OBJECTIVES:The use of surrogate endpoints poses challenges to health technology assessment (HTA) agencies and payers when informing the clinical and cost-effectiveness of health technologies. Decision makers often need to make recommendations in the absence of well-established evidence on their validation, particularly when the surrogate endpoint is novel without clear links to the longer-term outcome. This study explored the guidance needs of HTA agencies and identified how they have considered and dealt with surrogate endpoints in cost-effectiveness analysis. METHODS:A qualitative study was used to explore the professional experiences of international HTA staff and their collaborators. Data were collected using three focus groups with 29 participants representing 20 HTA agencies or associated organizations. Framework analysis was used to identify themes from the transcripts. RESULTS:HTA agencies frequently see submissions featuring surrogate endpoints. Issues they face include definitional concerns, absent or weak evidentiary links, and resource-intensive validation methods. Versatile guidance that is mindful of these challenges, such as those faced with rare diseases, is required. This would help to clarify expectations and help ascertain the required information from industry for economic modeling, on how to present the uncertainty arising from surrogate endpoints, and how to appropriately report the findings. CONCLUSIONS:Decision making using surrogate endpoints is a frequent and challenging problem faced by HTA agencies. These results provide the first-hand experiences and reflect the needs of HTA agencies globally. The resulting recommendations and considerations for the use of surrogate endpoints in economic modeling should benefit HTA agencies moving forward.

Objectives Federal and state drug pricing programs typically involve a review of comparative clinical evidence to understand the added benefit that interventions provide for the indicated and covered patient population. Contemporary (recent) comparative effectiveness research (CER) can be instrumental in illustrating benefit under conditions of current, real-world use to support these decisions. Methods We convened 7 subject-matter experts plus 2 expert moderators to discuss gaps, challenges, and opportunities around the use of contemporary CER for federal and state drug pricing programs. We synthesized and structured key recommendations for the use of CER for policy and pricing decision makers. Results Key gaps and challenges to using contemporary CER to support pricing decisions by the Centers for Medicare and Medicaid Services and state Prescription Drug Affordability Boards are centered around soliciting and generating fit-for-purpose evidence, improving transparency on how evidence is used in decision making, and mitigating resource constraints. Recommendations for policymakers include asking clear questions to solicit necessary data, considering a Population-Intervention-Comparator-Outcomes-Time framework, balancing usefulness with limitations, improving transparency on decision-making, and streamlining processes. Recommendations for manufacturers include leveraging resources, supporting scientific credibility, and tailoring evidence submissions to decision-maker realities. Conclusions Incorporating contemporary CER is critical for informing policymakers on the value of interventions for drug pricing negotiations. Evaluating evidence, answering research questions, and inferring how evidence applies to different populations are core principles in health economics and health policy, which should be applied more rigorously and transparently in drug pricing programs.

Genetic tests predict an individual’s risk of developing neurodegenerative diseases. A portion of the value provided by genetic tests can be attributed to the individual’s value of early knowledge of their risk, or the “value of knowing.” We developed a discrete choice experiment survey and administered it to a nationally representative sample of US adults. Respondents were presented with 8 choice tasks, each with two hypothetical tests and an opt-out option, where tests varied in cost, type, and accuracy. Respondents were randomly assigned to scenarios with varied disease severity, perceived risk, treatment availability, and whom the test was for. We used a generalized multinomial logit model to estimate preferences and willingness to pay (WTP). The final sample included 1,034 respondents. The alternative-specific constant implied a baseline model-derived WTP of 2,954 (95

The Centers for Medicare and Medicaid Services (CMS) can now negotiate the prices of a set of drugs that represent significant Medicare expenditures. The long-term success of negotiations will depend in part on stakeholders' views on the program's transparency and inclusivity. CMS has completed its first round of price negotiations for ten drugs; the prices will become effective on January 1, 2026. For future rounds, we advocate that CMS adopt a different price negotiation approach, one that embodies the best practices of health technology assessment-the discipline that determines a fair drug price in many settings worldwide. Our proposed framework consists of four components: selection of therapeutic alternatives, assessment of the value of the selected drugs, a decision matrix for weighting multiple negotiation factors, and a deliberation on the accumulated clinical and economic evidence by an independent advisory committee. Patient, caregiver, and other stakeholder engagement is integrated in each component.

Conducting high-quality health technology assessments requires high-quality evidence. With evolving regulatory standards for faster approval of new pharmaceutical products, health technology practitioners often find that the evidence base available to inform their work is lacking. This review article provides case examples of how health technology assessors have grappled with this tension, from the United States and European perspective, including experiences with new therapies for large populations, such as Alzheimer's disease, and gene therapies for ultra-rare conditions. The article concludes by offering some potential policy solutions that can meet the goals of robust evidence generation, patient access, and system affordability, including reimbursement with evidence development, outcomes-based contracts, and other types of managed entry agreements.

The FDA Commissioner's new National Priority Voucher program seeks to accelerate drug approvals for products meeting certain criteria. Interestingly, the program intends to increase affordability of new drugs. With few specifics available as to how the program will achieve that goal, this paper proposes a framework for leveraging independent value assessments to achieve affordable access while incentivizing evidence development and innovation.

ObjectiveTo assess the cost-effectiveness of emicizumab prophylaxis for patients having haemophilia A with inhibitors in the Indian context using an adaptive health technology assessment (aHTA) methodology.DesignEconomic evaluation using multiple approaches aimed at adjusting previously generated cost-effectiveness results based on (1) price differences only (‘simple’) and (2) differences in cost and expected treatment duration (‘moderate’) and differences in cost, inflation and life expectancy (‘complex’).SettingTypical haemophilia care in India.ParticipantsPatients with haemophilia A and inhibitors.InterventionEmicizumab prophylaxis using two vial strengths (30 or 150 mg/mL) in comparison to no prophylaxis.Main outcome measuresAdjusted incremental cost-effectiveness ratio (ICERa), incremental costs and incremental quality-adjusted life years associated with emicizumab prophylaxis from both the health system and societal perspectives.ResultsUsing the simple ICER adjustment method, emicizumab prophylaxis resulted in potential cost savings from the payers’ perspective for both vial strengths in patients aged ≥12 and <12 years. However, from a societal perspective, emicizumab prophylaxis was not cost-effective. Using the moderate adjustment method, emicizumab prophylaxis showed potential cost saving from the health system perspective. The complex adjustment method also revealed cost savings for emicizumab prophylaxis from the health system and societal perspectives across different age groups.ConclusionWe found that implementing emicizumab prophylaxis for patients with haemophilia A and inhibitors in India has the potential to result in cost savings. This study highlights the feasibility of using the expanded aHTA methodology for rapid evidence generation in the Indian context. However, it is crucial to address certain research gaps, including data limitations, challenges in translating international evidence to Indian context and associated uncertainties. Additionally, conducting a comprehensive budget impact analysis is necessary. These findings hold significant implications for decision-making regarding the potential provision of emicizumab prophylaxis through federal or/and state government-funded programmes and institutions in India.

BACKGROUND:Health technology assessment (HTA) involves a formal review of the clinical, economic, and societal implications of health technologies. Internationally, HTA supports decisions regarding access to novel therapeutics. However, the role of HTA in the decision-making processes of US-based health care payers remains unclear. OBJECTIVE:To assess how frequently US commercial health plans reference HTAs in their specialty drug coverage policies. METHODS:Using the Tufts Medical Center Specialty Drug Evidence and Coverage database, we reviewed the evidence cited in the publicly available specialty drug coverage policies of 17 US commercial health plans. We assessed the frequency of HTA citations and characterized them by (1) country of origin, (2) publishing organization, (3) whether it addressed a treatment's cost-effectiveness, (4) disease category addressed, and (5) whether it assessed orphan or nonorphan treatments. RESULTS:HTAs accounted for 450 of the 14,033 citations in our analysis (3.2%), with the frequency of HTA citations varying across health plans (0.1% to 7.4% of cited evidence). Ex-US HTAs were cited more frequently than US-based HTAs (65.3%). However, a single health plan accounted for the majority of HTA citations (57.1%) and ex-US citations (76.2%). Most cited HTAs included cost-effectiveness assessments (78.7%). The 3 disease categories for which plans most often cited HTAs were neurological disorders (24.8%), musculoskeletal disorders (21.5%), and cancers (14.6%). Health plans cited HTAs for nonorphan drugs more often than for orphan drugs (59.4%). CONCLUSIONS:HTAs represented a small portion of the evidence cited by health plans in specialty drug coverage decisions, with significant variation in citation frequency across plans. Plans cited both US and ex-US HTAs, and most cited HTAs included a cost-effectiveness assessment. These findings suggest that health plans may consider the information provided by HTAs when formulating coverage policies.

OBJECTIVES:This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS:Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS:Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS:CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

ImportanceThe arrival of new medications for Alzheimer disease (AD) has prompted efforts to measure their value using conventional cost-effectiveness analyses; however, these analyses focus on how much health improvement new medications generate per dollar spent. As AD disproportionately affects older adults, women, racial and ethnic minority individuals, and individuals with lower socioeconomic and educational levels, it is critical to also examine the health equity outcomes of treatment.ObjectiveTo estimate the health equity impact of a hypothetical disease-modifying treatment for early AD in the US and to examine targeted policies to mitigate health care disparities.Design, Setting, and ParticipantsThis economic evaluation, which used a distributional cost-effectiveness analysis, was conducted from June 16, 2022, to January 11, 2024. The study included subgroups defined by race and ethnicity and by social vulnerability quintiles in the US.ExposuresA hypothetical disease-modifying treatment compared with best supportive care.Main Outcomes and MeasuresThe main outcomes were population-level quality-adjusted life-years (QALYs), lifetime costs, and net health benefits. The social welfare impact and change in health inequality were estimated using the Atkinson index.ResultsThe distributional cost-effectiveness analysis simulated 316 037 100 individuals from the US population, including 25 subgroups defined by 5 categories of race and ethnicity and population quintiles of social vulnerability, with the fifth quintile representing the most socially vulnerable group. At an opportunity cost benchmark of $150 000 per QALY, treatment was associated with improved population health, adding 28 197 QALYs per year to the US population. Accounting for health inequality preferences (using an aversion level of 11, based on an Atkinson inequality aversion parameter that can range from 0 to infinity, with higher values assigning greater weight to health gains that accrue to the population with the lowest lifetime quality-adjusted life expectancy), treatment was associated with a 0.009% reduction in existing population health inequalities annually. Scenario analyses examining earlier and expanded treatment access suggested a population health improvement of up to 221 358 QALYs.Conclusions and RelevanceThe findings of this economic evaluation suggest that treatment for AD could improve population health and health equity. Policies to enable earlier diagnosis and treatment initiation, as well as expanded access to treatment, may further improve treatment and health equity impacts.

KEYWORDS: Health technology assessmentCost-effectiveness analysisPharmaceutical pricingHealth care costsUnited States

Operationalization guidance is needed to support health technology assessment (HTA) bodies considering implementing lifecycle HTA (LC-HTA) approaches. The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established a Task Force to develop a position paper on LC-HTA. In its first paper, the Task Force established a definition and framework for LC-HTA in order to tailor it to specific decision problems. This second paper focused on the provision of practical operational guidance to implement LC-HTA. Detailed descriptions of the three LC-HTA operational steps are provided (defining the decision problem, sequencing of HTA activities, and developing optimization criteria) and accompanied by worked examples and an operationalization checklist with 20 different questions for HTA bodies to consider when developing an LC-HTA approach. The questions were designed to be applicable across different types of HTA and scenarios, and require adaptation to local jurisdictions, remits, and context.

Objective: This manuscript highlights the importance of enhancing the uptake of Core Outcome Sets (COS) by building partnerships with Collaborators and addressing their needs in COS development. Methods and setting: This session was structured as a simulation, resembling a format akin to a classic television game show. The moderator posed a series of questions to eight different Collaborator groups who briefly described the importance of COS within their areas of interest. Previous studies examining the uptake of individual core outcomes revealed disparities in uptake rates. The Identified barriers to the uptake of COS include the lack of recommendations for validated instruments for each domain, insufficient involvement of patients and key Collaborator groups in COS development, and a lack of awareness regarding the existence of COS. Conclusions: This analysis underscores the need for COS development approaches that prioritize the inclusion of patients and diverse Collaborator groups at every stage. While current studies on COS uptake are limited, future research should explore the broader implementation of COS across diverse disease categories and delve into the factors that hinder or facilitate their uptake such as, the importance of COS developers extending their work to recommending domains with well validated instruments. Embracing patient leadership and multifaceted engagement is essential for advancing the relevance and impact of COS in clinical research.

Regulatory agencies worldwide have taken significant steps to expedite approval and market authorization of medicines based on their potential to address areas of significant unmet medical need and severe disease burden. However, initial approval of such medicines is often accompanied by limited evidence of benefit, posing a conundrum for payers and health systems who may desire greater certainty of their value. This paper describes a system of "accelerated access" to manage these tensions and coordinate activities across stakeholders, based on discussions held at a multi-stakeholder convening in June 2023. We focus on 6 core, near-term actions that can be taken to improve the current system: clarifying criteria for expedited regulatory approval, enhancing stakeholder coordination, creating expedited pathways in payer and health technology assessment settings, developing joint regulatory/payer/health technology assessment guidance on study design and data needs, linking pricing policy to data uncertainty, and improving patient and public understanding of the processes involved as well as the risks and benefits of the relevant medicines. Many of these actions will require additional resources and personnel, and some will necessitate unprecedented levels of coordination. Nevertheless, each action is designed to work with minimal adjustments to the current system rather than demanding an entirely new approach.

Accelerated and conditional regulatory pathways for drug approvals are intended to enable earlier patient access to potentially life-saving treatments, or treatments that provide benefits in addressing a significant unmet need. However, there are questions about how well such pathways work, how appropriately they are applied, and how the work of regulators can be better coordinated with that of health technology assessment (HTA) and payer bodies, providers and health systems, and other stakeholders. In June 2023, a multi-stakeholder, international workshop was convened in Adelaide, Australia, to deliberate the challenges, goals, and opportunities to improve accelerated access pathways. Workshop attendees included representatives from patient organizations, regulators, HTA/payer bodies, universities (ethicists, health economists), and companies developing and marketing new medicines from Australia, Asia, Europe, and North America. We reviewed the contents of this workshop to identify areas of agreement and disagreement, report the key themes of the discussion, and delineate next steps for improving accelerated access pathways. We found that there was general agreement among workshop attendees that accelerated access could be improved significantly by strengthening processes for stakeholder coordination, and that coordinated efforts will be required to implement meaningful change moving forward.