Assessment of economic burden of fatigue in adults with multiple sclerosis: An analysis of US National Health and Wellness Survey data.

BACKGROUND: Fatigue, a common disabling symptom in multiple sclerosis (MS), is reported by the majority of patients. However, evidence on the economic burden of fatigue in MS by fatigue status is limited. This study aimed to evaluate the economic burden of fatigue, including healthcare resource utilization (HCRU), labor force participation, and Work Productivity and Activity Impairment (WPAI), among adults with relapsing-remitting MS (RRMS) by low fatigue (LF) vs high fatigue (HF) and compared with adults without MS. METHODS: This cross-sectional, retrospective, observational study included pooled data from the 2017 and 2019 US National Health and Wellness Survey. The RRMS sample included respondents aged ≥18 years who reported being diagnosed with MS by a healthcare provider (HCP) and reported having RRMS. Non-MS controls included respondents aged ≥18 years who did not report being diagnosed with MS by an HCP. Fatigue was measured using the Modified Fatigue Impact Scale-5 (MFIS-5). Outcomes included HCRU (HCP visits, emergency department visits, and hospitalizations in the past 12 months), labor force participation (yes vs no), WPAI (absenteeism, presenteeism, total work productivity impairment, and activity impairment), and annualized costs (direct medical, indirect, and total). Respondents with RRMS were propensity-score matched to non-MS controls (ratio 1:3). RRMS respondents were categorized as having LF (MFIS-5<15; RRMS+LF) and HF (MFIS-5≥15; RRMS+HF). Bivariate analysis compared matched non-MS controls, RRMS+LF, and RRMS+HF. Multivariable analyses were conducted among RRMS to evaluate associations between fatigue (continuous variable) and outcomes. RESULTS: Overall, 498 respondents with RRMS (RRMS+LF, n=375; RRMS+HF, n=123) and 1494 matched non-MS controls were included. RRMS+HF and RRMS+LF had more HCRU in the past 12 months than non-MS controls, whereas RRMS+HF had greater HCRU than RRMS+LF (all p<0.05). WPAI was also higher among RRMS+HF and RRMS+LF, compared with non-MS controls, as well as higher in RRMS+HF vs RRMS+LF (all p<0.001). RRMS+HF had significantly higher annualized direct medical costs than RRMS+LF and matched non-MS controls ($19,978 vs $10,656, p=0.007; vs $8,048, p<0.001). Among employed respondents, RRMS+HF and RRMS+LF had higher annualized indirect costs than non-MS controls, with RRMS+HF also having higher annualized indirect costs than RRMS+LF ($23,647 vs $13,738 vs $8,001; all p<0.01); total annualized costs were higher in RRMS+HF and RRMS+LF, compared with non-MS controls, as well as RRMS+HF vs RRMS+LF (all p<0.01). In multivariable models, fatigue was significantly and positively associated with the number of HCP visits in the past 12 months (p=0.002); not participating in the labor force (p<0.001); and absenteeism, presenteeism, total work productivity impairment, and activity impairment (all p<0.001). CONCLUSION: RRMS poses a substantial economic burden on patients and society, and this burden is disproportionately associated with HF.

US budget impact analysis of esketamine nasal spray in major depressive disorder with acute suicidal ideation/behavior.

Background: Esketamine nasal spray plus an oral antidepressant is approved in adults with major depressive disorder with acute suicidal ideation or behavior (MDSI). Methods: A budget impact analysis from a US payer perspective was performed with a hypothetical 1-million-member plan, using pharmacy and medical costs associated with adding esketamine plus an oral antidepressant to usual care. Results: Estimated annual total healthcare costs of managing patients with MDSI increased from $32,988,247 without esketamine to $34,161,188 in Year 3 with esketamine (primarily due to medical costs). The per-member-per-month incremental costs were $0.02, $0.06 and $0.10 in Years 1, 2 and 3, respectively. Conclusion: Incorporation of esketamine results in a modest estimated impact on the annual budget over a 3-year time horizon.

Cost-per-remitter with esketamine nasal spray versus standard of care for treatment-resistant depression.

Aim: Estimate the cost-per-remitter with esketamine nasal spray plus an oral antidepressant (ESK + oral AD) versus oral AD plus nasal placebo (oral AD + PBO) among patients with treatment-resistant depression. Patients & methods: An Excel-based model was developed to estimate the cost-per-remitter for ESK + oral AD versus oral AD + PBO over 52 weeks from multiple US payer perspectives. Clinical end points and cost inputs were derived from clinical trials and the literature, respectively. Results: Under the base-case scenario, the cost-per-remitter for ESK + oral AD and oral AD + PBO were as follows: Commercial: US$85,808 versus US$100,198; Medicaid: US$76,236 versus US$96,067; Veteran's Affairs: US$77,765 versus US$104,519; and Integrated Delivery Network: US$103,924 versus US$142,766. Conclusion: The findings suggest that ESK + oral AD is a cost-efficient alternative treatment for treatment-resistant depression compared with oral AD + PBO.

Lay abstract The US FDA recently approved esketamine nasal spray plus an oral antidepressant (AD) as a new treatment for adults with treatment-resistant depression. We developed an Excel-based model to understand whether esketamine + oral AD treatment offers better value for the money spent, compared with treatment with oral AD alone. We find that the higher annual costs of esketamine + oral AD treatment are more than offset by the better clinical outcomes achieved with this treatment. Specifically, in a given year, more people treated with esketamine + oral AD versus oral AD alone achieved and remained in remission, and as a result, they incurred fewer other medical costs.

A retrospective chart review study to quantify the monthly medical resource use and costs of treating patients with treatment resistant depression in the United Kingdom.

INTRODUCTION: Major depressive disorder (MDD) is a globally prevalent chronic psychiatric illness with a significant disease impact. As many as 30% of patients with MDD do not adequately respond to two therapies and are considered to be treatment resistant. This study aimed to quantify healthcare costs associated with treatment resistant depression (TRD) in the UK. METHODS: A retrospective chart review of patients with TRD was conducted in primary and secondary care settings over a 2 year period. Data abstracted from medical records of patients included demographics, clinical characteristics and healthcare resource utilization (HCRU; number of consultations, use of Crisis Resolution and Home Treatment Teams [CRHTTs], non-drug and drug interventions, and hospitalizations). HCRU per patient per month (28 days) was calculated for three health states: major depressive episode (MDE), remission and recovery. Unit costs were from the British National Formulary (BNF) and the Personal Social Services Research Unit (PSSRU). RESULTS: A total of 295 patients with TRD were recruited between January 2016 and May 2018. The mean age of the total sample was 43.3 years; 60.3% were female. Costs per patient, per 28 days, were highest in the MDE state, with the average cost (£992) mainly driven by consultations, non-drug treatment, hospitalizations and CRHTT, with a considerable fall in costs as patients moved into remission and subsequent recovery. CONCLUSION: The results suggest that antidepressant treatments for TRD that are more effective in reducing the time spent in an MDE health state, and helping patients achieve remission and recovery, are essential for reducing the overall HCRU and costs in patients with TRD. Cost of TRD in the UK Strengths and limitations of this study This observational study of TRD is the first to assess the HCRU impact associated with different predefined health states. Using retrospective data from both primary and secondary care physicians from regions across the UK ensures a representative real-world patient population. One limitation is that the selection of patients is based on criteria that define TRD that rely on physician judgement. Although the study captures direct HCRU costs, the indirect costs of lost productivity and care are not included in the overall burden. This study has defined the current clinical management of patients with TRD in the UK and provides an estimate of the associated HCRU and associated costs.

Pitfalls of Cost-Effectiveness Analysis in Practice: A TRD Case Example in the United States with Esketamine Versus Oral Antidepressants.

DISCLOSURES: The writing of this letter was supported by Janssen Scientific Affairs. The authors are employees of Janssen Scientific Affairs or Janssen Global Services (Johnson & Johnson).

Budget Impact of Increasing Market Share of Patient Self-Testing and Patient Self-Management in Anticoagulation.

BACKGROUND: Patient self-testing (PST) and/or patient self-management (PSM) might provide better coagulation care than monitoring at specialized anticoagulation centers. Yet, it remains an underused strategy in the Netherlands. METHODS: Budget-impact analyses of current and new market-share scenarios of PST and/or PSM compared with monitoring at specialized centers were performed for a national cohort of 260,338 patients requiring long-term anticoagulation testing. A health care payer perspective and 1- to 5-year time horizons were applied. The occurrence of thromboembolic and hemorrhagic complications in the aforementioned patient population was assessed in a Markov model. Dutch-specific costs were applied, next to effectiveness data derived from a meta-analysis on PST and/or PSM. Sensitivity and scenario analyses were performed to assess uncertainty on budget-impact analysis results. RESULTS: Increasing PST and/or PSM usage in the national cohort from the current 15.4% to 50% resulted in savings ranging from €8 million after the first year to €184 million after 5 years. Further increases in the use of PST and/or PSM produced greater savings. Sensitivity analyses revealed budget-impact model sensitivity to the baseline and relative risks of thromboembolic complications. Unfavorable budget impact was found in scenarios exploring an increase in the use of PST alone as well as an increase in the market share of PST and PSM in patients with atrial fibrillation. CONCLUSIONS: Overall study findings indicated that PST and PSM are more favorable alternatives to monitoring at specialized centers in patients without atrial fibrillation.

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada.

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada. Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($). Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies. Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.

Direct costs of hypertensive patients admitted to hospital in Vietnam- a bottom-up micro-costing analysis.

BACKGROUND: There is an economic burden associated with hypertension both worldwide and in Vietnam. In Vietnam, patients with uncontrolled high blood pressure are hospitalized for further diagnosis and initiation of treatment. Because there is no evidence on costs of inpatient care for hypertensive patients available yet to inform policy makers, health insurance and hospitals, this study aims to quantify direct costs of inpatient care for these patients in Vietnam. METHODS: A retrospective study was conducted in a hospital in Vietnam. Direct costs were analyzed from the health-care provider's perspective. Hospital-based costing was performed using both bottom-up and micro-costing methods. Patients with sole essential or primary hypertension (ICD-code I10) and those comorbid with sphingolipid metabolism or other lipid storage disorders (ICD-code E75) were selected. Costs were quantified based on financial and other records of the hospital. Total cost per patient resulted from an aggregation of laboratory test costs, drug costs, inpatient-days' costs and other remaining costs, including appropriate allocation of overheads. Both mean and medians, as well as interquartile ranges (IQRs) were calculated. In addition to a base-case analysis, specific scenarios were analyzed. RESULTS: 230 patients were included in the study (147 cases with I10 code only and 83 cases with I10 combined with E75). Median length of hospital stay was 6 days. Median total direct costs per patient were US$65 (IQR: 37 -95). Total costs per patient were higher in the combined hypertensive and lipid population than in the sole hypertensive population at US$78 and US$53, respectively. In all scenarios, hospital inpatient days' costs were identified as the major cost driver in the total costs. CONCLUSIONS: Costs of hospitalization of hypertensive patients is relatively high compared to annual medication treatment at a community health station for hypertension as well as to the total health expenditure per capita in Vietnam. Given that untreated/undetected hypertension likely leads to more expensive treatments of complications, these findings may justify investments by the Vietnamese health-care sector to control high blood pressure in order to save downstream health care budgets.

Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands.

BACKGROUND: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs. OBJECTIVE: To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands. METHODS: Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER). RESULTS: Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust. CONCLUSIONS: In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.

The burden of unintended pregnancies in Brazil: a social and public health system cost analysis.

BACKGROUND: Unintended pregnancy (UP) is an unmet medical need with consequences worldwide. We evaluate the costs of UP based on pregnancies in Brazil from for the year 2010. METHODS: The consequences of UP were evaluated using decision analysis based on pregnancy rates and outcomes as miscarriage, induced abortion, and live birth, which were factored into the analysis. The model discriminated between maternal and child outcomes and accounted for costs (in Brazilian currency [Real$, R$]) within the Brazilian public health service attributed to preterm birth, neonatal admission, cerebral palsy, and neonatal and maternal mortality. Event probabilities were obtained from local resources. RESULTS: We estimate that 1.8 million UPs resulted in 159,151 miscarriages, 48,769 induced abortions, 1.58 million live births, and 312 maternal deaths, including ten (3%) attributed to unsafe abortions. The total estimated costs attributed to UP are R$4.1 billion annually, including R$32 million (0.8%) and R$4.07 billion (99.2%) attributed to miscarriages and births and complications, respectively. Direct birth costs accounted for approximately R$1.22 billion (30.0%), with labor and delivery responsible for most costs (R$988 million; 24.3%) for the year 2010. The remainder of costs were for infant complications (R$2.84 billion; 72.3%) with hospital readmission during the first year accounting for approximately R$2.15 billion (52.9%). Based on the national cost, we estimate the cost per UP to be R$2,293. CONCLUSION: Despite weaknesses in precise estimates in annual pregnancies and induced abortions, our estimates reflect the costs of UP for different pregnancy outcomes. The main costs associated with UP are in those carried to parturition. The health cost of abortion represents a small proportion of total costs as these are paid for outside of the public health system. Consequently, reductions in UP will generate not only cost savings, but reductions in woman and child morbidity and mortality.

Economic impact of childhood/adolescent ADHD in a European setting: the Netherlands as a reference case.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric disorder in children/adolescents. This study reviews available European-based studies of ADHD-related costs and applies the findings to the Netherlands to estimate annual national costs for children/adolescents from a societal perspective. A systematic literature search was conducted for primary studies in Europe, published January 1, 1990 through April 23, 2013. Per-person cost estimates were converted to 2012 Euros and used to estimate annual national ADHD-related costs based on the Dutch 2011 census, ADHD prevalence rates, family composition, and employment rates. Seven studies met the inclusion criteria. The average total ADHD-related costs ranged from €9,860 to 14,483 per patient and annual national costs were between €1,041 and €1,529 million (M). The largest cost category was education (€648 M), representing 62 and 42 % of the low- and high-value overall national estimates, respectively. By comparison, ADHD patient healthcare costs ranged between €84 M (8 %) and €377 M (25 %), and social services costs were €4.3 M (0.3-0.4 %). While the majority of the costs were incurred by ADHD patients themselves, €161 M (11-15 %) was healthcare costs to family members that were attributable to having an ADHD child/adolescent. In addition, productivity losses of family members were €143-€339 M (14-22 %). Despite uncertainties because of the small number of studies identified and the wide range in the national cost estimates, our results suggest that ADHD imposes a significant economic burden on multiple public sectors in Europe. The limited number of European-based studies examining the economic burden of ADHD highlights the need for more research in this area.

Cost-Effectiveness Analysis of Hepatitis B Immunization in Vietnam: Application of Cost-Effectiveness Affordability Curves in Health Care Decision Making.

OBJECTIVES: To perform a cost-effectiveness analysis and to identify the cost-effectiveness affordability levels for a newborn universal vaccination program against hepatitis B virus (HBV) in Vietnam. METHODS: By using a Markov model, we simulated a Vietnamese birth cohort using 1,639,000 newborns in 2002 and estimated the incremental cost-effectiveness ratios for quality-adjusted life-year gained following universal newborn HBV vaccination. Two types of analyses were performed, including and excluding expenditures on the treatment of chronic hepatitis B and its complications. We used Monte Carlo simulations to examine cost-effectiveness acceptability and affordability from the payer's perspective and constructed a cost-effectiveness affordability curve to assess the costs and health effects of the program. RESULTS: In the base-case analysis, newborn universal HBV vaccination reduced the carrier rate by 58% at a cost of US $42 per carrier averted. From the payer's perspective, incremental cost-effectiveness ratio per quality-adjusted life-year gained was US $3.77, much lower than the 2002 per-capita gross domestic product of US $440. Vaccination could potentially be affordable starting at a US $2.1 million budget. At the cost-effectiveness threshold of US $3.77 per quality-adjusted life-year and an annual budget of US $5.9 million, the probability that vaccination will be both cost-effective and affordable was 21%. CONCLUSIONS: Universal newborn HBV vaccination is highly cost-effective in Vietnam. In low-income, high-endemic countries, where funds are limited and the economic results are uncertain, our findings on the cost-effectiveness affordability options may assist decision makers in proper health investments.