were common. CDA-AMC re-analyses frequently had modest impacts on cost-effectiveness. Further guidance is needed to capture benefits and assess uncertainties with more consistency for early-stage cancers.