Temporal trends in healthcare resource use and associated costs of patients with cystic fibrosis.

BACKGROUND: Better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life expectancy of affected individuals. This study evaluated how the combination of modified demographics and changes in CF management impacted resource consumption and the cost of care. METHODS: Medical records of CF patients from 2006 to 2016 in the French CF Registry were linked to their corresponding claims data (SNDS). Medications, medical visits, procedures, hospitalisations, and indirect costs were annualized by calendar year from 2006 to 2017. RESULTS: Of the 7,671 patients included in the French CF Registry, 6,187 patients (80.7%) were linked to the SNDS (51.9% male, mean age = 24.7 years). The average cost per patient was €14,174 in 2006, €21,920 in 2011 and €44,585 in 2017. Costs associated with hospital stays increased from €3,843 per patient in 2006 to €6,741 in 2017. In 2017, the mean cost per CF patient was allocated as follows: 72% for medications (of which 51% for modulator therapies), 15% for hospital stays, 7% for medical visits, 3% for indirect costs, 2% for medical devices, 1% for outpatient medical procedures. CONCLUSION: There was a strong increase in the mean annual cost per CF patient between 2006 and 2017, mostly due to the cost of therapy after the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. The combination of an increase in the number of CF patients - particularly adult patients - and an increase in the annual cost per patient led to a substantial increase in the total cost of CF disease care for the health systems.

Health care costs related to home spirometry in the eICE randomized trial.

BACKGROUND: Home spirometry with regular symptom assessment is one strategy to track lung health to intervene early in episodes of pulmonary exacerbations (PE). In a multi-center randomized controlled trial home spirometry and symptom tracking demonstrated no significant differences regarding the primary clinical endpoint, FEV1, compared to usual care, but did identify differences in healthcare utilization. We used data from the Early Intervention in Cystic Fibrosis Exacerbation (eICE) study to evaluate whether home monitoring of PE is a cost-minimizing intervention in the context of this randomized trial. METHODS: We reviewed healthcare resource utilization of all 267 eICE participants, including outpatient visits, antibiotics and hospitalizations. Prices were identified in the IBM/Watson MarketScanⓇ Commercial Claims and Encounters Databases and averaged over the 2014-2017 period. Using total healthcare utilization costs, we generated summary statistics by intervention and protocol arm (total cost, mean cost, standard deviation). We performed Welch Two Sample t-tests to determine if total costs and cost by type of utilization differed significantly between groups. RESULTS: Outpatient visit costs were significantly higher by 13% in the Early Intervention (EI) than in the usual care (UC) arm ($3,345 vs. $2,966). We found no significant differences in outpatient antibiotic, hospitalization, or total health care costs between the arms. CONCLUSIONS: Within the context of the eICE trial, outpatient visits were significantly higher in those with experimental home spirometry care, but that did not translate into statistically significant differences of overall health care costs between the two arms.

Financial impacts of the COVID-19 pandemic on cystic fibrosis care: lessons for the future.

BACKGROUND: Chronic care delivery models faced unprecedented financial pressures, with a reduction of in-person visits and adoption of telehealth during the COVID-19 pandemic. We sought to understand the reported financial impact of pandemic-related changes to the cystic fibrosis (CF) care model. METHODS: The U.S. CF Foundation State of Care surveys fielded in Summer 2020 (SoC1) and Spring 2021 (SoC2) included questions for CF programs on the impact of pandemic-related restrictions on overall finances, staffing, licensure, and reimbursement of telehealth services. Descriptive analyses were conducted based on program type. RESULTS: Among the 286 respondents (128 pediatric, 118 adult, 40 affiliate), the majority (62%) reported a detrimental financial impact to their CF care program in SoC1, though fewer (42%) reported detrimental impacts in SoC2. The most common reported impacts in SoC1 were redeployment of clinical staff (68%), furloughs (52%), hiring freezes (51%), decreases in salaries (34%), or layoffs (10%). Reports of lower reimbursement for telehealth increased from 30% to 40% from SoC1 to SoC2. Projecting towards the future, only a minority (17%) of program directors in SoC2 felt that financial support would remain below pre-pandemic levels. CONCLUSIONS: The COVID-19 pandemic resulted in financial strain on the CF care model, including challenges with reimbursement for telehealth services and reductions in staffing due to institutional changes. Planning for the future of CF care model needs to address these short-term impacts, particularly to ensure a lack of interruption in high-quality multi-disciplinary care.

Telehealth use in cystic fibrosis during COVID-19: Association with race, ethnicity, and socioeconomic factors.

BACKGROUND: Due to the COVID-19 pandemic, there was an uptake of telehealth in cystic fibrosis care. Previous studies show disparities in telehealth use based on socioeconomic status (SES). We aimed to: (1) understand telehealth use and perceptions and (2) identify the facilitators and barriers to telehealth use among people with CF and their families (PwCF) from diverse racial/ethnic and socioeconomic backgrounds. METHODS: We conducted an analysis of the 2020 Cystic Fibrosis State of Care surveys completed by PwCF (PFSoC), CF Care Programs (SoC1) and the CF Foundation Patient Registry (CFFPR). RESULTS: A total of 424 PwCF and 286 programs responded to the PFSoC and SoC1. Among PwCF, 90% self-identified as White, 6% as Hispanic/Latino, and 2% as Black. Racial/ethnic minorities were less likely to have had a telehealth visit (p=.015). This difference was pronounced among the Hispanic/Latino population (p<.01). Telehealth use did not differ by health insurance and was similarly offered independent of financial status. Compared to PwCF who denied financial constraints, those who reported financial difficulties found telehealth more difficult to use (p=.018) and were less likely to think that their concerns (p=.010) or issues that mattered most to them (p=.020) were addressed during telehealth. Programs perceived lack of technology, language barriers, and home conditions as barriers to telehealth in vulnerable populations. CONCLUSION: PFSoC and SoC1 identified differences in telehealth use and care perceptions by ethnicity, race, and socioeconomic characteristics. Further studies are needed to understand how telehealth can change access to CF care in diverse subpopulations.

CFTR modulators: transformative therapies for cystic fibrosis.

DISCLOSURES: No funding contributed to the writing of this commentary. Both authors are employed by the Cystic Fibrosis Foundation. The Cystic Fibrosis Foundation has entered into therapeutic development award agreements and licensing agreements to assist with the development of CFTR modulators that may result in intellectual property rights, royalties, and other forms of consideration provided to CFF. Some of these agreements are subject to confidentiality restrictions and, thus, CFF cannot comment on them.

The effectiveness and value of novel treatments for cystic fibrosis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Seidner, Rind, and Pearson are employed by ICER. Tice reports contracts to his institution, University of California, San Francisco, from ICER during the conduct of this study. Wherry has nothing to disclose.

Cost-Effectiveness of Ivacaftor Therapy for Treatment of Cystic Fibrosis Patients With the G551D Gating Mutation.

OBJECTIVES: Cystic fibrosis (CF) is a rare genetic disease with no cure. Until recently, treatment has targeted symptoms of the disease and not the disease-causing genetic defect. Ivacaftor is included in a new class of breakthrough drugs targeting the genetic defects of CF. We sought to estimate the long-term cost-effectiveness of ivacaftor from a US payer perspective. METHODS: We developed an individual-level microsimulation model that followed a cohort of heterogeneous US CF patients over a lifetime. The primary outcome of interest was quality-adjusted life years (QALYs). We also compared unadjusted life years, count of acute pulmonary exacerbations, and count of lung transplants over a lifetime between patients treated with ivacaftor plus best supportive care and patients treated with best supportive care alone. We conducted one-way and probabilistic sensitivity analyses to test the impact of various model inputs and uncertainties. RESULTS: We found a substantial increase in QALYs, life years, and treatment costs over a lifetime for patients treated with ivacaftor plus best supportive care versus best supportive care alone. Discounted results for ivacaftor were 22.92 QALYs and $8 797 840 in total lifetime costs compared to 16.12 QALYs and $2 336 366 lifetime costs for best supportive care alone. The incremental cost-effectiveness ratios (ICERs) were $950 217 per QALY. Results from the probabilistic sensitivity analysis indicated a 0% chance that ivacaftor was cost-effective at a willingness-to-pay (WTP) threshold of $500 000 per QALY. CONCLUSIONS: Treatment with ivacaftor plus best supportive care versus best supportive care alone is not cost-effective at or near commonly accepted WTP thresholds.

Cost-effectiveness of the CFTR gene-sequencing test for asymptomatic carriers in the Colombian population / [Costo-efectividad de la prueba de secuenciación del gen CFTR para portadores asintomáticos en la población colombiana].

Introduction: Cystic fibrosis is an autosomal recessive genetic disease classified as a highcost orphan disease. Objective: To determine the cost-effectiveness ratio of the diagnostic test for the CFTR gene-sequencing in asymptomatic family carriers in the first, second, and third degree of consanguinity. Materials and methods: We conducted a systematic search evaluating operative characteristics of the diagnostic test and decision-tree models in cost-effectiveness studies. A decision-tree model was elaborated taking prevention of future conceptions as a unit of analysis. We obtained the costs of the disease from the high-cost report of the Ministerio de Salud y Protección Social. The costs of the test were referenced by national laboratories. We carried out a deterministic and probabilistic sensitivity analysis with a third-payer perspective and a one-year horizon. Results: An ICER of USD$ 5051.10 was obtained as the incremental cost for obtaining 10.89% more probability of avoiding the birth of a child with cystic fibrosis per screened couple. For family members in second and third degrees, the ICER was USD$ 19,380.94 and USD$ 55,913.53, respectively, evidenced when applying the GDP per capita. This technology was cost-effective in 39%, 61.18%, and 74.36% for 1, 2, and 3 GDP per capita in first degree of consanguinity relatives. Conclusions: The genetic test for the detection of CFTR gene carriers was cost-effective depending on the threshold of availability to pay and the assumptions and limitations established in the model.

Introducción. La fibrosis quística es una enfermedad genética de carácter autosómico recesivo clasificada como enfermedad huérfana de alto costo. Objetivo. Determinar la razón de costo-efectividad de la prueba diagnóstica de secuenciación del gen CFTR para los portadores asintomáticos familiares en primer, segundo y tercer grados de consanguinidad. Materiales y métodos. Se hizo una búsqueda sistemática sobre la evaluación de las características operativas de la prueba diagnóstica y los modelos de árbol de decisiones en estudios de costo-efectividad. Se elaboró un modelo de árbol de decisiones tomando como unidad de análisis la prevención de futuras concepciones. Los costos de la enfermedad se obtuvieron del reporte de alto costo del Ministerio de Salud de Colombia. Los costos de la prueba se obtuvieron de laboratorios nacionales. Se hizo un análisis de sensibilidad, determinístico y probabilístico, con la perspectiva del tercer pagador y horizonte a un año. Resultados. Se obtuvo una razón incremental de costo-efectividad (RICE) de USD$5.051,10 por obtener 10,89 % más de probabilidades de evitar el nacimiento de un niño enfermo con fibrosis quística por pareja. Para los familiares de segundo y tercer grados, se encontró una RICE de USD$ 19.380,94 y USD$ 55.913,53, respectivamente, al aplicar el PIB per cápita. Esta tecnología fue costo-efectiva en 39 %, 61,18 % y 74,36 % para 1, 2 y 3 PIB per cápita en familiares de primer grado de consanguinidad. Conclusiones. La prueba genética de detección de portadores del gen CFTR resultó costo-efectiva dependiendo del umbral de la disponibilidad de pagar, y de los supuestos y limitaciones establecidas en el modelo.

A Critical Look at the Efficacy and Costs of Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyposis.

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent disease that results in significant healthcare-related costs as well as costs to society with lost productivity and time. Unfortunately, a significant percentage of patients who suffer with this disease will not find relief from current standard of care medications and surgery. With ongoing efforts to understand the pathophysiology of CRSwNP has come the introduction of monoclonal antibodies, or "biologics," targeting specific elements of the inflammatory pathway in CRSwNP. Despite efficacy, these come at significant cost and, to date, no studies on the cost-efficacy of these biologics in CRSwNP have been published. RECENT FINDINGS: Multiple studies have now demonstrated efficacy for biologics in the treatment of CRSwNP as a primary indication. However, the gains in quality of life and objective measures, while consistent, are small and, arguably, the clinical significance is still unclear. In addition, the high cost of these medications may be hard to justify when evaluated in cost-efficacy studies against standard of care therapy in CRSwNP. Furthermore, while the current literature is most robust in showing the benefit of the biologics in asthma, it does not fully support cost-efficacy for biologics. This review evaluates the current literature regarding efficacy of monoclonal antibodies for the treatment of CRSwNP and considers this efficacy in light of the cost implications to individuals and society.

Comparison of US Federal and Foundation Funding of Research for Sickle Cell Disease and Cystic Fibrosis and Factors Associated With Research Productivity.

Importance: Sickle cell disease (SCD) and cystic fibrosis (CF) are severe autosomal recessive disorders associated with intermittent disease exacerbations that require hospitalizations, progressive chronic organ injury, and substantial premature mortality. Research funding is a limited resource and may contribute to health care disparities, especially for rare diseases that disproportionally affect economically disadvantaged groups. Objective: To compare disease-specific funding between SCD and CF and the association between funding and research productivity. Design, Setting, and Participants: This cross-sectional study examined federal and foundation funding, publications indexed in PubMed, clinical trials registered in ClinicalTrials.gov, and new drug approvals from January 1, 2008, to December 31, 2018, in an estimated US population of approximately 90 000 individuals with SCD and approximately 30 000 individuals with CF. Main Outcomes and Measures: Federal and foundation funding, publications indexed in PubMed, clinical trial registrations, and new drug approvals. Results: From 2008 through 2018, federal funding was greater per person with CF compared with SCD (mean [SD], $2807 [$175] vs $812 [$147]; P < .001). Foundation expenditures were greater for CF than for SCD (mean [SD], $7690 [$3974] vs $102 [$13.7]; P < .001). Significantly more research articles (mean [SD], 1594 [225] vs 926 [157]; P < .001) and US Food and Drug Administration drug approvals (4 vs 1) were found for CF compared with SCD, but the total number of clinical trials was similar (mean [SD], 27.3 [6.9] vs 23.8 [6.3]; P = .22). Conclusions and Relevance: The findings show that disparities in funding between SCD and CF may be associated with decreased research productivity and novel drug development for SCD. Increased federal and foundation funding is needed for SCD and other diseases that disproportionately affect economically disadvantaged groups to address health care disparities.

Adherence to lumacaftor-ivacaftor therapy in patients with cystic fibrosis in France.

BACKGROUND: Lumacaftor-ivacaftor combination is a promising treatment for cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. Optimal adherence is essential to achieve full health outcomes benefits. METHODS: This retrospective study used pharmacy refills data to calculate proportion of days covered (PDC). Adherence was defined as a PDC ≥80%. A logistic regression analysis was conducted to examine factors associated with medication adherence. RESULTS: Ninety-six patients were included in the final cohort for analysis. The mean PDC was 96%  ± 14 at 6 months, and 91% ± 17 at 12 months. The proportion of adherent patients was 89% and 83% at 6 and 12 months respectively. Age and ppFEV1 were found to affect medication adherence. CONCLUSIONS: Considering the medico-economic impact of CFTR modulator therapy, high adherence rates to lumacaftor-ivacaftor found in this study are encouraging.

Cystic fibrosis outpatient treatment and medical costs: a retrospective analysis / Tratamiento ambulatorio de fibrois quística y costes médicos: un análisis retrospectivo

BACKGROUND: Cystic fibrosis (CF) is the most serious and frequent hereditary autosomal disease that causes respiratory, hepatic and pancreatic dysfunction. The aim of the study was to assess the pharmaceutical and medical cost in CF outpatients from the Adult Cystic Fibrosis Unit at third level hospital. MATERIAL AND METHODS: Retrospective observational study in adult CF patients throughout the year 2017. Demographic and clinical variables were included. All of the medical variables considered were directly related to the disease. Considered cost were laboratory selling price notified in Nomenclator. Medical costs were calculated based on laboratory's price list and hospital medical procedures. RESULTS: 89 CF patients enter the study, and 57 patients were finally included. The mean age was 32.5 years, 56.1% were female. 36.5% patients were homozygous for Phe508del, 40.4% heterozygous, and 22.8% had another mutation. The average FEV1 was 72.2%. 33.3% patients were colonized by sensitive Pseudomonas aeruginosa (PA) and 7.0% by multidrug-resistant PA. Total costs per year was EUR 623,981.3, (87.6% drug costs and 12.4% medical costs). Medical, drug and total costs were higher in Phe508del/Phe508del mutation group than Phe508del/other and other/other (p < 0.05). Microbial colonization increased costs (p < 0.05); colonized by sensitive PA had statistically significant higher drug and total costs, similar in multidrug resistant PA. Medical costs increase with severity level of lung function (p = 0.001), also drug and total costs with the exception of severe patients. CF is a relative costly disease for the healthcare system. In our study homozygous Phe508del mutation patients, lows values of FEV1 and colonization had higher cost

INTRODUCCIÓN: La fibrosis quística (FQ) es la enfermedad autosómica hereditaria más grave y frecuente que cursa con disfunción respiratoria, hepática y pancreática. El objetivo del estudio fue evaluar el coste farmacéutico y médico directo en pacientes ambulatorios de FQ de la Unidad de Fibrosis Quística de Adultos en un hospital de tercer nivel. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo, en pacientes adultos con FQ a lo largo del año 2017. Se recogieron variables demográficas y clínicas. Todas las variables médicas consideradas estaban directamente relacionadas con la enfermedad. Los costes considerados fueron los precios de venta de laboratorio notificado en Nomenclator. Los costes médicos se calcularon en base a la lista de precios del laboratorio y los procedimientos médicos hospitalarios. RESULTADOS: Se realizó el screening en 89 pacientes con FQ, y finalmente se incluyeron 57 pacientes. La edad media fue de 32,5 años, el 56,1% eran mujeres. El 36,5% de los pacientes eran homocigotos para Phe508del, el 40,4% heterocigoto y el 22,8% tenían otra mutación. El FEV1 medio fue de 72,2%. El 33,3% de los pacientes estaban colonizados por Pseudomonas aeruginosa (PA) sensibles y 7,0% por PA multirresistentes. Los costes totales anuales fueron de 623.981,3 euros (87,6% de costes de medicamentos y 12,4% de gastos médicos directos). Los costes médicos, farmacéuticos y totales fueron mayores en el grupo de mutación Phe508del/Phe508del, que en Phe508del/otro y otros (p < 0.05). La colonización microbiana aumentó los costes (p < 0,05); la colonización por PA sensibles supuso costes más altos de fármacos y totales, de manera similar para PA multirresistentes, todas las diferencias estadísticamente significativas. Los costes médicos aumentaron con el nivel de gravedad de la función pulmonar (p < 0,001), también los costes de medicamentos y totales, con la excepción de los pacientes más graves. CONCLUSIÓN: La CF es una enfermedad relativamente costosa para el sistema de salud. En nuestro estudio, los pacientes con mutación homocigota Phe508del, los valores bajos de FEV1 y la colonización tuvieron un costo más alto

Orphan Drug Pricing and Costs: A Case Study of Kalydeco and Orkambi.

BACKGROUND: A common narrative is that high prices are necessary for "orphan drugs" because of the fewer patients. In the context of state health insurance systems, the high prices create significant challenges because of limited budgets. RESULTS: This study carefully examines both costs and revenues of two drugs for cystic fibrosis (ivacaftor and lumacaftor), showing that, for this important example, prices are not high because of fewer patients. The study then explores the justifications usually given for high orphan drug prices, including the need to support research and development for new drugs. Each of these standard justifications is shown to be inadequate; instead, it appears that the exercise of market power in the presence of insurance is the dominant driver of high prices. INTERPRETATION: Insurers need to re-examine how they address high-priced drugs.

A Latent Class Approach to Modeling Trajectories of Health Care Cost in Pediatric Cystic Fibrosis.

Introduction. Estimating costs of medical care attributable to treatments over time is difficult due to costs that cannot be explained solely by observed risk factors. Unobserved risk factors cannot be accounted for using standard econometric techniques, potentially leading to imprecise prediction. The goal of this work is to describe methodology to account for latent variables in the prediction of longitudinal costs. Methods. Latent class growth mixture models (LCGMMs) predict class membership using observed risk factors and class-specific distributions of costs over time. Our motivating example models cost of care for children with cystic fibrosis from birth to age 17. We compare a generalized linear mixed model (GLMM) with LCGMMs. Both models use the same covariates and distribution to predict average costs by combinations of observed risk factors. We adopt a Bayesian estimation approach to both models and compare results using the deviance information criterion (DIC). Results. The 3-class LCGMM model has a lower DIC than the GLMM. The LCGMM latent classes include a low-cost group where costs increase slowly over time, a medium-cost group with initial higher costs than the low-cost group and with more rapidly increasing costs at older ages, and a high-cost group with a U-shaped trajectory. The risk profile-specific mixtures of classes are used to predict costs over time. The LCGMM model shows more delineation of costs by age by risk profile and with less uncertainty than the GLMM model. Conclusions. The LCGMM approach creates flexible prediction models when using longitudinal cost data. The Bayesian estimation approach to LCGMM presented fits well into cost-effectiveness modeling where the estimated trajectories and class membership can be used for prediction.

The Economic Burden of Cystic Fibrosis in Germany from a Payer Perspective.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder that is most common in white children and young adults. Long-term survival has improved steadily and will likely increase with the recent introduction of neonatal screening and causative treatment. However, these advances have substantial economic consequences for healthcare systems and payers. OBJECTIVE: This study aims to determine the economic burden of CF and to elucidate the structure of costs and the distribution of resources for different subpopulations, treatment strategies and sites of care for CF in Germany. METHODS: We conducted an observational cohort study to evaluate the economic burden of CF and the costs of treatment within different CF substrata from a payer perspective. Using claims data from a large German sickness fund, we identify the causal effect of CF on costs, service utilisation, and premature mortality. We compare the outcomes of a CF and a control group using entropy balancing and regression techniques, conduct further analyses for the CF group to gain insight into the economic burden associated with different levels of disease severity, and analyse pharmaceutical expenditures by collecting all CF-related expenses on outpatient drug treatment from the sickness fund database. RESULTS: Direct medical costs caused by CF in Germany in 2016 average €17,551 per patient-year and appear to be mainly driven by the cost of outpatient drug prescriptions (€12,869). We estimate that the national burden of disease totals €159 million. Costs increase with disease severity and related complications. If all eligible CF patients in the German population were to receive CF mutation-specific drugs, the economic burden of disease would more than triple to €594 million. CONCLUSION: CF has a constant and wide-ranging economic impact on payers, with considerable differences in the distribution of costs and service utilisation between younger and older patients as well as mild vs. severe patients. Pharmaceutical expenses will increase in the future as causative treatment gains importance. We encourage the use of a control group approach for burden-of-disease studies to be able to identify causal effects and thus to obtain more precise estimates.