Managed Entry Agreement Research Articles

From Indication-Based Pricing to Blended Approach: Evidence on the Price and Reimbursement Negotiation in Italy.

New indications for existing medicines are increasing over time. In most countries, drug pricing and reimbursement conditions are renegotiated every time a new indication is approved. There is a growing interest in the price negotiation model for new indications, specifically comparing an indication-based versus blended approach. However, little evidence currently exists regarding the complexity of these negotiations and their impact on actual prices. Italy has recently transitioned from an indication-based approach to a blended price model. This study aims to measure the impact of price and reimbursement negotiation of new indications on discounts (i.e. actual prices) and on the negotiation duration, used as a proxy of its complexity. We considered new indications approved through a European centralized procedure from January 2013 to March 2022 for which the price and reimbursement status was approved in Italy between January 2015 and March 2022, amounting to 52 new indications. Data on the timeframe of the Italian price and reimbursement process and its phases were obtained from publicly available sources. Discounts for the first indication and their subsequent increases for new indications were estimated by comparing ex-factory prices and tendered prices. To calculate p-values, we employed the Mann-Whitney test, and multiple regression models were utilized to examine correlations between negotiation time and the characteristics of the medicines. The mean time to reimbursement was 603 days, in contrast to 583 days for the first launch. Price negotiation took longer for rare diseases, cancer drugs, and in case of therapies with minor added therapeutic value. On average, the additional discount (on top of discounts for prior indications) was 13%, significantly lower than the mean discount for the first indications approved (24.9%). The discounts increment was lower, but negotiation took longer if a Managed Entry Agreement accompanied the final agreement. Additionally, discounts have increased over the years. The negotiation for new indications takes longer than the first one, and provides, on average, an additional discount of 13%. While our findings bear the potential for significant policy implications, they necessitate prudent interpretation due to a limited number of observations. The increasing trend in additional discounts over time applied to all indications in recent negotiations, may suggest a descending trend of value for new indications and a shift from an indication-based pricing approach to a blended model. Otherwise, budget impact considerations might have outweighed a value-based approach in the recent negotiations. If so, two potential options for restoring a value-based approach are returning to an indication-based pricing or giving explicit and higher weight to value within a blended model.

HPR154 When Could a Managed Entry Agreement Create a Win-Win-Win Situation - Exploring the Window of Opportunity

HPR154 When Could a Managed Entry Agreement Create a Win-Win-Win Situation - Exploring the Window of Opportunity

HPR9 Value Criteria for Outcomes Based Managed Entry Agreement of CAR-T in Relapsed or Refractory Multiple Myeloma (RRMM) through MCDA

HPR9 Value Criteria for Outcomes Based Managed Entry Agreement of CAR-T in Relapsed or Refractory Multiple Myeloma (RRMM) through MCDA

EE97 Budget Impact Analysis with and without Performance-Based Managed Entry Agreement (PBMEA) of Different Treatments for Spinal Muscular Atrophy (SMA) in the Kingdom of Saudi Arabia

EE97 Budget Impact Analysis with and without Performance-Based Managed Entry Agreement (PBMEA) of Different Treatments for Spinal Muscular Atrophy (SMA) in the Kingdom of Saudi Arabia

Terms of the managed entry agreement and particularities of the procedure for concluding such agreements

The article is devoted to the study of managed access agreements and some peculiarities of the procedure for their conclusion. The author analyses the current legislation on the terms and conditions that must be included in a managed entry agreement and the main stages of the managed entry agreement procedure.The article’s author focuses on the fact that in the context of the global trend of increasing prices for medicines, particularly for innovative medicines, the use of managed entry agreements in the practice of states is reaching a new level. Achieving a balance between healthcare expenditures and access to new medicines in the face of rising budgetary costs is a challenge for many national governments, indicating this issue’s global nature.The use of this type of agreement helps to curb healthcare costs, save budgetary funds and provide the population with access to treatment with innovative medicines.Budgetary savings are achieved by, among other things, setting the price in the contract. The procedure for determining the price and other terms of the managed entry agreement is the result of agreements between the parties to the agreement, starting from the stage of forming a negotiation team, preparing for negotiations on the conclusion of the managed entry agreement, holding consultations, negotiations, determining the type and terms of such an agreement, etc.The author establishes that pre-contractual work, the procedure for concluding this type of agreement, and the terms of the managed entry agreement itself have their own peculiarities.In this article, the author classifies the terms and conditions of a managed entry agreement: 1) general terms and conditions that are common to most agreements; 2) special terms and conditions that are special due to their use in managed access agreements; 3) terms and conditions used in certain agreements, in particular, supply agreements, agreements for the supply of medicines, etc.

Implementing a Managed Entry Agreement Framework in Cyprus

ABSTRACT Introduction The aim of this study is to explore the current practice in Cyprus regarding the introduction and reimbursement of innovative pharmaceuticals through Managed Entry Agreements (MEA), assess its operational context, and suggest approaches toward spanning the knowledge gap consequential to these efforts, especially the barriers of a small country context. Areas covered The recent introduction of a National Health System (NHS), brought about fundamental reforms in Cyprus’ Healthcare sector. Among such reforms, of particular interest, has been the introduction of a Managed Entry Agreements (MEA) mechanism. The first preliminary results indicate that despite being a small and unattractive market, Cyprus can apply a substantial MEA program. Concomitantly, it annotates the need to design an operational framework which should include, the definition of important technical parameters, clear demarcation of the scope, cooperation principles ensuring the effective operation of scientific committees, and clear delineation of what ‘value’ is. Moreover, in the context of the unified healthcare market, budget transfers should be considered, which could alleviate the inordinate budget impact of new products, which nevertheless will cut down on hospital expenditures. Narrative synthesis and health policy analysis-related resources were used. Expert opinion The implementation of MEA in Cyprus provides an ideal testing ground for innovative reimbursement approaches. This will streamline the country’s efforts toward reimbursement of innovation, while concomitantly add to the collective MEA experience.

HTA36 The First Managed Entry Agreements Based on Health Technology Assessment Approved in Ukraine: Analysis and Future Perspectives

The legal grounds for the procurement of medicines through the use of managed entry agreement (MEA) mechanism in Ukraine have been established since 2020. This research aims to provide a review of MEA implementation based on health technology assessment (HTA) in Ukraine.

Goals and methods of managed entry agreements – can we get what we want?

ObjectiveWe aimed to examine managed entry agreement (MEA) methods and their relation to nationwide drug reimbursement policy goals in the context of the Hungarian health care system. MethodFirst, a targeted literature review was performed that identified the most relevant MEA methods and drug reimbursement goals. Then, by using the findings of the review, a survey was developed: the first part of the survey aimed to ensure that interviewees have similar understanding of different types of MEAs and related policy goals; in the second part the interviewees were asked to prioritize drug reimbursement goals and indicate their perception about the impact of MEA techniques on the reimbursement policy goals. ResultsThree groups of MEA techniques were identified: cap type, clawback type and rebates or free treatment doses. Six policy goals were identified: cost containment, reduction of uncertainty of effectiveness, sustainable finance, patient access improvement, cost-effectiveness improvement, handling administrative burden. None of the MEA techniques showed clear advantage over all others. Cost containment, improvement of patient access and reduction of uncertainty around effectiveness were ranked as most important drug reimbursement goals. Cap type agreements were deemed to uniformly support the policy goals of cost containment and sustainable financing. Clawback type agreements strongly support cost containment policies. Rebates and free treatment dose(s) methods had positive impact on four policy goals. ConclusionThe implementation of managed entry agreements shall be considered and motivated by pre-defined drug reimbursement policy goals. During the application of MEAs, setting priorities and making trade-offs between different policy goals are inevitable.

Budget impact analysis of daratumumab for light-chain amyloidosis in Cyprus

ABSTRACT Objective The aim of this study is to assess the budget impact of daratumumab for light-chain amyloidosis in Cyprus Methods A budget impact model assessed the cost prior and after the introduction of daratumumab for light-chain amyloidosis. All related costs were set from the perspective of Cyprus NHS. Clinical data were extracted from the published trials. One-way sensitivity analysis was conducted. We reported incremental budget impact, per member per month, per year, and per treated member per month Results The introduction of D-VCd led to a net budget impact of €254,264 in the first year, which escalated to €497,007 by fifth year. The PMPY was estimated at €0.2893 in the first year, reaching €0.5246 at fifth year, the PMPM were at €0.0241 at the first year escalating to €0.0437 at the fifth year, and the PTMPM costs were €2,379 at the first year and gauged to €4,435 by fifth year. Our results were sensitive to incidence of the disease, percentage of patients without cardiac involvement and daratumumab cost. Conclusions The introduction of daratumumab for AL amyloidosis, with a 90% annual uptake over 5 years, leads to a substantial budget impact. Managed entry agreement schemes can be considered in order to mitigate the impact.

HPR132 Budget Cap With Pay Back As Managed Entry Agreement Policy: Bulgarian Example for Rheumatology Medicines

To analyse the influence of budget cap with pay back managed entry agreement (MEA) as cost-containment measure in Bulgaria on public spending for rheumatology medicines.

PP13 Development Of Recommendations And Proposal For A Value-Based Managed Entry Agreement For Italian Setting

IntroductionThe continuous and pressing challenge that the drug regulatory authorities in Italy and in Europe are facing is that of guaranteeing patients’ quick access to new drugs, ensuring the economic sustainability of the system at the same time. In recent years, flexible and diversified approaches have been developed known as Managed Entry Agreements (MEA).MethodsWe performed an analysis of the Italian legislative and regulatory aspects in reference to a new Value-based Managed Entry Agreement (VBMEA) pathway. Thus, we tried to investigate the rationale for a new pathway analyzing three main dimensions related to the new medical product (MP): value; time to entry access; and, data quality and registry design. Moreover, we shared the discussion of the proposal with an international experts’ panel.ResultsThe proposal for a new pathway of VBMEA from a procedural point of view shows the novelty related to the possibility to organize joint CTS (Technical Scientific Committee) and CPR (Price and Reimbursement Committee) assessment. A 24-month contract with an ex-factory price (PP) equal to X EUR per dose and a transfer price to the National Public Health System (NPHS), following application of a confidential discount for public structures (-X%), of X EUR per dose. After 24-months, an analysis of VBMEA is carried out. The price of the MP is therefore established based on AIFA registries and VBMEA results. The cost value incurred by the NPHS, intended as the difference between the price in market (entry) access phase and the price negotiated (PVB) in the light of the VBMEA results, shall be returned by the pharmaceutical company in the form of a payback.ConclusionsCurrently, MEAs represent one of the main topics of discussion between the European National Payers Authorities. There is very little information on product performance that results from MEAs. This research project could provide advice to policy makers to decrease negotiation time by ensuring earlier access to innovation for patients.

PP113 Reimbursement Of Oncology Therapies With Limited Clinical Evidence In The Netherlands

IntroductionThe number of novel therapies that achieve registration in oncology based on limited clinical evidence like non-randomized studies (NRS) is increasing. Dutch health authorities determine the therapeutic value of medicines evaluated in randomized controlled trials based on formal criteria for minimal relative efficacy or clinical treatment guidelines. However, there are no criteria to determine the therapeutic benefit of treatments assessed in NRS, which impacts reimbursement and patient access. Additionally, clinicians in the Netherlands see potential clinical benefit in off-label use but are currently unable to prescribe these because of absent clinical evidence.This review aims to identify and summarize initiatives to improve patient access to oncology therapies with limited or no clinical evidence in the Netherlands.MethodsRelevant public reimbursement documents for the Netherlands were identified through a pragmatic literature review.ResultsThe main initiatives to improve access for therapies with limited clinical evidence are outside regular reimbursement pathways.The Drug Rediscovery Protocol (DRUP, initiated 2016) and drug access protocol (DAP, initiated 2021) are two initiatives to improve access in solid tumor oncology. DRUP collects real-world data and provides access for targeted therapies in patients with targetable mutations in off-label indications. At least 25 therapies have been included to date.DAP uses the same data framework to reimburse on-label solid tumor therapies through a managed entry agreement based on response. The first participating therapies are cemiplimab (NRS, failed ZiN reimbursement), entrectinib and larotrectinib (both NRS, tumor-agnostic).Finally, Dutch clinical experts proposed criteria for therapeutic value of therapies studied NRS in oncology.ConclusionsPatient access to both off-label and on-label oncology therapies is addressed in DRUP and DAP. New criteria for the therapeutic value of therapies studied in NRS may decrease the relevance of DAP, although these criteria would not address the need for comparative evidence for cost-effectiveness analysis.

Critical Reflections on Reimbursement and Access of Advanced Therapies.

Background: The health economic literature has questioned the cost-effectiveness and affordability of advanced therapies, proposed adjustments to value assessment frameworks, and discussed the use of outcome-based managed entry agreements and staggered payments in the last few years. The aim of this manuscript is to conduct a critical reflection on assessment criteria and access conditions for reimbursement of advanced therapies. Methods: A narrative review of the peer-reviewed literature and grey literature was conducted in April 2021 by searching PubMed; Google Scholar; policy and legislative documents; websites of health technology assessment agencies, advanced therapy organisations, governmental advanced therapy innovation programmes, consultancy agencies; ISPOR conference abstracts and presentations. Results: Based on the available evidence, this manuscript argues that: a) advanced therapies can be cost-effective at high prices set by manufacturers; b) the economic evaluation framework adopted by many payers under-values these products; c) advanced therapies can be affordable and may not require spread payments; d) outcome-based managed entry agreements are theoretically attractive, but challenging in practice; e) the cost-effectiveness of advanced therapies depends on the outcome-based managed entry agreement and payment approach; f) there is a role for multinational collaborations to manage reimbursement and access of advanced therapies. Conclusions: This manuscript shows that there is no single approach to reimbursement and access of advanced therapies. Instead, we support a more tailored assessment of health economic aspects of advanced therapies, which considers the heterogeneity of these products and their target populations.

How reliable are ICER's results published in current pharmacoeconomic literature? The controversial issue of price confidentiality.

Pharmacoeconomic data are widely used along drug life cycle for supporting decision-making processes on research and development, pricing and reimbursement, and market access. In this context, the incremental cost-effectiveness ratio (ICER) is the gold standard of either cost-effectiveness analyses (CEAs) or cost-utility analyses (CUAs) of pharmaceuticals and health technologies. However, the widespread use of confidentiality clauses in the agreements between pharmaceutical companies and the payers may affect the reliability of ICER value based on transparent price. The aim of this article is to evaluate a case study and simulate the impact of price confidentiality and other managed-entry agreement conditions on the ICER value. The case study was conducted selecting a CEA submitted to the Health Economic Evaluations Office of the Italian Medicines Agency by the pharmaceutical company, which specifically compared two alternative options reimbursed by the Italian NHS using confidential managed-entry agreements. So, a real model was used to collect the output of ICERs generated by the simulation model, considering price inputs of alternative options ranging from the transparent prices to the confidential net price. The simulation showed that price confidentiality may affect the estimated value of the ICER of a new medicine and, consequently, its interpretation. From a different point of view, the published ICER values may also give a completely false economic evidence if non-disclosure agreements are not taken into account. A proposal for editors of pharmacoeconomic journals to improve reliability of CEA is also discussed.

Assessing the Value of Nusinersen for Spinal Muscular Atrophy: A Comparative Analysis of Reimbursement Submission and Appraisal in European Countries.

Background: Nusinersen is an orphan drug intended for the treatment of spinal muscular atrophy (SMA), a severe genetic neuromuscular disorder. Considering the very high costs of orphan drugs and the expected market entry of cell and gene therapies, there is increased interest in the use of health technology assessment (HTA) for orphan drugs. This study explores the role of the economic evaluation and budget impact analysis on the reimbursement of nusinersen. Methods: Appraisal reports for nusinersen were retrieved from reimbursement and HTA agencies in Belgium, Canada, France, England and Wales, Germany, Italy, Ireland, Scotland, Sweden, the Netherlands, and the United States. Detailed information was extracted on the economic evaluation, the budget impact, the overall reimbursement decision, and the managed entry agreement (MEA). Costs were adjusted for inflation and currency. Results: Overall, the reports included limited data on budget impact, excluding information on the sources of data for cost and patient estimates. Only three jurisdictions reported on total budget impact, estimated between 30 and 40 million euros per year. For early-onset SMA, the incremental cost-effectiveness threshold (ICER) ranged from €464,891 to €6,399,097 per quality-adjusted life year (QALY) gained for nusinersen versus standard of care. For later-onset SMA, the ICER varied from €493,756 to €10,611,936 per QALY. Although none of the jurisdictions found nusinersen to be cost-effective, reimbursement was granted in each jurisdiction. Remarkably, only four reports included arguments in favor of reimbursement. However, the majority of the jurisdictions set up an MEA, which may have promoted a positive reimbursement decision. Conclusion: There is a need for more transparency on the appraisal process and conditions included in the MEA. Additionally, by considering all relevant criteria explicitly during the appraisal process, decision-makers are in a better position to justify their allocation of funds among the rising number of orphan drugs that are coming to the market in the near future.

POSA65 Utilization-Based Managed Entry Agreements: Is There a Future for These Arrangements Across the EU4?

Many high-cost orphan and oncology agents require some form of managed entry agreement (MEA) to help EU payers marry the clinical value with the financial costs of such therapies. In the US, manufacturers launching high-cost therapies with weight-based dosing and/or a need for titration have implemented patient utilization adjustment (PUA) contracts to mitigate the risk of escalating or variable costs associated with individualized dosing. We aim to understand what potential value EU4 payers assign to a PUA contract and how this compares to existing contract structures.

Early access programs and managed entry agreements for medicines in Italy: results of a Focus Group (Early Access Programs and Managed Entry Agreement).

Early access of medicines occurs with an uncertainty in the evidence even higher than the one experienced when price and reimbursement status is negotiated. Our aim is discussing the role of managed entry agreements (MEA) within early access programs (EAP) in Italy. The discussion relied on a Focus Group, participated by twelve experts, including clinicians and representatives of regulatory authorities, regional and local pharmaceutical departments, pharmaceutical companies, and an association advocating for active citizenship. The Focus Group emphasised that the topic under discussion should be embedded into a more general reform of EAP in Italy. The 648 List mostly includes mature products and indications that are rarely launched into the market afterwards. The 5% Fund is affected by an important administrative burden uncertainty of the timing of reimbursement. Starting from the discussion on MEA and EAP, the Focus Group recommended a new legislation better regulating EAP, that early access concerns specific classes of medicines selected on the grounds of the need to guarantee a rapid access and to collect real world data, that early access can be accompanied by outcome-based and population-based MEA, and that MEA are embedded into the subsequent price and reimbursement negotiation.

Managed entry agreementsas a new legal framework for access to medicines

Key words: managed entry agreements, availability of medicines, original medicines,purchase of medicines, medicinal immunobiological drugs
 The article concerns the new provisions of national legislativea legal mechanism for access to medicines, namely managed entry agreements. Theuse of managed entry agreements in European contract practice is widespread.Ukraine, in responding to the COVID-19 pandemic, has reviewed the legal mechanismsfor access to medicines contained in national legislation and had taken the firststeps towards implementing managed access agreements.Ukrainian legislation did not contain such a concept as a managed entry agreementby March 2020, and such agreement was never used in Ukrainian contract practicefor the purchase of medicines. On March 17, 2020, changes were made to the nationallegislation, namely the Law of Ukraine «On amendments to certain laws ofUkraine aimed at increasing the availability of medicines, medical products and theiraccessories, which are purchased by the person authorized to carry out purchases inthe field of health care» which were amended, in particular, to the Law of Ukraine«Fundamentals of the legislation of Ukraine on health care» and supplemented by article791 of which a managed entry agreement to national legislation was introduced.
 The provision of Article 79-1 of the Fundamentals of the legislation of Ukraine onhealth care regarding the parties, subject matter, content of managed entry agreementsis analysed.January 27, 2021, the Cabinet of Ministers of Ukraine adopted a decision approvingthe procedure for the negotiation, execution, modification and termination ofmanaged entry agreement. A standard form of agreement for a managed entry agreementhas been approved. The managed entry agreements procedure has been introducedin Ukraine February 15, 2021.The legal and regulatory provisions concerning managed entry agreements havebeen analysed and highlighted their particularities.

How Managed Entry Agreements can improve allocation in the public health system: a mechanism design approach.

The process of introducing a new health technology into a healthcare system is characterized by uncertainty and risk for those involved-pharmaceutical companies, payers, patients and the government. In view of the accelerated introduction of new technologies in recent years, mechanisms to reduce uncertainty are of growing interest. One example is the Managed Entry Agreement (MEA), which we explore using a mechanism design approach. We make use of the Israeli experience, in which pharmaceutical companies and health plans (i.e., payers) negotiate over the introduction of new technologies into the national Health Services Basket (HSB) with the Ministry of Health acting as a mediator. We use the framework of bargaining within a mechanism design framework to show that in the process of negotiation the parties, the pharmaceutical company (PC) and the health plan (HP), have independent private valuations and that a situation of common knowledge that gains from MEA exists is rare. Adding a mediator (i.e., the MEA team) to the mechanism, as in a direct-revelation mechanism, reduces the level of uncertainty for both sides (i.e., the PC and the HP), thus making it possible to meet the budget constraint while increasing value for patients and enhancing ex-post efficiency.

Lessons learned from the reimbursement policy for immune checkpoint inhibitors and real-world data collection in Taiwan.

This paper describes the reimbursement policy for immune checkpoint inhibitors in Taiwan and provides a perspective to improve the quality, consistency, and transparency of decision making. Global trends for cancer treatment have shifted from chemotherapies to targeted therapies and immuno-oncology (IO) medicine, leading to significant increases in treatment costs. To enhance the accessibility of advanced therapy, the Taiwan National Health Insurance Administration announced two pathways for high-cost medicine: the managed entry agreement and a set of general rules of reimbursement submission for high-cost drugs. To further manage the financial burden on Taiwan's national health insurance system, the policy makers introduced novel inhibitory drugs for cancer immune checkpoints, subject to a maximum annual budget of NT$800 million (≈US$26.7 million). In April 2019, a national registry was established for patients undergoing cancer immunotherapy. Clinical characteristics, treatment duration, toxicity, and the outcome of the postcheckpoint inhibitor treatments were recorded. By analyzing real-world data, we assess the therapeutic effect of IO treatment in Taiwanese patients, thereby enabling payers to adjust payment regulations and rules for reimbursement. The Health Technology Assessment Team plays an important role in drawing upon the evidence to support policy making. Under an implemented cost-management mechanism, Taiwan's high-cost drug policy has enabled patients to access new medicines and maximized patient benefits.