Out-of-pocket cost by cancer stage at diagnosis in commercially insured patients in the United States.

AIMS: Out-of-pocket (OOP) costs may constitute a substantial financial burden to patients diagnosed with cancer. Earlier stage diagnosis and treatment of cancers may promote decreased morbidity and mortality, subsequently also lowering costs. To better understand costs experienced by patients with cancer, OOP costs by stage post-diagnosis were estimated. MATERIALS AND METHODS: A retrospective analysis was conducted using Optum's de-identified Integrated Claims-Clinical dataset with Enriched Oncology, which includes data from commercially insured members (June 1, 2015-July 31, 2020). Mean annual and cumulative OOP costs (co-pay + co-insurance + deductible) (2020 USD) were reported through a 3-year period post-cancer diagnosis among adult commercially insured members (not including Medicare Advantage members) diagnosed with staged breast, cervical, colorectal, lung, ovarian, or prostate cancer between January 1, 2016 and June 30, 2020 with continuous enrollment for ≥1-month post-diagnosis. RESULTS: A total of 7,494 eligible members were identified who were diagnosed with breast, cervical, colorectal, lung, ovarian, or prostate cancer. A greater proportion of OOP costs were incurred in year 1 post-diagnosis but remained relatively high through year 3 post-diagnosis. Cumulative mean OOP costs were as high as $35,243 (lung stage IV) per commercially insured patient by year 3 post-diagnosis and were generally higher among those diagnosed at later stages (III/IV) than those diagnosed at earlier stages (I/II) across all cancers. LIMITATIONS: Generalizability of these results is limited to those with commercial health insurance coverage. Additionally, cancer staging was dependent on accuracy of staging as recorded in the electronic medical record and as determined by Optum's proprietary algorithm using natural language processing. CONCLUSION: Cumulative mean OOP costs among commercially insured patients during the 3-year period post-cancer diagnosis were substantial and generally higher among those with later stage cancer diagnoses. Diagnosis of cancer at earlier stages may allow for more timely treatment and lessen patient OOP costs.

Patients diagnosed with cancer may face significant out-of-pocket costs (expenses that are not reimbursed by insurance) for care. However, lower costs may be achieved if the cancer is identified, diagnosed, and treated at earlier stages before the cancer tumor can grow or spread to other parts of the body. In this study, we examined patient out-of-pocket costs on an annual basis and over a 3-year period by cancer stage (I­IV) at diagnosis. Data were obtained from a large healthcare database (Optum's Claims-Clinical dataset with Enriched Oncology) that has administrative claims with out-of-pocket cost records as well as health records to determine cancer type and stage at diagnosis. Out-of-pocket costs recorded in the database included the co-pay, co-insurance, and deductible. Data from 7,494 adult patients with commercial insurance (not including Medicare Advantage) who were newly diagnosed with breast, cervical, colorectal, lung, ovarian, or prostate cancer between January 1, 2016 and June 30, 2020 were identified and analyzed. Patients incurred most of their out-of-pocket costs during the first year after a cancer diagnosis and these costs remained high for an additional 2 years. In general, patients diagnosed with cancer at later stages (III/IV) had a higher 3-year total out-of-pocket cost compared to those diagnosed at earlier stages (I/II) and this reached as high as $35,243 among patients diagnosed with stage IV lung cancer. Diagnosis of cancer at an earlier stage may reduce out-of-pocket costs for patients.

Estimating the Cost per Clinical Outcome of Second-Line Liso-Cel Versus Autologous Stem Cell Transplantation in Patients with Transplantation-Intended Relapsed/Refractory Large B Cell Lymphoma.

It is important to consider the total cost of care (TCOC) associated with a therapy and clinical benefit for relapsed or refractory (R/R) large B cell lymphoma (LBCL). We estimated the 1-year TCOC and cost per clinical outcome for patients with R/R LBCL treated with second-line lisocabtagene maraleucel (liso-cel) versus autologous stem cell transplantation (ASCT) using data from the TRANSFORM study (ClinicalTrials.gov NCT03575351). A cost per clinical outcome analysis using a Monte Carlo simulation approach was conducted. Cost inputs were generated from a retrospective microcosting analysis of healthcare resource utilization (HCRU). Patient-level data from an interim analysis (March 2021) were used to derive HCRU and clinical inputs. Clinical inputs included median event-free survival (EFS), median progression-free survival (PFS), objective response rate, and complete response (CR) rate. In the intention-to-treat analysis, the mean (standard deviation) TCOC per patient was $550,864 ($173,087) for liso-cel and $413,200 ($290,802) for ASCT. The cost per clinical outcome model estimated a mean cost for liso-cel versus ASCT per EFS month of $57,295 versus $186,369, per PFS month of $40,949 versus $78,797, per overall responder of $653,965 versus $881,804, and per complete responder of $828,045 versus $1,063,822. This economic model shows reductions in mean estimated TCOC per EFS month, PFS month, overall responder, and complete responder with liso-cel versus ASCT owing to the superior efficacy of liso-cel. Although liso-cel-treated patients incurred greater upfront costs, fewer required subsequent therapy, and they accumulated less downstream costs. These results underscore the importance of considering the durability of response and clinical benefit when assessing total costs.

Time duration and health care resource use during cancer diagnoses in the United States: A large claims database analysis.

BACKGROUND: Cancer diagnostic pathways are highly variable and not clearly established in the United States, which can lead to a diagnosis process that takes more time and exposes patients to invasive or unnecessary procedures, delays in treatment, worsening patient outcomes, and elevated health care resource utilization (HRU) and health care system costs. OBJECTIVE: To investigate current trends in time to diagnosis and diagnostic-related HRU preceding the patient's cancer diagnosis across all cancer types in the United States. METHODS: A retrospective claims analysis was conducted on patients newly diagnosed with cancer identified from 2018-2019 using Optum's de-identified Clinformatics Data Mart database, which includes Medicare Advantage and commercially insured members. Patients were identified using International Classification of Diseases, Tenth Revision codes and were required to have at least 2 outpatient visits at least 30 days apart or at least 1 inpatient cancer visit without prior cancer claims. The first diagnostic test was identified based on an algorithm of a 60-day gap between diagnostic tests prior to diagnosis. The index date was defined as the first diagnostic test date or an office visit less than 4 weeks prior to the first diagnostic test date. Patient characteristics, time to diagnosis, and HRU were descriptively analyzed for all patients and by cancer type. RESULTS: Among the 458,818 patients newly diagnosed with cancer included in this analysis, the mean age was 70.6 years, approximately half were female, and most were White people (65.0%) with Medicare Advantage coverage (74.0%). Patients with cancer had an overall mean (SD) time to diagnosis of 156.2 (164.9) days and 15.4% of patients waited longer than 180 days before a cancer diagnosis. High heterogeneity among cancer types was observed, with a mean time to diagnosis ranging from 121.6 days (bladder cancer) to 229.0 days (multiple myeloma). Imaging resource use during the diagnostic pathway was high for radiology (60.7%), computerized tomography (50.8%), magnetic resonance imaging (48.6%), and ultrasound (42.6%). A total of 69.3% of patients had endoscopy without biopsy, 36.5% had endoscopy with biopsy, 62.5% had other biopsies, and most patients did general urine and serum tests (91.3%) and nongenetic cancer-specific laboratory tests (84.3%). Resource use was highly varied by cancer type but tended to increase with a longer time to diagnosis. CONCLUSIONS: The proportion of patients experiencing a diagnostic process of longer than 180 days is clinically and economically meaningful. Diagnostic-related HRU was significant and highly variable, highlighting the inefficiencies in the cancer diagnostic process in the United States and the need for policies, guidelines, or medical interventions to streamline cancer diagnostic pathways to optimize patient outcomes and reduce health care system burden. DISCLOSURES: Dr Cong is an employee of Grail, LLC, which supported this study. Drs Gitlin and McGarvey are employees of BluePath Solutions, and Ms Shivaprakash was an employee of BluePath Solutions, which received financial support from Grail, LLC, for study-related research activities. This study was sponsored by Grail, LLC, a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated October 29, 2021. The sponsor had no role in the collection, management, and analysis of the data. The sponsor contributed to study design and data interpretation.

Estimating the Lifetime Medical Cost Burden of an Allogeneic Hematopoietic Cell Transplantation Patient.

Allogeneic hematopoietic cell transplantation (allo-HCT) has the potential for curative outcomes for a variety of hematologic malignancies. Current allo-HCT studies often describe the outcomes and costs in the near term; however, research on the lifetime economic burden post-allo-HCT remains limited. This study was conducted to estimate the average total lifetime direct medical costs of an allo-HCT patient and the potential net monetary savings from an alternative treatment associated with improved graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). A disease-state model was constructed using a short-term decision tree and a long-term semi-Markov partitioned survival model to estimate the average per-patient lifetime cost and expected quality-adjusted life years (QALYs) for an allo-HCT patient from a US healthcare system perspective. Key clinical inputs included overall survival, GRFS, incidence of both acute and chronic GVHD, relapse of the primary disease, and infections. Cost results were reported as ranges based on varying the percentage of chronic GVHD patients that remained on treatment after 2 years (15% or 39%). Over a lifetime, the average per-patient medical cost of allo-HCT was estimated to range from $942,373 to $1,247,917. The majority of the costs were for chronic GVHD treatment (37% to 53%), followed by the allo-HCT procedure (15% to 19%). The expected lifetime QALYs of an allo-HCT patient were estimated as 4.7. Lifetime per-patient treatment costs often exceed $1,000,000 for allo-HCT patients. Innovative research efforts focused on the reduction or elimination of late complications, particularly chronic GVHD, may provide the greatest value to improved patient outcomes.

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among postmenopausal women across eight European countries.

A population-level, cross-sectional model was developed to estimate the clinical and economic burden of osteoporosis among women (≥ 70 years) across eight European countries. Results demonstrated that interventions aimed at improving fracture risk assessment and adherence would save 15.2% of annual costs in 2040. PURPOSE: Osteoporosis is associated with significant clinical and economic burden, expected to further increase with an ageing population. This modelling analysis assessed clinical and economic outcomes under different hypothetical disease management interventions to reduce this burden. METHODS: A population-level, cross-sectional cohort model was developed to estimate numbers of incident fractures and direct costs of care among women (≥ 70 years) in eight European countries under different hypothetical interventions: (1) an improvement in the risk assessment rate, (2) an improvement in the treatment adherence rate and (3) a combination of interventions 1 and 2. A 50% improvement from the status quo, based on existing disease management patterns, was evaluated in the main analysis; scenario analyses evaluated improvement of either 10 or 100%. RESULTS: Based on existing disease management patterns, a 44% increase in the annual number of fractures and costs was predicted from 2020 to 2040: from 1.2 million fractures and €12.8 billion in 2020 to 1.8 million fractures and €18.4 billion in 2040. Intervention 3 provided the greatest fracture reduction and cost savings (a decrease of 17.9% and 15.2% in fractures and cost, respectively) in 2040 compared with intervention 1 (decreases of 8.7% and 7.0% in fractures and cost, respectively) and intervention 2 (10.0% and 8.8% reductions in fracture and cost, respectively). Scenario analyses showed similar patterns. CONCLUSION: These analyses suggest that interventions which improve fracture risk assessment and adherence to treatments would relieve the burden of osteoporosis, and that a combination strategy would achieve greatest benefits.

A Model to Estimate Cytokine Release Syndrome and Neurological Event Management Costs Associated With CAR T-Cell Therapy.

Chimeric antigen receptor (CAR) T-cell therapies demonstrated efficacy in relapsed/refractory large B-cell lymphoma (LBCL) but are associated with cytokine release syndrome (CRS) and neurological events (NE). We wanted to estimate the total cost of CRS and NE management among patients with relapsed/refractory LBCL treated with lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel), or tisagenlecleucel (tisa-cel) in the third- or later-line setting. An economic decision tree model was developed using clinical and economic data to estimate a weighted average per-patient adverse event (AE) management cost from a United States health care system perspective in 2020 dollars. In 2 predefined analyses, mean expected cost and 95% confidence intervals of the average treated patient were estimated via Monte Carlo simulations, with per-patient costs for each CAR T-cell therapy further stratified by AE and grade. In the base case, the overall weighted average per-patient cost was $18,718, $47,665, and $42,538 for liso-cel, axi-cel, and tisa-cel, respectively. The weighted average per-patient cost per CRS event was $8213, $20,442, and $26,009 for liso-cel, axi-cel, and tisa-cel, respectively; the weighted average per-patient cost per NE was $10,505, $27,223, and $16,528, respectively. Differences in the base-case scenario estimated total mean costs for liso-cel were -$28,947 and -$23,819 compared with axi-cel and tisa-cel, respectively. In the scenario analysis (alternative cost input), differences in the estimated total mean costs were -$24,498 for liso-cel versus axi-cel, and -$19,326 for liso-cel versus tisa-cel. Across the base case and scenario analysis, liso-cel had the lowest weighted average CRS and NE costs per treated patient compared with axi-cel and tisa-cel owing to lower incidence rates and symptom severity. These findings highlight the economic implications of differences in safety among CAR T-cell therapies.

Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients.

INTRODUCTION: Extended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D. METHODS: Medical records of 376 adult patients with stage 3-4 CKD and a history of SHPT and VDI from 15 United States (US) nephrology clinics were reviewed for up to 1 year pre- and post-ERC, NVD or AVD initiation. Key study variables included patient demographics, concomitant usage of medications and laboratory data. The mean age of the study population was 69.5 years, with gender and racial distributions representative of the US CKD population. Enrolled patients were grouped by treatment into three cohorts: ERC (n = 174), AVD (n = 55) and NVD (n = 147), and mean baseline levels were similar for serum 25D (18.8-23.5 ng/mL), calcium (Ca: 9.1-9.3 mg/dL), phosphorus (P: 3.7-3.8 mg/dL) and estimated glomerular filtration rate (eGFR: 30.3-35.7 mL/min/1.73m2). Mean baseline PTH was 181.4 pg/mL for the ERC cohort versus 156.9 for the AVD cohort and 134.8 pg/mL (p < 0.001) for the NVD cohort. Mean follow-up during treatment ranged from 20.0 to 28.8 weeks. RESULTS: Serum 25D rose in all cohorts (p < 0.001) during treatment. ERC yielded the highest increase (p < 0.001) of 23.7 ± 1.6 ng/mL versus 9.7 ± 1.5 and 5.5 ± 1.3 ng/mL for NVD and AVD, respectively. PTH declined with ERC treatment by 34.1 ± 6.6 pg/mL (p < 0.001) but remained unchanged in the other two cohorts. Serum Ca increased 0.2 ± 0.1 pg/mL (p < 0.001) with AVD but remained otherwise stable. Serum alkaline phosphatase remained unchanged. CONCLUSIONS: Real-world clinical effectiveness and safety varied across the therapies under investigation, but only ERC effectively raised mean 25D (to well above 30 ng/mL) and reduced mean PTH levels without causing hypercalcemia.

Increased healthcare costs by later stage cancer diagnosis.

BACKGROUND: Cancer represents a significant source of disease burden in the United States (US), both clinically and economically. Diagnosis and treatment of cancer at earlier stages may reduce this burden. To better understand potential impacts of earlier diagnosis, healthcare costs among patients with cancer were assessed by cancer type and stage at diagnosis. METHODS: A retrospective analysis was conducted using Optum's de-identified Integrated Claims-Clinical data set with Enriched Oncology, which includes data from Medicare Advantage and commercially insured members. Adult members newly diagnosed with solid tumor cancers, cancer stage at diagnosis (diagnosed 1/1/2016-6/30/2020), and continuous enrollment for at least one month post diagnosis were identified. Patients with breast, cervical, colorectal, lung, ovarian, or prostate cancer were reported. Mean standardized costs (2020 USD) were calculated in each month on an annual and cumulative basis through four years post-cancer diagnosis. In each month, costs were calculated for those with continuous enrollment and no death reported in the month. Mean annual cost per patient was estimated by summing month one to 12 mean costs and stratifying by stage at cancer diagnosis; annual year one to four costs were summed to determine cumulative costs. RESULTS: Among members diagnosed 2016-2020 with breast, cervical, colorectal, lung, ovarian, or prostate cancer, 20,422 eligible members were identified. Mean costs increased by stage of diagnosis across all cancers at the annual and cumulative level through year four post diagnosis. Cumulative mean costs grew over time at a relatively similar rate across stages I to III and more dramatically in stage IV, except for cervical and lung cancer where the rate was relatively stable or slightly fluctuated across stages and ovarian cancer where stages III and IV both increased more sharply compared to stages I and II. CONCLUSIONS: Mean annual and cumulative healthcare costs through year four post cancer diagnosis were significantly higher among those diagnosed at later versus earlier cancer stages. The steeper increase in cumulative costs among those diagnosed in stage IV for many cancer types highlights the importance of earlier cancer diagnosis. Earlier cancer diagnosis may enable more efficient treatment, improve patient outcomes and reduce healthcare costs.

Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol.

INTRODUCTION: The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC's efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population. MATERIALS AND METHODS: Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations. RESULTS: The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (p < 0.001) with nominal changes of 0.1 mg/dL (p > 0.05) in serum calcium (Ca) and phosphorus (P) levels. DISCUSSION/CONCLUSION: Analysis of postlaunch data confirmed ERC's effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among women in Japan: a simulation projection model from 2020 to 2040.

Impact of increased osteoporosis diagnosis and treatment among postmenopausal women (PMW) on reduction in fractures and associated costs in Japan from 2020 to 2040 was modeled. INTRODUCTION: Japan is currently home to the world's oldest population and the 65 + years demographic is expected to grow to 35% by 2040. Thus, identifying strategies to reduce clinical and economic burden associated with osteoporosis among this at-risk population is critical. METHODS: A microsimulation model was developed to project osteoporotic annual fracture incidence and costs among PMW 2020-2040. Fracture risk was estimated using a simplified Fracture Risk Assessment Tool (FRAX). Fracture estimates were based on annualized FRAX risk and treatment impact. Published literature informed inputs for direct and indirect fracture costs, DXA screening costs, and treatment costs and efficacy. Japan's current screening and treatment rates were compared against 50% increases to (1) case finding (screening rate and subsequent treatment rate) and (2) treatment rate among those at highest fracture risk. RESULTS: From 2020 to 2040, 21.6 million fractures are projected costing US $410.2 billion. Increased case finding scenario resulted in the prevention of 456.9 thousand primary and 340.9 thousand second + fractures saving US $4.25 billion. Increased treatment scenario led to 500.5 thousand and 435.5 thousand fewer primary and second + fractures, respectively, and reduced economic burden by $3.1 billion. CONCLUSION: Improvements to rates of osteoporosis screening and preventive treatment in Japan's aging population through disease awareness campaigns and post-fracture care programs, among others, will likely reduce osteoporosis-associated clinical and economic burden.

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among women in China: a simulation projection model from 2020 to 2040.

Annual osteoporotic fractures is projected to increase by 135% from 6.9 M (2020) to 16.2 M (2040), increasing the economic burden by 121% from $29.9B (2020) to $65.9B (2040). INTRODUCTION: Globally, aging populations drive significant increases in osteoporosis prevalence. In China, the number of women aged ≥ 65 years is expected to more than double from 2020 (91.5 M) to 2040 (183.6 M). Using a microsimulation model, impact of increased diagnosis and treatment of postmenopausal women (PMW) with osteoporosis on anticipated reduction in fractures and associated costs in China from 2020 to 2040 was projected. METHODS: A microsimulation model was developed to project annual incidence and costs of osteoporotic fractures among PMW in China from 2020 to 2040. Fracture risk was estimated using the simplified Fracture Risk Assessment Tool (FRAX). Fractures estimates were based on annualized FRAX risk and impact of treatment. Published literature informed inputs for direct and indirect fracture costs, DXA screening costs, and treatment costs and efficacy. China's current screening and treatment rates were compared against 50% increases to (i) case finding (screening rate and subsequent treatment rate) and (ii) treatment rate among those at highest fracture risk. RESULTS: From 2020 to 2040, 241.7 M osteoporotic fractures are projected to cost $997B. Increased treatment scenario prevented 24.6 M fractures and saved $56B. Increased case finding scenario prevented 26 M fractures and saved $61.7B. CONCLUSION: Osteoporosis underdiagnosis and undertreatment among the aging Chinese population will considerably burden patients, caregivers, and society. Policy changes to increase screening and treatment rates may result in significant cost savings and clinical benefits.

Travel-Related Economic Burden of Chimeric Antigen Receptor T Cell Therapy Administration by Site of Care.

INTRODUCTION: We previously examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacted patient travel distances and time. In the current study, we estimated travel-related economic burden associated with site-of-care options among patients with relapsed/refractory diffuse large B cell lymphoma. METHODS: We used geographic information system methods to quantify travel-related economic burden across three site-of-care scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Socioeconomic status, administration sites, and county of residence were derived from the US Census Bureau and publicly available sources. Travel costs were based on governmental guidelines, US census wage data, and Bureau of Transportation Statistics. Travel distance and time to the nearest CAR T cell therapy administration sites were estimated from previous research. RESULTS: Total national estimated costs associated with traveling for CAR T cell therapy were $21.1 million if CAR T cell therapy was offered exclusively in academic hospitals, and $14.7 million if expanded to include community hospitals plus nonacademic specialty oncology network centers, representing a $6.5-million reduction associated with expanding access to eligible patients. The largest cost-saving component was lodging/meals. Regional and demographic cost differences were statistically significant between academic hospitals and nonacademic hospitals/specialty oncology centers. In all scenarios, patients living below the federal poverty level (FPL) had higher weighted mean total costs versus patients living above the FPL. White and Native American patients were estimated to have the highest weighted mean total costs across race/ethnicity groups. For all subgroups, costs were reduced by expanding access beyond academic hospitals. CONCLUSION: CAR T cell therapy is currently restricted to academic hospitals; total travel costs could be substantially decreased if access is expanded to nonacademic hospitals and specialty oncology centers. Patients in rural areas and those living below the FPL are particularly disadvantaged by restricted access.

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among women in South Korea: a simulation projection model from 2020 to 2040.

Using a microsimulation model, the impact of increased diagnosis and treatment of postmenopausal women with osteoporosis on anticipated reduction in fractures and associated costs in South Korea from 2020 to 2040 was projected. INTRODUCTION: The economic burden of osteoporosis was US $5.1B in 2011 in South Korea. Osteoporosis is expected to strain resources in South Korea as the population most susceptible to osteoporotic fracture, females > 50 years old, is projected to increase by 32% from 2020 to 2040. METHODS: A microsimulation model was developed to project annual incidence and costs of osteoporotic fractures among postmenopausal women from 2020 to 2040. Fracture risk was estimated using the simplified Fracture Risk Assessment Tool (FRAX). The fracture estimates were based on annualized FRAX risk and impact of treatment. Korean National Health Insurance data informed treatment and case-finding rates in the reference case. Two scenarios were evaluated: 50% increases to (i) case finding (screening rate and subsequent treatment rate) and (ii) treatment rate among those at highest risk. RESULTS: Among individuals modeled in the reference case from 2020 to 2040, 41.2 M fractures at a cost of US $263.6B were projected. Increased treatment scenario prevented 4.4 M fractures and saved US $13.5B. Increased case-finding scenario prevented 4.0 M fractures and saved US $11.1B. CONCLUSION: Implementation of policies to enable increasing case finding or treatment may result in fewer fractures and substantial cost savings across the healthcare system. These results highlight the importance of early screening, diagnosis, and preventive treatment.

Postinfusion monitoring costs by site of care for patients with relapsed/refractory large B-cell lymphoma receiving third- or later-line treatment with lisocabtagene maraleucel in the TRANSCEND NHL 001 and OUTREACH trials.

This retrospective study estimated postinfusion health care resource utilization (HCRU) by site of care among 303 patients with relapsed/refractory large B-cell lymphoma who received third- or later-line treatment with lisocabtagene maraleucel (liso-cel) in the TRANSCEND NHL 001 and OUTREACH trials. Inpatients (n = 256) had higher rates of hospitalization versus outpatients (n = 47; >99% vs 62%), by definition, and higher rates of tocilizumab use for cytokine release syndrome and/or neurological events (22% vs 9%). Rates of intensive care unit admission, corticosteroid use, vasopressor use, hemodialysis, and intubation were generally low and similar between groups. Median (range) total hospital length of stay was 15 (0-88) days (inpatients) and 4 (0-77) days (outpatients). Over 6 months, estimated mean postinfusion cost of care was $89,535 (inpatients) and $36,702 (outpatients). Most costs were incurred in the first month post infusion (inpatients, $50,369 [56%]; outpatients, $19,837 [54%]). Lower overall HCRU was observed with outpatient postinfusion monitoring.

Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel-treated patients in the TRANSCEND NHL 001 trial.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell-specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

Economic Evaluation of Chimeric Antigen Receptor T-Cell Therapy by Site of Care Among Patients With Relapsed or Refractory Large B-Cell Lymphoma.

Importance: Chimeric antigen receptor (CAR) T-cell therapies are currently administered at a limited number of cancer centers and are primarily delivered in an inpatient setting. However, variations in total costs associated with these therapies remain unknown. Objective: To estimate the economic differences in the administration of CAR T-cell therapy by the site of care and the incidence of key adverse events. Design, Setting, and Participants: A decision-tree model was designed to capture clinical outcomes and associated costs during a predefined period (from lymphodepletion to 30 days after the receipt of CAR T-cell infusion) to account for the potential incidence of acute adverse events and to evaluate variations in total costs for the administration of CAR T-cell therapy by site of care. Cost estimates were from the health care practitioner perspective and were based on data obtained from the literature and publicly available databases, including the Healthcare Cost and Utilization Project National Inpatient Sample, the Medicare Hospital Outpatient Prospective Payment System, the Medicare physician fee schedule, the Centers for Medicare and Medicaid Services Healthcare Common Procedure Coding System, and the IBM Micromedex RED BOOK. The model evaluated an average adult patient with relapsed or refractory large B-cell lymphoma who received CAR T-cell therapy in an academic inpatient hospital or nonacademic specialty oncology network. Intervention: The administration of CAR T-cell therapy. Main Outcomes and Measures: Total cost of the administration of CAR T-cell therapy by site of care. The costs associated with lymphodepletion, acquisition and infusion of CAR T cells, and management of acute adverse events were also examined. Results: The estimated total cost of care associated with the administration of CAR T-cell therapy was $454 611 (95% CI, $452 466-$458 267) in the academic hospital inpatient setting compared with $421 624 (95% CI, $417 204-$422 325) in the nonacademic specialty oncology network setting, for a difference of $32 987. After excluding the CAR T-cell acquisition cost, hospitalization and office visit costs were $53 360 (65.3% of the total cost) in academic inpatient hospitals and $23 526 (48.4% of the total cost) in nonacademic specialty oncology networks. The administration of CAR T-cell therapy in nonacademic specialty oncology networks was associated with a $29 834 (55.9%) decrease in hospitalization and office visit costs and a $3154 (20.1%) decrease in procedure costs. Conclusions and Relevance: The potential availability of CAR T-cell therapies that are associated with a lower incidence of adverse events and are suitable for outpatient administration may reduce the total costs of care by enabling the use of these therapies in nonacademic specialty oncology networks.

Cost-Effectiveness and Estimated Health Benefits of Treating Patients with Vitamin D in Pre-Dialysis.

Background The optimal timing of treatment with vitamin D therapy for patients with chronic kidney disease (CKD), vitamin D insufficiency, and secondary hyperparathyroidism (SHPT) is a pressing question in nephrology with economic and patient outcome implications. Objective The objective of this study was to estimate the cost-effectiveness of earlier vitamin D treatment in CKD patients not on dialysis with vitamin D insufficiency and SHPT. Design A cost-effectiveness analysis based on a Markov model of CKD progression was developed from the Medicare perspective. The model follows a hypothetical cohort of 1000 Stage 3 or 4 CKD patients over a 5-year time horizon. The intervention was vitamin D therapy initiated in CKD stages 3 or 4 through CKD stage 5/end-stage renal disease (ESRD) versus initiation in CKD stage 5/ESRD only. The outcomes of interest were cardiovascular (CV) events averted, fractures averted, time in CKD stage 5/ESRD, mortality, quality-adjusted life years (QALYs), and costs associated with clinical events and CKD stage. Results Vitamin D treatment in CKD stages 3 and 4 was a dominant strategy when compared to waiting to treat until CKD stage 5/ESRD. Total cost savings associated with treatment during CKD stages 3 and 4, compared to waiting until CKD stage 5/ESRD, was estimated to be $19.9 million. The model estimated that early treatment results in 159 averted CV events, 5 averted fractures, 269 fewer patient-years in CKD stage 5, 41 fewer deaths, and 191 additional QALYs. Conclusions Initiating vitamin D therapy in CKD stages 3 or 4 appears to be cost-effective, largely driven by the annual costs of care by CKD stage, CV event costs, and risks of hypercalcemia. Further research demonstrating causal relationships between vitamin D therapy and patient outcomes is needed to inform decision making regarding vitamin D therapy timing.

A Systematic Review of the Health Economics of Pompe Disease.

BACKGROUND: Pompe disease is a rare, severe neuromuscular disease with high mortality and substantial clinical and humanistic burden. However, the economic burden of Pompe disease and the health economic value of its treatments are not well understood. The objectives of this systematic review were to characterize the health economic evidence on Pompe disease, including healthcare resource use and costs (direct and indirect), health utilities, and the cost-effectiveness of current treatments used to manage patients with Pompe disease. METHODS: A systematic search of MEDLINE® and Embase® was performed to retrieve publications on the health economics of Pompe disease. Publications were screened according to predefined criteria, extracted, and quality assessed using the Newcastle-Ottawa Scale. Data were narratively synthesized. RESULTS: Eight publications evaluated patients with infantile-onset Pompe disease (IOPD) (two studies), late-onset Pompe disease (LOPD) (four studies), or both (two studies). In IOPD, total cost of supportive therapy (excluding treatment) was €32,871 (equivalent to US$41,667 when adjusted for currency and inflation to 2017 US dollars) over a life expectancy of 0.4 years. In adult LOPD, the average annual cost per patient of supportive therapy was €22,475 (adjusted $28,489). Resource use in LOPD was high, with nursing home admissions accounting for 19% of annual direct medical costs. Health economic evaluations estimating incremental costs per quality-adjusted life year (QALY) gained with enzyme-replacement therapy (ERT) versus supportive therapy ranged from £109,991 (adjusted, $186,851) per QALY gained in Columbia to €1,043,868 (adjusted, $1,323,207) in the Netherlands. DISCUSSION: Despite a full systematic literature search, only eight relevant publications were identified, most of which were of relatively poor quality. However, a significant economic burden of Pompe disease on patients, families, healthcare systems, and society was found, with the majority of costs driven by the only currently approved treatment, ERT. Health economic evaluations of ERT versus supportive therapy vary significantly, with the majority well above willingness-to-pay thresholds. New therapies and approaches to care are needed to address the persistent and lifelong economic burden of Pompe disease and the large incremental cost-effectiveness ratios observed.

Predicted Economic Benefits of a Novel Biomarker for Earlier Sepsis Identification and Treatment: A Counterfactual Analysis.

To estimate the potential clinical and health economic value of earlier sepsis identification in the emergency department using a novel diagnostic marker, monocyte distribution width. DESIGN: The analysis was conducted in two phases: 1) an analysis of the pivotal registration trial evidence to estimate the potential benefit of monocyte distribution width for early sepsis identification and (2) a cost-consequence analysis to estimate the potential economic and clinical benefits that could have resulted from earlier administration of antibiotics for those patients. SETTING: Sepsis identified in the emergency department which led to inpatient hospitalizations. PATIENTS: Adult sepsis patients admitted through the emergency department. INTERVENTIONS: None. This was a model simulation of clinical and economic outcomes of monocyte distribution width based on results from a noninterventional, multicenter clinical trial. MEASUREMENTS AND MAIN RESULTS: Among the 385 patients with sepsis, a total of 349 were eligible for inclusion. Sixty-seven percent of patients were predicted to benefit from monocyte distribution width results, resulting in an estimated mean reduction in time to antibiotics administration from 3.98 hours using standard of care to 2.07 hours using monocyte distribution width + standard of care. Based on this simulated reduction in time to antibiotics, monocyte distribution width + standard of care could have resulted in a less than or equal to 14.2% reduction (27.9% vs 32.5%) in mortality, a mean reduction of 1.48 days (10.0 vs 11.5 d) in length of stay, and $3,460 ($23,466 vs $26,926) savings per hospitalization. At the hospital level, based on an established national mean of 206 sepsis hospitalizations per hospital per year, earlier identification with monocyte distribution width is predicted to result in a total of $712,783 in annual cost savings per hospital. CONCLUSIONS: Improved early identification of sepsis using monocyte distribution width along with current standard of care is estimated to improve both clinical and economic outcomes of sepsis patients presenting in the emergency department. Further research is warranted to confirm these model projections.