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%.

Epidemiology and Costs of Sepsis in the United States-An Analysis Based on Timing of Diagnosis and Severity Level.

OBJECTIVES: To characterize the current burden, outcomes, and costs of managing sepsis patients in U.S. hospitals. DESIGN: A retrospective observational study was conducted using the Premier Healthcare Database, which represents ~20% of U.S. inpatient discharges among private and academic hospitals. Hospital costs were obtained from billing records per the cost accounting method used by each hospital. Descriptive statistics were performed on patient demographics, characteristics, and clinical and economic outcomes for the index hospitalization and 30-day readmissions. SETTING: Sepsis patient hospitalizations, including inpatient, general ward, and ICU (intermediate and/or step-down). PATIENTS: Adults over 18 years old with a hospital discharge diagnosis code of sepsis from January 1, 2010, to September 30, 2016. INTERVENTIONS: None. This was a retrospective observational study of deidentified data. MEASUREMENTS AND MAIN RESULTS: The final study cohort consisted of 2,566,689 sepsis cases, representing patients with a mean age of 65 years (50.8% female). Overall mortality was 12.5% but varied greatly by severity (5.6%, 14.9%, and 34.2%) for sepsis without organ dysfunction, severe sepsis, and septic shock, respectively. Costs followed a similar pattern increasing by severity level: $16,324, $24,638, and $38,298 and varied widely by sepsis present at admission ($18,023) and not present at admission ($51,022). CONCLUSIONS: The highest burden of incidence and total costs occurred in the lowest severity sepsis cohort population. Sepsis cases not diagnosed until after admission, and those with increasing severity had a higher economic burden and mortality on a case-by-case basis. Methods to improve early identification of sepsis may provide opportunities for reducing the severity and economic burden of sepsis in the United States.

Red blood cell (RBC) transfusion rates among US chronic dialysis patients during changes to Medicare end-stage renal disease (ESRD) reimbursement systems and erythropoiesis stimulating agent (ESA) labels.

BACKGROUND: Several major ESRD-related regulatory and reimbursement changes were introduced in the United States in 2011. In several large, national datasets, these changes have been associated with decreases in erythropoiesis stimulating agent (ESA) utilization and hemoglobin concentrations in the ESRD population, as well as an increase in the use of red blood cell (RBC) transfusions in this population. Our objective was to examine the use of RBC transfusion before and after the regulatory and reimbursement changes implemented in 2011 in a prevalent population of chronic dialysis patients in a large national claims database. METHODS: Patients in the Truven Health MarketScan Commercial and Medicare Databases with evidence of chronic dialysis were selected for the study. The proportion of chronic dialysis patients who received any RBC transfusion and RBC transfusion event rates per 100 patient-months were calculated in each month from January 1, 2007 to March 31, 2012. The results were analyzed overall and stratified by primary health insurance payer (commercial payer or Medicare). RESULTS: Overall, the percent of chronic dialysis patients with RBC transfusion and RBC transfusion event rates per 100 patient-months increased between January 2007 and March 2012. When stratified by primary health insurance payer, it appears that the increase was driven by the primary Medicare insurance population. While the percent of patients with RBC transfusion and RBC transfusion event rates did not increase in the commercially insured population between 2007 and 2012 they did increase in the primary Medicare insurance population; the majority of the increase occurred in 2011 during the same time frame as the ESRD-related regulatory and reimbursement changes. CONCLUSIONS: The regulatory and reimbursement changes implemented in 2011 may have contributed to an increase in the use of RBC transfusions in chronic dialysis patients in the MarketScan dataset who were covered by Medicare plus Medicare supplemental insurance.

Early trends from the Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS).

BACKGROUND: Launched in January 2011, the prospective payment system (PPS) for the US Medicare End-Stage Renal Disease Program bundled payment for services previously reimbursed independently. Small dialysis organizations may be particularly susceptible to the financial implications of the PPS. The ongoing Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS) was designed to describe trends in care and outcomes over the period of PPS implementation. This report details early results between October 2010 and June 2011. STUDY DESIGN: Prospective observational cohort study of patients from a sample of 51 small dialysis organizations. SETTING & PARTICIPANTS: 1,873 adult hemodialysis and peritoneal dialysis patients. OUTCOMES: Secular trends in processes of care, anemia, metabolic bone disease management, and red blood cell transfusions. MEASUREMENTS: Facility-level data are collected quarterly. Patient characteristics were collected at enrollment and scheduled intervals thereafter. Clinical outcomes are collected on an ongoing basis. RESULTS: Over time, no significant changes were observed in patient to staff ratios. There was a temporal trend toward greater use of peritoneal dialysis (from 2.4% to 3.6%; P = 0.09). Use of cinacalcet, phosphate binders, and oral vitamin D increased; intravenous (IV) vitamin D use decreased (P for trend for all <0.001). Parathyroid hormone levels increased (from 273 to 324 pg/dL; P < 0.001). Erythropoiesis-stimulating agent doses decreased (P < 0.001 for IV epoetin alfa and IV darbepoetin alfa), particularly high doses. Mean hemoglobin levels decreased (P < 0.001), the percentage of patients with hemoglobin levels <10 g/dL increased (from 12.7% to 16.8%), and transfusion rates increased (from 14.3 to 19.6/100 person-years; P = 0.1). Changes in anemia management were more pronounced for African American patients. LIMITATIONS: Limited data were available for the prebundle period. Secular trends may be subject to the ecologic fallacy and are not causal in nature. CONCLUSIONS: In the period after PPS implementation, IV vitamin D use decreased, use of oral therapies for metabolic bone disease increased, erythropoiesis-stimulating agent use and hemoglobin levels decreased, and transfusion rates increased numerically.

An update on the impact of pre-transplant transfusions and allosensitization on time to renal transplant and on allograft survival.

BACKGROUND: Blood transfusions have the potential to improve graft survival, induce sensitization, and transmit infections. Current clinical practice is to minimize transfusions in renal transplantation candidates, but it is unclear if the evidence continues to support pre-transplant transfusion avoidance. Changes in the Medicare prospective payment system may increase transfusion rates. Thus there is a need to re-evaluate the literature to improve the management options for renal transplant candidates. METHODS: A review applying a systematic approach and conducted using MEDLINE(®), Embase(®), and the Cochrane Library for English-language publications (timeframe: 01/1984-03/2011) captured 180 studies and data from publically available registries and assessed the impact of transfusions on allosensitization and graft survival, and the impact of allosensitization on graft survival and wait time. RESULTS: Blood transfusions continued to be a major cause of allosensitization, with allosensitization associated with increased rejection and graft loss, and longer wait times to transplantation. Although older studies showed a beneficial effect of transfusion on graft survival, this benefit has largely disappeared in the post-cyclosporine era due to improved graft outcomes with current practice. Recent data suggested that it may be the donor-specific antibody component of allosensitization that carried the risk to graft outcomes. CONCLUSIONS: Results of this review indicated that avoiding transfusions whenever possible is a sound management option that could prevent detrimental effects in patients awaiting kidney transplantation.

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.

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 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.

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.

Factors in nephrologists' decision to treat pre-dialysis CKD patients with vitamin D insufficiency and SHPT: A discrete choice experiment.

Little is known about the most important factors that inform a nephrologist's decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider's DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute's relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients' 25D and Ca levels contributed to more than half of nephrologists' DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes.

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.

Systematic review of the impact of erythropoiesis-stimulating agents on fatigue in dialysis patients.

BACKGROUND: One of the cardinal symptoms of anemia in chronic kidney disease (CKD) patients is fatigue. Recently, results from Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) raised questions about the role of erythropoiesis-stimulating agents (ESAs) in improving fatigue and the appropriate hemoglobin (Hb) target in anemic patients with CKD. These discussions should be considered with all available evidence to determine the level of benefits and risks associated with ESA therapy on fatigue among both early-stage CKD patients and end-stage renal disease patients on dialysis. METHODS: The study was a systematic review of the literature on fatigue in adults on maintenance dialysis therapy. The requirement for inclusion in the review was the measurement of fatigue before and after ESA treatment. Outcomes that were assessed were fatigue as measured by the Kidney Disease Questionnaire, the 36-item Short-Form general health survey, the Nottingham Health Profile, the Profile of Mood States or the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Several different measures of fatigue were used in the studies. RESULTS: Fifteen articles met the criteria for inclusion, including 10 distinct studies and one extension study. There was one placebo-controlled randomized clinical trial (RCT) and one extension, five single-arm, three high versus low, one intravenous versus subcutaneous and one switch from epoetin alfa to darbepoetin alfa. The only placebo-controlled RCT found a 22-26% improvement in fatigue. Single-arm cohort studies demonstrated a reduction in fatigue after a substantial increase in Hb. Studies with a baseline Hb <10 g/dL and partial correction to a minimum Hb ≥ 10 g/dL showed an average improvement in fatigue of 34.6%. Studies with a baseline Hb ≥ 11 g/dL and full correction to a minimum Hb ≥ 12 g/dL showed an average improvement in fatigue of 5.5%, while studies with no change in Hb (either placebo or control group) showed a decline of 0.7% in fatigue outcomes. CONCLUSION: Partial correction of anemia with ESA results in improvement of fatigue among patients on dialysis, most strikingly in those patients with baseline Hb levels <10 g/dL.

Outpatient red blood cell transfusion payments among patients on chronic dialysis.

BACKGROUND: Payments for red blood cell (RBC) transfusions are separate from US Medicare bundled payments for dialysis-related services and medications. Our objective was to examine the economic burden for payers when chronic dialysis patients receive outpatient RBC transfusions. METHODS: Using Truven Health MarketScan® data (1/1/02-10/31/10) in this retrospective micro-costing economic analysis, we analyzed data from chronic dialysis patients who underwent at least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of transfusion-associated resource use based on current literature was employed to estimate outpatient RBC transfusion payments. Total payments per RBC transfusion episode included screening/monitoring (within 3 days), blood acquisition/administration (within 2 days), and associated complications (within 3 days for acute events; up to 45 days for chronic events). RESULTS: A total of 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD]) age was 60.9 (15.0) years, and mean Charlson comorbidity index was 4.3 (2.5). During a mean (SD) follow-up of 495 (474) days, patients had a mean of 2.2 (3.8) outpatient RBC transfusion episodes. Mean/median (SD) total payment per RBC transfusion episode was $854/$427 ($2,060) with 72.1% attributable to blood acquisition and administration payments. Complication payments ranged from mean (SD) $213 ($168) for delayed hemolytic transfusion reaction to $19,466 ($15,424) for congestive heart failure. CONCLUSIONS: Payments for outpatient RBC transfusion episodes were driven by blood acquisition and administration payments. While infrequent, transfusion complications increased payments substantially when they occurred.

Breast, Colorectal, Lung, Prostate, and Cervical Cancer Screening Prevalence in a Large Commercial and Medicare Advantage Plan, 2008-2020.

This study aimed to comprehensively assess breast, colorectal, cervical, lung, and prostate cancer screening rates and trends in the United States over time among individuals for whom screening is recommended by the United States Preventive Services Task Force (USPSTF). This retrospective study was conducted in two-year intervals from January 1, 2008 to February 29, 2020, using Optum's de-identified Clinformatics® Data Mart Database, which includes Medicare Advantage and commercially insured members. Screening-eligible individuals, who had not previously had the cancer being screened and met USPSTF criteria for screening, were identified at various time points within the study timeframe for relevant screening tests within five cancer types: breast, colorectal, cervical, lung, and prostate. In the 2020 analysis period, patients who were eligible for cancer screening included: breast: 1,620,588; colorectal: 2,763,736; cervical: 1,371,506; lung: 1,491,594; prostate: 1,126,249. Breast and cervical cancer screening prevalence rates were highest (64.4% and 63.8%, respectively), followed by colorectal (29.5%), prostate (11.7%), and lung (3.8%). Black/African American individuals and Hispanics had moderately low screening rates for cervical (58.6%) and breast (61.8%) cancer, respectively; Hispanics had the lowest screening rates for prostate cancer (6.1%). Those residing in the West had lower screening rates for breast (58.9%), cervical (62.1%), and prostate (5.6%) cancer. Screening rates remained stable over time for breast, colorectal, and lung cancer, and changed significantly for cervical (-9.5%, 2012-2020) and prostate (+7.3%, 2008-2020) cancer. Real-world cancer screening rates remain suboptimal and low, and efforts to increase screening uptake and reduce cancer health disparities remain critical.

Electronic medical records: a survey of use and satisfaction in small dialysis organizations.

Little is known about electronic medical record (EMR) use in small dialysis organizations (SDOs). The objective was to determine the prevalence of EMRs in SDOs in the United States. A random sample telephone survey of SDOs was conducted in October, 2008. Approximately 60.7% of the facilities was found to be using an EMR, but only 33.5% had comprehensive systems that recorded medications, tests, and clinical notes. While 75.3% of the respondents indicated they were satisfied or very satisfied with their EMRs, just over one-third of those said they were planning to upgrade or replace their current systems.

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.