Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Kidney Failure Attributed to Focal Segmental Glomerulosclerosis: A USRDS Retrospective Cohort Study of Epidemiology, Treatment Modalities, and Economic Burden.

Rationale & Objective: This study describes the epidemiology, characteristics, and clinical outcomes of patients with focal segmental glomerulosclerosis (FSGS)-attributed kidney failure in the US Renal Data System (USRDS) during 2008-2018, and health care resource utilization and costs among those with Medicare-linked data. Study Design: This was a retrospective cohort study. Setting & Population: Patients with FSGS-attributed kidney failure in the USRDS were enrolled in the study. Outcomes: The outcomes were as follows: Prevalence and incidence, clinical and demographic characteristics, time to kidney transplant or death, health care resource utilization, and direct health care costs. Analytical Approach: Patients with FSGS as the primary cause of kidney failure were followed from USRDS registration (index date) until death or data end. Prevalence and incidence were calculated per 1,000,000 US persons. Patient characteristics at index and treatment modalities during follow-up were described. Time to kidney transplant or death was assessed with Kaplan-Meier and competing risk analyses. Health care resource utilization and costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including (Medicare Coverage subgroup) or excluding (1-year Medicare Coverage subgroup) those who died. Results: The FSGS cohort and Medicare Coverage and 1-year Medicare Coverage subgroups included 25,699, 6,340, and 5,575 patients, respectively. Mean annual period prevalence and incidence rates of FSGS-attributed kidney failure were 87.6 and 7.5 per 1,000,000 US persons, respectively. Initial treatment for most patients was in-center hemodialysis (72.1%), whereas 7.3% received kidney transplant. Accounting for competing risk of death, year 1 and 5 kidney transplant rates were 15% and 34%, respectively. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 76.6% and 74.2% required inpatient admission, 69.9% and 67.3% visited the emergency room, and mean monthly health care costs were $6,752 and $5,575 in the year postindex, respectively. Limitations: Drug costs may be underestimated because Medicare Part D coverage was not required; kidney acquisition costs were not available. Conclusions: FSGS-attributed kidney failure is associated with substantial clinical and economic burden, prompting the need for novel therapies for FSGS to delay kidney failure.

This study of patients in the US Renal Data System observed increasing prevalence and fluctuating incidence of focal segmental glomerulosclerosis (FSGS)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, including more than 3 years of treatment with dialysis, one-third receiving a kidney transplant, and one-third dying during follow-up. In the first year after US Renal Data System registration, three-quarters of patients with Medicare coverage required hospitalization, and more than two-thirds visited the emergency room. The total annual health care costs were >$68,000 per patient with FSGS-attributed kidney failure, underscoring the high economic burden of this disorder and the treatments required to sustain life. Novel therapies for FSGS are needed to delay or ideally prevent the need dialysis and transplantation after kidney failure.

Kidney Failure Attributed to Immunoglobulin A Nephropathy: A USRDS Retrospective Cohort Study of Epidemiology, Treatment Modalities, and Economic Burden.

Rationale & Objective: This study describes the epidemiology, characteristics, and outcomes of patients with immunoglobulin A nephropathy (IgAN)-attributed kidney failure in the US Renal Data System (USRDS) from 2008 to 2018, including health care resource utilization and costs among patients with Medicare-linked data. Study Design: Retrospective cohort study. Setting & Population: Patients with IgAN-attributed kidney failure in the USRDS. Outcomes: Prevalence/incidence, clinical/demographic characteristics, time to kidney transplant, and health care resource utilization and costs. Analytical Approach: Patients with IgAN as primary cause of kidney failure (IgAN cohort) were followed from USRDS registration (index date) until data end/death. Prevalence/incidence were calculated per 1,000,000 US persons. Demographic and clinical characteristics at index and treatment modality during follow-up were summarized. Time from index to kidney transplant was assessed using Kaplan-Meier and competing risk analyses. Health care resource utilization and health care costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including or excluding those who died (Medicare Coverage and 1-year Medicare Coverage subgroups, respectively). Results: The IgAN cohort, Medicare Coverage, and 1-year Medicare Coverage subgroups included 10,101, 1,696, and 1,510 patients, respectively. Mean annual period prevalence and incidence of IgAN-attributed kidney failure were 39.3 and 2.9 per 1,000,000 US persons, respectively. Initial treatment was in-center hemodialysis (63.1%) or kidney transplant (15.1%). Year 1 and 5 kidney transplant rates were 5% and 17%, respectively, accounting for competing risk of death. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 74.4% and 72.3%, respectively, required inpatient admission, 67.3% and 64.4%, respectively, visited the emergency room, and mean total health care costs were $6,293 (SD: $6,934) and $5,284 ($3,455), respectively, per-patient-per-month in the year postindex. Limitations: Drug costs may be underestimated as Medicare Part D coverage was not required; kidney acquisition costs were unavailable. Conclusions: IgAN-attributed kidney failure is associated with substantial clinical and economic burdens. Novel therapies for IgAN that delay kidney failure are needed.

This study of patients in the United States Renal Data System (USRDS) observed fluctuating incidence and increasing prevalence of immunoglobulin A nephropathy (IgAN)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, with 63% receiving in-center dialysis and over 15% receiving transplantation as initial therapy. In the first year after USRDS registration, nearly three-quarters of patients with Medicare coverage required hospitalization, and around two-thirds visited the emergency room. The total annual health care costs were >$63,000 per patient with IgAN-attributed kidney failure, underscoring the high economic burden of this disorder and currently available treatments. Novel therapies for IgAN are needed to delay or prevent the need for costly dialysis and transplantation after kidney failure.

Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway.

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. RESULTS: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. CONCLUSIONS: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Study Design: Retrospective cohort study. Setting & Study Population: Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. Predictor: High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Outcomes: Standardized prevalence, health care resource utilization, costs. Analytical Approach: Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. Results: The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Limitations: Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Conclusions: Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Plain-Language Summary: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

Humanistic and Economic Burden of IgA Nephropathy: Systematic Literature Reviews and Narrative Synthesis.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a progressive inflammatory kidney disease requiring long-term treatment to reduce the risk of progression to kidney failure. Here, we present two systematic literature reviews (SLRs) to identify and summarize literature reporting the humanistic and economic burden of IgAN. METHODS: Electronic literature databases (Ovid Embase, PubMed, and Cochrane) were searched for relevant literature on 29 November 2021, supplemented with gray literature searches. Studies reporting any health-related quality of life (HRQoL) or health state utility outcomes in IgAN patients were included in the humanistic impact SLR, and studies reporting the costs and healthcare resource utilization associated with or economic models of IgAN disease management were included in the economic burden SLR. Narrative synthesis was used to discuss the heterogeneous studies included in the SLRs. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Cochrane guidelines were followed, and all included studies were assessed for risk of bias using the Center for Evidence-Based Management tool for Critical Appraisal of a Survey or the Drummond Checklist. RESULTS: A total of 876 and 1122 references were identified from electronic and gray literature searches for humanistic and economic burden, respectively. Three studies reporting humanistic impact and five studies reporting economic burden met criteria for inclusion in these SLRs. The included humanistic studies reported patient preferences in the USA and China, HRQoL for patients with IgAN in Poland, and impact of exercise on HRQoL for patients with IgAN in China. The five economic studies reported costs of IgAN treatment in Canada, Italy, and China, along with two economic models from Japan. DISCUSSION: Current literature suggests IgAN is associated with substantial humanistic and economic burdens. However, these SLRs demonstrate the paucity of research conducted to specifically describe the humanistic or economic burden of IgAN and highlight the need for further research.

Reducing the physical, social, and emotional impact of episodic migraine: Results from erenumab STRIVE and ARISE phase III randomized trials.

OBJECTIVE: The purpose of this study was to examine changes in the functional impact of migraine following treatment with erenumab, as measured by the Migraine Functional Impact Questionnaire (MFIQ). BACKGROUND: The MFIQ, a novel patient-reported outcome (PRO) measuring the impact of migraine on four domains (physical function, social function, and emotional function [PF, SF, and EF]; usual activities [UAs]) and a single item assessing overall impact on UA, was included in phase III trials evaluating erenumab 70 and 140 mg monthly for migraine prevention among people with episodic migraine (EM). METHODS: In the ARISE study, 577 patients with EM were randomized to erenumab 70 mg or placebo. In the STRIVE study, 955 patients with EM were randomized to erenumab, 70 mg or 140 mg or placebo. Pairwise comparisons of least-squares mean (LSM) change from baseline in MFIQ scores (with associated 95% confidence interval [CI]) were assessed for each active treatment versus placebo. RESULTS: In ARISE, greater reductions from baseline to month 3 were observed for 70 mg versus placebo for PF (LSM [95% CI]: -3.2 [-6.4 to -0.1]; p = 0.046) and EF (-4.0 [-7.3 to -0.7]; p = 0.019) domain scores. In STRIVE, between-group differences also reflected reductions from baseline to the average of months 4-6 that favored erenumab on all four MFIQ domain scores. Reductions in impact for 70 mg compared to placebo were -4.3 (95% CI: -6.8 to -1.7; p < 0.001) for PF, -4.0 (-6.3 to -1.7; p < 0.001) for UA, -3.7 (-6.1 to -1.2; p = 0.003) for SF, and -5.3 (-7.9 to -2.6; p < 0.001) for EF domain scores. Improvements were also observed for 140 mg versus placebo with between-group differences of -5.7 (95% CI: -8.2 to -3.2; p < 0.001) in PF, -5.1 (-7.5 to -2.8; p < 0.001) in UA, -5.0 (-7.4 to -2.6; p < 0.001) in SF, and -7.2 (-9.9 to -4.5; p < 0.001) in EF domain scores. There were also greater improvements in the overall impact on UA score for 70 mg (LSM [95% CI]: -4.3 [-7.0 to -1.7]; p = 0.001) and 140 mg (-5.3 [-8.5 to -3.2]; p < 0.001) versus placebo. CONCLUSIONS: The MFIQ measures the frequency of impacts and level of difficulty on multiple functional domains that provide a more complete picture of the effects of migraine. MFIQ scores showed that in comparison with placebo, patients treated with erenumab had greater reductions in the functional impact of migraine, providing insight into treatment benefits that extend beyond improvements in clinical status and health-related quality of life previously reported based on clinical end points and other PROs.

Migraine Characteristics, Comorbidities, Healthcare Resource Utilization, and Associated Costs of Early Users of Erenumab in the USA: A Retrospective Cohort Study Using Administrative Claims Data.

INTRODUCTION: Erenumab is indicated for migraine preventive treatment in adults. The objective of this study was to provide descriptive information on real-world use of erenumab including patient profile and treatment patterns. METHODS: We completed a retrospective review of US data (through May 2019) from the IBM MarketScan® Early View Databases, identifying adult patients newly treated with erenumab with a migraine claim in the year prior to first erenumab claim (index) and at least 1 year of continuous pre-index medical and pharmacy insurance coverage, to assess pre- and post-erenumab migraine characteristics, comorbidities, healthcare resource utilization, and associated costs. All data were summarized using descriptive statistics. RESULTS: A total of 9753 patients met inclusion criteria. The average (SD) age was 46 (12) years, 85% of patients were female, and 64% had at least one claim for chronic migraine; 70% of erenumab users had an initial dose of 70 mg; 77% of patients in the 6-month follow-up sample (n = 4437) remained on their initial erenumab dose. Persistence at 6-month follow-up was 47.3% with a mean (95% CI) proportion of days covered of 0.68 (0.67, 0.68). In the post-erenumab period, claims for comorbidities of non-migraine headaches and anxiety were reduced and there was a shift to decreased use of acute and preventive medications. Reductions in overall use and associated cost of healthcare resources such as inpatient hospitalization and outpatient office visits were minimal, with slightly more pronounced reductions in the subgroup of patients that were persistent to erenumab. CONCLUSIONS: We observed reductions in claims for important migraine characteristics, comorbidities, and a shift to decreased use of acute and preventive migraine medications-observations indicative of the real-world effectiveness of erenumab. Further examination is required as persistence to erenumab, which may be influenced by dose titration, appears to be an important factor in changes to healthcare resource utilization and costs.

Real-World Treatment Profiles, Clinical Outcomes, and Healthcare Resource Utilization of Patients with Migraine Prescribed Erenumab: A Multicenter Chart-Review Study of US Headache Centers.

INTRODUCTION: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers. METHODS: A retrospective chart review of patients with migraine treated with erenumab for at least 3 months across five major headache centers was conducted. Data was collected from patient charts between April 2019 and April 2020 and included patient and clinical characteristics, migraine medication use, and outpatient visits. The date of the first prescription fill of erenumab was defined as the index date. The baseline period comprised the 3 months prior to the index date and the study period comprised the at least 3 months on erenumab treatment. RESULTS: Data from a total of 1034 patients with chronic migraine with a mean of 9.3 months of erenumab treatment were analyzed. Patients were on average 48 years old, 86% were female, and 79% were white. Patients had a mean of 5 preventive treatment failures prior to erenumab initiation. Patients used a mean of 2 preventive treatments (excluding erenumab) and 2 acute treatments during baseline and study periods. Among patients with effectiveness data, 45% of patients had improvement in physician-reported migraine severity and 35% experienced at least 50% reduction in mean headache/migraine days per month. The average number of monthly outpatient visits was 0.43 and 0.30 before and after erenumab initiation, respectively. CONCLUSION: In this predominantly refractory chronic migraine population treated in select headache centers, patients had fewer headache/migraine days per month and outpatient visits after initiating erenumab. However, patients largely continued to be managed via a polypharmacy approach after erenumab initiation.

Erenumab patient characteristics, medication adherence, and treatment patterns in the United States.

OBJECTIVE: To describe patient characteristics, adherence, and treatment patterns, among adult migraine patients in the United States prescribed erenumab. BACKGROUND: Migraine is a highly prevalent and debilitating disease characterized by recurrent attacks of moderate to severe headache accompanied by non-headache symptoms. Erenumab is a first-in-class calcitonin gene-related peptide receptor (CGRP-R) antagonist indicated for migraine prophylaxis in adults. METHODS: This retrospective longitudinal cohort study used IQVIA's open-source longitudinal pharmacy (LRx) and medical (Dx) claims databases to identify adult migraine patients with an initial claim (index date) for erenumab between May 1, 2018 and April 30, 2019. Patients were required to have ≥180 days of follow-up. Erenumab dosing patterns, persistence, and adherence (using medication possession ratio [MPR] and proportion of days covered [PDC]), and discontinuation of other commonly prescribed acute and prophylactic anti-migraine therapies were assessed. Dose changes in acute therapies after initiation of erenumab were assessed in a subset of patients with an adequate trial of erenumab (≥2 additional erenumab claims within the 80 days following the index claim). RESULTS: A total of 64,174 patients met the study criteria. Mean (SD) age was 48 (13) years and 85.2% (n = 54,656) were female. The initial erenumab dose was 70 mg for the majority of patients (65.1%; n = 41,790); most (81.4%; n = 34,019) maintained their index dose during follow-up. Overall, 30.8% (n = 19,797) of patients had a PDC ≥ 0.80 and 41.7% (n = 26,769) had a MPR ≥ 0.80. Discontinuation rates of acute and other prophylactic migraine therapies after initiation of erenumab (among users of the respective therapies) were 48.7% (22,965/47,190) and 36.1% (16,602/46,006), respectively. Dose decreases among triptan, ergot compound, opioid, and barbiturate users were observed after initiation of erenumab. CONCLUSIONS: Almost all patients had prior use of acute or preventive therapy. Adherence to erenumab was higher than traditional oral prophylactic migraine therapies; however, overall adherence was still suboptimal. The decrease in use of acute and preventive prescription medications following initiation of erenumab suggests effectiveness in the real-world setting.

Development and content validation of the Satisfaction and Experience Questionnaire for Granulocyte Colony-Stimulating Factor (SEQ-G-CSF).

BACKGROUND: Several options for granulocyte colony-stimulating factor (G-CSF) prophylaxis of chemotherapy-induced febrile neutropenia are available to patients worldwide. We have developed a novel patient-reported outcome measure, the Satisfaction and Experience Questionnaire for G-CSF (SEQ-G-CSF), to help understand patients' perspectives of and satisfaction with different G-CSF options. RESULTS: Three oncology nurses and 40 adult oncology patients in the United States were enrolled and participated in focus group discussions to develop and refine the SEQ-G-CSF. Nurses had ≥ 5 years of experience treating oncology patients and were currently involved in the management of oncology patients receiving G-CSF prophylaxis. The patients had breast cancer, lung cancer, non-Hodgkin lymphoma, or prostate cancer (10 patients in each group) and were receiving G-CSF prophylaxis via injection or the on-body injector (OBI) device. The preliminary SEQ-G-CSF contained an item relevance questionnaire and three SEQ modules (sociodemographic, medical history, and G-CSF-related healthcare characteristics questionnaires). Twenty-one patients (53% of total sample size) discussed their experience and satisfaction with G-CSF. Their most common experiences were G-CSF effectiveness, convenience and benefits of the OBI, and relationships with healthcare providers. Side effects and having to undergo additional treatment were also reported. Satisfaction with aspects of G-CSF included the OBI and effectiveness of G-CSF treatment; dissatisfaction included inconvenience (having to return to the clinic the next day and administration of the injection) and the insurance approval process. The SEQ-G-CSF was finalized after three rounds of cognitive interviews and includes five domains related to general satisfaction (one item), treatment burden (four items), travel burden (two items), time burden (four items), and treatment compliance (two items). CONCLUSIONS: The SEQ-G-CSF is a novel instrument that quantifies a patient's experience and satisfaction with different G-CSF options using 13 easy-to-understand items. This study provides evidence for the content validity of SEQ-G-CSF. Although further psychometric testing is required, the SEQ-G-CSF may be a useful addition to clinical trials, observational studies, and clinical practice.

Estimating the economic burden of migraine on US employers.

Migraine is a leading cause of disability globally. Individuals with migraine experience reduced work productivity and greater health care costs compared with the general population. The Migraine Impact Model (MIM) is an interactive calculator developed to estimate the economic burden of migraine on United States-based employers. We demonstrate use of the model with 4 case studies from different industries (education, manufacturing, retail/trade, and entertainment). The MIM estimates migraine prevalence among employees and the employer's annual migraine-associated costs by applying published, licensed, and publicly available data and several underlying assumptions to employee population information that is inputted by users. User inputs include the employer's industry, geographic location, and workforce characteristics (number of employees, gender distribution, and average age and compensation). Model outputs include estimated migraine prevalence, annual workdays affected by migraine, and annual migraine-associated indirect and direct costs to the employer. In the case studies presented, workforce size ranged from 18,800 to 250,000, representing midsized to larger employers. Employee gender distribution ranged from 29% to 74% women, and mean employee age was either 41 or 44 years. The model-estimated percentage of employees with migraine ranged from 14% to 19%. The model projected approximately 60,000 to 686,000 annual workdays to be affected by lost productive time due to migraine (often referred to as "absenteeism" and "presenteeism") and estimated annual indirect costs to total between 6.2 and 8.5 times the annual direct costs. The MIM estimates the economic burden of migraine on a company's workforce, which may aid employers in making data-driven decisions to reduce that burden for employees and business.

Correction: Cost-effectiveness analysis of a mobile ear screening and surveillance service versus an outreach screening, surveillance and surgical service for indigenous children in Australia.

[This corrects the article DOI: 10.1371/journal.pone.0138369.].

United States Patients' Perspective of Living With Migraine: Country-Specific Results From the Global "My Migraine Voice" Survey.

BACKGROUND: Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. OBJECTIVE: This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. METHODS: The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. RESULTS: Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. CONCLUSIONS: Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.

Primary immune thrombocytopenia in US clinical practice: incidence and healthcare burden in first 12 months following diagnosis.

Introduction: Primary immune thrombocytopenia (ITP), an autoimmune disorder characterized by low platelet count, can lead to serious bleeding events. Little is known about the current epidemiology of ITP in the US, and even less is known about the current healthcare burden of ITP, especially in the 12-month period following ITP diagnosis.Method: We used a retrospective cohort design and data from two US private healthcare claims databases (2010-2016) to identify persons with evidence of newly diagnosed ITP. We weighted estimates of the annual incidence of ITP by age and sex to reflect the US population, and summarized healthcare utilization and expenditures (2016 US$) during the first 12 months after ITP diagnosis ("follow-up period").Results: Annual incidence of ITP in the US was 6.1 per 100,000 persons, higher among females versus males (6.7 vs. 5.5), and highest among children aged 0-4 years (8.1) and adults aged ≥65 years (13.7). Patients with ITP averaged 0.33 (95% CI: 0.32-0.35) hospitalizations and 15.3 (15.1-15.6) ambulatory encounters during the follow-up period; mean total healthcare expenditures during this period were $21,290 (20,502-22,031). Hospitalizations were more common during the first 3 months following diagnosis, and were twice as frequent among children versus adults; expenditures for ambulatory encounters were substantially higher for adults versus children aged 0-4 years.Conclusions: Our findings suggest that nearly 20,000 children and adults are newly diagnosed with ITP each year in the US, substantially higher than previously reported. Among patients requiring formal medical care, the economic burden during the first 12 months following diagnosis is high, with estimated US expenditures totaling over $400 million.

Febrile neutropenia-related care and associated costs in elderly patients with breast cancer, lung cancer, or non-Hodgkin lymphoma.

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.

Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years.

Filgrastim prophylaxis, both primary and secondary, was rapidly incorporated into clinical practice in the 1990s. When pegfilgrastim became available in 2002, it quickly replaced filgrastim as the colony-stimulating factor (CSF) of choice for prophylaxis. Use of prophylaxis increased markedly in the first decade of this century and has stabilized during the present decade. Data concerning real-world CSF prophylactic practice patterns are limited but suggest that both primary and secondary prophylaxis are common, and that use is frequently inappropriate according to guidelines. The extent of inappropriate use is controversial, as are issues concerning the cost-effectiveness of prophylaxis versus no prophylaxis and the cost-effectiveness of primary prophylaxis versus secondary prophylaxis. Nevertheless, CSF prophylaxis is firmly established as a valuable adjunct to chemotherapy and will almost certainly continue to be widely used for the foreseeable future. In this article, we chronicle the use and impact of CSF prophylaxis in US patients receiving myelosuppressive chemotherapy for non-myeloid malignancies. We emphasize the interplay of expert opinion, clinical evidence, and economic factors in shaping the use of CSFs in clinical practice over time, and, with the recent introduction of new CSF agents and options, we aim to provide useful clinical and economic information for healthcare decision makers.

Trends in the use of primary prophylactic colony-stimulating factors and neutropenia-related hospitalization in elderly cancer patients receiving myelosuppressive chemotherapy in the USA: 1995-2015.

PURPOSE: To assess changes in neutropenia-related hospitalization, myelosuppressive chemotherapy, and primary prophylactic colony-stimulating factor (PP-CSF) use in elderly cancer patients receiving myelosuppressive chemotherapy. METHODS: We identified annual cohorts of patients aged ≥ 66 years with breast cancer, lung cancer, or non-Hodgkin lymphoma (NHL) initiating myelosuppressive chemotherapy during 1995-2015 using Medicare 5% (1994-2008) and 20% (2007-2015) data. We described myelosuppressive chemotherapy changes by febrile neutropenia (FN) risk category (high, intermediate, unclassified), PP-CSF use, and, in the first cycle of myelosuppressive chemotherapy, neutropenia-related hospitalization (ICD-9-CM: 288.0X, first 5 positions). We evaluated hospitalization trends using a logistic regression model with spline curve of calendar year adjusting for baseline characteristics. RESULTS: Annual cohorts included 1451-2114 eligible patients for 1995-2007 and 5272-7603 for 2008-2015. Myelosuppressive chemotherapy use with high/intermediate FN risk increased from 31% in 1995 to 56% in 1999, stabilized through 2008 (range 56-61%), then decreased to 52% in 2015. PP-CSF use increased from 5.5% in 1995 to 52.7% in 2015, mainly due to pegfilgrastim introduction in 2002. Crude neutropenia-related hospitalization incidence decreased from 5.2% in 1995 to 2.7% in 2015; adjusted incidence decreased, on average, by 4.7% yearly before 2010 (p < 0.0001) and was flat from 2010 onward (p = 0.53). CONCLUSIONS: Among elderly patients with breast cancer, lung cancer, or NHL receiving myelosuppressive chemotherapy, PP-CSF use increased substantially after 2002. Neutropenia-related hospitalization incidence in the first cycle decreased yearly before 2010 and was flat afterward. Further studies are needed to understand overall decreasing neutropenia-related hospitalization trends and effects of changes in myelosuppressive chemotherapy and FN management.