Budget impact of resmetirom for the treatment of adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

AIMS: This study assessed the budget impact of resmetirom as a treatment for adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis and estimated total costs for a hypothetical private payer in the United States. MATERIALS AND METHODS: A three-year budget impact analysis based on an open cohort state transition model was developed for a hypothetical one-million-member private health plan. The comparator was Standard of Care (SOC), defined as routine care for non-cirrhotic NASH patients with moderate-to-advanced liver fibrosis. Each year, the number of resmetirom treatment-eligible patients was estimated through prevalent, incident, and diagnostic rate estimates. Costs included resources incurred by the medical and pharmacy benefits of private payers, including resmetirom drug acquisition costs, diagnosis and monitoring, other medical and other prescription costs stratified by disease progression status (i.e. non-cirrhotic vs. cirrhotic/advanced liver diseases). Resmetirom adverse event management costs were included in sensitivity analysis. Drug costs were estimated based on the average wholesale acquisition cost as of March 2024. Other costs were based on published sources and inflated to 2023 US dollars. Budget impact outcomes were presented in aggregate, net, and on a per-member per-month (PMPM) basis. RESULTS: Compared with a scenario without resmetirom, the introduction of resmetirom yielded results ranging from 50 to 238 treated patients, net budget impact of $2.2 to $9.5 million, and PMPM from $0.19 to $0.80 over years one and three. Net costs excluding resmetirom declined over time. In sensitivity analyses, results were most sensitive to diagnostic and epidemiologic inputs. LIMITATIONS: Market shares are based on internal forecasts, a short time horizon, average treatment effects, and other limitations common to BIMs. CONCLUSION: The adoption of resmetirom on the formulary for the treatment of non-cirrhotic NASH with moderate-to-advanced liver fibrosis resulted in a moderate increase in budget impact with declining costs related to NASH progression.

Non-alcoholic steatohepatitis (NASH) is a serious liver disease that can lead to significant liver damage, other health complications, and increased healthcare costs. As the disease progresses, patients typically experience worsening health outcomes. Until recently, there were no Food and Drug Administration (FDA) approved treatments for NASH in the United States. However, in March 2024, the FDA approved REZDIFFRA, a new drug specifically designed to treat NASH patients with moderate-to-advanced liver fibrosis (i.e. NASH with moderate-to-advanced scarring of the liver). Clinical trials have shown that REZDIFFRA can improve health outcomes in these patients.To identify patients who could benefit from REZDIFFRA and to estimate the associated costs, we developed a budget impact model. In this study, we detail the development of this model and present its findings. Our analysis revealed that, while REZDIFFRA is associated with higher overall costs, primarily due to the price of the drug itself, there are potential cost savings when considering the drug's ability to slow disease progression.

Economic burden of respiratory syncytial virus in adults in Germany - a health claims analysis between 2015 and 2018.

AIMS: Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden. To fill this gap, this study aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. METHODS: In this retrospective, observational study on nationwide, representative, anonymized claims data (2015-2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV ("RSV-specific"). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV ("RSV-possible"). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). RESULTS: Direct inpatient and outpatient mean episode costs were 3,473€ and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€ vs. 3,450€; outpatients: 127€ vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€ per episode vs 10,093€ per year; outpatients: 46€ per quarter vs 114€ per year). LIMITATIONS: While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation of the total costs of RSV. CONCLUSIONS: The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term, and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

The Effects of Physician Vertical Integration on Referral Patterns, Patient Welfare, and Market Dynamics.

The growth of physician vertical integration raises concerns about distorted referral patterns, higher spending, and market foreclosure. Using 100% Medicare data, we combine reduced-form analysis with a discrete choice model to estimate the effects of physician vertical integration on patients' provider choices and welfare for two common "downstream" surgical procedures. Physician-hospital integration results in an approximately 10% increase in referrals to higher-priced facilities instead of lower-priced providers. Our counterfactual analysis implies that if all primary care physicians become integrated, total Medicare spending will increase by $315 million.

Health care resource use and costs in patients with food allergies: a United States insurance claims database analysis.

AIMS: Food allergies impose a large clinical and financial burden on patients and the health care system. However, little is known about the factors associated with health care resource use and costs. The aim of this study was to investigate health care resource use and costs in individuals with food allergies utilizing health care in the United States. METHODS: We conducted a retrospective analysis of insurance claims data from the Merative MarketScan Research Databases (indexed from 1 January 2015 to 30 June 2022). All-cause and food allergy-related health care resource use, direct medical, and out-of-pocket costs for medical services were estimated for 12 months post-index using International Classification of Diseases [ICD] codes. RESULTS: Of 355,520 individuals with food allergies continuously enrolled in a health insurance plan for ≥12 months pre- and post-index, 17% had a food allergy-related emergency department visit and 0.9% were hospitalized. The top patient characteristic associated with all-cause and food allergy-related hospitalizations, all-cause costs, and food allergy-related outpatient visit costs was a Charlson Comorbidity Index score of ≥2. Food allergy-related direct medical and out-of-pocket costs were high among patients with a food allergy-related visit. Out-of-pocket cost per patient per year for outpatient visits, emergency department visits, and hospitalizations had an estimated mean of $1631 for patients with food allergy-related visits, which is ∼11% of the total costs for these services ($14,395 per patient per year). LIMITATIONS: Study limitations are primarily related to the nature of claims databases, including generalizability and reliance on ICD codes. Nevertheless, MarketScan databases provide robust patient-level insights into health care resource use and costs from a large, commercially insured patient population. CONCLUSION: The health care resource use of patients with food allergies imposes a burden on both the health care system and on patients and their families, especially if patients had comorbidities.

Some people with food allergies might need extra visits to the doctor or hospital to manage allergic reactions to food, and these visits add to the cost of medical services for both families and for health care providers. Using records of health insurance claims, we looked into the factors affecting medical visits and costs in people with food allergies in the United States. For people with food allergies, having additional medical conditions (measured using the Charleson Comorbidity Index) were linked with extra medical visits and costs. Out-of-pocket costs were high for people who visited a doctor or hospital for their food allergies (costing each person more than $1,600 per year). The total medical cost of food allergy-related care was $14,395 per person per year, paid for by families and health care providers. Our findings might help to better manage and treat people with food allergies and reduce medical costs.

Micro-costing of genetic diagnostics in acute leukemia in Sweden: from standard-of-care to whole-genome sequencing.

AIMS AND BACKGROUND: Whole-genome sequencing (WGS) is increasingly applied in clinical practice and expected to replace standard-of-care (SoC) genetic diagnostics in hematological malignancies. This study aims to assess and compare the fully burdened cost ('micro-costing') per patient for Swedish laboratories using WGS and SoC, respectively, in pediatric and adult patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). METHODS: The resource use and cost details associated with SoC, e.g. chromosome banding analysis, fluorescent in situ hybridization, and targeted sequencing analysis, were collected via activity-based costing methods from four diagnostic laboratories. For WGS, corresponding data was collected from two of the centers. A simulation-based scenario model was developed for analyzing the WGS cost based on different annual sample throughput to evaluate economy of scale. RESULTS: The average SoC total cost per patient was €2,465 for pediatric AML and €2,201 for pediatric ALL, while in adults, the corresponding cost was €2,458 for AML and €1,207 for ALL. The average WGS cost (90x tumor/30x normal; sequenced on the Illumina NovaSeq 6000 platform) was estimated to €3,472 based on an annual throughput of 2,500 analyses, however, with an annual volume of 7,500 analyses the average cost would decrease by 23% to €2,671. CONCLUSION: In summary, WGS is currently more costly than SoC, however the cost can be reduced by utilizing laboratories with higher throughput and by the expected decline in cost of reagents. Our data provides guidance to decision-makers for the resource allocation needed when implementing WGS in diagnostics of hematological malignancies.

The economic impact of suboptimal treatment and treatment switch among patients with Crohn's disease treated with a first-line biologic - A US retrospective claims database study.

AIMS: Suboptimal treatment indicators, including treatment switch, are common among patients with Crohn's disease (CD), but little is known about their associated healthcare resource utilization (HRU) and costs. This study assessed the impact of suboptimal treatment indicators on HRU and costs among adults with CD newly treated with a first-line biologic. METHODS: Adult patients with CD were identified in the IBM MarketScan Commercial Subset (10/01/2015-03/31/2020). The index date was defined as initiation of the first-line biologic, and the study period was defined as the 12 months following the index date. Patients were classified into Suboptimal Treatment and Optimal Treatment cohorts based on observed indicators of suboptimal treatment during the study period. Patients in the Suboptimal Treatment Cohort with a treatment switch were classified into the Treatment Switch Cohort and compared to patients with no treatment switch. All-cause HRU and costs were measured during the study period and assessed for patients with suboptimal vs optimal treatment and patients with vs without a treatment switch. RESULTS: The study included 4,006 patients (Suboptimal Treatment: 2,091, Optimal Treatment: 1,915). Treatment switch was a common indicator of suboptimal treatment (Treatment Switch: 640, No Treatment Switch: 3,366). HRU and costs were significantly higher among patients with suboptimal treatment than those with optimal treatment (annual costs: $92,043 vs $73,764; p < 0.01), and among those with a treatment switch than those with no treatment switch (annual costs: $95,689 vs $81,027; p < 0.01). Increases in the number of suboptimal treatment indicators were associated with increased costs. LIMITATIONS: Claims data were used to identify suboptimal treatment indicators based on observed treatment patterns; reasons for treatment decisions could not be assessed. CONCLUSION: This study demonstrates that patients with suboptimal treatment indicators, including treatment switch, incur substantially higher HRU and costs compared to patients receiving optimal treatment and those that do not switch treatments.

An assessment of the direct and indirect costs of bladder cancer preceding and following a cystectomy: a real-world evidence study.

INTRODUCTION: To estimate the direct and indirect costs of bladder cancer prior to and following cystectomy in a U.S. sample of patients. METHODS: This retrospective, observational analysis of de-identified patients with bladder cancer utilized the MarketScan Commercial Claims & Encounters and Health & Productivity Management databases. Adult patients with bladder cancer plus ≥ 1 claim for partial or radical cystectomy between 1 October 2015 and 31 December 2020 (date of the cystectomy = index date) and who were continuously enrolled for 6 months pre- (baseline) and post-index (follow-up) were included in the sample. All-cause total healthcare costs and indirect costs associated with short-term and long-term disability (STD and LTD) employer claims were assessed during each of the 6-month baseline and follow-up periods. RESULTS: The study included N = 142 patients; mean age 56 ± 6 years, 76% (male), and 42% had a baseline Deyo-Charlson Comorbidity Index ≥ 2. Baseline mean total all-cause direct healthcare costs were $51,473 ± $48,560 (median: $36,202), and $99,524 ± 86,839 (median: $75,444) during follow-up. At baseline, 32% of patients had ≥ 1 STD claim, equating to a mean 134 ± 303 h lost and $2,353 ± $6,445 in total payments per patient. Follow up STD claims increased 23.4% equating to a mean 218 ± 324 h lost and $3,679 ± $7,795 per patient. Patient LTD claims increased from baseline to follow-up (1-3%), with post-cystectomy LTD claims resulting in 574 ± 490 h lost, and $1,636 ± $1,429 in total payments. Over 85% of the population had a cystectomy related complication, the most common were genitourinary-related (47.9%) and infection/sepsis (33.1%). CONCLUSIONS: Cystectomy was associated with complications and decreased work productivity post-surgery. Findings may aid to inform decisions regarding cystectomy vs. bladder preservation approaches, and underscores an ongoing need to further develop bladder preservation therapies within the bladder cancer treatment landscape.

Real-world treatment patterns of patients with major depressive disorder treated with Auvelity in the United States.

AIMS: Major depressive disorder (MDD) is a prevalent, chronic disorder. Auvelity (dextromethorphan-bupropion) is a novel, oral N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist approved (August 2022) by the FDA for treating MDD in adults. This is the first analysis on real-world Auvelity usage in the United States. METHODS: Adult patients initiating Auvelity in the Symphony IDV databases by September 2023 were identified (index date: the first Auvelity claim). Patients had continuous eligibility over the 12-month pre-index period and ≥1 MDD diagnosis (ICD-10-CM codes: F32.*, F33.*) over the 5-year pre-index period. Demographic and clinical characteristics, comorbidities, prior MDD-related medications, and Auvelity initiation status were assessed. RESULTS: This analysis included 22,288 patients with MDD treated with Auvelity (mean age 45.1 years; 68.1% women); 40.0% lived in the South and 58.5% had commercial insurance. Comorbidities included mental health disorders (53.5%; 47.6% had anxiety disorders). Overall, 83.7% of the patients had received treatment with selective serotonin reuptake inhibitors (SSRIs; 54.9%), the norepinephrine-dopamine reuptake inhibitor (NDRI [bupropion]; 40.4%), and/or serotonin-norepinephrine reuptake inhibitors (SNRIs; 35.9%) over the 12-month pre-index period. The last MDD-related treatment prior to Auvelity comprised SSRI (22.4%), SNRI (13.2%), and NDRI (12.8%) monotherapies; 294 (1.3%) patients received esketamine. In total, 6,418 (28.8%) patients initiated Auvelity as monotherapy vs 15,870 (71.2%) as an add-on; Auvelity was most frequently added to an SSRI alone (10.7%) or SNRI alone (6.5%). A total of 2,254 (10.1%) patients initiated Auvelity without prior treatment in the 12-month pre-index period. LIMITATIONS: Incomplete data due to reporting; diagnoses captured subject to coding error; and limited generalizability to other populations. CONCLUSIONS: Using a large demographically distributed claims database, 22,288 patients with MDD initiated Auvelity within a year of its approval; 10.1% were treatment-naïve and 28.8% initiated Auvelity as monotherapy. Most patients had mental health-related comorbidities and attempted various MDD-related treatments prior to Auvelity.

Major depressive disorder (medical terminology for "depression") is a common medical condition that makes people feel persistently sad or hopeless, affecting their ability to handle daily activities. Effective treatment, which may include medication, is crucial for improving their quality of life. This study explores how people in the United States use a new medication called Auvelity to treat depression. Researchers reviewed the medical records of over 22,000 adults with depression, looking at their age, gender, location, type of health insurance, other health conditions, and use of other depression medications. The study focused on people who started using Auvelity in the first year after its Food and Drug Administration (FDA) approval. On average, Auvelity users were 45 years old. They lived across various regions of the US, had different types of health insurance, and over two-thirds were women. Many Auvelity users had other mental health disorders, including anxiety. Most had tried different types of medications for depression in the previous year, while about 10% had not used any other depression medicines in the previous year. When starting Auvelity, almost one-third of patients used it as their only depression medicine. Over two-thirds of patients started Auvelity alongside another depression medicine. Initial Auvelity prescriptions were issued by a diverse range of medical professionals, including psychiatrists, primary care physicians, nurse practitioners, and physician assistants. These findings provide valuable insights into how this new medicine is used in real life and can inform treatment decisions of healthcare providers who help manage depression in their patients.

Cost-efficiency and budget-neutral expanded access modeling of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer.

AIMS: To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings. METHODS: Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%-10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials' median PFS were also conducted. RESULTS: In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case. CONCLUSION: Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

An estimated 49,647 patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) will be treated with a PD-1 inhibitor in the US in 2024. Toripalimab, a PD-1 inhibitor recently approved by the US Food and Drug Administration for the treatment of nasopharyngeal carcinoma, has also been found to be beneficial in patients with nonsquamous NSCLC when used in combination with chemotherapy. We conducted an economic simulation of the costs of toripalimab + pemetrexed + carboplatin versus the costs of a similar regimen with the PD-1 inhibitor pembrolizumab in the treatment of patients with nonsquamous NSCLC. Our simulation models used two US cost inputs for toripalimab: the wholesale acquisition cost or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a hypothetical toripalimab price point of 80% of the pembrolizumab ASP. We compared the savings in each scenario when between 1% and 10% of the 49,647 nonsquamous NSCLC patients are treated with the toripalimab regimen. We then evaluated how these savings could be re-allocated, without requiring extra funding, to provide more patients with access to toripalimab treatment on a budget-neutral basis. We found that, if 1% of new cases of advanced/metastatic nonsquamous NSCLC were treated with toripalimab for 1 year, these savings are enough to purchase up to 1,753 additional toripalimab maintenance cycles; or these savings could provide up to an additional 97 patients with full one-year regimens with all agents (toripalimab + chemotherapy). If 10% of new cases were treated with toripalimab for 1 year, the savings are enough to purchase up to 17,533 additional toripalimab maintenance cycles; or these savings could provide up to an additional 972 patients with full one-year regimens with all agents.

Do newer drugs treat fewer diseases, controlling for time since launch? Evidence from France and the U.S.

Background: More recently approved drugs have significantly fewer indications than drugs approved many years ago. One possible reason for this may be that, controlling for the number of years since approval or launch, more recently approved drugs have fewer indications (e.g. at the time of launch). The role of precision and personalised medicine has increased, and the goal of precision medicine is to provide a more precise approach for the prevention, diagnosis and treatment of disease. Drugs that have fewer indications may be 'more precise' than drugs that have many indications. Methods: We use different kinds of data from two countries - France and the U.S. - to analyze the relationship across many drugs between the number of indications of a drug, the drug's vintage - i.e. the year in which the drug was first marketed or approved - and its age - the number of years it has been marketed. Results: All the evidence from both countries indicates that, controlling for drug age, more recently approved drugs tend to have fewer indications than drugs approved many years ago. In the U.S., a 10-year increase in vintage is associated with a 10.7% decline in the effective number of indications of all drugs, and a 19.4% decline in the effective number of indications of drugs approved after 1989. In France, the positive effect on the number of indications of the increase in drug age was more than offset by the negative effect of the increase in drug vintage. Conclusions: More recently approved drugs are less likely to be 'general-purpose technologies' (or even multi-purpose technologies) than older drugs. The relative importance of 'precision medicine' has increased in recent decades. Drugs that have fewer indications may be 'more precise' than drugs that have many indications.

Savings associated with surgical aortic valve replacement with a RESILIA tissue valve based on seven-year COMMENCE trial results.

BACKGROUND: Bioprostheses with RESILIA tissue demonstrate a reduction in calcification and improve health outcomes in pre-clinical and clinical studies. Prior economic analyses which relied on 5 years of evidence from the COMMENCE trial demonstrate financial savings for RESILIA tissue valves relative to mechanical valves after surgical aortic valve replacement (SAVR). Given the recent release of 7-year COMMENCE data, this economic evaluation updates the estimate for long-run savings of bioprosthetic valves with RESILIA. METHODS: Simulation models estimated disease progression across two hypothetical SAVR cohorts (tissue vs. mechanical) of 10,000 patients each in the US. The primary comparison calculated the SAVR-related expenditures associated with each valve type ($US, 2023). Health outcome probabilities were based on the COMMENCE trial though year 7 and projected for an additional 8 years based on prior studies of tissue and mechanical SAVR. Costs for key outcomes (mortality, reoperation, bleeding, thromboembolism, endocarditis) and anticoagulant monitoring were sourced from the literature. Incidence rates of health outcomes associated with mechanical valves relied on relative risks of tissue valve versus mechanical valve patients. RESULTS: Seven-year savings are $13,415 (95% CI = $10,472-$17,321) per patient when comparing RESILIA versus mechanical SAVR. Projected 15-year savings were $23,001 ($US, 2023; 95% CI = $17,802-$30,421). Most of the 15-year savings are primarily attributed to lower anti-coagulation monitoring costs ($21,073 in ACM savings over 15 years), but lower bleeding cost (savings: $2,294) and thromboembolism-related expenditures (savings: $852) also contribute. Reoperation and endocarditis expenditures were slightly larger in the RESILIA cohort. If reoperation relative risk reverts from 1.1 to 2.2 (the level in legacy tissue valves) after year 7, savings are $18,064. RESILIA SAVR also reduce costs relative to legacy tissue valves. CONCLUSION: Patients receiving RESILIA tissue valves are projected to have lower SAVR-related health expenditures relative to mechanical and legacy tissue valves.

Evaluation of bacteriophage ϕ11 host recognition protein and its host-binding peptides for diagnosing/targeting Staphylococcus aureus infections.

BACKGROUND: Evaluating the potential of using both synthetic and biological products as targeting agents for the diagnosis, imaging, and treatment of infections due to particularly antibiotic-resistant pathogens is important for controlling infections. This study examined the interaction between Gp45, a receptor-binding protein of the ϕ11 lysogenic phage, and its host Staphylococcus aureus (S. aureus), a common cause of nosocomial infections. METHODS: Using molecular dynamics and docking simulations, this study identified the peptides that bind to S. aureus wall teichoic acids via Gp45. It compared the binding affinity of Gp45 and the two highest-scoring peptide sequences (P1 and P3) and their scrambled forms using microscopy, spectroscopy, and ELISA. RESULTS: It was found that rGp45 (recombinant Gp45) and chemically synthesised P1 had a higher binding affinity for S. aureus compared with all other peptides, except for Escherichia coli. Furthermore, rGp45 had a capture efficiency of > 86%; P1 had a capture efficiency of > 64%. CONCLUSION: These findings suggest that receptor-binding proteins such as rGp45, which provide a critical initiation of the phage life cycle for host adsorption, might play an important role in the diagnosis, imaging, and targeting of bacterial infections. Studying such proteins could accordingly enable the development of effective strategies for controlling infections.

Cost-effectiveness analysis of mosunetuzumab for treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in the United States.

AIMS: Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective. MATERIALS AND METHODS: A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len. LIMITATIONS: Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties. CONCLUSION: Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

Costs associated with adverse events during treatment episodes for adult attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) medication is frequently associated with adverse events (AEs), but limited real-world data exist regarding their costs from a payer's perspective. Therefore, this study evaluated the healthcare costs associated with common AEs among adult patients treated for ADHD in the US. METHODS: Eligible adults treated for ADHD were identified from a large US claims database (1 October 2015-30 September 2021). A retrospective cohort study design was used to assess excess healthcare costs and costs directly related to AE-specific claims per-patient-per-month (PPPM) associated with 10 selected AEs during ADHD treatment. To account for all costs associated with the AE, treatment episodes with a given AE were compared to similar treatment episodes without this AE. Entropy balancing was used to create cohorts with similar characteristics. Studied AEs were selected based on their prevalence in clinical trials for common ADHD medications and were identified from ICD-10-CM diagnosis codes recorded in claims. RESULTS: Among the 461,464 patients included (mean age: 34.2 years; 45.5% males), 49.4% had ≥1 AE during their treatment episode. Treatment episodes with AEs were associated with statistically significant AE-specific medical costs (erectile dysfunction: $57; fatigue: $82; dry mouth: $90; diarrhea: $162; insomnia: $147; anxiety: $281; nausea: $299; constipation: $356; urinary hesitation: $491; feeling jittery: $723) and excess healthcare costs PPPM (erectile dysfunction: $120, fatigue: $248, insomnia: $265, anxiety: $380, diarrhea: $441, dry mouth: $485, nausea: $709, constipation: $802, urinary hesitation: $1,105, feeling jittery: $1,160; p < .05). LIMITATIONS: AEs were identified based on recorded diagnosis on medical claims and likely represent more severe AEs. Therefore, costs may not be representative of milder AEs. CONCLUSIONS: This study found that AEs occurring during ADHD treatment episodes are associated with significant healthcare costs. This highlights the potential of treatments with favorable safety profiles to alleviate the burden experienced by patients and the healthcare system.

Exploring kidney dialysis costs in the United States: a scoping review.

AIMS: The increasing prevalence of end-stage renal disease (ESRD) in the United States (US) represents a considerable economic burden due to the high cost of dialysis treatment. This review examines data from real-world studies to identify cost drivers and explore areas where dialysis costs could be reduced. METHODS: We identified and synthesized evidence published from 2016-2023 reporting direct dialysis costs in adult US patients from a comprehensive literature search of MEDLINE, Embase, and grey literature sources (e.g. US Renal Data System reports). RESULTS: Most identified data related to Medicare expenditures. Overall Medicare spending in 2020 was $29B for hemodialysis and $2.8B for peritoneal dialysis (PD). Dialysis costs accounted for almost 80% of total Medicare expenditures on ESRD beneficiaries. Private insurance payers consistently pay more for dialysis; for example, per person per month spending by private insurers on outpatient dialysis was estimated at $10,149 compared with Medicare spending of $3,364. Dialysis costs were higher in specific high-risk patient groups (e.g. type 2 diabetes, hepatitis C). Spending on hemodialysis was higher than on PD, but the gap in spending between PD and hemodialysis is closing. Vascular access costs accounted for a substantial proportion of dialysis costs. LIMITATIONS: Insufficient detail in the identified studies, especially related to outpatient costs, limits opportunities to identify key drivers. Differences between the studies in methods of measuring dialysis costs make generalization of these results difficult. CONCLUSIONS: These findings indicate that prevention of or delay in progression to ESRD could have considerable cost savings for Medicare and private payers, particularly in patients with high-risk conditions such as type 2 diabetes. More efficient use of resources is needed, including low-cost medication, to improve clinical outcomes and lower overall costs, especially in high-risk groups. Widening access to PD where it is safe and appropriate may help to reduce dialysis costs.

Previous papers have studied the cost of treating patients who need dialysis for kidney failure. We reviewed these costs and looked for patterns. Dialysis was the most expensive part of treatment for people with kidney disease who have Medicare. Dialysis with private insurance was much more expensive than with Medicare. People with diabetes experienced higher costs of dialysis than those without diabetes. Dialysis in a hospital costs more than dialysis at home. There are opportunities to reduce the cost of dialysis that should be explored further, such as more use of low-cost medication that can prevent the worsening of kidney disease and reduce the need for dialysis.

An integrated analysis revealing the angiogenic function of TP53I11 in tumor microenvironment.

Despite growing evidence suggesting an important contribution of Tumor Protein P53 Inducible Protein 11 (TP53I11) in cancer progression, the role of TP53I11 remains unclear. Our first pan-cancer analysis of TP53I11 showed some tumor tissues displayed reduced TP53I11 expression compared to normal tissues, while others exhibited high TP53I11 expression. Meanwhile, TP53I11 expression carries a particular pan-cancer risk, as high TP53I11 expression levels are detrimental to survival for BRCA, KIRP, MESO, and UVM, but to beneficial survival for KIRC. We demonstrated that TP53I11 expression negatively correlates with DNA methylation in most cancers, and the S14 residue of TP53I11 is phosphorylated in several cancer types. Additionally, TP53I11 was found to be associated with endothelial cells in pan-cancer, and functional enrichment analysis provided strong evidence for its role in tumor angiogenesis. In vitro angiogenesis assays confirmed that TP53I11 can promote angiogenic function of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistic investigations reveal that TP53I11 is transcriptionally up-regulated by HIF2A under hypoxia.

Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression.

AIMS: Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States. MATERIALS AND METHODS: Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18). RESULTS: Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible. LIMITATIONS: Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results. CONCLUSIONS: Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

Cost-efficiency and budget-neutral expanded access modeling of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIMS: To estimate, in the setting of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) for an assumed 1,207 incident US cases in 2024, (1) the cost-efficiency of a toripalimab-gemcitabine-cisplatin regimen compared to a similar pembrolizumab regimen; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens afforded by the accrued savings. METHODS: Simulation modeling utilized two cost inputs (wholesale acquisition cost (WAC) at market entry and an ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) and drug administration costs over 1 and 2 years of treatment with treatment rates ranging from 45% to 90%. In the absence of trial data for pembrolizumab-gemcitabine-cisplatin in R/M NPC, it is assumed that such a regimen would be comparable to toripalimab-gemcitabine-cisplatin in efficacy and safety. RESULTS: In the models utilizing the WAC, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 1,207-patient panel, estimated 1-year savings range from $21,733,702 (45% treatment rate) to $43,467,404 (90% rate). Reallocating these savings permits budget-neutral expanded access to an additional 2,359 (45% rate) to 4,717 (90% rate) toripalimab maintenance cycles or to an additional 126 (45% rate) to 252 (90%) full 1-year toripalimab regimens with all agents. Two-year savings range from $42,259,976 (45% rate) to $84,519,952 (90% rate). Reallocating these efficiencies provides expanded access, ranging from an additional 4,586 (45% rate) to 9,172 (90% rate) toripalimab cycles or to an additional 128-257 full 2-year toripalimab regimens. The ex ante ASP model showed similar results. CONCLUSION: This simulation demonstrates that treatment with toripalimab generates savings that enable budget-neutral funding for up to an additional 252 regimens with toripalimab-gemcitabine-cisplatin for one full year, the equivalent of approximately 21% of the 2024 incident cases of R/M NPC in the US.

An estimated 1,207 patients will be diagnosed with late-stage nasopharyngeal cancer in the US in 2024. Toripalimab is a novel PD-1 inhibitor drug approved by the US Food and Drug Administration on October 27, 2023 as first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer when used in combination with gemcitabine and cisplatin. We conducted economic evaluations of the costs of this toripalimab regimen versus the costs of a similar regimen with the PD-1 inhibitor pembrolizumab. Our simulation models used two pricing scenarios: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, an estimated toripalimab price point of 80% of the pembrolizumab ASP. We compared the savings in each scenario when between 45% and 90% of the 1,207 patients are treated with the toripalimab regimen. We then evaluated how these savings could be re-allocated, on a budget-neutral basis and without requiring extra cash outlays, to provide more patients with access to toripalimab treatment; specifically, how many toripalimab doses and how many full toripalimab regimens could be purchased to provide more patients with treatment. We found that, if 90% of new cases of recurrent or metastatic nasopharyngeal cancer were treated with toripalimab over 1 year, these savings are enough to purchase up to 4,717 additional doses on a budget-neutral basis, which could provide up to an additional 252 newly diagnosed patients with 1 year of treatment with toripalimab. In combination with gemcitabine and cisplatin, toripalimab can markedly improve access to care for patients with recurrent or metastatic nasopharyngeal cancer in a cost-responsible way.

The cost-effectiveness of zuranolone versus selective serotonin reuptake inhibitors for the treatment of postpartum depression in the United States.

AIMS: The objective of this research is to evaluate the cost-effectiveness of zuranolone, the first oral treatment indicated for postpartum depression (PPD) in adults approved by the United States Food and Drug Administration. METHODS: Zuranolone and selective serotonin reuptake inhibitor (SSRI) trial-based efficacy was derived from an indirect treatment comparison. Long-term efficacy outcomes were based on a large longitudinal cohort study. Maternal health utility values were derived from trial-based, short-form 6-D responses. Other inputs were derived from literature and economic data from the US Bureau of Labor Statistics. We estimated costs (2023 US dollars) and quality-adjusted life-years (QALYs) for patients with PPD treated with zuranolone (14-day dosing) or SSRIs (chronic dosing). The indirect costs and QALYs of the children and partners were also estimated. RESULTS: The incremental cost-effectiveness ratio for zuranolone versus SSRIs was $94,741 per QALY gained over an 11-year time horizon. Maternal total direct medical costs averaged $84,318 in the zuranolone arm, compared to $86,365 in the SSRI arm. Zuranolone-treated adults averaged 6.178 QALYs compared to 6.116 QALYs for the SSRI arm. Costs and utilities for the child and partner were also included in the base case. Drug and administration costs for zuranolone averaged $15,902, compared to $30 for SSRIs over the studied time horizon. Results were sensitive to the model time horizon. LIMITATIONS: As head-to-head trials were not available to permit direct comparison, efficacy inputs were derived from an indirect treatment comparison which can be confounded by cross-trial differences. The data used are reflective of a general PPD population rather than marginalized individuals who may be at a greater risk for adverse PPD outcomes. The model likely excludes unmeasured effects for patient, child, and partner. CONCLUSIONS: This economic model's results suggest that zuranolone is a more cost-effective therapy compared to SSRIs for treating adults with PPD.

QUESTION: Is zuranolone cost-effective compared to selective serotonin-reuptake inhibitors for the treatment of postpartum depression (PPD) in adults in a United States (US) health care setting? FINDINGS: The model, which incorporated clinical trial data, long-term longitudinal cohort data, US Bureau of Labor Statistics data on compensation, and other peer-reviewed literature, projects that zuranolone is cost-effective compared to selective serotonin-reuptake inhibitors for the treatment of PPD at a willingness-to-pay threshold of $150,000 (USD).Meaning: For adults with PPD requiring pharmacological intervention, zuranolone may be a cost-effective treatment option with the potential to confer quality-of-life benefits for these patients and their families as well as economic benefits for society.

Characterizing the real-world economic burden of metastatic castration-sensitive prostate cancer in the United States.

AIMS: To describe healthcare resource utilization (HRU) and costs of patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: Linked data from Flatiron Metastatic PC Core Registry and Komodo's Healthcare Map were evaluated (01/2016-12/2021). Patients with chart-confirmed diagnoses for metastatic PC without confirmed castration resistance in Flatiron who initiated androgen deprivation therapy (ADT) monotherapy or advanced therapy for mCSPC in 2017 or later (index date) with a corresponding pharmacy or medical claim in Komodo Health were included. Advanced therapies considered were androgen-receptor signaling inhibitors, chemotherapies, estrogens, immunotherapies, poly ADP-ribose polymerase inhibitors, and radiopharmaceuticals. Patients with <12 months of continuous insurance eligibility before index were excluded. Per-patient-per-month (PPPM) all-cause and PC-related HRU and costs (medical and pharmacy; from a payer's perspective in 2022 $USD) were described in the 12-month baseline period and follow-up period (from the index date to castration resistance, end of continuous insurance eligibility, end of data availability, or death). RESULTS: Of 871 patients included (mean age: 70.6 years), 52% initiated ADT monotherapy as their index treatment without documented advanced therapy use. During baseline, 31% of patients had a PC-related inpatient admission and 94% had a PC-related outpatient visit; mean all-cause costs were $2551 PPPM and PC-related costs were $839 PPPM with $787 PPPM attributable to medical costs. Patients had a mean follow-up of 15 months, during which 38% had a PC-related inpatient admission and 98% had a PC-related outpatient visit; mean all-cause costs were $5950 PPPM with PC-related total costs of $4363 PPPM, including medical costs of $2012 PPPM. LIMITATIONS: All analyses were descriptive; statistical testing was not performed. Treatment effectiveness and clinical outcomes were not assessed. CONCLUSION: This real-world study demonstrated a significant economic burden in mCSPC patients, and a propensity to use ADT monotherapy in clinical practice despite the availability and guideline recommendations of advanced life-prolonging therapies.