Presentation (CTI)

OBJECTIVES: Advanced therapy medicinal products (ATMPs) and high-value therapies introduce major uncertainty regarding long-term effectiveness, durability of response, and payer affordability. This study evaluated whether longitudinal risk-sharing agreements, including refund and instalment mechanisms, could improve budget feasibility for a hypothetical Greek Innovation Fund under a €50 million annual statutory cap.
METHODS: A longitudinal microsimulation model was developed for a mature 2028 portfolio of 15 EU JCA-relevant oncology, rare disease, and advanced therapy products, including 841 projected eligible patients. Three payment regimes were evaluated: upfront payment, refund agreements, and instalment agreements. Upfront Innovation Fund payment applied a 15% flat reduction and 5% invoice discount. Refund agreements linked expected payer liability to durable response over the contractual horizon, while instalment agreements distributed payment over time conditional on maintained clinical response. Treatment durability was modeled using a 5% annual failure-rate assumption, and costs were discounted at 3.5% to estimate net present value. Agreement durations of 2, 5, 10, 20, and 40 years were assessed. Decision fragility was evaluated using 5,000-run Monte Carlo simulation.
RESULTS: Under the Traditional Cost Method, the 2028 portfolio generated a budget impact of €29.99 million. In contrast, upfront Innovation Fund payment resulted in €93.11 million, exceeding the statutory cap by 86%. Risk-sharing agreements restored affordability. Under a 5-year horizon, refund agreements reduced expected NPV cost to €35.00 million, while instalment agreements reduced NPV cost to €38.39 million, both below the €47.5 million effective operating cap. Compared with upfront payment, 5-year refund and instalment agreements generated savings of €58.11 million and €54.72 million, respectively. Monte Carlo analysis confirmed budget stability, with CVaR95 of €39.80 million for refund agreements and €41.84 million for instalments.
CONCLUSIONS: Longitudinal risk-sharing agreements can transform fixed-budget financing by linking payer exposure to treatment durability, improving affordability while highlighting the need for real-world outcome tracking.