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The uptake of complex technologies and platforms has resulted in several challenges in the pricing and reimbursement of innovative pharmaceuticals. To address these challenges, plenty of concepts have already been described in the scientific literature about innovative value judgment or payment models, which are either (1) remaining theoretical; or (2) applied only in pilots with limited impact on patient access; or (3) applied so heterogeneously in many different countries that it prevents the health care industry from meeting expectations of HTA bodies and health care payers in the evidence requirements or offerings in different jurisdictions. This paper provides perspectives on how to reduce the heterogeneity of pharmaceutical payment models across European countries in five areas, including 1) extended evaluation frameworks, 2) performance-based risk-sharing agreements, 3) pooled procurement for low volume or urgent technologies, 4) alternative access schemes, and 5) delayed payment models for technologies with high upfront costs. Whilst pricing and reimbursement decisions will remain a competence of EU member states, there is a need for alignment of European pharmaceutical payment model components in critical areas with the ultimate objective of improving the equitable access of European patients to increasingly complex pharmaceutical technologies. [ABSTRACT FROM AUTHOR]

To understand the use of alternative payment models to address the reimbursement challenges of cell and gene therapies (CGT) in the U.S.A.. A literature search focused on CGT reimbursement in the U.S. market was conducted to identify information gaps and inform survey development. U.S. developers (n = 100) and payers (n = 195) were invited to complete an online survey between June and August 2022. The overall response rate was 16%; payer respondents represented 98 plans covering 338 million lives. Most developers (81%) and payers (84%) had implemented or were planning to implement at least one alternative payment model. Payers pursued these models to 'reduce product performance uncertainties' (81%), 'align therapy costs with benefits' (58%), and 'manage actuarial uncertainty' (54%). Developers aimed to 'streamline patient access' (92%) and 'mitigate budget impact' (77%). Common perceived barriers included increased administrative burden (developers 79% and payers 67%), defining performance measures (developers 71%, payers 83%) and addressing patient mobility (developers 71% and payers 63%). Both parties expressed a willingness to use real-world evidence for contract adjudication. Although limited by the number of participants, this survey indicates early discussions coupled with understanding motivations are essential for developing contracts that appeal to both parties and ensure patient access. [ABSTRACT FROM AUTHOR]

Changes to the Medicaid Drug Rebate Program (MDRP) determination of Medicaid Best Price (MBP) enables Value-based purchasing arrangements (VBPAs) to address financial uncertainty. This study estimates the likely effectiveness of MDRP-enabled VBPAs for chronically dosed medicines. Monte Carlo simulations examined: Multiple Best Prices and Bundled Sales MBP approaches authorized under MDRP and a third National Pooling approach using payment misalignment; needed payer size for practical participation; and the resulting potential number of covered lives under a VBPA as evaluation metrics. Both Multiple Best Prices and National Pooling enable VBPAs for 95% of scenarios (including all 5i chronic products with ≥1,000 treated patients per year), with 75% of those with payment misalignment ≤9%. National pooling for retail drugs has less participation and worse misalignment (5i: 95% contracted, 75% ≤9% misalignment; retail: 71%, 66%). Bundled Sales performed worst (5i: 40%, 75% ≤9%; retail: 31%, 88%) due to rebate volatility risk of breaking best price and Average Manufacturer Price impact. Medicaid sees worse misalignment for the 60% drug performance scenarios because of comparison to the statutory rebate (23.1%). The Multiple Best Prices approach has the lowest misalignment and could be applied to most chronic therapies, even rare ones. [ABSTRACT FROM AUTHOR]

Cell and gene therapies promise durable benefits but face financial challenges from the uncertainty in their performance. Value-based purchasing arrangements (VBPAs) can address uncertainty but have been inhibited in the US by the Medicaid Drug Rebate Program (MDRP) approach to determining Medicaid Best Price (MBP) rebates. The likely effectiveness of MDRP reform proposals enabling VBPAs is examined in this study for durable cell and gene therapies. Monte Carlo simulations examined three potential reforms (Multiple Best Prices, Bundled Sales, and National Pooling) to determine the impact on payment misalignment, the required payer size to participate, and the percentage of total lives covered by a VBPA. Simulation results suggest that 11% to 54% of commercial US lives would be feasibly covered by a VBPA depending on reform type and condition size. MPB reform achieved the highest commercial contracted percentage and lowest misalignment for commercial payers compared to National Pooling and Bundled Sales. State Medicaid plan results suggest lower extreme misalignment across all successfully contracted instances than commercial payers. The Multiple Best Prices will likely enable VBPAs for many durable cell and gene therapies and larger payers. Further reforms may be needed to extend VBPAs to ultra-orphan conditions. [ABSTRACT FROM AUTHOR]

Clinicians and patients often try a treatment for an initial period to inform longer‐term therapeutic decisions. A more rigorous approach involves N‐of‐1 trials. In these single‐patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double‐blinded, random sequence of alternating periods to determine the most effective treatment for that patient. However, to date, these trials are rarely done outside of research settings and have not been integrated into general care where they could offer substantial benefit. Designating this classical, N‐of‐1 trial design as type 1, there also are new and evolving uses of N‐of‐1 trials that we designate as type 2. In these, rather than focusing on optimizing treatment for chronic diseases when multiple approved choices are available, as is typical of type 1, a type 2 N‐of‐1 trial tests treatments designed specifically for a patient with a rare disease, to facilitate personalized medicine. While the aims differ, both types face the challenge of collecting individual‐patient evidence using standard, trusted, widely accepted methods. To fulfill their potential for producing both clinical and research benefits, and to be available for wide use, N‐of‐1 trials will have to fit into the current healthcare ecosystem. This will require generalizable and accepted processes, platforms, methods, and standards. This also will require sustainable value‐based arrangements among key stakeholders. In this article, we review opportunities, stakeholders, issues, and possible approaches that could support general use of N‐of‐1 trials and deliver benefit to patients and the healthcare enterprise. To assess and expand the benefits of N‐of‐1 trials, we propose multistakeholder meetings, workshops, and the generation of methods, standards, and platforms that would support wider availability and the value of N‐of‐1 trials. [ABSTRACT FROM AUTHOR]

Basic scientists and drug developers are accelerating innovations toward the goal of precision medicine. Regulators create pathways for timely patient access to precision medicines, including individualized therapies. Healthcare payors acknowledge the need for change but downstream innovation for coverage and reimbursement is only haltingly occurring. Performance uncertainty, high price‐tags, payment timing, and actuarial risk issues associated with precision medicines present novel financial challenges for payors. With traditional drug reimbursement frameworks, payment is based on an assumed randomized controlled trial (RCT) projection of real‐world effectiveness, a "trial‐and‐project" strategy; the clinical benefit realized for patients is not usually ascertained ex post by collection of real‐world data (RWD). To mitigate financial risks resulting from clinical performance uncertainty, manufacturers and payors devised "track‐and‐pay" frameworks (i.e., the tracking of a pre‐agreed treatment outcome which is linked to financial consequences). Whereas some track‐and‐pay arrangements have been successful, inherent weaknesses include the potential for misalignment of incentives, the risk of channeling of patients, and a failure to use the RWD generated to enable continuous learning about treatments. "Precision reimbursement" (PR) intends to overcome inherent weaknesses of simple track‐and‐pay schemes. In combining the collection of RWD with advanced analytics (e.g., artificial intelligence and machine learning) to generate actionable real‐world evidence, with prospective alignment of incentives across all stakeholders (including providers and patients), and with pre‐agreed use and dissemination of information generated, PR becomes a "learn‐and‐predict" model of payment for performance. We here describe in detail the concept of PR and lay out the next steps to make it a reality. [ABSTRACT FROM AUTHOR]

Background: Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan–Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching the milestone. Objective: To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). Method: The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. Results: All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect are dependent on the EDSS state of the patient. Greater age, longer time in a state, highest prior EDSS, having progressive MS and treatment had significant impacts, whereas age at onset had minor impact. Conclusion: Our study confirms that established factors associated with MS disease worsening in time to disease milestones also have impacts on annual progression. This approach adds granularity to what EDSS these factors have an influence. [ABSTRACT FROM AUTHOR]

Objectives: Value assessment frameworks have gained prominence recently in the context of U.S. healthcare. Such frameworks set out a series of factors that are considered in funding decisions. The UK's National Institute of Health and Care Excellence (NICE) is an established health technology assessment (HTA) agency. We present a novel application of text analysis that characterizes NICE's Technology Appraisals in the context of the newer assessment frameworks and present the results in a visual way. Methods: A total of 243 documents of NICE's medicines guidance from 2007 to 2016 were analyzed. Text analysis was used to identify a hierarchical set of decision factors considered in the assessments. The frequency of decision factors stated in the documents was determined and their association with terms related to uncertainty. The results were incorporated into visual representations of hierarchical factors. Results: We identified 125 decision factors, and hierarchically grouped these into eight domains: Clinical Effectiveness, Cost Effectiveness, Condition, Current Practice, Clinical Need, New Treatment, Studies, and Other Factors. Textual analysis showed all domains appeared consistently in the guidance documents. Many factors were commonly associated with terms relating to uncertainty. A series of visual representations was created. Conclusions: This study reveals the complexity and consistency of NICE's decision-making processes and demonstrates that cost effectiveness is not the only decision-criteria. The study highlights the importance of processes and methodology that can take both quantitative and qualitative information into account. Visualizations can help effectively communicate this complex information during the decision-making process and subsequently to stakeholders. [ABSTRACT FROM AUTHOR]

After nearly a decade of discussion, analysis, and development, the Medicines Adaptive Pathways to Patients (MAPPs) initiative is beginning to see acceptance from regulators, industry, patients, and payers, with the first live pilot project initiated under the guidance of the European Medicines Agency in 2014. Although it is a significant achievement to see the first asset being placed into human trials under an adaptive pathway, there is much to be learned regarding the multinational and multi-stakeholder effort that has driven the growing acceptance of MAPPs as a methodology and concept, as well as the need for continued and increasing international collaboration to foster the wider adoption of MAPPs. Changes in available science and technology, as well as a number of challenges in the current system, outlined in this paper, are transforming approaches to medicines development and approval. It is these challenges that have led directly to the groundbreaking MAPPs collaboration between the Massachusetts Institute of Technology Center for Biomedical Innovation’s New Drug Development Paradigms Initiative, the EMA, patient, payer and health technology assessment groups, the European Federation of Pharmaceutical Industries and Associations, and the Innovative Medicines Initiative—a European public-private partnership. This article examines the development of MAPPs, from inception of the concept, to the establishment of this trans-Atlantic initiative, and examines challenges for the future. [ABSTRACT FROM AUTHOR]

Successfully advancing Adaptive Llicensing requires coordinated planning and action across multiple stakeholders. The Janus Initiative combines a safe haven multi-stakeholder process with an integrated, best-of-breed quantitative simulation toolset to facilitate biomedical eco-system innovation discussions grounded in case-based realities. The process engages stakeholders from academia, patient advocacy, providers, payers, heath technology assessment, regulators and product sponsors. The quantitative toolset reflects the critical relationships among the parameters, decision domains and metrics relevant to these stakeholders from clinical development through regulatory approval, reimbursement authorization and clinical adoption over the entire product life span. The Janus Initiative, as part of the NEWDIGS program at MIT is moving forward with its first case studies and will continue to develop across multiple therapeutic areas and global regions. [ABSTRACT FROM AUTHOR]

Co-developing a drug with a diagnostic to create a stratified medicine - a therapy that is targeted to a specific patient population on the basis of a clinical characteristic such as a biomarker that predicts treatment response - presents challenges for product developers, regulators, payers and physicians. With the aim of developing a shared framework and tools for addressing these challenges, here we present an analysis using data from case studies in oncology and Alzheimer's disease, coupled with integrated computational modelling of clinical outcomes and developer economic value, to quantify the effects of decisions related to key issues such as the design of clinical trials. This illustrates how such analyses can aid the coordination of diagnostic and drug development, and the selection of optimal development and commercialization strategies. It also illustrates the impact of the interplay of these factors on the economic feasibility of stratified medicine, which has important implications for public policy makers. [ABSTRACT FROM AUTHOR]

While much has been written about the distinctions between biologics and small molecules in terms of their scientific, manufacturing and regulatory experiences, relatively little has been published comparing their clinical and commercial experiences. Employing a data base encompassing all 96 biologics and 212 small molecules newly launched in the U.S. between 1998Q1 and 2008Q4, we compare their downstream clinical and commercial characteristics. Substantial heterogeneity occurs across therapeutic classes. Biologics are more concentrated than small molecules in their therapeutic class composition, but have obtained FDA indication approvals in 13 of 15 classes. While average delays between FDA approval and first observed sales revenues are similar, biologics are twice as likely as small molecules to be Orphan Drugs, are slightly more likely to be designated FDA priority rather than standard review status, and gain slightly more supplemental indication approvals. Although 9.4% of new small molecules permanently exited the market for a variety of reasons, 7.3% of new biologics exited, but 26% of biologics had black box warnings compared to 20% of small molecules. Both biologics and small molecules take 21-22 quarters from launch to reach $100 million in real revenues. Small molecules have an initially more rapid uptake, but thereafter biologics' mean revenues tend to be slightly greater than for small molecules. While launch prices for biologics are commonly perceived as being greater than for small molecules, price growth per standard unit is generally greater for small molecules than biologics, with rates of price growth increasing for small molecules in the first five years since launch, and decreasing thereafter. We conclude that the market dynamics of biologics differ substantially from those of small molecules, although therapeutic class composition plays a major role. [ABSTRACT FROM AUTHOR]

The potential to use biomarkers for identifying patients that are more likely to benefit or experience an adverse reaction in response to a given therapy, and thereby better match patients with therapies, is anticipated to have a major effect on both clinical practice and the development of new drugs and diagnostics. In this article, we consider current and emerging examples in which therapies are matched with specific patient population characteristics using clinical biomarkers — which we call stratified medicine — and discuss the implications of this approach to future product development strategies and market structures. [ABSTRACT FROM AUTHOR]

This Viewpoint discusses a "Netflix" subscription model of drug payment being investigated by Louisiana for hepatitis C (HCV) drugs, in which a statewide coalition of payers would pay subscription fees over a fixed number of years for HCV drugs to treat all state residents and for efforts by the manufacturers to enhance treatment rates through patient outreach. [ABSTRACT FROM AUTHOR]

The article describe the structure of the pharmaceutical reward system and the way in which existing and proposed policies affect and introduce the "reward box" to summarize the financial returns across the phases of drug discovery approval, and sales. Topic include pharmaceutical policy can be understood in terms of how it affects the financial condition.

The article offers information on the worldwide use of personalized medicines for the treatment of central nervous system and immunological conditions. It mentions several criteria including drug approval from the U.S. Food and Drug Administration (FDA) and the European Medicine Agency for the use of personalized medicines. A graph of worldwide utilization of biologic personalized medicines from 1998 to 2009 is also presented.

Biologic drugs account for a disproportionate share of the increase in pharmaceutical spending in the US and worldwide. Against this backdrop, many look to the expanding market for biosimilars- follow-on products to biologic drugs-as a vehicle for controlling pharmaceutical spending. This study explores the early years of entry of biosimilars and related follow-on products in the US. Using monthly sales data from the period 2005-19 for ten drug classes, we examine how quickly biosimilars/follow-on products gained market share and the subsequent trajectory of prevailing (national average invoice) prices. Our analysis suggests that although uptake has been slower than what is typically seen in generic drug markets, the most recent entrants have captured market share more rapidly than comparable earlier biosimilars/ follow-on products. We also document that from biosimilar/follow-on products' time of entry, their lower prices help offset the overall trend in average annual reference-product price increases. Our findings can provide insight into future policy reforms aimed at increasing competition and use of biosimilars, leading to expanded patient access and significant cost savings. [ABSTRACT FROM AUTHOR]