Introduction
A subset of advanced therapy medicinal products (ATMPs) are administered once, or over a short course, with effects that may persist for years. The combination of high upfront cost, limited pre-launch evidence in small populations, and long-term uncertainty has led payers and manufacturers to consider payment and contracting models that differ from conventional arrangements. These approaches include managed entry agreements (MEAs), outcomes-based agreements (OBAs), and payment profiles that spread cash flow over time, often alongside requirements for post-launch evidence generation and outcome tracking. (OECD)
Why one-time therapies stress standard reimbursement approaches
Traditional reimbursement is generally aligned to repeated dosing, relatively predictable utilisation, and outcomes that can be assessed within shorter follow-up periods. For one-time therapies, affordability concerns are driven by the timing of payment rather than only the total cost, particularly where there is a significant eligible population and where treatment is concentrated in specialist centres. This interacts with uncertainty about durability, the counterfactual scenario of standard of care without the new therapy, and how quickly real-world outcomes can be observed in routine practice.
A further complication is that beneficiaries may not continue with the same budget holders over extended time periods. Where payer membership changes, the organisation that pays for treatment may not capture downstream health gains, strengthening interest in risk-sharing constructs that can be aligned to observable milestones or performance measures.
Main contract families used in practice
MEAs span both financial-based and performance-based arrangements. Financial-based agreements include confidential discounts, budget caps, and price-volume components that primarily address affordability and utilisation uncertainty without tying payment to outcomes. Performance-based structures link all or part of net payment to outcomes, using pre-specified measures, timelines, and adjudication rules. OECD work describing MEA designs highlights the practical importance of defining objectives such as budget predictability, access under uncertainty and evidence generation before selecting an agreement type.
For one-time therapies, “spread payments” are often discussed as instalment or annuity-like payment profiles. These can be purely financial (fixed instalments) or hybrid (instalments contingent on milestone attainment or persistence). In practice, the “spread” addresses cash flow and budget management but does not by itself resolve uncertainty unless paired with performance terms and an operational pathway for measuring outcomes.
Subscription-style approaches, in which a payer pays a fixed amount for access to a therapy under defined conditions, are conceptually attractive where population demand is predictable and outcomes are difficult to adjudicate case by case. However, these models depend on legal and administrative feasibility and require clear rules on eligibility, duration, and what constitutes “covered” use.
Outcome specification and measurement choices
Outcome-linked payment requires decisions on what is measurable, attributable, and timely. For ATMPs, payers often seek outcomes that reflect clinically meaningful benefit and that can be assessed within a timeframe compatible with contracting cycles. Where durability is central, surrogate or intermediate outcomes may be used initially, with longer-term follow-up obligations that inform later reconciliation or renegotiation.
Endpoints must be operationalised in a way that is reproducible across sites and compatible with routine data capture. This can create tension between clinically rich outcomes, which may require specialist assessment, and administratively feasible measures, which may be cruder but more consistently recorded. Even when outcomes are agreed, handling missing data, loss to follow-up, and changes in standard of care over time can materially affect contract performance calculations.
Data infrastructure and governance for outcomes-linked payment
Execution of OBAs depends on data availability, data permissions, and the existence of systems that can link treatment exposure to subsequent outcomes with sufficient quality. National or regional registries can support this, but they vary in coverage, governance, and timeliness. The Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) operates monitoring registers intended to support appropriate use and expenditure control for medicines subject to monitoring, illustrating one model of structured data collection linked to access and management processes.
Where registry infrastructure is limited, parties may rely on claims, electronic health records, or centre-level reporting. This often increases administrative burden and reduces comparability across sites. Data protection constraints and contracting confidentiality further shape what can be shared, how outcomes are validated, and who has authority to adjudicate disputes.
Budgeting, accounting, and legal constraints
Even where there is agreement in principle, public financial rules can constrain implementation. Instalment-based payments may be treated as deferred expenditure in some contexts but can also trigger accounting questions around when a liability is recognised. Similarly, payers may have limited authority to commit funds beyond annual appropriations, particularly where contracting spans multiple years.
In the United States Medicaid context, value-based purchasing (VBP) arrangements interact with statutory rebate mechanics and “best price” reporting. CMS has issued technical guidance describing how manufacturers can report multiple best prices associated with VBP arrangements offered to all states, reflecting an attempt to reduce disincentives for outcomes-based pricing structures within existing rebate rules.
Cross-country variation and implementation realities
The same contract concept can look materially different across health systems because of differences in who holds budgets, what data can be used, and how outcomes are measured and audited. OECD evidence indicates that MEAs are used in many OECD and European Union settings, but designs and data sources vary substantially, and performance-based approaches are often more difficult to implement than financial-based agreements.
Internationally, practical implementation often favours hybrid solutions: an initial financial component to manage affordability combined with a limited set of measurable outcomes and a defined evidence-generation plan. For access teams, this places emphasis on early alignment of clinical and epidemiology data, finance, and legal stakeholders, since contract feasibility is frequently determined by operational details rather than the high-level contracting intent.
Summary
One-time therapies create affordability and uncertainty challenges that are not fully addressed by conventional single-payment reimbursement. Managed entry agreements (MEAs) and outcomes-based agreements (OBAs) are used to balance earlier access with risk sharing, but they depend on clear objectives and administratively feasible designs. Instalment-style payments can improve cash-flow alignment yet typically require accompanying performance terms if they are to address durability uncertainty. Outcome-linked payment is constrained by endpoint selection, attribution, missing data, and the availability of credible data infrastructure. Implementation is shaped by local budgeting, accounting, and legal rules, leading to marked cross-country variation in what is feasible in practice.
Links
Italian Medicines Agency: Monitoring Registers.
Scientific publications
Dabbous M, Chachoua L, Caban A, Toumi M. Managed entry agreements: policy analysis from the European perspective. Value Health. 2020;23(4):425-33. doi:10.1016/j.jval.2019.12.008.
Greco A, Frederix GWJ, Hooft L, Ten Ham RMT. A systematic review of challenges and opportunities in the implementation of managed entry agreements for advanced therapy medicinal products. Clin Ther. 2025;47(2):e16-e26. doi:10.1016/j.clinthera.2024.11.019.
Horrow C, Kesselheim AS. Confronting high costs and clinical uncertainty: innovative payment models for gene therapies. Health Aff 2023;42(11):1532-40. doi:10.1377/hlthaff.2023.00527.
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Quinn C, Ciaramitaro M, Sils B, Phares S, Trusheim M. Medicaid best price reforms to enable innovative payment models for cell and gene therapies. Expert Rev Pharmacoecon Outcomes Res. 2023;23(2):191-203. doi:10.1080/14737167.2023.2159813.