The value of the accelerated approval pathway: real-world outcomes associated with reducing the time between innovations.

Aim: We investigated the effect of shortening time between innovations with the accelerated approval (AA) pathway on patient outcomes for three solid tumors. Methods: This real-world analysis evaluated patients receiving sequential AA pathway-approved innovations after initial treatment with existing therapies in three solid tumor case studies. Outcomes attributable to AA were estimated and assumed approval occurred at the time of conversion to approval and extrapolated to the US population. Results: Survival gains from accessing innovative therapies were 2.3-3.8-times higher when using the AA pathway. At the US population level, AA was associated with ∼8000 life-years gained across all three tumor case studies. Conclusion: In areas of rapid clinical development, the value of existing therapies can be enhanced by earlier access to AA pathway innovations and should be considered when evaluating the AA program.

What is this study about? The US Food and Drug Administration's accelerated approval pathway provides patients with access to innovative drugs sooner than standard regulatory pathways. Using three case studies in solid tumors, this study measured how many patients on current cancer drugs received future cancer drugs because of the accelerated approval pathway and asked whether quicker access to new drugs resulted in them living longer. What were the results? In three cancer case studies, the accelerated approval pathway led to more patients receiving future cancer drugs. Patients who received future drugs through the AA pathway lived longer than patients who did not have access to them. What do the results of the study mean? The accelerated approval pathway is important because it can improve outcomes of current cancer drugs by giving patients additional treatments to choose from in the future and therefore a chance to live longer. Policymakers should consider this when thinking about making changes to the accelerated approval pathway.

Assessing the impact of grief on quality of life, work productivity, and health outcomes for parents bereaved from SMA: A study protocol.

BACKGROUND: U.S. cost-effectiveness recommendations suggest that analyses should include all costs and effects relevant to the decision problem [1]. However, in many diseases, including spinal muscular atrophy (SMA), few studies have evaluated bereaved family outcomes after a child has died, neglecting potential impacts on their health-related quality of life (HRQoL), work productivity, and mental health. Additionally, grief-related outcomes are rarely included in economic evaluations. This manuscript outlines the protocol of a study that will estimate the HRQoL, work functioning, and mental health of bereaved parents of children with SMA type 1 to determine how outcomes vary based on parent's sex and the time since a child's death. METHODS: This study will involve two phases. In Phase 1, we will conduct a literature review to identify prior research that has measured how parental grief impacts HRQoL, work productivity, and mental health. We will also interview four bereaved parents of children with SMA type 1, stratified by parent sex and time since their child's death, and analyze findings using a thematic analysis. In Phase 2, we will develop a survey draft based on Phase 1 findings. Parents bereaved from SMA type 1 will review our survey draft and we will revise the survey based on their feedback. We will send a cross-sectional survey to approximately 880 parents bereaved from SMA type 1. We will analyze findings from the survey to investigate whether the severity of grief symptoms is correlated with HRQoL, productivity, depression and anxiety symptom severity. We will also evaluate whether the mean scores of grief and each of the outcomes vary significantly when stratified by parent sex and the time since the child's death. DISCUSSION: Our results will provide preliminary information on how parental grief can impact HRQoL, productivity, and mental health outcomes over time. Increasing the availability of family outcomes data will potentially assist organizations performing health economic evaluations, such as the Institute of Clinical and Economic Review (ICER) in the U.S. This research will also help to inform the development of future economic guidelines on this topic.

Estimating the US Baseline Distribution of Health Inequalities Across Race, Ethnicity, and Geography for Equity-Informative Cost-Effectiveness Analysis.

OBJECTIVES: Information on how life expectancy, disability-free life expectancy, and quality-adjusted life expectancy varies across equity-relevant subgroups is required to conduct distributional cost-effectiveness analysis. These summary measures are not comprehensively available in the United States, given limitations in nationally representative data across racial and ethnic groups. METHODS: Through linkage of US national survey data sets and use of Bayesian models to address missing and suppressed mortality data, we estimate health outcomes across 5 racial and ethnic subgroups (non-Hispanic American Indian or Alaska Native, non-Hispanic Asian and Pacific Islander, non-Hispanic black, non-Hispanic white, and Hispanic). Mortality, disability, and social determinant of health data were combined to estimate sex- and age-based outcomes for equity-relevant subgroups based on race and ethnicity, as well as county-level social vulnerability. RESULTS: Life expectancy, disability-free life expectancy, and quality-adjusted life expectancy at birth declined from 79.5, 69.4, and 64.3 years, respectively, among the 20% least socially vulnerable (best-off) counties to 76.8, 63.6, and 61.1 years, respectively, among the 20% most socially vulnerable (worst-off) counties. Considering differences across racial and ethnic subgroups, as well as geography, gaps between the best-off (Asian and Pacific Islander; 20% least socially vulnerable counties) and worst-off (American Indian/Alaska Native; 20% most socially vulnerable counties) subgroups were large (17.6 life-years, 20.9 disability-free life-years, and 18.0 quality-adjusted life-years) and increased with age. CONCLUSIONS: Existing disparities in health across geographies and racial and ethnic subgroups may lead to distributional differences in the impact of health interventions. Data from this study support routine estimation of equity effects in healthcare decision making, including distributional cost-effectiveness analysis.

The Value of New: Consideration of Product Novelty in Health Technology Assessments of Pharmaceuticals.

BACKGROUND: Efforts to understand how treatments affect patients and society have broadened the criteria that health technology assessment (HTA) organizations apply to value assessments. We examined whether HTA agencies in eight countries consider treatment novelty in methods and deliberations. METHODS: We defined a novel pharmaceutical product to be one that offers a new approach to treatment (e.g., new mechanism of action), addresses an unmet need (e.g., targets a rare condition without effective treatments), or has a broader impact beyond what is typically measured in an HTA. We reviewed peer-reviewed publications and technical guidance materials from HTA organizations in Australia, Canada, England, France, The Netherlands, Norway, Sweden, and the United States (US). In addition, we explored how HTA organizations integrated novelty considerations into deliberations and recommendations related to two newer therapies-voretigene neparvovec for an inherited retinal disorder and ocrelizumab for multiple sclerosis. RESULTS: None of the HTA organizations acknowledge treatment novelty as an explicit value criterion in their assessments of pharmaceutical products. However, drugs that have novel characteristics are given special consideration, particularly when they address an unmet need. Several organizations document a willingness to expend more resources and accept greater evidence uncertainty for such treatments. Qualitative deliberations about the additional unquantified potential benefits of treatment may also influence HTA recommendations. CONCLUSION: Major HTA organizations do not recognize novelty as an explicit value criterion, although drugs with novel characteristics may receive special consideration. There is an opportunity for organizations to codify their approach to evaluating novelty in value assessment.

Distributional Cost-Effectiveness Analysis of Health Technologies: Data Requirements and Challenges.

Governments and health technology assessment agencies are putting greater focus on and efforts in understanding and addressing health inequities. Cost-effectiveness analyses are used to evaluate the costs and health gains of different interventions to inform the decision-making process on funding of new treatments. Distributional cost-effectiveness analysis (DCEA) is an extension of cost-effectiveness analysis that quantifies the equity impact of funding new treatments. Key challenges for the routine and consistent implementation of DCEA are the lack of clearly defined equity concerns from decision makers and endorsed measures to define equity subgroups and the availability of evidence that allows analysis of differences in data inputs associated with the equity characteristics of interest. In this article, we detail the data gaps and challenges to build robust DCEA analysis routinely in health technology assessment and suggest actions to overcome these hurdles.

The Impact of Funding Inpatient Treatments for COVID-19 on Health Equity in the United States: A Distributional Cost-Effectiveness Analysis.

OBJECTIVES: We conducted a distributional cost-effectiveness analysis (DCEA) to evaluate how Medicare funding of inpatient COVID-19 treatments affected health equity in the United States. METHODS: A DCEA, based on an existing cost-effectiveness analysis model, was conducted from the perspective of a single US payer, Medicare. The US population was divided based on race and ethnicity (Hispanic, non-Hispanic black, and non-Hispanic white) and county-level social vulnerability index (5 quintile groups) into 15 equity-relevant subgroups. The baseline distribution of quality-adjusted life expectancy was estimated across the equity subgroups. Opportunity costs were estimated by converting total spend on COVID-19 inpatient treatments into health losses, expressed as quality-adjusted life-years (QALYs), using base-case assumptions of an opportunity cost threshold of $150 000 per QALY gained and an equal distribution of opportunity costs across equity-relevant subgroups. RESULTS: More socially vulnerable populations received larger per capita health benefits due to higher COVID-19 incidence and baseline in-hospital mortality. The total direct medical cost of inpatient COVID-19 interventions in the United States in 2020 was estimated at $25.83 billion with an estimated net benefit of 735 569 QALYs after adjusting for opportunity costs. Funding inpatient COVID-19 treatment reduced the population-level burden of health inequality by 0.234%. Conclusions remained robust across scenario and sensitivity analyses. CONCLUSIONS: To the best of our knowledge, this is the first DCEA to quantify the equity implications of funding COVID-19 treatments in the United States. Medicare funding of COVID-19 treatments in the United States could improve overall health while reducing existing health inequalities.

A Pragmatic Guide to Assessing Real Option Value for Medical Technologies.

OBJECTIVES: This study aimed to provide recommendations for identifying and implementing real option value (ROV) calculations in value assessment. METHODS: We identified the primary mechanisms through which ROV can be created based on a theoretical framework for ROV, assessed approaches for predicting future innovations and improvements in health, and described the steps for estimating ROV in a cost-effectiveness analysis framework. RESULTS: The 3 primary mechanisms by which ROV can be created are when a current treatment (1) prolongs survival to increase the proportion of patients who can receive future innovations, (2) slows disease progression to increase patients' eligibility for future innovations, and (3) directly affects the efficacy of future innovations. We provide 5 recommendations for implementing ROV in value assessment. First, the decision to quantify ROV should be based on a qualitative evaluation of whether the treatment can enable greater benefits from future innovations. Second, ROV should be quantified in the same value assessment framework (eg, cost-effectiveness analysis using quality-adjusted life-year) as the conventional value. Third, method for quantifying ROV should consider data availability, rate of innovation, and sources of future health improvements. Fourth, ROV estimate should be presented alongside the conventional value as a separate element due to its inherently large uncertainty. Finally, generalizability of ROV estimate should be evaluated, and local data should be used when available. CONCLUSIONS: ROV can arise from a variety of mechanisms that should be considered before investing in an ROV analysis. Calculating ROV includes exploring different approaches for forecasting future innovations and future improvements in health.

When are breakthrough therapies cost-effective?

BACKGROUND: An increasing proportion of novel drug approvals use accelerated pathways, with notable growth in the US Food and Drug Administration-designated breakthrough pathway in recent years. Breakthrough therapy (BT) designation suggests that these therapies offer substantial potential to improve health outcomes but their value for money is not fully understood, as BTs typically cost more than non-BTs (NBTs). OBJECTIVE: To assess the economic value of BTs and factors associated with their reported value. METHODS: Using the Tufts Medical Center Cost-Effectiveness (CE) Analysis Registry, we (1) summarized the CE of BTs, as measured by cost per quality-adjusted-life-year (QALY); (2) compared the CE of BTs and NBTs in the United States; and (3) identified factors associated with BT CE using general estimating equation models across US willingness-to-pay (WTP) benchmarks ($50K-$150K/QALY). RESULTS: Between 2013 and 2018, the US Food and Drug Administration approved 279 drugs, designating 83 (32%) as BTs. Incremental costs and health gains (QALYs) were higher for BTs relative to NBTs ($29,000 vs $20,000 and 0.7 vs 0.2 QALYs, respectively), and BTs had more favorable CE ratios compared with NBTs (median values $38,000/QALY vs $50,000/QALY, respectively). For BTs, hepatitis C treatments had the most favorable CE ratios, which may be driven by the curative nature of some hepatitis C therapies. Furthermore, BT CE ratios for new molecular entities (NMEs) were about 40% lower than ratios for non-NME BTs on average, which may signal more value for money when the BT has a new active molecule. Regression analysis to identify trends driving CE found that BT drugs compared with active comparators (instead of best supportive care) were less likely to be cost-effective at standard US WTP thresholds (odds ratio [OR] = 0.1-0.6) and that BTs in the neoplasm space also trended less likely to be cost-effective (OR = 0.12-0.43). CE ratios reported by studies with industry funding were also more likely to be cost-effective than ratios from studies with other funding sources (OR = 4.3-4.5), though this finding was not significant at WTP thresholds over $50,000/QALY gained. CONCLUSIONS: Evidence from published, peer-reviewed CE studies suggests that BTs may confer greater health benefits than NBTs in terms of overall QALYs. Our analysis supports that the US Food and Drug Administration BT designation may be associated with increased value for money for these BTs. However, factors such as the disease area, NME status, and comparator (active vs standard of care) will also influence whether these therapies are cost-effective. DISCLOSURES: Dr Cohen reports grants or contracts from PhRMA Foundation, National Pharmaceutical Council, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Gilead Sciences, Regeneron, Pfizer, Merck, Johnson & Johnson, Vir Biotechnology, Moderna, Amgen, and Lundbeck; consulting fees from AbbVie, Biogen, IQVIA, Novartis, Partnership for Health Analytic Research, Pharmerit, Precision Health Economics, Sage, Sanofi, and Sarepta; and stock or stock options from Bristol-Myers Squibb, Johnson & Johnson, and Merck. Ms Kowal is an employee and stockholder of Genentech, Inc. Dr Yeh is an employee and stockholder of Roche, Inc.

Modeling the Ex Ante Clinical Real Option Value in an Innovative Therapeutic Area: ALK-Positive Non-Small-Cell Lung Cancer.

OBJECTIVES: A drug that improves survival and/or disease progression can create real option value (ROV)-the additional health gain from future innovations enabled by a longer survival. ROV can be a relevant consideration for both clinical and payer decision-makers. We aimed to estimate the ex ante ROV for first-line (1L) alectinib in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). METHODS: We developed a Markov model to estimate life-years (LYs) and quality-adjusted life-years (QALYs) gained with 1L alectinib versus 1L crizotinib due to potential future second-line (2L) drugs. Transition probabilities were derived from the phase 3 trial of 1L alectinib and phase 2 trial of 2L brigatinib. We identified drugs being studied in phase 2 and 3 trials in ALK-positive NSCLC at the time of alectinib's 1L approval and projected the likelihood and timing of their arrival and their potential efficacy based on publicly available data. RESULTS: The discounted incremental LYs and QALYs for alectinib increased by 12.9% (95% CR - 2.96%, 34.82%; 1.25 vs. 1.11) and 11.2% (95% CR - 2.14%, 29.29%; 1.03 vs. 0.92), respectively, after accounting for ROV. The incremental ROV of alectinib was sensitive to the projected efficacy of future drugs, uptake level, and the hazard ratio of progression-free survival of alectinib (vs. crizotinib). CONCLUSIONS: Ex ante ROV can be a significant value consideration in therapeutic areas with high levels of expected innovation. The potential efficacy of future drugs and incremental survival with alectinib at the projected time of arrival are important considerations in assessing ROV.

Evaluating Real-World National and Regional Trends in Definitive Closure in U.S. Burn Care: A Survey of U.S. Burn Centers.

To better understand trends in burn treatment patterns related to definitive closure, this study sought to benchmark real-world survey data with national data contained within the National Burn Repository version 8.0 (NBR v8.0) across key burn center practice patterns, resource utilization, and clinical outcomes. A survey, administered to a representative sample of U.S. burn surgeons, collected information across several domains: burn center characteristics, patient characteristics including number of patients and burn size and depth, aggregate number of procedures, resource use such as autograft procedure time and dressing changes, and costs. Survey findings were aggregated by key outcomes (number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Benchmarking survey results against the NBR v8.0 demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. An overall reduction in the number of autograft procedures was observed compared to NBR v8.0, and time efficiencies improved as the intervention time per TBSA decreases as TBSA increases. Both nationally and regionally, an increase in costs was observed. The results suggest resource use estimates from NBR v8.0 may be higher than current practices, thus highlighting the importance of improved and timely NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization, thus increasing our understanding of burn center operations and behavior.

Cost-effectiveness of intensification with SGLT2 inhibitors for type 2 diabetes.

OBJECTIVES: Using a US payer perspective, this study aimed to compare the lifetime cost-effectiveness of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors vs switching to glucagon-like peptide 1 receptor agonists (GLP-1 RAs) among patients with type 2 diabetes who were not at glycated hemoglobin A1c target after dual therapy with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. STUDY DESIGN: The cost-effectiveness analysis was performed with the validated IQVIA Core Diabetes Model. Treatment effects were obtained from randomized clinical trials with economic data based on published literature. METHODS: Risk of treatment-emergent adverse events and complications were simulated using submodels informed by published risk equations adjusted for patient characteristics, physiological parameters, and history of complications. Outcomes included cumulative incidence of micro- and macrovascular complications, life-years (LYs), quality-adjusted life-years (QALYs), and total costs. Scenario analyses were performed to assess robustness of results to variations in clinical and cost inputs and assumptions. RESULTS: Over a lifetime time horizon, adding an SGLT2 inhibitor dominated the strategy of switching to a GLP-1 RA, improving survival by 0.049 LYs and 0.026 QALYs, and was associated with cost savings of $9511. The majority of the scenario analyses confirmed dominance of the DPP-4 inhibitor + SGLT2 inhibitor pathway vs the GLP-1 RA pathway. The probabilistic sensitivity analysis reinforced the base-case finding of cost savings while gaining QALYs. CONCLUSIONS: Intensification with an SGLT2 inhibitor on top of a DPP-4 inhibitor demonstrated slightly better efficacy and cost savings compared with switching to a GLP-1 RA in patients not at glycemic goal with metformin and a DPP-4 inhibitor.

Stakeholder point of view on prescription drug affordability - a systematic literature review and content analysis.

OBJECTIVES: The objectives of this research were to: 1) understand perspectives on affordability of pharmaceutical drugs from the point of view of stakeholders as reported in published peer-reviewed journals and conferences; 2) evaluate if (and how) perspectives on affordability overlapped across stakeholders. METHODS: The systematic literature review followed Cochrane and PRISMA guidelines. Content analysis with iterative and systematic coding of text was conducted, to identify themes. RESULTS: A total of 7,372 unique citations were eligible, and 126 articles included for final synthesis. For patients, 6 core themes emerged: financial barriers, adherence, access, patient-provider communication, financial distress, and factors that impact affordability. For payers, 5 core themes: financing schemes, cost-effectiveness, budget impact, private vs. public preferences, and ethics. For providers, 3 themes: patient-provider communication, physician prescribing behavior, and finding alternatives to support patient access. For policymakers, 2 themes: measuring affordability and the role of government. Limited articles representing the manufacturer perspective were identified. Perspectives of decision makers (payers, policymakers) did not overlap with those affected by affordability (patients, providers). CONCLUSIONS: This research highlights the multi-dimensionality of drug "affordability." Multiple factors beyond cost influence patient affordability implying interventions can help alleviate affordability issues for some patients. The lack of overlap highlights potential hazards that decisions related to out-of-pocket spending, insurance coverage, reimbursement, and rationing occur without explicitly considering patient and provider perspectives.

Developing a Framework for the Health Technology Assessment of Histology-independent Precision Oncology Therapies.

The arrival of precision oncology is challenging the evidence standards under which technologies are evaluated for regulatory approval as well as for health technology assessment (HTA) purposes. Several key concepts are discussed to highlight the source of the challenges in evaluating these products, particularly those impacting the HTA of histology-independent therapies. These include the basket trial design, high uncertainty in (potentially substantial) benefits for histology-independent therapies, and the inability to identify and quantify benefits of standard of care in daily practice when the biomarker is not currently used in practice. There is little precedent for a technology with the unique mixture of challenges for HTA of histology-independent therapies and they will be evaluated using standard HTA, as there currently is no evidence suggesting the standard HTA framework is not appropriate. A number of questions proposed to help guide HTA bodies when assessing the appropriateness of local processes to optimally evaluate histology-independent therapies. Pragmatic solutions are further proposed to decrease uncertainty in the benefits of histology independent therapies as well as fill gaps in comparative evidence. The proposed solutions ensure a consistent and streamlined approach to evaluation across histology-independent products, although with varying strengths and limitations. Alongside these solutions, sponsors should engage early with HTA bodies/payers and regulatory agencies through parallel/joint scientific advice to facilitate the integration of both regulatory and HTA perspectives into one clinical development programme, potentially reconciling evidence requirements.

A Cost-Effectiveness Framework for COVID-19 Treatments for Hospitalized Patients in the United States.

INTRODUCTION: The COVID-19 pandemic is a global crisis impacting population health and the economy. We describe a cost-effectiveness framework for evaluating acute treatments for hospitalized patients with COVID-19, considering a broad spectrum of potential treatment profiles and perspectives within the US healthcare system to ensure incorporation of the most relevant clinical parameters, given evidence currently available. METHODS: A lifetime model, with a short-term acute care decision tree followed by a post-discharge three-state Markov cohort model, was developed to estimate the impact of a potential treatment relative to best supportive care (BSC) for patients hospitalized with COVID-19. The model included information on costs and resources across inpatient levels of care, use of mechanical ventilation, post-discharge morbidity from ventilation, and lifetime healthcare and societal costs. Published literature informed clinical and treatment inputs, healthcare resource use, unit costs, and utilities. The potential health impacts and cost-effectiveness outcomes were assessed from US health payer, societal, and fee-for-service (FFS) payment model perspectives. RESULTS: Viewing results in aggregate, treatments that conferred at least a mortality benefit were likely to be cost-effective, as all deterministic and sensitivity analyses results fell far below willingness-to-pay thresholds using both a US health payer and FFS payment perspective, with and without societal costs included. In the base case, incremental cost-effectiveness ratios (ICER) ranged from $22,933 from a health payer perspective using bundled payments to $8028 from a societal perspective using a FFS payment model. Even with conservative assumptions on societal impact, inclusion of societal costs consistently produced ICERs 40-60% lower than ICERs for the payer perspective. CONCLUSION: Effective COVID-19 treatments for hospitalized patients may not only reduce disease burden but also represent good value for the health system and society. Though data limitations remain, this cost-effectiveness framework expands beyond current models to include societal costs and post-discharge ventilation morbidity effects of potential COVID-19 treatments.

Budget Impact of Oral Semaglutide Intensification versus Sitagliptin among US Patients with Type 2 Diabetes Mellitus Uncontrolled with Metformin.

BACKGROUND: Oral semaglutide was approved in 2019 for blood glucose control in patients with type 2 diabetes mellitus (T2DM) and was the first oral glucagon-like peptide 1 receptor agonist (GLP-1 RA). T2DM is associated with substantial healthcare expenditures in the US, so the cost of a new intervention should be weighed against clinical benefits. OBJECTIVE: This study evaluated the budget impact of a treatment pathway with oral semaglutide 14 mg daily versus oral sitagliptin 100 mg daily among patients not achieving target glycated hemoglobin (HbA1c) level despite treatment with metformin. METHODS: This study used the validated IQVIA™ CORE Diabetes Model to simulate the treatment impact of oral semaglutide 14 mg and sitagliptin 100 mg over a 5-year time horizon from a US healthcare sector (payer) perspective. Trial data (PIONEER 3) informed cohort characteristics and treatment effects, and literature sources informed event costs. Population and market share data were from the literature and data on file. The analysis evaluated the estimated budget impact of oral semaglutide 14 mg use for patients currently using sitagliptin 100 mg considering both direct medical and treatment costs to understand the impact on total cost of care, given underlying treatment performance and impact on avoidable events. RESULTS: In a hypothetical plan of 1 million lives, an estimated 1993 patients were treated with sitagliptin 100 mg in the target population. Following these patients over 5 years, the incremental direct medical and treatment costs of a patient using oral semaglutide 14 mg versus sitagliptin 100 mg was $US16,562, a 70.7% increase (year 2019 values). A hypothetical payer would spend an additional $US3,300,143 (7.1%) over 5 years for every 10% of market share that oral semaglutide 14 mg takes away from sitagliptin 100 mg. Univariate and scenario analyses with alternate inputs and assumptions demonstrated consistent results. CONCLUSIONS: Use of oral semaglutide 14 mg in patients currently receiving sitagliptin 100 mg substantially increases the budget impact for patients with T2DM whose blood glucose level is not controlled with metformin over a 5-year time horizon for US healthcare payers.

Patients with type 2 diabetes mellitus (T2DM) have many treatment options. Choices depend on factors such as cost, preference, and patient characteristics. Oral semaglutide was recently approved for the treatment of T2DM as the first oral therapy of its class. This study estimated the cost for patients treated with sitagliptin 100 mg, a commonly used T2DM treatment, versus oral semaglutide 14 mg for patients whose disease is not well controlled with metformin. Costs and effects were estimated over 5 years for each treatment strategy using predictive model equations and clinical trial data for the two treatments. These costs were considered for both a hypothetical healthcare plan of 1 million lives and the full US population. A patient treated with oral semaglutide 14 mg would expect to see 70.7% higher costs than a patient treated with sitagliptin 100 mg over 5 years. For every 10% of patients who would switch from sitagliptin 100 mg to oral semaglutide 14 mg, costs would increase by 7.1%. Changing the cost of oral semaglutide 14 mg had the greatest impact on model results. The findings from the analysis were consistent across a range of alternate model inputs. Oral semaglutide 14 mg is more costly than sitagliptin 100 mg over 5 years.

Relationship Between Patient Characteristics and Number of Procedures as well as Length of Stay for Patients Surviving Severe Burn Injuries: Analysis of the American Burn Association National Burn Repository.

This study establishes important, national benchmarks for burn centers to assess length of stay (LOS) and number of procedures across patient profiles. We examined the relationship between patient characteristics such as age and total body surface area (TBSA) burned and number of procedures and LOS in the United States, using the American Burn Association National Burn Repository (NBR) database version 8.0 (2002-2011). Among 21,175 surviving burn patients (TBSA > 10-60%), mean age was 33 years, and mean injury size was 19.9% TBSA. Outcomes included the number of debridement, excision, autograft procedures, and LOS. Independent variables considered were: age (linear, squared, and cubed to account for nonlinearity), TBSA, TBSAs of partial-thickness and mixed/full-thickness burns, sex, hospital-acquired infection, other infection, inhalation injury, and diabetes status. Regression methods included a mixed-effects model for LOS and ordinary least squares for number of procedures. A backward stepwise procedure (P <0.2) was used to select variables. Number of excision and autografting procedures increased with TBSA; however, this relationship did not hold for debridement. After adjusting for sex, age, and comorbidities, predicted LOS for adults (18+) was 12.1, 21.7, 32.2, 43.7, and 56.1 days for 10, 20, 30, 40, and 50% TBSA, respectively. Similarly, predicted LOS for pediatrics (age < 18) was 8.1, 18.8, 33.2, 47.6, and 56.1 days for the same TBSA groups, respectively. While average estimates for adults (1.12 days) and pediatrics (1.01) are close to the one day/TBSA rule-of-thumb, consideration of other important patient and burn features in the NBR can better refine predictions for LOS.

A Budget Impact and Cost Per Additional Responder Analysis for Baricitinib for the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients with an Inadequate Response to Tumor Necrosis Factor Inhibitors in the USA.

BACKGROUND/OBJECTIVE: Baricitinib is a selective and reversible Janus kinase (JAK) inhibitor indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor inhibitors (TNFis) and has been shown to improve multiple clinical and patient-reported outcomes. However, it is unclear what the budgetary impact would be for US commercial payers to add baricitinib to their formulary and how the efficacy of baricitinib compares to other disease-modifying antirheumatic drugs (DMARDs) with a similar indication. METHODS: A budget impact model (BIM) was developed for a hypothetical population of 1 million plan members that compared a world without and with baricitinib. A retrospective observational study was carried out to estimate market utilization of advanced therapies. Number needed to treat (NNT) and cost per additional responder were calculated for American College of Rheumatology (ACR) 20%/50%/70% improvement criteria (ACR20/50/70) response outcomes combining cost estimates from the BIM and efficacy values from a network meta-analysis (NMA). The model included costs related to drug acquisition and monitoring costs. RESULTS: Adding baricitinib would save a commercial payer $US169,742 for second-line therapy and $US135,471 for third-line therapy over a 2-year time horizon (all costs correspond to 2019 US dollars). Cost savings were driven by baricitinib drawing market share away from more expensive comparators. The NMA, based on nine studies, found no statistically significant differences in the median treatment difference between baricitinib and comparators except for versus a conventional synthetic DMARD (csDMARD), and thus NNT versus a csDMARD was similar. The cost per additional responder for baricitinib in patients with inadequate response to a TNFi was substantially lower than all other treatments for all three ACR response criteria at 12 weeks (ACR20: $US129,672; ACR50: $US237,732; ACR70: $US475,464), and among the lowest at 24 weeks (ACR20: $US167,811; ACR50: $US259,344; ACR70: $US570,557). CONCLUSIONS: Baricitinib, compared to other DMARDs, was a less expensive option (- $US0.01 incremental cost per member per month in second- and third-line therapy over a 2-year time horizon) with comparable efficacy in patients with inadequate response to TNFi. Adding baricitinib to formulary would likely be cost saving for US payers and expands treatment options for these patients.

Correction to: A Budget Impact and Cost Per Additional Responder Analysis for Baricitinib for the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients with an Inadequate Response to Tumor Necrosis Factor Inhibitors in the USA.

Due to a single error in the annual cost of sarilumab the following needs to be corrected in the article.

Cost-effectiveness of DPP-4 inhibitor and SGLT2 inhibitor combination therapy for type 2 diabetes.

OBJECTIVES: Maintaining glycemic control limits costly health risks in patients with type 2 diabetes (T2D), but accomplishing this may require individualized strategies. Generic medications (eg, sulfonylureas [SU], insulin) are common in T2D management due to their efficacy and costs; however, relatively new drug classes (eg, dipeptidyl peptidase 4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT2] inhibitors) have demonstrated clinical benefits in combination therapy. The objective of this study was to evaluate the long-term cost-effectiveness of a strategy involving branded combination therapy with DPP-4 inhibitors and SGLT2 inhibitors (pathway 1) compared with a generic alternative with SU and insulin (pathway 2) on a background of metformin. STUDY DESIGN: Cost-effectiveness analysis using the validated IQVIA CORE Diabetes Model from the US payer perspective. METHODS: Cost-effectiveness analysis. Lifetime clinical and economic outcomes (discounted 3%/year) were modeled for a T2D cohort failing to achieve glycemic goal on metformin monotherapy. Patient baseline data and treatment effects reflect results of clinical trials. Direct medical cost inputs are from multiple published sources. Scenario analyses on key intervention effects and assumptions tested robustness of results. RESULTS: Pathway 1 had higher direct medical costs compared with pathway 2, yet also increased total quality-adjusted life-years (QALYs) by 0.24. Increased costs were partially offset by a reduction in diabetes-related complications and delayed insulin initiation. The incremental cost-effectiveness ratio (ICER) for pathway 1 is favorable at $64,784/QALY. Scenario analyses showed limited impact; nearly all ICERs were less than $100,000/QALY. CONCLUSIONS: In the United States, sequential addition of SGLT2 inhibitors to DPP-4 inhibitors may be considered cost-effective compared with traditional treatment with generic medications for patients who fail to achieve glycemic goal on metformin.

Cost-Effectiveness of the Use of Autologous Cell Harvesting Device Compared to Standard of Care for Treatment of Severe Burns in the United States.

INTRODUCTION: When introducing a new intervention into burn care, it is important to consider both clinical and economic impacts, as the financial burden of burns in the USA is significant. This study utilizes a health economic modeling approach to estimate cost-effectiveness and burn center budget-impact for the use of the RECELL® Autologous Cell Harvesting Device to prepare autologous skin cell suspension (ASCS) compared to standard of care (SOC) split-thickness skin graft (STSG) for the treatment of severe burn injuries requiring surgical intervention for definitive closure. METHODS: A hospital-perspective model using sequential decision trees depicts the acute burn care pathway (wound assessment, debridement/excision, temporary coverage, definitive closure) and predicts the relative differences between use of ASCS compared to SOC. Clinical inputs and ASCS impact on length of stay (LOS) were derived from clinical trials and real-world use data, American Burn Association National Burn Repository database analyses, and burn surgeon interviews. Hospital resource use and unit costs were derived from three US burn centers. A budget impact calculation leverages Monte Carlo simulation to estimate the overall impact to a burn center. RESULTS: ASCS treatment is cost-saving or cost-neutral (< 2% difference) and results in lower LOS compared to SOC across expected patient profiles and scenarios. In aggregate, ASCS treatment saves a burn center 14-17.3% annually. Results are sensitive to, but remain robust across, changing assumptions for relative impact of ASCS use on LOS, procedure time, and number of procedures. CONCLUSIONS: Use of ASCS compared to SOC reduces hospital costs and LOS of severe burns in the USA. FUNDING: AVITA Medical.