Financial Characteristics of Outcomes-Based Agreements: What Do Canadian Public Payers and Pharmaceutical Manufacturers Prefer?

OBJECTIVES: This study sought to gain insight into the financial characteristics of outcomes-based agreements (OBAs) considered most suitable to Canadian public payers and pharmaceutical manufacturers, and the rationale for their preferences. METHODS: A total of 17 public payers and pharmaceutical manufacturers participated in semistructured qualitative interviews, which assessed their knowledge of OBAs and their preferred financial characteristics. RESULTS: Payers identified 5 OBA financial models that they considered both acceptable and feasible, in no preferential order: (1) discontinuation of therapy, (2) rebates for nonresponders, (3) free trial period, (4) adjustable pricing, and (5) blended rebate. Payers had a clear preference for short-term OBAs (<1 year), whereas both payers and manufacturers agreed OBAs with longer durations (up to 5 years) would be manageable if appropriately designed. Six key success factors to design suitable and acceptable OBA financial models were identified, including the areas of interim reporting, easily measurable health outcomes, trusted data sources, engaging unbiased third-party data experts, harmonizing OBA billing methods, and the inclusion of budget caps. CONCLUSIONS: Manufacturers and payers showed high level of interest in OBAs and a robust understanding of their potential role in supporting timely market access for patients in need, with the caveat that they need to be carefully designed to provide value. Further opportunities for discussion and engagement between public payers and manufacturers are needed to establish how to implement OBAs at a pan-Canadian level and how individual provinces and territories can incorporate them within their existing governance infrastructures.

Financing and Reimbursement of Approved Advanced Therapies in Several European Countries.

OBJECTIVES: The uncertainty in the cost-benefit of advanced therapy medicinal products (ATMPs) is a current challenge for their reimbursement in health systems. This study aimed to provide a comparative analysis of the National Health Authorities (NHAs) reimbursement recommendations issued in different European countries. METHODS: The NHA reimbursement recommendations for the approved ATMPs were compared among 8 European Union (EU) Countries (EU8: Ireland, England/Wales, Scotland, The Netherlands, France, Germany, Spain, and Italy). The search was carried out until December 31, 2021. RESULTS: A total of 19 approved ATMPs and 76 appraisal reports were analyzed. The majority of the ATMPs were reimbursed, although with uncertainty in added therapeutic value. No relationship between the type of the European Medicines Agency approval and reimbursement was found. Managed entry agreements, such as payment by results, were necessary to ensure market access. The main issue during the evaluation was to base the cost-effectiveness analyses on assumptions because of the limited long-term data. The estimated incremental cost-effectiveness ratio among countries reveals high variability. Overall, the median time to NHA recommendation for the EU8 is in the range of 9 to 17 months. CONCLUSIONS: Transparent, harmonized, and systematic assessments across the EU NHAs in terms of cost-effectiveness, added therapeutic value, and grade of innovativeness are needed. This could lead to a more aligned access, increasing the EU market attractiveness and raising public fairness in terms of patient access and pricing.

Opportunities and hurdles to European market access for multi-herbal traditional Chinese medicine products: An analysis of EU regulations for combination herbal medicinal products.

TCM herbal remedies are popular among European patients. However, a very limited number of TCM products have been approved as herbal medicinal products (HMPs) in Europe. Multi-herbal TCM products, the most prevalent form of medication in TCM practice, are even rare. This indicates multi-herbal TCM products are facing considerable obstacles in the access to EU market. To further identify such obstacles, we make a systematic analysis of current advances in both EU herbal monographs and combination HMPs granted in member states and present main features of the regulation as well as challenges for multi-herbal TCM products. The results show the EU is open to combination HMPs based on TCM or other non-European traditions. The regulation allows appropriate flexibility in the range of drug extraction rations, variation in concentrations of extraction solvent and number of herbal drugs presented in the product, if plausible pharmacological effects could be justified. Meanwhile, to guarantee the safety and efficacy based on medicinal usage, especially to justify the rationale or plausibility of the combination, is the key element for well-established use or traditional use combination HMPs. Additionally, EU herbal monographs also have great value in their marketing procedure. Nonetheless, there are many challenges in the European market access of multi-herbal TCM products which lies in quality control, safety and efficacy evaluation and others e.g., practical standard for full marketing authorization. Enforced scientific research and communication among research institutions, industries and authorities are necessary to further facilitate the access of multi-herbal TCM products to EU market. The results of this article may provide guidance for HMPs based on TCM or other non-European traditions with intention to entering EU market.

A Conceptual Framework for Life-Cycle Health Technology Assessment.

OBJECTIVES: Health technology assessment (HTA) uses evidence appraisal and synthesis with economic evaluation to inform adoption decisions. Standard HTA processes sometimes struggle to (1) support decisions that involve significant uncertainty and (2) encourage continued generation of and adaptation to new evidence. We propose the life-cycle (LC)-HTA framework, addressing these challenges by providing additional tools to decision makers and improving outcomes for all stakeholders. METHODS: Under the LC-HTA framework, HTA processes align to LC management. LC-HTA introduces changes in HTA methods to minimize analytic time while optimizing decision certainty. Where decision uncertainty exists, we recommend risk-based pricing and research-oriented managed access (ROMA). Contractual procurement agreements define the terms of reassessment and provide additional decision options to HTA agencies. LC-HTA extends value-of-information methods to inform ROMA agreements, leveraging routine, administrative data, and registries to reduce uncertainty. RESULTS: LC-HTA enables the adoption of high-value high-risk innovations while improving health system sustainability through risk-sharing and reducing uncertainty. Responsiveness to evolving evidence is improved through contractually embedded decision rules to simplify reassessment. ROMA allows conditional adoption to obtain additional information, with confidence that the net value of that adoption decision is positive. CONCLUSIONS: The LC-HTA framework improves outcomes for patients, sponsors, and payers. Patients benefit through earlier access to new technologies. Payers increase the value of the technologies they invest in and gain mechanisms to review investments. Sponsors benefit through greater certainty in outcomes related to their investment, swifter access to markets, and greater opportunities to demonstrate value.

Market access and value-based pricing of digital health applications in Germany.

In December 2019, the Digital Health Care Act ("Digitale-Versorgung-Gesetz") introduced a general entitlement to the provision and reimbursement of digital health applications (DiGA) for insured persons in the German statutory health insurance. As establishing a new digital service area within the solidarity-based insurance system implies several administrative and regulatory challenges, this paper aims to describe the legal framework for DiGA market access and pricing as well as the status quo of the DiGA market. Furthermore, we provide a basic approach to deriving value-based DiGA prices.To become eligible for reimbursement, the Federal Institute for Drugs and Medical Devices evaluates the compliance of a DiGA with general requirements (e.g., safety and data protection) and its positive healthcare effects (i.e., medical benefit or improvements of care structure and processes) in a fast-track process. Manufacturers may provide evidence for the benefits of their DiGA either directly with the application for the fast-track process or generate it during a trial phase that includes temporary reimbursement. After one year of \]reimbursement, the freely-set manufacturer price is replaced by a price negotiated between the National Association of Statutory Health Insurance Funds and the manufacturer. By February 2022, 30 DiGA had successfully completed the fast-track process. 73% make use of the trial phase and have not yet proven their benefit. Given this dynamic growth of the DiGA market and the low minimum evidence standards, fair pricing remains the central point of contention. The regulatory framework makes the patient-relevant benefits of a DiGA a pricing criterion to be considered in particular. Yet, it does not indicate how the benefits of a DiGA should be translated into a reasonable price. Our evidence-based approach to value-based DiGA pricing approximates the SHI's willingness to pay by the average cost-effectiveness of one or more established therapy in a field of indication and furthermore considers the positive healthcare effects of a DiGA.The proposed approach can be fitted into DiGA pricing processes under the given regulatory framework and can provide objective guidance for price negotiations. However, it is only one piece of the pricing puzzle, and numerous methodological and procedural issues related to DiGA pricing are still open. Thus, it remains to be seen to what extent DiGA prices will follow the premise of value-based pricing.

[Digital therapeutics: Which barriers for market access?] / Les thérapies digitales : quels freins pour leur prise en charge ?

Integrated to the e-health field, digital therapeutics can be defined as "software, combined or not to a device, in the purpose of prevention, treatment or monitoring of a disease, participating actively in a mechanism of action and based on strong clinical evidence". The aim of this work was to assess the level of digital therapeutics clinical validation and to reflect on their business model. A qualitative study has been conducted and different health actors have been interviewed. The semi-guided interviews made have been analysed through a three-level coding. Twenty-two interviews have been analysed and six categories have been identified. The interlocutors highlighted the leading role of digital therapeutics in the follow-up and prevention, supporting the empowerment of patients. However, the absence of consensus in their definition has led to heterogeneity of definition and a difficulty to limit their scope. Furthermore, the conduct of clinical trials, not really suited for digital therapeutics, forced the editors/manufacturers to search for funding for which availability and continuity are uncertain. By raising the issue of clinical efficacy, demonstration of digital therapeutics, this study has led to new perspectives in assessment and business model. We could see in digital therapeutics a new nature of innovation associated with new organisations of our healthcare system and not necessarily by new therapeutics.

Regulatory, Legal, and Market Aspects of Smart Wearables for Cardiac Monitoring.

In the area of cardiac monitoring, the use of digitally driven technologies is on the rise. While the development of medical products is advancing rapidly, allowing for new use-cases in cardiac monitoring and other areas, regulatory and legal requirements that govern market access are often evolving slowly, sometimes creating market barriers. This article gives a brief overview of the existing clinical studies regarding the use of smart wearables in cardiac monitoring and provides insight into the main regulatory and legal aspects that need to be considered when such products are intended to be used in a health care setting. Based on this brief overview, the article elaborates on the specific requirements in the main areas of authorization/certification and reimbursement/compensation, as well as data protection and data security. Three case studies are presented as examples of specific market access procedures: the USA, Germany, and Belgium. This article concludes that, despite the differences in specific requirements, market access pathways in most countries are characterized by a number of similarities, which should be considered early on in product development. The article also elaborates on how regulatory and legal requirements are currently being adapted for digitally driven wearables and proposes an ongoing evolution of these requirements to facilitate market access for beneficial medical technology in the future.

Gender differentiated small-scale farm mechanization in Nepal hills: An application of exogenous switching treatment regression.

Farm mechanization among smallholder farming systems in developing countries is emerging as a viable option to off-set the effects of labor out-migration and shortages that undermine agricultural productivity. However, there is limited empirical literature on gender and farm mechanization. This study assesses the impacts of the gender of household heads on mini-tiller adoption in the hills of Nepal, using an exogenous switching treatment regression model. Our findings reveal that there is a significant gender gap in mini-tiller adoption between male-headed households (MH-HHs) and female-headed households (FH-HHs). Compared to MH-HHs, the mini-tiller adoption rate is significantly lower among the FH-HHs, and a large amount of unobserved heterogeneity is deriving this difference. Moreover, when MH-HHs and FH-HHs have similar observed attributes, the mini-tiller adoption rate among the food insecure FH-HHs is higher than in the food secure group. The gender-differentiated mini-tiller adoption rate can be minimized primarily by enhancing market access. Findings suggest that farm mechanization policies and programs targeted to the FH-HHs can reduce the gender-differentiated adoption gap in Nepal and similar hill production agro-ecologies in South Asia, which will enhance the farm yield and profitability.

[In search of a travel guide-results from a survey of E­health startup companies]. / Reiseführer gesucht ­ Ergebnisse einer Umfrage bei E­Health-Start-ups.

As is the case in other sectors, innovative digital products have started to enter the health market, too. If digital products like apps are considered medical devices, startups are often confronted with regulatory procedures that they deem to be slow and with which they are not familiar. This applies to both the certification procedures and the requirements and procedures for reimbursement, where problems could occur. The aim of this article is to better understand the startups' experience in navigating through these procedures, the hurdles they encounter, and their need for support. Therefore, the digital association Bitkom e. V. and the Federal Institute for Drugs and Medical Devices (BfArM) conducted a web-based survey on five themes with a total of 23 questions. These questions focused inter alia on the composition of the team, product planning, familiarity with regulatory requirements, experience with institutions and different sources of information, the assessment of challenges in the process, and the resulting need for support.The analysis on the basis of 18 complete replies has shown that startups work on products with documentation and communications functions, but also integrate diagnostic and therapeutic features. The latter are characteristics of medical devices. Startups consider themselves to be relatively familiar with regulatory requirements regarding medical devices. The largest hurdles are associated with reimbursement: long and costly processes until the startups' products could be reimbursed.Both with regard to reimbursement and certification, startups see a need for low-threshold, cost-efficient advisory services and a simplification and acceleration of existing procedures with regard to medical devices.

[From idea to standard care-a field report]. / Der lange Weg von der Idee bis zur Erstattung ­ ein Reisebericht.

Digital health products and services have started to fundamentally change healthcare and prevention. Products intended for a medical use require CE-marking and potentially certification (ISO 13485) of the company. Startups play an important role in the development of new digital products and services. Two startups share their experience with these processes. Becoming a part of standard care and hence being reimbursed is a challenge for startups. For this reason, startups pursue alternative sources of income, too. The statutory health insurance's procedures for assessing new products and services are perceived as long. Startups are required to provide evidence of the benefit of their product at an early stage in the procedure. This requires time-consuming and costly studies. Startups would therefore appreciate support in generating this evidence, e. g. through adequate procedures for testing.

Controversies and consensus in the innovation access for cancer therapy in the European countries: on the subject of metastatic prostate cancer.

Innovative cancer therapies and advances in drug development have created new hopes for patients and health providers. The purpose of this article was to evaluate the discrepancies in the assessment of the magnitude of benefit of four new drugs (abiraterone acetate, enzalutamide, cabazitaxel, radium-223 dichloride) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The comparison was done among three European countries (UK, Germany and France) and Canada, according to the statement of each country and to the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale. Whereas those drugs are authorized by the European Medical Agency, one can observed that clear discrepancies in the magnitude of benefit assessment exist between selected countries, as well as between national pricing evaluation agencies and ESMO. However, price setting and reimbursement decisions remain national responsibility with differences in assessment of the medical value of new treatment across countries, leading to a heterogeneous accessibility to cancer treatments. In conclusion, several procedures have to be implemented to overcome the patchwork of administrative assessments. Among them, the assessment of medical value should be based on independent statements of learned societies, and the harmonization of access to cancer therapy in Europe has to be driven by a common European reimbursement and pricing policy.

An overview of biosimilars and non-biologic complex drugs in Europe, the United States, and Canada and their relevance to multiple sclerosis.

The advent of biological medicines has significantly transformed the landscapes of many disease spaces and improved the lives of millions around the world. However, the structural complexity and sensitivity of such products result in a high price tag, adding to already financially strained healthcare systems. As these and other expensive complex drugs lose market exclusivity, stakeholders eagerly await the arrival of lower cost alternatives, such as biosimilars and subsequent entry non-biological complex drugs (NBCDs). Nevertheless, stakeholders remain uncertain about key issues which have resulted in heterogeneous reimbursement policies and varying levels of biosimilar uptake and subsequent entry NBCD approval processes between different markets. With the imminent introduction of both subsequent entry NBCDs and biosimilars for multiple sclerosis (MS), it is important to get a better understanding of this new class of products and how healthcare systems have been adapting to their use. This article defines biosimilars and subsequent entry NBCDs and provides an overview of how these products have been introduced in Europe, the United States, and Canada from a regulatory, health technology, and reimbursement perspective. In addition, this article briefly explores the potential impact and outlook of biosimilar and NBCD products related to MS.

Linking the Regulatory and Reimbursement Processes for Medical Devices: The Need for Integrated Assessments.

Much criticism has been directed at the licencing requirements for medical devices (MDs) as they often result in a lack of robust evidence to inform health technology assessment (HTA) decisions. To better understand the current international decisional framework on MD technologies, we undertook three linked research studies: a review of the device regulatory procedures, a survey of current HTA practices and an empirical comparison of HTA reports of drugs versus MDs. Our review confirms that current device regulatory processes across the globe are substantially less stringent than drugs. As a result, international HTA agencies report that they face a number of challenges when assessing MDs, including reliance on suboptimal data to make clinical and cost-effectiveness decisions. Whilst many HTA agencies have adapted their processes and procedures to handle MD technology submissions, in our comparison of HTA reports we found little evidence of the application of methodologies that take account of device-specific issues, such as incremental development. Overall, our research reinforces the need for better linkage between licencing and HTA and the development and application of innovative HTA methodologies with the objective of securing faster patient access for those technologies that can be shown to represent good value for money. © 2017 The Authors. Health Economics Published by John Wiley & Sons, Ltd.

HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT FOR THE ADOPTION OF INNOVATIVE MEDICAL DEVICES WITHIN FRENCH HOSPITALS: OPPORTUNITIES AND CHALLENGES FOR INDUSTRY.

OBJECTIVES: Within French university hospitals, some internal committees are in charge of conducting hospital-based health technology assessment (Hb-HTA) to support managerial decisions regarding the adoption of innovations. For manufacturers, hospitals are usually the entry point for new and innovative medical devices, which cannot be accessed without the Hb-HTA committees' approval. Thus, the main objective of this pilot survey was to explore manufacturers' insights into Hb-HTA processes. METHODS: A two-step pilot survey was conducted in 2014. First, semi-structured phone interviews were carried out to capture manufacturers' feedback on the Hb-HTA procedure. Second, a prospective and iterative questionnaire designed to explore manufacturers' market access strategies was administered. RESULTS: Eight manufacturers from the medical device industry completed the retrospective phone interviews, and five of them participated in the prospective survey. According to the overall feedback, the Hb-HTA process timeline and transparency are major issues, and the expectations of internal committees, especially in terms of clinical evidence, remain difficult to understand. However, despite this and due to the complexity of reimbursement processes at the national level, manufacturers are increasingly considering hospital adoption through Hb-HTA submission as a viable market access and coverage opportunity. CONCLUSIONS: Our study reaffirms the primary role of hospitals in the diffusion of innovative medical devices. However, to ensure efficient and broad access to innovation, cooperation between local and national HTA bodies is critical and should be promoted.

[The French medecine pricing committee and the medicine economic policy: Rules and competences]. / Le comité économique des produits de santé et la politique économique du médicament : règles et compétences.

The French medicine pricing committee (CEPS), a governmental and inter-institutional body exercises essential competences for the regulation of the economy of the reimbursable drugs in France. It provides a good example of administered price regulation. It also supervises the proper use of products (control of promotion, conventional control of sales volumes). Finally, it regulates the annual envelope of drug expenditures by means of discounts paid by pharmaceutical companies. The article presents the legal criteria and the doctrine of price setting used in France. It details the types of market access contracts concluded by the CEPS. It specifies the conditions governing the annual envelope of expenditures on reimbursable medicines.

Delayed access to treatments for rare diseases: who's to blame?

The development and commercialization of drugs for rare diseases, termed 'orphan drugs', has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health-care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions--especially for rare disease therapies.

Early dialogue with health technology assessment bodies: a European perspective.

INTRODUCTION: Evidence requirements may differ across HTA bodies, and so pharmaceutical companies must plan to synergize their evidence generation strategy, across global regulatory and HTA bodies. Until recently, companies had no official platform to discuss the clinical development of a drug with HTA bodies; however, this is changing. OBJECTIVES: To achieve broad usage in the EU, products must achieve both regulatory and reimbursement approval, the latter of which is based on HTA appraisal in many markets. The objective of this study is to present and evaluate the different options available for early HTA consultation (during drug development/Phase III) in the major European markets from the industry perspective. METHODS: An exploratory (nonsystematic) literature review was performed to identify the European markets offering early HTA consultations, and each process was analyzed using a set of predefined metrics that are relevant to industry (the ability to consult with the regulatory body in parallel, consultation fees, length of consultation meeting, language of consultation meeting, maximum number of pharmaceutical company employees attending, procedural timelines, nature of data for which consultative advice can be sought, the output of the process, and the ability to involve external experts). RESULTS: Four different types of early HTA consultation processes were identified across the major European HTA markets. The nature of these processes varied in terms of the types and number of questions that can be addressed, the length of the meeting, the reporting output, and the ability to involve external experts. CONCLUSIONS: The availability of various options for early HTA consultation may help to avoid a mismatch between the evidence generated by means of a product's clinical development program, and the evidence expected by HTA bodies and payers, which can facilitate the pricing and reimbursement process upon a product's market authorization.

Research on the mechanism of leader-follower product sales competition based on market access restrictions and forward contract considerations.

Market access restrictions have been the focus of attention for various market players, but there are fewer studies on the competitive mechanism of market access restrictions on firms' product sales. This paper investigates the competitive mechanism of leader-follower product sales based on market access restrictions and forward contracts. First, the mechanism of leader-follower sales decisions based on market access restrictions and forward contracts is clarified. Second, it models the forward default risk suffered by followers and the profit rate of leader-follower based on market access restrictions and forward considerations by Bayes' posterior probability method. Moreover, it severely explores the impact mechanisms of the degree of market access restrictions on leaders and followers when followers do not adopt and adopt forwards and makes a simulation analysis. The results show that: (i) When followers do not employ forward contracts, the less restrictive degree of market access increases the supply of leaders, and leaders' competition for product sales further leads to a decrease in the provision of followers. (ii) When followers use forwards, leaders' and followers' expected discounted profit rates decrease with the total supply of products in the market increases. (iii) If the degree of market access restrictions is low, the followers suffer an increased forward default risk, resulting in their rate of revenue decrease. The findings of this paper have some practical significance and policy implications for the regulator to adjust the degree of market access restriction in each restricted access area, to establish a reasonable and efficient competitive environment for product sales, as well as for firms to choose the optimal way of competing for product sales.

Requirements to bring a medical device to market.

A roadmap for medical device innovators is presented that highlights the essential steps for regulatory authorization, market access, and reimbursement strategies in the USA, with a focus on strategic planning for commercial success, underscoring the integration of regulatory and market access considerations from the initial development of a medical device.