Life-cycle health technology assessment (HTA) requires an index economic model to establish how estimated cost-effectiveness evolves with emerging evidence. We developed an open-source index economic evaluation of entrectinib, a tumor-agnostic therapy with conditional market authorization. Our objective was to replicate the initial HTA report from publicly available information, aiming to identify key operational and methodological aspects for operationalizing life-cycle decision-making.

We used partitioned survival analysis to determine tumor-agnostic and tumor-specific cost-effectiveness, using publicly available HTA reviews for parameterization. We estimated incremental costs in 2021 Canadian and US dollars (CAD and USD) from a public-payer healthcare perspective, quality-adjusted life years (QALYs), and incremental net monetary benefit (INMB). We assessed the impact of treatment effectiveness, extrapolation assumptions, and next-generation sequencing (NGS) costs.

One-third of the parameters (n = 30) were unavailable in the Canadian reimbursement review and were sourced from international reviews. Tumor-agnostic incremental costs were CAD 68,451 (95 percent confidence interval: 35,466, 92,155) and USD 54,608 (28,294, 73,518), and QALYs were 0.13 (−0.42, 0.42), yielding INMB CAD −55,803 at 100,000/QALY (USD −44,518). Full extrapolation of treatment effectiveness also yielded negative INMB (CAD −66,664). Inclusion of NGS costs diminished the expected value. Heterogeneity was considerable across tumor indications.

We developed an open-source index economic evaluation to operationalize life-cycle HTA for a conditionally authorized tumor-agnostic therapy. Our findings outline key operational and methodological considerations necessary for the development of index economic models that support life-cycle HTA, offering insights into their potential integration into regular HTA and policy decision-making processes.