Health-Related Quality-of-Life Impacts Associated with Transfusion-Dependent ß-Thalassemia in the USA and UK: A Qualitative Assessment.

BACKGROUND: Individuals living with transfusion-dependent ß-thalassemia (TDT) experience reduced health-related quality of life due to fatigue and chronic pain, which cause disruptions to daily life. Currently, limited qualitative data exist that describe these impacts. OBJECTIVE: This study aimed to examine the ways in which symptoms and current treatments of TDT impact health-related quality of life, to holistically describe the humanistic burden of TDT, and to identify the unmet needs of individuals living with TDT. METHODS: Adults (aged ≥ 18 years) with TDT and caregivers of adolescents (aged 12‒17 years) with TDT participated in semi-structured one-on-one virtual interviews and focus group discussions. Interviews were conducted in the USA and UK and lasted approximately 60 minutes. After transcription, the interviews were analyzed thematically using a framework approach. RESULTS: A total of ten interviews/focus group discussions (six interviews and four focus group discussions) were conducted with 14 adults with TDT and two caregivers of adolescents with TDT. A framework analysis revealed five themes describing health-related quality of life (negative impacts on daily activities, social life, family life, work and education, and psychological well-being) and three themes describing the lived experience of TDT (impact of red blood cell transfusions and iron chelation therapy, treatment, and stigma). Physical, psychological, and treatment-related factors contributed to negative impacts on daily activities, social and family life, and work and education. Concerns about reduced lifespan, relationships and family planning, and financial independence were detrimental to participants' mental well-being. Participants reported having high resilience to the many physical and psychological challenges of living with TDT. A lack of TDT-specific knowledge among healthcare professionals, particularly regarding chronic pain associated with the disease, left some participants feeling ignored or undermined. Additionally, many participants experienced stigma and were reluctant to disclose their disease to others. CONCLUSIONS: Individuals living with TDT experience substantial negative impacts on health-related quality of life that disrupt their daily lives, disruptions that are intensified by inadequate healthcare interactions, demanding treatment schedules, and stigma. Our study highlights the unmet needs of individuals living with TDT, especially for alternative treatments that reduce or eliminate the need for red blood cell transfusions and iron chelation therapy.

Economic and clinical burden of managing transfusion-dependent ß-thalassemia in the United States.

AIMS: To describe clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with transfusion-dependent ß-thalassemia (TDT) in the United States. MATERIALS AND METHODS: Merative MarketScan Databases were used to identify patients with ß-thalassemia between 1 March 2010, and 1 March 2019. Patients were eligible for inclusion with ≥1 inpatient claim or ≥2 outpatient claims for ß-thalassemia and ≥8 red blood cell transfusions (RBCTs) during any 12-month period after and including the date of the first qualifying ß-thalassemia diagnosis code. Matched controls consisted of individuals without ß-thalassemia. Clinical and economic outcomes of patients were assessed during ≥12 months of follow-up, defined as the period from the index date (i.e. the first RBCT) to either the end of continuous enrollment in benefits, inpatient death, or 1 March 2020. RESULTS: Overall, 207 patients with TDT and 1035 matched controls were identified. Most patients received iron chelation therapy (ICT) (91.3%), with a mean of 12.1 (standard deviation [SD] = 10.3) ICT claims per-patient-per-year (PPPY). Many also received RBCTs, with a mean of 14.2 (SD = 4.7) RBCTs PPPY. TDT was associated with higher annual ($137,125) and lifetime ($7.1 million) healthcare costs vs. matched controls ($4183 and $235,000, respectively). Annual costs were driven by ICT (52.1%) and RBCT use (23.6%). Patients with TDT had 7-times more total outpatient visits/encounters, 3-times more prescriptions, and 33-times higher total annual costs than matched controls. LIMITATIONS: This analysis may underestimate the burden of TDT, as indirect healthcare costs (e.g. absenteeism, presenteeism, etc.) were not included. Results may not be generalizable to patients excluded from this analysis, including those with other types of insurance or without insurance. CONCLUSIONS: Patients with TDT have high HCRU and direct healthcare costs. Treatments that eliminate the need for RBCTs could reduce the clinical and economic burden of managing TDT.

Economic and Clinical Burden of Managing Sickle Cell Disease with Recurrent Vaso-Occlusive Crises in the United States.

INTRODUCTION: The aim of this study was to describe the clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in the US. METHODS: Merative MarketScan Databases were used to identify patients with SCD with recurrent VOCs from March 1, 2010, to March 1, 2019. Inclusion criteria were ≥ 1 inpatient or ≥ 2 outpatient claims for SCD and ≥ 2 VOCs per year in any 2 consecutive years after the first qualifying SCD diagnosis. Individuals without SCD in these databases were used as matched controls. Patients were followed for ≥ 12 months, from their second VOC in the 2nd year (index date) to the earliest of inpatient death, end of continuous enrollment in medical/pharmacy benefits, or March 1, 2020. Outcomes were assessed during follow-up. RESULTS: In total, 3420 patients with SCD with recurrent VOCs and 16,722 matched controls were identified. Patients with SCD with recurrent VOCs had a mean of 5.0 VOCs (standard deviation [SD] = 6.0), 2.7 inpatient admissions (SD 2.9), and 5.0 emergency department visits (SD 8.0) per patient per year during follow-up. Compared to matched controls, patients with SCD with recurrent VOCs incurred higher annual ($67,282 vs. $4134) and lifetime ($3.8 million vs. $229,000 over 50 years) healthcare costs. CONCLUSION: Patients with SCD with recurrent VOCs experience substantial clinical and economic burden driven by inpatient costs and frequent VOCs. There is a major unmet need for treatments that alleviate or eliminate clinical complications, including VOCs, and reduce healthcare costs in this patient population.

Levels, source apportionment, and risk assessment of polycyclic aromatic hydrocarbons in vegetable bases of northwest China.

Dietary consumption of contaminated vegetables is the main route of human exposure to polycyclic aromatic hydrocarbons (PAHs). However, there is a lack of research on PAHs in vegetables from northwest China. In this study, the concentrations, sources, and risk assessment of PAHs in the soil and vegetables of Urumqi, an urbanized city in Xinjiang, China, were investigated. The total concentrations of 16 PAHs in soil and vegetable samples ranged 10.58-77.20 and 93.7-1071.8 ng/g, with average values of 2.86 and 242.76 ng/g, respectively. Among vegetable samples, the concentrations were in the order: leafy vegetables (299.08 ng/g) > fruits (192.65 ng/g) > vegetable roots (152.05 ng/g). The source apportionment of PAHs was identified using positive matrix factorization. The primary sources of PAHs in soil samples are oil spills, traffic emissions, coal combustion, and coke combustion. The main sources of PAHs in vegetable samples are oil spills and burning of grass, wood, coal, and coke. In soil samples, the ecological risk caused by PAHs is at a safe level, and the incremental lifetime cancer risks (ILCRs) of ingestion exposure exceed 1.0 × 10-6, which will pose potential risks to human body. The ILCRs of vegetable samples revealed that all groups had potential risks from onion and cabbage consumption (ILCRs > 1.0 × 10-6). In particular, adult women had a higher risk of cancer (ILCRs > 1.0 × 10-4). These results emphasize the importance of combating PAHs pollution in vegetable bases.

Levels, sources, and risk assessment of PAHs residues in soil and plants in urban parks of Northwest China.

Polycyclic aromatic hydrocarbons (PAHs) will be ingested by people through different ways to threaten their health during play, so the environmental quality of the park directly affects the health of tourists and residents. Using eight typical parks in Urumqi in Northwest China as the study area, we used GC-MS to detect the PAHs content in the park surface soil and 10 common plants in the park in different seasons. The results showed that the content of PAHs in park soil in the summer was 5-6 times that in the winter, and the monomer PAHs in some park soil sampling points were higher than the soil pollution risk screening value. And the contamination level at these sampling sites was also higher compared to other sampling sites. In summer, the plants with high PAHs content in leaves are short herbs, while in winter, they are tall arbors. The PAHs of the park soil are mainly composed of high-cyclic aromatic hydrocarbons, and are mainly of traffic origin. The proportion of low-ring aromatic hydrocarbons in the winter was significantly higher than that in the summer. The source of PAHs in plants in summer is similar to that in soil, but the source of PAHs in plants in winter is more complex. The toxicity equivalent concentration method values of soil PAHs in South Park, Zhiwu Park, Shihua Park and Toutunhe Park were higher than that in other parks. The lifetime carcinogenic risk (ILCRs) values of some sampling points in these four parks in the summer were relatively high. The average ILCRs of adults and children in all parks reached a low-risk level in summer. The carcinogenic risk in children is much higher than that of adults.

[Typical Pesticide Residues and Their Risk Assessment in Farmland Environment of Different Plant Types in Shaya County, Xinjiang].

In order to investigate the characteristics of typical pesticide residues in farmland soil of different plant types in Shaya County and to evaluate the level of human health risk and ecological risk caused by pesticide residues, a total of 55 samples of plants, soil, and water from nine areas of Shaya county were collected on September 29, 2020. The occurrence levels of 47 typical pesticides in the samples were analyzed using gas chromatography-mass spectrometry (GC-MS). The results showed that a total of 23 pesticides were detected in three environmental media, and the maximum concentrations of pesticides in soil, plants, and water were 70.58 µg·kg-1, 1832.18 µg·kg-1, and 188.53 µg·L-1, respectively. The levels of pesticide residues in the three environmental media in Shaya county were characterized as plants>water>soil. From the detection of pesticides in different plant types, P1, P2, P6, and P8 in the center of the county were the most seriously polluted. The plants with a high pesticide load level in the corresponding areas were cotton, walnut, red jujube, and poplar, and the pesticides with a high concentration contribution were hexachlorocyclohexanes, chlorpyrifos, cyhalothrin, fluvalinate, metalaxyl, difenoconazole, and procymidone. The human health risks of adults and children caused by oral intake, skin contact, and respiratory inhalation were evaluated. The results showed that oral intake was the main exposure route, and the risk level of children was significantly higher than that of adults but was within the acceptable range. The ecological risk level of earthworms in soil was subsequently evaluated. The results showed that the potential ecological risk level of a single pesticide was low, and the potential ecological risk level of bifenthrin was the largest. The calculation of the total ecological risk of mixed pesticides showed that areas P1, P4, P7, and P9 were at moderate risk, whereas other areas were at low risk. Therefore, the use of some pesticides in Shaya County should be restricted.

Association of factor expression levels with health-related quality of life and direct medical costs for people with haemophilia B.

AIMS: Gene therapy trials aim to provide a functional cure for patients with haemophilia B (HB), and treatment impact is analyzed by factor IX expression levels (FELs). We investigated the relationship of FELs with health-related quality of life (HRQoL) and costs. MATERIALS AND METHODS: This was a retrospective cross-sectional analysis of the European (CHESS I-II) and US (CHESS-US) CHESS population studies. Physicians recruited consecutive patients and extracted information from the medical records; patients completed questionnaires between 2014 and 2015 (CHESS-I), 2018-2019 (CHESS-II) and 2019 (CHESS US). Patients with inhibitors were excluded. HRQoL was assessed using the EQ-5D-5L. Twelve-month haemophilia-related direct medical costs included office visits and hospitalizations based on country-level unit costs. A Tobit model was used to analyze FELs and HRQoL and generalized linear models for direct medical costs. RESULTS: A total of 191 men with HB completed the EQ-5D questionnaire; the mean age was 36.8 years, with a mean FEL of 10.1 IU/dL (median, 4.0). Mean EQ-5D was 0.77 (SD, 0.23). The Tobit model adjusting for age, body mass index and blood-borne viruses showed every 1% increase in FEL was associated with +0.006 points in the mean EQ-5D score (p = .003). Mean haemophilia-related direct medical costs excluding factor replacement therapy were €2,028/year (median, €919) in CHESS I-II (EU, n = 226), and $7,171/year (median, $586) in CHESS US (n = 181). Adjusted EU and US models showed every 1% increase in FEL was associated with a decrease in haemophilia-related direct medical costs of €108/year and $529/year, respectively. LIMITATIONS: Direct medical costs were based on physician extraction of encounters from medical records, potentially underestimating costs of care. The voluntary nature of participation may have introduced selection biases. CONCLUSIONS: We observed a significant association of increases in FEL with increased HRQoL and decreased costs in Europe and the United States among men with HB and no inhibitors.

Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe.

BACKGROUND: Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019-2020). All outcomes were summarised using descriptive statistics. RESULTS: A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67. CONCLUSIONS: These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society.

Hemophilia Gene Therapy Value Assessment: Methodological Challenges and Recommendations.

Gene therapy for hemophilia is designed to produce health gains for patients over many years. Rewarding that value creation on the basis of a one-time treatment implies a large upfront cost. This cost can only be justified by long-term health benefits and being cost-effective compared with conventional treatments. Yet, uncertainties about the long-term benefits make it challenging to assess clinical and economic value of gene therapies at launch. We identify and discuss key methodological challenges in assessing the value of gene therapy for hemophilia, including the immaturity of evidence on the durability of benefits, lack of definition and valuation of cure for chronic diseases, absence of randomized controlled trials, limitations of traditional quality of life measures in hemophilia, approach for qualifying cost-savings compared with current treatments, and choice of perspective. The Institute for Clinical and Economic Review has developed a framework for assessing single or short-term therapies (ICER-SST) and has applied it in hemophilia. After reviewing this framework and its application, we recommend the following when assessing the value of hemophilia gene therapies: (1) leveraging expert clinical opinion to justify assumptions on the durability of benefits; (2) using external synthetic controls and lead-in, self-controlled trials to assess comparative effectiveness; (3) addressing limitations of traditional quality of life measures through the use of modified utility collection approaches; (4) adjusting cost offsets from gene therapies with caution; (5) considering outcome-based contracting to address uncertainties about prices and long-term outcomes; and (6) presenting societal and healthcare system perspectives in parallel.

Health care resource utilization and cost burden of hemophilia B in the United States.

Hemophilia B is a rare congenital blood disorder characterized by factor IX deficiency. Clinical profiles of hemophilia B range from mild to severe forms of the disease. The objective of this study was to characterize the economic burden associated with differing clinical profiles of hemophilia B from a US health system perspective. Using the IBM MarketScan database (June 2011-February 2019), a claims-based algorithm was developed to identify 4 distinct profiles (mild, moderate, moderate-severe, and severe) in adult males with hemophilia B based on the frequency of hemorrhage events and factor IX replacement claims. Mean annual health care resource use (HRU) and costs were statistically compared between patients with hemophilia B (N = 454) and 1:1 demographic-matched controls (N = 454), both overall and with stratification by clinical profile. Compared with matched controls, patients with hemophilia B had a significantly higher comorbidity burden (Charlson Comorbidity Index, mean ± standard deviation [SD]: 0.9 ± 1.7 vs 0.3 ± 0.9, P < .001). Across all clinical profiles, patients with hemophilia B had significantly higher HRU vs matched controls (mean ± SD: 0.3 ± 0.6 vs 0.1 ± 0.3 inpatient admissions; 0.6 ± 1.2 vs 0.2 ± 0.6 emergency department visits; 17.7 ± 22.9 vs 8.0 ± 11.0 outpatient visits; all P < .001). Annual total health care costs per patient among patients with hemophilia B were more than 25-fold higher vs matched controls (mean ± SD: $201 635 ± $411 530 vs $7879 ± $29 040, respectively, P < .001). Annual total health care costs per patient increased with increasing severity (mean ± SD: mild, $80 811 ± $284 313; moderate, $137 455 ± $222 021; moderate-severe, $251 619 ± $576 886; severe, $632 088 ± $501 270). The findings of this study highlight the substantial burden of illness associated with hemophilia B.

Clinical, humanistic, and economic burden of severe hemophilia B in the United States: Results from the CHESS US and CHESS US+ population surveys.

BACKGROUND: Hemophilia B is a rare congenital bleeding disorder that has a significant negative impact on patients' functionality and health-related quality of life. The standard of care for severe hemophilia B in the United States is prophylactic factor IX replacement therapy, which incurs substantial costs for this lifelong condition. Accurate estimates of the burden of hemophilia B are important for population health management and policy decisions, but have only recently accounted for current management strategies. The 'Cost of Severe Hemophilia across the US: a Socioeconomic Survey' (CHESS US) is a cross-sectional database of medical record abstractions and physician-reported information, completed by hematologists and care providers. CHESS US+ is a complementary database of completed questionnaires from patients with hemophilia. Together, CHESS US and CHESS US+ provide contemporary, comprehensive information on the burden of severe hemophilia from the provider and patient perspectives. We used the CHESS US and CHESS US+ data to analyze the clinical, humanistic, and economic burden of hemophilia B for patients treated with factor IX prophylaxis between 2017 and 2019 in the US. RESULTS: We conducted analysis to assess clinical burden and direct medical costs from 44 patient records in CHESS US, and of direct non-medical costs, indirect costs, and humanistic burden (using the EQ-5D-5L) from 57 patients in CHESS US+. The mean annual bleed rate was 1.73 (standard deviation, 1.39); approximately 9% of patients experienced a bleed-related hospitalization during the 12-month study period. Nearly all patients (85%) reported chronic pain, and the mean EQ-5D-5L utility value was 0.76 (0.24). The mean annual direct medical cost was $614,886, driven by factor IX treatment (mean annual cost, $611,971). Subgroup analyses showed mean annual costs of $397,491 and $788,491 for standard and extended half-life factor IX treatment, respectively. The mean annual non-medical direct costs and indirect costs of hemophilia B were $2,371 and $6,931. CONCLUSIONS: This analysis of patient records and patient-reported outcomes from CHESS US and CHESS US+ provides updated information on the considerable clinical, humanistic, and economic burden of hemophilia B in the US. Substantial unmet needs remain to improve patient care with sustainable population health strategies.

Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model.

AIMS: Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. MATERIALS AND METHODS: With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including "bleed into joint", "bleed not into joint", "no bleed" and "death". Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. RESULTS: Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment accounts for >90% of the total HB treatment costs. CONCLUSIONS: This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm.

Linking water environmental factors and the local watershed landscape to the chlorophyll a concentration in reservoir bays.

The frequency of harmful algal blooms caused by eutrophication is increasing globally, posing serious threats to human health and economic development. Reservoir bays, affected by water environment and local watershed landscape, are more prone to eutrophication and algal blooms. The chlorophyll a (Chl a) concentration is an important indicator for the degree of eutrophication and algal bloom. Exploring the complex relationships between water environment and landscape background, and Chl a concentration in the reservoir bays are crucial for ensuring high-quality drinking water from reservoirs. In this study, we monitored Chl a concentrations of 66 bays in Danjiangkou Reservoir and the related water quality parameters (e.g., water temperature, turbidity, nutrients) in waterbodies of these reservoir bays in the storage and discharge periods from 2015 to 2018. Partial least squares-structural equation modeling (PLS-SEM) was used to quantify the relationship between water environmental factors and watershed landscapes, and Chl a concentrations in reservoir bays. The results showed that mean Chl a concentration was higher in storage period than that in discharge period. Two optimal PLS-SEMs explained 66.8% and 53.6% of Chl a concentration variation in the storage and discharge periods, respectively. The net effect of water chemistry on Chl a concentration was more pronounced during the discharge period (total effect = 0.61, 37% of the total effect on Chl a), while the net effect of land-use composition on Chl a concentration was more significant during the storage period (total effect = 0.57, 30% of the total effect on Chl a). The landscape pattern had significant indirect effects on Chl a concentration, especially during the discharge period (indirect effect = -0.31, 19% of the total effect on Chl a). Our results provide valuable information for managers to make rational decisions, thereby contributing to the prevention of eutrophication and algal blooms in reservoir bays.

Cost-Effectiveness Analysis of Recombinant Factor VIII Fc-Fusion Protein (rFVIIIFc) for the Treatment of Severe Hemophilia A in Italy Incorporating Real-World Dosing and Joint Health Data.

BACKGROUND: Patients with severe hemophilia A (SHA) in Italy are routinely treated with standard half-life recombinant factor VIII (rFVIII) products. rFVIII Fc-fusion protein (rFVIIIFc) is an extended half-life rFVIII product that enables less frequent administration than rFVIII, which may support improved adherence. Available data indicate low breakthrough bleed rates and potentially improved long-term joint health for patients treated with rFVIIIFc prophylaxis. OBJECTIVE: This study assessed the cost effectiveness of rFVIIIFc versus rFVIII from an Italian healthcare perspective. METHODS: A Semi-Markov model was constructed to assess the lifetime costs and benefits of rFVIII and rFVIIIFc prophylaxis. rFVIII product acquisition costs from a published Italian database were included for both prophylaxis and the resolution of breakthrough bleeding. Clinical outcomes within the model were determined based on published annualized bleeding rates and literature regarding the development of target joints (TJs) as the incidence of bleeds and TJs is associated with impaired health-related quality of life. Cost effectiveness was assessed using cost per quality-adjusted life-year (QALY) gained. RESULTS: Compared with rFVIII, rFVIIIFc was associated with a per-patient cost saving of approximately €1.3 million and QALY gains of 0.39 over a lifetime horizon. Sensitivity analyses considering alternative efficacy, dosing, and structural assumptions each showed that rFVIIIFc dominated rFVIII (i.e., provided more QALYs at a reduced cost). CONCLUSIONS: This cost-effectiveness analysis demonstrated that rFVIIIFc may offer a cost-effective treatment option for patients with SHA in Italy.

Clinical burden and healthcare resource utilization among patients with chronic hypoparathyroidism, overall and by adequately vs not adequately controlled disease: a multi-country chart review.

Aims: To assess the real-world clinical burden and healthcare resource utilization (HRU) among patients with chronic hypoparathyroidism, overall and by adequately controlled (AC) vs not adequately controlled (NAC) disease, informed by guideline-recommended clinical management targets, including biochemistry and symptoms. Materials and methods: In this retrospective online chart review, endocrinologists in the US, Canada, the UK, France, Germany, Italy, and Spain were randomly selected to review the medical charts of adult patients with chronic hypoparathyroidism receiving calcium and activated vitamin D. Patients' demographics, disease characteristics, symptoms, comorbidities, and hypoparathyroidism-related HRU during the 1 year before the review date were assessed. Clinical burden and HRU were compared between patients with NAC and AC hypoparathyroidism. Results: Of 614 patients with hypoparathyroidism (AC, N = 442; NAC, N = 172), the mean age was 43.6 years, and the majority were female (61.6%), Caucasian (78.8%), and had post-surgical hypoparathyroidism (74.4%). Mean duration of hypoparathyroidism was 46.0 months. Hypoparathyroidism-related symptoms and comorbidities were reported in 59.4% and 46.7% of patients, respectively; 90.7% of patients had ≥1 hypoparathyroidism-related HRU event. More patients with NAC (57.6%) vs AC (42.5%) hypoparathyroidism experienced ≥1 comorbidity including calcium/phosphate imbalances, and brain, cardiovascular, metabolic, and renal disorders (all p < 0.01). More patients with NAC vs AC hypoparathyroidism incurred ≥1 hypoparathyroidism-related hospitalization (27.9% vs 16.3%) and emergency room visits (47.7% vs 38.5%), and patients with NAC vs AC hypoparathyroidism had a higher number of outpatient visits (3.6 vs 2.6; all p < 0.05), in the 1-year observation period. Limitations and conclusions: Limitations of this online chart review include possible under-estimation of disease burden, limited sample size, and the inability to rule out selection bias. Findings indicate that patients with chronic hypoparathyroidism experience substantial symptomatic and comorbid burdens resulting in frequent HRU, suggesting an unmet need, particularly in NAC disease.

Cost Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the treatment of adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective. METHODS: A lifetime partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness. RESULTS: In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY. CONCLUSIONS: This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed FLT3-mutated AML, from a US third-party payer perspective.

Real-World Economic Outcomes During Time on Treatment Among Patients Who Initiated Sunitinib or Pazopanib as First Targeted Therapy for Advanced Renal Cell Carcinoma: A Retrospective Analysis of Medicare Claims Data.

BACKGROUND: The median age at renal cell carcinoma (RCC) diagnosis is 64 years. However, few studies have assessed the real-world time on treatment (TOT), health resource utilization (HRU), costs, or treatment compliance associated with targeted therapy use among patients in this age group with RCC. OBJECTIVE: To assess the HRU, costs, and compliance during TOT among Medicare patients aged ≥ 65 years with advanced RCC (aRCC) who initiated first targeted therapy with pazopanib or sunitinib. METHODS: Patients with aRCC were identified in the 100% Medicare + Part D databases administered by the Centers for Medicare & Medicaid Services. Eligible patients initiated first targeted therapy with sunitinib or pazopanib (index drug) on or after their first diagnosis of secondary neoplasm between October 19, 2009, and January 1, 2014, and were aged ≥ 65 years as of 1 year before first targeted therapy initiation (index date). Included patients were stratified into pazopanib and sunitinib cohorts based on first targeted therapy and matched 1:1 on baseline characteristics using propensity scores. TOT was defined as the time from the index date to treatment discontinuation (prescription gap > 90 days) or death. Compliance was defined as the ratio of drug supply days to TOT. Monthly all-cause costs and costs associated with RCC diagnosis (medical and pharmacy in 2015 U.S. dollars) and HRU (inpatient [admissions, readmissions, and days], outpatient, and emergency room visits) were assessed in the 1-year post-index period during TOT. Matched cohorts' TOT was compared using Kaplan-Meier analyses and univariable Cox models, and compliance, HRU, and costs were compared using Wilcoxon signed-rank tests. RESULTS: Of 1,711 included patients, 526 initiated pazopanib and 1,185 initiated sunitinib. Before matching, more patients in the pazopanib cohort were white, diagnosed in 2010-2014 versus 2006-2009, and had lung metastases compared with the sunitinib cohort (all P < 0.05). The pazopanib cohort also had higher mean outpatient visits and costs but lower mean total all-cause pharmacy costs, than the sunitinib cohort (all P < 0.05). After matching, the pazopanib and sunitinib cohorts had similar characteristics (mean age 75 years, 58% male, and Charlson Comorbidity Index score of 9.2 in both cohorts) and median TOT (4.8 and 4.1 months, respectively). Among the 522 matched pairs, pazopanib was associated with significantly lower total all-cause health care costs ($8,527 vs. $10,924, respectively [mean difference = $2,397]); total medical costs ($3,991 vs. $5,881, respectively, [$1,890]); and inpatient costs ($2,040 vs. $3,731, respectively, [$1,692]; all P < 0.01) compared with sunitinib. Patients receiving pazopanib had significantly fewer inpatient admissions (0.179 vs. 0.289, respectively) and days (1.063 vs. 1.904, respectively; both P < 0.01) than patients receiving sunitinib. Mean treatment compliance was lower for the pazopanib versus sunitinib cohort (0.91 vs. 0.94, respectively; P < 0.01). CONCLUSIONS: In this retrospective analysis of Medicare patients with aRCC from a TOT perspective, first targeted therapy with pazopanib was associated with significantly lower all-cause health care costs and HRU, but lower compliance, compared with sunitinib. DISCLOSURES: Funding for this research was provided by Novartis Pharmaceuticals. The sponsor was involved in all stages of the study's conduct and reporting. Vogelzang has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, and Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. Pal has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. Agarwal has been a consultant or advisor for Novartis, Pfizer, Exelixis, Cerulean Pharma, Medivation, Eisai, and Argos Therapeutics. Swallow, Peeples, Zichlin, and Meiselbach are employees of Analysis Group, which received consultancy fees from Novartis for this project. Li was an employee of Analysis Group during the conduct of this study. Ghate is an employee of Novartis and owns stock/stock options. Perez was an employee of Novartis during the conduct of this study. A synopsis of the economic outcomes was presented at the Academy of Managed Care Pharmacy Nexus 2017 in Denver, Colorado, during March 27-30, 2017. A synopsis of the clinical outcomes was presented at the 22nd ISPOR Annual International Meeting in Boston, Massachusetts, during May 20-24, 2017.

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers.

AIMS: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. METHODS: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010-2014). RESULTS: Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1-22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). LIMITATIONS: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. CONCLUSIONS: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.

Clinical and Economic Outcomes in Elderly Advanced Renal Cell Carcinoma Patients Starting Pazopanib or Sunitinib Treatment: A Retrospective Medicare Claims Analysis.

INTRODUCTION: Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment. METHODS: Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014). Patients were stratified by index drug and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death and compared by Kaplan-Meier analyses and univariable Cox models; patients were censored at the end of eligibility/data. Monthly HRU and costs from an intent-to-treat perspective were compared by Wilcoxon signed-rank tests. RESULTS: Baseline characteristics were balanced after matching (both N = 522). Treatment with pazopanib was associated with significantly longer median OS compared with treatment with sunitinib (18.2 months vs 14.6 months, respectively; log-rank p = 0.015). Pazopanib was associated with significantly lower monthly all-cause costs compared with sunitinib ($8845 vs $10,416, respectively), as well as lower inpatient costs associated with RCC diagnosis ($1542 vs $2522), fewer monthly inpatient admissions (0.179 vs 0.262), and shorter length of inpatient stay (1.375 days vs 1.883 days; all p ≤ 0.004). CONCLUSIONS: Among elderly Medicare patients with advanced RCC, first-line pazopanib tretament was associated with significantly longer OS, as well as lower healthcare costs and HRU, compared with first-line sunitinib treatment.