Education, employment, and income among people living with cystic fibrosis across three decades - A matched cohort study using Danish health registries.

BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.

Patient and Care Partner Burden in CKD Patients With and Without Anemia: A US-Based Survey.

Rationale & Objective: Chronic kidney disease (CKD) has a far-reaching impact on both patients and care partners, which can be further compounded by frequent complications such as anemia. This study assessed the burden experienced by patients with CKD and the care partners of patients with CKD, with and without anemia. Study Design: Online survey. Setting & Participants: Adult patients with CKD and the care partners of adult patients with CKD living in the United States were recruited through the American Association of Kidney Patients and a third-party online panel (January 9, 2020-March 12, 2020). Outcomes: Patient and care partner characteristics, care received or provided; health-related quality of life, and work productivity. Analytical Approach: Descriptive statistics were reported separately based on the presence or absence of anemia. Results: In total, 410 patients (anemia: n=190, no anemia: n=220) and 258 care partners (anemia: n=110, no anemia: n=148) completed the survey. Most patients reported receiving paid or unpaid care because of their health condition (anemia: 58.9%, no anemia: 50.9%), with an overall average of 14.2 and 11.3 h/wk among the anemia and no anemia patients, respectively. The care partners also reported providing numerous hours of care (anemia: 33.6 h/wk, no anemia: 38.0 h/wk), especially care partners living with their care recipient (anemia: 52.6 h/wk, no anemia: 42.8 h/wk). Among the patients, those with anemia reported a numerically lower average health-related quality of life (Functional Assessment of Cancer Therapy-Anemia score, anemia: 110.1; no anemia: 121.6). Most care partners reported a severe or very severe burden (Burden Scale for Family Caregivers-Short Version score≥15, anemia: 69.1%; no anemia: 58.8%). The work productivity impairment was substantial among employed patients (anemia: 44.9%, no anemia: 35.4%) and employed care partners (anemia: 47.9%, no anemia: 40.7%). Limitations: The survey results may have been subject to selection and recall biases; moreover, the observational nature of the study does not allow for causal inferences. Conclusions: Patients with CKD and the care partners of patients with CKD experience a considerable burden, especially when anemia is present.

Cost impact of hydroxocobalamin in the treatment of patients with known or suspected cyanide poisoning due to smoke inhalation from closed-space fires.

BACKGROUND & OBJECTIVES: Cyanide poisoning can occur due to exposure to smoke in closed-space fires. With no point of care cyanide test at the scene of a fire, first responders and clinicians base decisions to treat with cyanide antidote on patient history, clinical signs, and other indirect data points that have not been proven to correspond with actual systemic levels of cyanide. The aim of this exploratory study was to determine the economic implications of treating patients with known or suspected cyanide poisoning due to smoke inhalation with hydroxocobalamin. METHODS: A decision analysis model was developed from the US hospital perspective. Healthcare resource utilization was estimated from a retrospective evaluation of clinical outcomes in hydroxocobalamin-treated patients and in historical controls without hydroxocobalamin use (Nguyen, et al. 2017). Epidemiologic parameters and costs were estimated from the published literature, and publicly-available hospital charges were identified. Outcomes reported in the analysis included expected healthcare resource utilization in the US population and per-patient costs with and without the use of hydroxocobalamin. A cost-to-charge ratio was applied so that all costs would reflect hospital costs rather than hospital charges. Deterministic sensitivity analysis was performed to identify the most influential model parameters. All costs were reported in 2017 US dollars. RESULTS: Use of hydroxocobalamin reduces healthcare resource utilization and contributes to decreased per-patient hospital costs ($15,381 with hydroxocobalamin treatment versus $22,607 with no cyanide antidote). The most substantive cost-savings resulted from decreased hospital length of stay (i.e., intensive care unit [ICU] and non-ICU). Costs attributed to mechanical ventilation also decreased with use of hydroxocobalamin. A univariate sensitivity analysis demonstrated that the most impactful variables in the cost analysis were related to hospital length of stay (ICU followed by non-ICU stay), followed by the daily cost of ICU stay. CONCLUSIONS: Use of hydroxocobalamin in patients with known or suspected cyanide poisoning from closed-space fire smoke inhalation may decrease hospital costs and contribute to more efficient healthcare resource utilization.

Costs associated with the administration of erythropoiesis-stimulating agents for the treatment of anemia in patients with non-dialysis-dependent chronic kidney disease: a US societal perspective.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia due to chronic kidney disease (CKD). In addition to drug acquisition costs, the administration of ESAs can include direct and indirect costs due to the needle-based route of administration (eg, time spent by health care staff administering therapy, and patients' and caregivers' time spent receiving or assisting with therapy). However, a comprehensive assessment of the costs associated with the administration of ESAs is lacking. OBJECTIVE: To estimate the excess costs associated with the needle-based administration of ESAs for the treatment of anemia due to non-dialysis-dependent (NDD) CKD in the United States in 2019 from a societal perspective. METHODS: Excess costs associated with ESA administration were estimated as the sum of annual costs that could be avoided with the introduction of an oral treatment with comparable safety and efficacy to ESAs. Cost components included direct health care costs, transportation costs, and work productivity loss costs from the perspective of both patients and caregivers (as applicable). Costs were estimated based on scientific publications, governmental agencies, and the results of a recent survey of US patients and caregivers of patients with anemia and CKD. The setting of the administration (ie, at home vs in clinic), frequency of administration, and insurance type were considered. RESULTS: At the societal level, annual excess costs associated with ESA administration were estimated at $2.5 billion in the United States in 2019, based on an estimated 462,005 patients with anemia and NDD-CKD treated with ESAs. Overall, 94.4% ($2.4 billion) of these costs were incurred from in-clinic ESA administration. When stratifying costs by insurance type, Medicare-insured patients accounted for 79.4% ($2.0 billion) of total annual excess costs. The largest contributor to total annual excess costs was direct health care costs ($1.4 billion, 54.9%), followed by patient work productivity loss costs ($846 million, 33.9%), caregiver work productivity loss costs ($197 million, 7.9%), and transportation costs ($81 million, 3.3%). Total annual excess costs of in-clinic administration ranged from $2,572 per patient receiving monthly administration to $20,948 per patient receiving thrice-weekly administration, while the total annual excess costs of at-home administration ranged from $1,123 per patient receiving monthly administration to $2,109 per patient receiving thrice-weekly administration. At the ESA administration level (ie, for each ESA administration), total excess costs were estimated at $128 per in-clinic ESA administration and $7 per at-home ESA administration, excluding monitoring costs. CONCLUSIONS: The needle-based administration of ESAs in patients with NDD-CKD is associated with a substantial economic burden. The introduction of an oral treatment has the potential to result in important cost savings from a societal perspective. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc., and Akebia Therapeutics, Inc. The study sponsors participated in the study design, data collection, analysis, interpretation of the data, writing of the report, and in the decision to submit the manuscript for publication. Gauthier-Loiselle, Cloutier, Serra, Bungay, and Guérin are employees of Analysis Group, Inc., a consulting firm that received funding from Otsuka Pharmaceutical Development & Commercialization, Inc., for the conduct of this study. Michalopoulos was an employee of Otsuka Pharmaceutical Development & Commercialization, Inc., at the time the study was conducted. Szabo is an employee of Akebia Therapeutics, Inc.

Cost-Utility of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1 Infection.

OBJECTIVE: To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. METHODS: A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA (< or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS: EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients. CONCLUSIONS: Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations.

Deficiencies in addressing effect modification in network meta-analyses: a meta-epidemiological survey.

OBJECTIVE: The objectives of this study were to evaluate the current state of reporting and handling of effect modification in network meta-analyses (NMAs) and perform exploratory analyses to identify variables that are potentially associated with incomplete reporting of effect modifiers in NMAs. STUDY DESIGN AND SETTING: We conducted a meta-epidemiological survey using a systematic review of NMAs published in 2013 and identified through MEDLINE and Embase databases. RESULTS: The review identified 77 NMAs. The most common type of effect modifiers identified and explored were patient characteristics (50.7% or 39/77), and the most common adjustment method used was sensitivity analysis (51.7% or 30/58). Over 45% (35/77) of studies did not describe a plan, nearly 40% (30/77) did not report the results of analyses, and approximately 47% (36/77) of studies had incomplete reporting. Exploratory univariate regression analyses yielded a statistically significant association for the variables of journal impact factor, ratio of randomized controlled trials to number of comparisons, and total number of randomized controlled trials. CONCLUSION: Current reporting practices are largely deficient, given that almost half of identified published NMAs do not explore or report effect modification. Journal impact factor and amount of available information in a network were associated with completeness of reporting.

Cost-Effectiveness of Florbetapir-PET in Alzheimer's Disease: A Spanish Societal Perspective.

BACKGROUND: The rising prevalence of Alzheimer's disease (AD), and other diseases associated with dementia, imposes significant burden to various stakeholders who care for the elderly. Management of AD is complicated by multiple factors including disease-specific features which make it difficult to diagnose accurately during milder stages. Florbetapir F18 positron emission tomography (florbetapir-PET) is an approved imaging tool used to capture beta-amyloid neuritic plaque density in brains of cognitively impaired adults undergoing evaluation for AD and other causes of cognitive impairment. It has the potential to help improve healthcare outcomes as it may help clinicians identify patients with AD early so that treatments are initiated when most effective. AIMS OF THE STUDY: Evaluate the potential long-term clinical and economic outcomes of adopting florbetapir-PET--adjunctive to standard clinical evaluation (SCE)--versus SCE alone in the diagnostic assessment of cognitively impaired patients with suspected AD. METHODS: A decision analysis with a ten-year time horizon was developed in compliance with Good Research Practices and CHEERS guidelines. The target population was comprised of Spanish patients who were undergoing initial assessment for cognitive impairment (Mini-Mental State Examination [MMSE] score=20). Diagnostic accuracy, rate of cognitive decline, effect of drugs on cognition and dwelling status, economic burden (direct and indirect costs), and quality of life (QoL) were based on relevant clinical studies and published literature. Scenario analysis was applied to explore outcomes under different conditions, which included: (i) use of florbetapir-PET earlier in disease progression (MMSE score=22); and (ii) the addition of fluorodeoxyglucose (FDG)-PET to SCE. RESULTS: Adjunctive florbetapir-PET increased quality-adjusted life years (QALYs) by 0.008 years and increased costs by 36 compared to SCE alone (incremental cost-effectiveness ratio [ICER], 4,769). Use of florbetapir-PET was dominant in alternate scenarios. Sensitivity analyses indicated rates of institutionalization (by MMSE) and MMSE score upon initiation of acetylcholinesterase inhibitor (AChEI) treatment most influenced the primary outcome (ICER) in the base case scenario. Over 82% of probabilistic simulations were cost-effective using the Spanish threshold (30,000/QALY). DISCUSSION: The addition of florbetapir-PET to SCE is expected to improve the accuracy of AD diagnoses for patients experiencing cognitive impairment; it is cost-effective due to decreased healthcare costs and caregiver burden. Prospective studies of the clinical utility of florbetapir-PET are necessary to evaluate the long-term implications of adopting florbetapir-PET on clinical outcomes and costs in real-world settings. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Florbetapir-PET is expected to improve decision-making regarding appropriate and sufficient care for cognitively impaired patients with suspected AD, while cost-effective. IMPLICATIONS FOR HEALTH POLICIES: Earlier and more accurate diagnosis of AD may help to improve patient's health status and reduce treatment costs by effectively allocating healthcare resources and maximizing the benefit of treatments and supportive services. IMPLICATIONS FOR FURTHER RESEARCH: Use of florbetapir-PET may help accurately identify patients with AD. The development of novel therapeutics for use with companion diagnostics may provide additional benefits by slowing or halting progressive cognitive decline with AD, increase QoL and prolong survival.

An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population.

OBJECTIVE: Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population. METHODS: Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of both first- and second trimester screening. Costs were assigned for each prenatal test component and for an affected birth. The overall cost to the healthcare system considered screening costs, the number of aneuploid cases detected, invasive procedures performed, procedure-related euploid losses, and affected pregnancies averted. Sensitivity analyses evaluated the effect of variation in parameters. Costs were reported in 2014 US Dollars. RESULTS: Replacing conventional screening with NIPT would reduce healthcare costs if it can be provided for $744 or less in the general pregnancy population. The most influential variables were timing of screening entry, screening costs, and pregnancy termination rates. Of the 13,176 affected pregnancies undergoing screening, NIPT detected 96.5% (12,717/13,176) of cases, compared with 85.9% (11,314/13,176) by conventional approaches. NIPT reduced invasive procedures by 60.0%, with NIPT and conventional methods resulting in 24,596 and 61,430 invasive procedures, respectively. The number of procedure-related euploid fetal losses was reduced by 73.5% (194/264) in the general screening population. CONCLUSION: Based on our analysis, universal application of NIPT would increase fetal aneuploidy detection rates and can be economically justified. Offering this testing to all pregnant women is associated with substantial prenatal healthcare benefits.

Outcomes and costs of incorporating a multibiomarker disease activity test in the management of patients with rheumatoid arthritis.

OBJECTIVE: The multibiomarker disease activity (MBDA) blood test has been clinically validated as a measure of disease activity in patients with RA. We aimed to estimate the effect of the MBDA test on physical function for patients with RA (based on HAQ), quality-adjusted life years and costs over 10 years. METHODS: A decision analysis was conducted to quantify the effect of using the MBDA test on RA-related outcomes and costs to private payers and employers. Results of a clinical management study reporting changes to anti-rheumatic drug recommendations after use of the MBDA test informed clinical utility. The effect of treatment changes on HAQ was derived from 5 tight-control and 13 treatment-switch trials. Baseline HAQ scores and the HAQ score relationship with medical costs and quality of life were derived from published National Data Bank for Rheumatic Diseases data. RESULTS: Use of the MBDA test is projected to improve HAQ scores by 0.09 units in year 1, declining to 0.02 units after 10 years. Over the 10 year time horizon, quality-adjusted life years increased by 0.08 years and costs decreased by US$457 (cost savings in disability-related medical costs, US$659; in productivity costs, US$2137). The most influential variable in the analysis was the effect of the MBDA test on clinician treatment recommendations and subsequent HAQ changes. CONCLUSION: The MBDA test aids in the assessment of disease activity in patients with RA by changing treatment decisions, improving the functional status of patients and cost savings. Further validation is ongoing and future longitudinal studies are warranted.

Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

PURPOSE: Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. METHODS: A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. RESULTS: Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p < 0.05). CONCLUSIONS: Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients' anxiety about the selected adjuvant therapy decreased with use of the GEP.

Influence of a genomic classifier on post-operative treatment decisions in high-risk prostate cancer patients: results from the PRO-ACT study.

OBJECTIVE: To assess the effect of an individualized genomic classifier (GC) test, for predicting metastasis following radical prostatectomy (RP), on urologists' adjuvant treatment decisions when caring for high-risk patients. PATIENTS AND METHODS: Data were submitted by US board-certified urologists in community practices (n = 15), who ordered the GC test for 146 prostate cancer patients with adverse pathologic features following RP (i.e., pathologic stage pT3 or positive surgical margins). Treatment recommendations were reported using an electronic data collection instrument, before and after reviewing the GC test report. Physicians also completed a Decision Conflict Scale (DCS), a decisional conflict measure, to assess their confidence with their treatment recommendations. RESULTS: Over 60% of high-risk patients were re-classified as low risk after review of the GC test results. Overall, adjuvant treatment recommendations were modified for 30.8% (95% CI = 23-39%) of patients. With GC test results, 42.5% of patients who were initially recommended adjuvant therapy were subsequently recommended observation. Although the number of patients recommended adjuvant therapy remained the same before and after review of the GC test results, it did influence patient treatment strategies. Multivariable analysis confirmed GC risk was the only significant predictor of treatment recommendations (OR = 4.04; 95% CI = 2.36, 6.92; p < 0.0001). Decisional conflict with regard to adjuvant treatment decisions was significantly less with the use of the GC test (p < 0.0001). CONCLUSIONS: Information on individualized metastasis risk based on a patient's tumor biology, with use of the GC test, significantly changed urologists' adjuvant treatment recommendations for post-operative patients with prostate cancer, who were at high risk of metastasis. Namely, the results of this study provide evidence for the utility of the GC test, and show it may guide use of adjuvant radiation.