Risk-Sharing Agreements have been hailed as a solution to attain access for innovative medicines with limited evidence packages or high price tags, but do the majority address questions around value, or just protect list pricing in a healthcare era more and more concerned with budget impact?
by Rachel Galloway, Senior Consultant at RJW&partners
Risk sharing agreements (RSAs) have been an important tool for manufacturers and payers. They have enabled early access to new treatments that have a high level of uncertainty regarding their clinical effectiveness, value or budget impact.
The popularity of RSAs continues to grow as more and more high-cost therapies, including advanced therapy medicinal products (ATMPs), come to market.
GlobalData’s1 risk-sharing database indicates that the implementation of these agreements is currently growing at average annual growth rate (AAGR) of 24%, with over 1,000 agreements made between 2012 and 2022. Key drivers behind this trend are economic pressures leading to increased focused on healthcare budgets and the increasing use of HTA, neither of which look set to decrease anytime soon.
Figure 1: total risk-sharing agreements implemented by year and annual growth of RSAs implemented
Risk sharing agreements fall into two main categories:
Finance-based agreements, which primarily seek to manage budget uncertainty
Performance-based agreements, which seek to manage clinical or value uncertainty
Figure 2: types of risk sharing agreements
GlobalData reports that most RSAs implemented to date have been finance-based (approximately 80%) and the majority of those have been simple discount schemes1.
Despite changing payer willingness to negotiate and implement performance-based agreements, finance-based agreements will likely remain more popular thanks to their easier, lower-cost implementation and lower administrative burden. Some payers go as far as explicitly stating their preference for simple discount schemes in their pricing and reimbursement guidance.
Figure 3: total risk-sharing agreements by year by type1
The distribution of RSAs across countries reveals that 3 countries account for almost 75% of all RSAs; the UK (54%), Australia (11%) and the USA (5%)1. The UK’s pole position is not surprising;
NICE does not negotiate, publicly set or publicly indicate prices, therefore if a medicine is not deemed cost-effective and not recommended for use by the NHS, a Patient Access Scheme (PAS) involving a simple discount can be an effective tool to attain cost-effectiveness with a lower but confidential net price
Additionally, if the budget impact of a new medicine exceeds £20 million in any of the first 3 years, NHS England is permitted to engage in commercial discussions with the company, leading to multiple commercial and managed access agreements being implemented since the budget impact test was introduced in 2017.
While the US “only” ranked 3rd it’s important to note that contracting is par for the course in US pharma. Particularly in competitive therapeutic classes, it’s an essential tool to obtain formulary access, preferred tier placement and/or a lower patient-cost sharing burden. So, while confidential discounts or rebates are abundant in the US, they are often not considered risk-sharing agreements and/or their existence is not publicly available information.
GlobalData report that around half of RSAs implemented so far have been for oncology medicines1 but as more high-cost treatments, principally cell- and gene-therapies, launch for rare diseases with single arm trial data, surrogate endpoint data, and/or high price tags, we may see the balance shift.
Figure 4: distribution of RSAs by therapy area1
Global versus local trends
Do these global trends hold true at a local level? Are there countries or regions more willing to implement complex performance-based agreements and what are the latest trends?
Let’s explore some of these countries in more detail.
England
Patient access schemes (PAS) have been permitted in England since 2009 when the PPRS was implemented. They are confidential pricing agreements that enable patients to gain access to drugs that otherwise are not considered cost-effective by NICE or recommended for use by the NHS2,3. In addition to PASs, commercial access agreements (CAA) and managed access agreements (MAA) may also be implemented.
As highlighted by the GlobalData report1, the status quo in the UK has a big impact on global RSA trends with the UK accounting for more than 50% of RSAs implemented across the globe over the past decade1 . In the UK, simple discount schemes account for over 70% of RSAs implemented2.
Figure 5: distribution of RSAs types in England2.
The dominance of simple discount schemes is no surprise; the PAS Liaison Unit (PASLU) explicitly states on the PAS proposal template5 “simple discount PASs are preferred to complex schemes because they create no significant implementation burden for the NHS” and that those proposing complex schemes “will need to explain and justify their choice of scheme”.
CAAs and MAAs have been permissible for less than a decade in England. Since their introduction they have become an important tool, particularly in oncology, to allow early market access for therapies with immature evidence packages that treat patient populations with high unmet needs and/or treat diseases with high mortality. However, when we analyse the number of CAA or MAA agreements implemented by year, there are no obvious growth trends.
Figure 6: number of CAAs and/or MAAs implemented in England by year2.
Note: excludes CAAs for which the PAS was withdrawn
Italy
Italy is well-known as a pioneer when it comes to negotiating and implementing performance-based agreements, being the first country ever to implement a payment at results funding model back in 2019 for Kymriah, and its extensive experience with payment by results funding models.
AIFA’s (Agenzia Italiana del Farmaco) ability to implement complex agreements (referred to as managed entry agreements (MEA) in Italy) is facilitated by a well-established system of national registries that are centrally managed through a web-based platform. These registries facilitate monitoring of the appropriate use of medicines and clinical data collection6.
According to AIFA, there are currently 272 active national level registries in Italy7 but 243 are active monitoring only and not associated with any finance- or performance-based agreement. This is largely due to the fact that reimbursement contracts with AIFA are normally limited to 2 years.
The below chart of active MEAs in Italy is a snapshot of the distribution of MEA types for recently launched therapies only. Similar to the rest of the world, finance-based agreements are the most common type of RSA in Italy too, but the split is less skewed7.
Figure 7: number of registries linked to active managed entry agreements by type7.
Note: Cost sharing agreements require a manufacturer to offer a full or partial discount for initial cycles of treatment for eligible patients. Success fee agreements require payment only for patients who respond to treatment.
To date many of the performance-based agreements implemented in Italy have been for oncology medicines, where quick access to treatment is important and successful treatment outcomes may be measured objectively and easily – especially when compared to chronic, life-style related diseases8.
Recently, more manufacturers have been opting for financial-based agreements. The rationale for this could be that manufacturers are aiming to minimise the risk of price decreases when a MEA expires. For example, if the real-world clinical performance of a drug is poorer than that demonstrated during clinical trials, AIFA could leverage this to negotiate lower net pricing when an agreement expires and a new contract or price must be negotiated, since they would have ample data to reference. However, AIFA has faced criticism on the effectiveness of performance-based agreements in realising cost-savings. A 2012 study highlighted that only 3.3% of money spent via performance-based agreements was refunded9. Additionally, a 2016 paper titled “Performance-Based Agreements in Italy: ‘Trendy Outcomes’ or Mere Illusions?” criticised AIFA by highlighting that the agency had not published a report detailing clinical outcomes for any drug covered under a performance-based agreement and that more data are needed to thoroughly assess their effectiveness10.
Despite Italy’s track record, AIFA and the Italian healthcare system still face challenges administrating performance-based agreements:
The national registries that collect clinical data are not linked to regional level databases that collect hospitalisation data8, which makes responses tied to hospitalization outcomes particularly challenging to monitor
Performance-based agreements involve a lot of paperwork for physicians that must be completed before a prescription can be validated or a non-response recorded
Manufacturers can reject refund requests made for patients deemed non-responders if there is disagreement on the clinical assessment and outcomes
Some of these challenges may be addressed by AIFA’s “success fee” scheme (first introduced in 2015 for pirfenidone) that requires manufacturers to provide a therapy for free then, only after agreed clinical outcomes are met, does the national health service start paying for treatment. This shifts more risk and a greater administrative burden onto the manufacturer.
The Kingdom of Saudi Arabia (KSA)
Value-Based Health Care (VBHC) is a strategic objective of the Kingdom of Saudi Arabia’s Vision 203011. The country is establishing a health technology assessment body11 and increasingly using value-based, risk sharing agreements.
A 2023 review12 of the current status of risk sharing agreements in KSA highlights that performance-based agreements are being used across therapy areas.
Table 2: example of risk sharing agreements implemented in KSA12
Reviewing the approximate annual cost of treatment reveals that, for the risk-sharing agreements outlined in the review, there’s no obvious trend between the type of RSA implemented and the annual cost of therapy, with both the lowest and highest annual treatment cost therapies being covered by performance-based agreements.
Figure 8: approximate annual cost of treatment for therapies covered by RSAs by type of RSA11,12.
Abbreviations: RCC - Renal Cell Carcinoma, MM – Multiple Myeloma, NSCLC - Non-small cell lung cancer, FH - Familial Hypercholesterolemia , MS – Multiple Sclerosis, mBC – metastatic Breast Cancer, SMA - Spinal Muscular Atrophy. Annual costs are approximate and will vary depending on the specific dosing regimen prescribed where multiple treatment regimens exist and/or medicines use weight-based dosing.
Finance-based agreements are implemented widely in KSA, but the details of many are kept confidential12 making analyses on the overall distribution of RSA by type and therapy area not possible via publicly available sources.
While KSA’s experience with performance-based risk sharing agreements is still in the early phase, recent agreements include regular assessments of clinical outcomes demonstrating a willingness to implement RSAs with higher administrative costs and burden.
Catalonia
While many countries have improved data collection infrastructure to support performance-based agreements, some lack an efficient process to evaluate the clinical and economic impact of agreements or use insight from evaluations of existing agreements to refine regulations for future RSAs.
A study describing the different types of RSAs implemented in Catalonia between 2016 and 2019, sought to evaluate their health and economic outcomes13.
During the study period CatSalut (the Catalan Health Service) bucked the trend and implemented more performance-based agreements than finance-based agreements – only just though with a total of 8 performance-linked reimbursement schemes and 7 finance-based agreements that ranged in complexity from discounts to budget caps. Similar to the global trend, most agreements were implemented for oncology therapies.
Figure 9: Distribution of RSAs by type and therapy area13
The study evaluated total medication costs and refunds under both schemes and found that a higher proportion of costs were refunded from performance-based agreements, with nearly all refunds coming from oncology medicines.
A total of 951 patients were included in performance-based agreements and 73% of patients achieved the target health outcomes13.
Figure 10: total medicine costs and refunds by RSA type13.
Interestingly a total of 11% of expenditures from all performance-based agreements were refunded – a figure over 3 times greater than the 3.3% reported in Navarria’s 2015 Italian study9. It would be helpful to understand the drivers behind this delta if clinical outcomes are not the only factor – does the Catalonian system involve less paperwork resulting in more efficient reporting and paybacks? Does the regional collection of data permit more comprehensive data collection and analyses, resulting in more efficient identification of non-responders?
Conclusion
Across the globe, finance-based agreements continue to prevail as they remain payers’ preferred choice of contract to manage uncertainty related to an innovative therapy's budget impact or cost effectiveness. In instances where maintaining a high list price is the short- and long-term priority, finance-based agreements are a pragmatic, win-win solution. Payers pay a lower net price with minimal administrative burden, and manufacturers may keep their visible list price at/near target, which can help them attain higher prices in countries that use external reference pricing and include the country in question as a reference-price country. Additionally, the payer is less likely to have a database of country-specific clinical outcome data for that therapy to reference during future pricing negotiations, which it could leverage to its advantage if real-world outcomes were poorer than expected.
Despite their higher administrative costs and burden, performance-based agreements have been adopted by many countries as a tool to manage clinical uncertainty, especially for innovative oncology medicines. The extent to which that is driven by a desire or need for faster access with evidence generation, and the ability to objectively measure treatment outcomes for cancer patients versus chronic diseases where outcomes are significantly affected by lifestyle behaviours, is yet to be evaluated.
Performance-based agreements have also been an important tool to gain access and generate evidence for some of the first ATMPs, such as the CAR-T therapies. However, their popularity has dipped in recent years1. Could that be a result of the COVID-19 pandemic and economic climate directing attention and resources elsewhere, and will an increasing number of ATMP approvals spark a new-found willingness to implement more of these agreements? Watch this space to find out more.
References
https://www.pharmaceutical-technology.com/pricing-and-market-access/risk-sharing-agreements/
https://www.nice.org.uk/about/what-we-do/patient-access-schemes-liaison-unit
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https://www.england.nhs.uk/medicines-2/commercial-medicines/nhs-commercial-framework-for-new-medicines/#can-you-further-clarify-the-difference-between-a-managed-access-agreement-maa-and-a-commercial-access-agreement-caa
https://www.nice.org.uk/Media/Default/About/what-we-do/PASLU/proposal-template-simple-scheme-V1-7.doc
Xoxi E, Facey KM, Cicchetti A. The Evolution of AIFA Registries to Support Managed Entry Agreements for Orphan Medicinal Products in Italy. Front Pharmacol. 2021 Aug 10;12:699466. doi: 10.3389/fphar.2021.699466. PMID: 34456724; PMCID: PMC8386173
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https://www.pharmexec.com/view/risk-sharing-italian-style
Andrea Navarria, Valentina Drago, Lucia Gozzo, Laura LongoPharm, Silvana Mansueto, Giacomo Pignataro, Filippo Drago, “Do the Current Performance-Based Schemes in Italy Really Work? ‘Success Fee’: A Novel Measure for Cost-Containment of Drug Expenditure,” Value in Health, Volume 18, Issue 2, March 2015Garattini L, Curto A. Performance-Based Agreements in Italy: 'Trendy Outcomes' or Mere Illusions? Pharmacoeconomics. 2016 Oct;34(10):967-9. doi: 10.1007/s40273-016-0420-1. PMID: 27260615.
Al-Omar HA, Attuwaijri AA, Aljuffali IA. What local experts expect from a health technology assessment (HTA) entity in Saudi Arabia: workshop conclusions. Expert Rev Pharmacoecon Outcomes Res. 2020 Feb;20(1):99-104. doi: 10.1080/14737167.2019.1610398. Epub 2019 Apr 29. PMID: 31032687.
Abu-Shraie N, Alhammad A, Balkhi B, Al-Jedai A. Implementation of risk-sharing agreements in Saudi Arabia: Comparison and reflection on the NICE Model. Trop J Pharm Res 2023; 22(5):1121-1131 doi: 10.4314/tjpr.v22i5.27
https://www.sfda.gov.sa/en/drugs-list
Guarga, L, Gasol, M, Reyes, A, et al. Implementing risk-sharing arrangements for innovative medicines: The experience in Catalonia (Spain). Value Health. 2021;25:803–809.
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