Cost-effectiveness of baloxavir marboxil compared to laninamivir for the treatment of influenza in Japan

BackgroundBaloxavir marboxil (baloxavir) is a new oral antiviral for influenza types A and B.ObjectivesTo determine the cost-effectiveness of baloxavir versus laninamivir in otherwise healthy (OwH) adults in Japan.MethodsA decision tree was utilized to describe the course of influenza and predict associated costs and quality-adjusted life-years (QALYs) over one year by antiviral. Costs were valued from the public healthcare payer perspective, including influenza test, antiviral acquisition, other medications, physician visits, other outpatient costs associated with influenza or drug-related adverse events (DRAEs), and hospitalizations. Resource utilization and unit costs were obtained from the analysis of the JammNet claims database. Health state utilities were obtained from a clinical trial of baloxavir and previous models, and were driven by influenza symptoms, DRAEs, and complications caused by influenza. Sensitivity analyses were also performed.ResultsThe total payer expenditure per patient for baloxavir versus laninamivir was ¥9383 versus ¥9132. The additional acquisition costs of baloxavir were partly offset by the DRAE costs avoided. Baloxavir showed a small gain in QALYs versus laninamivir and the incremental cost per QALY gained (¥2,231,260) was lower than the considered willingness-to-pay threshold (¥5,000,000/QALY). Key model drivers were the probability of DRAEs and the duration of symptoms. The probability of baloxavir being cost-effective was 64%.ConclusionThis cost-effectiveness study on baloxavir suggests that it would be cost-effective compared to laninamivir in OwH adults in Japan. Further studies are needed in different settings such as high-risk population and with different comparators.     

Comparative Cost-utility Analysis Between Aprepitant- and Fosaprepitant-containing Regimens To Prevent Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Japan

PurposeClinical trials have shown that the addition of aprepitant (APR) or a phosphorylated prodrug of aprepitant, fosaprepitant (FosAPR) as prophylactic antiemetic therapy consisting of a 5-hydrotryptamine-3 receptor antagonist and dexamethasone is effective in patients receiving highly emetogenic chemotherapy. These combination therapies have been commonly used in Japan. In the present study, we performed a cost-utility analysis of APR and FosAPR in the context of the Japanese medical insurance system, and economic efficiency was compared.MethodsData from randomized controlled trials that examined the efficacy of APR and FosAPR in the Japanese population were used. A decision tree was constructed to estimate the effectiveness of chemotherapy for 5 days from the day of the treatment and the cost associated with outpatient chemotherapy from the perspective of a payer. Health outcome was expressed in quality-adjusted life-years (QALYs), and costs were estimated based on medical fees and drug prices from 2018. An incremental cost-effectiveness ratio (ICER) was calculated for each regimen containing either APR or FosAPR. The robustness of the model was assessed using 1-way and probabilistic sensitivity analysis.FindingsThe base-case analysis estimated that the addition of APR or FosAPR would have incremental effects of 0.00166 and 0.00143 QALY and incremental costs of 8305 and 11,348 JPY (74 and 101 USD [1 USD = 112.17 JPY]), resulting in ICERs of 4,992,172 and 7,955,560 JPY/QALY (44,505 and 70,924 USD/QALY), respectively. Sensitivity analysis revealed that the probability of a complete response for delayed chemotherapy-induced nausea and vomiting had the most influence on the ICERs. Reductions in the drug costs of APR and FosAPR also had an effect on the ICERs. According to the probabilistic sensitivity analysis, APR and FosAPR were dominant in terms of cost-effectiveness in 48.7% and 8.55% of cases, respectively.ImplicationsThe ICER of outpatient prophylactic antiemetic therapy in patients receiving highly emetogenic chemotherapy was calculated in the context of the Japanese medical insurance system. Assuming the willingness-to-pay of 5,000,000 JPY/QALY based on the calculated ICER, our findings suggest that although the addition of APR is cost-effective, FosAPR is not cost-effective.     

Comparative Cost-utility Analysis of Regorafenib and Trifluridine/Tipiracil in The Treatment of Metastatic Colorectal Cancer in Japan

PurposeThis study evaluated the cost utility of regorafenib and trifluridine/tipiracil (T/T) compared with that of best supportive care (BSC) in the treatment of patients with metastatic colorectal cancer previously treated with, or not considered candidates for, available therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies; anti–vascular endothelial growth factor agents; and anti–epidermal growth factor receptor agents, in Japan.MethodsEfficacy data, utility values, and costs were extracted from published studies. The cost and effectiveness of regorafenib and of T/T were compared with those of BSC and examined between the 2 agents over a 5-year time horizon using a partitioned survival analysis. The health outcomes were life-years (LYs) and quality-adjusted life-years (QALYs) gained. The costs were year-2018 revisions to the drug prices and medical fees. The uncertainty and robustness of the model were verified by 1-way sensitivity analysis, probability sensitivity analysis, and scenario analysis compared with different clinical studies. A 2% per-annum discount was applied to expenses and QALYs. The willingness-to-pay threshold used was 5 million Japanese yen (JPY).FindingsRegorafenib and T/T had incremental costs of 11,898,982 JPY (107,781 US dollars [USD]) and 5,000,141 JPY (45,291 USD), incremental effects of 0.249 QALYs (0.280 LYs) and 0.344 QALYs (0.421 LYs), and incremental cost-effectiveness ratios of 47,773,791 JPY (432,734 USD) and 14,550,577 JPY (131,799 USD) per QALY, respectively. Results of sensitivity analyses all exceeded the willingness-to-pay threshold of 15 million JPY. In the comparison of the 2 agents, T/T was a dominant alternative over regorafenib.ImplicationsAs a third-line or later treatment of metastatic colorectal cancer in Japan, T/T is cost-effective compared with BSC, whereas regorafenib is not. It is necessary to adjust the price of regorafenib based on the results of this analysis, with the improvement of clinical parameters such as survival time and adverse events.     

Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States

PurposeTo assess the cost-effectiveness and cost-effective price of tisagenlecleucel, a novel, effective chimeric antigen receptor T-cell therapy, versus salvage chemotherapy (SC) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) using a willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY) gained from a US third-party payer's perspective.MethodsA three-state (progression-free survival, progressive disease, and death), responder-based partitioned survival model with a lifetime horizon and 3% annual discount rate was developed. Overall survival (OS) and progression-free survival of tisagenlecleucel were estimated separately for patients with and without an overall response (OR), using data from JULIET ( Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients). OS of SC was informed by SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research). Mixture cure models were used to inform the survival of tisagenlecleucel responders, supported by JULIET. The median OS was 11.1 months in all tisagenlecleucel-treated patients but not reached for responders; no progression or death occurred among responders since month 22 of treatment. For tisagenlecleucel nonresponders and SC, survival was based on standard parametric models until month 60and the survival of DLBCL long-term survivors thereafter. The model prediction validated well against the observed trial data. Costs and utilities were from the literature; utilities depended on health states and were used to estimate QALYs. Total costs, QALYs, and incremental cost per QALY gained were estimated. A cost-effective price range was estimated for all tisagenlecleucel-treated patients, OR responders, and complete response (CR) responders. Deterministic sensitivity and scenario analyses and a probabilistic sensitivity analysis were performed. All costs were reported in or inflated to 2020 US dollars.FindingsTisagenlecleucel was associated with 3.35 QALYs gained versus SC.,The estimated incremental costs per QALY gained versus SC were $78,652 using the wholesale acquisition cost of $373,000 for tisagenlecleucel. The estimated cost-effective price of tisagenlecleucel in all treated patients was $612,270 at the WTP threshold of $150,000. Tisagenlecleucel OR and CR responders had an increase of 7.82 and 9.34 QALYs versus SC, with cost-effective prices estimated at $1,281,456 and $1,551,974, respectively. Sensitivity analysis results supported the base case findings.ImplicationsTisagenlecleucel is a cost-effective treatment versus SC for r/r DLBCL from the perspective of a US third-party payer. The estimated cost-effective prices ranged from $612,270 (all tisagenlecleucel-treated patients) to up to $1.5 million (patients achieving CR). Limitations include the use of single-arm trials due to data availability.     

Cost-effectiveness of second-line vasopressors for the treatment of septic shock

PurposeTo determine the cost-effectiveness of escalating doses of norepinephrine or norepinephrine plus the adjunctive use of vasopressin or angiotensin II as a second-line vasopressor for septic shock.Materials and methodsDecision tree analysis was performed to compare costs and outcomes associated with norepinephrine monotherapy or the two adjunctive second-line vasopressors. Short- and long-term outcomes modeled included ICU survival and lifetime quality-adjusted-life-years (QALY) gained. Costs were modeled from a payer's perspective, with a willingness-to-pay threshold set at $100,000/unit gained. One-way (tornado diagrams) and probabilistic sensitivity analyses were performed.ResultsAdjunctive vasopressin was the most cost-effective therapy, and dominated both norepinephrine monotherapy and adjunctive angiotensin II by producing higher ICU survival at less cost. For the lifetime horizon, while norepinephrine monotherapy was least expensive, adjunctive vasopressin was the most cost-effective with an incremental cost-effectiveness ratio of $19,762 / QALY gained. Although adjunctive angiotensin II produced more QALYs compared to norepinephrine monotherapy, it was dominated in the long-term evaluation by second-line vasopressin. Sensitivity analyses demonstrated model robustness and medication costs were not significant drivers of model results.ConclusionsVasopressin is the most cost-effective second-line vasopressor in both the short- and long-term evaluations. Vasopressor price is a minor contributor to overall cost.     

Cost Effectiveness of an Electrocardiographic Deep Learning Algorithm to Detect Asymptomatic Left Ventricular Dysfunction

ObjectiveTo evaluate the cost-effectiveness of an artificial intelligence electrocardiogram (AI-ECG) algorithm under various clinical and cost scenarios when used for universal screening at age 65.Patients and MethodsWe used decision analytic modeling to perform a cost-effectiveness analysis of the use of AI-ECG to screen for asymptomatic left ventricular dysfunction (ALVD) once at age 65 compared with no screening. This screening consisted of an initial screening decision tree and subsequent construction of a Markov model. One-way sensitivity analysis on various disease and cost parameters to evaluate cost-effectiveness at both $50,000 per quality-adjusted life year (QALY) and $100,000 per QALY willingness-to-pay threshold.ResultsWe found that for universal screening at age 65, the novel AI-ECG algorithm would cost $43,351 per QALY gained, test performance, disease characteristics, and testing cost parameters significantly affect cost-effectiveness, and screening at ages 55 and 75 would cost $48,649 and $52,072 per QALY gained, respectively. Overall, under most of the clinical scenarios modeled, coupled with its robust test performance in both testing and validation cohorts, screening with the novel AI-ECG algorithm appears to be cost-effective at a willingness-to-pay threshold of $50,000.ConclusionUniversal screening for ALVD with the novel AI-ECG appears to be cost-effective under most clinical scenarios with a cost of <$50,000 per QALY. Cost-effectiveness is particularly sensitive to both the probability of disease progression and the cost of screening and downstream testing. To improve cost-effectiveness modeling, further study of the natural progression and treatment of ALVD and external validation of AI-ECG should be undertaken.     

Clinical and Economic Benefits of Fidaxomicin Compared to Vancomycin for Clostridium difficile Infection

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.     

Cost-Effectiveness and Net Monetary Benefit of Olaparib Maintenance Therapy Versus No Maintenance Therapy After First-line Platinum-based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-mutated Ovarian Cancer in the Italian National Health Service

PurposeThe aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective.MethodsWe developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based chemotherapy to compare cost-effectiveness and net monetary benefit of the 2 strategies. Data on clinical outcomes were obtained from related clinical trial literature and extrapolated using parametric survival analyses. Data on costs were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio (ICUR), and incremental net monetary benefit (INMB) were computed and compared against an incremental cost per quality-adjusted life-year (QALY) gained of €16,372 willingness-to-pay (WTP) threshold. We used deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) to assess how uncertainty affects results; we also performed scenario analyses to compare results under different pricing settings.FindingsIn the base-case scenario, during a 50-year time horizon, the total costs for patients treated with olaparib therapy and active surveillance were €124,359 and €97,043, respectively, and QALYs gained were 7.29 and 4.88, respectively, with an ICER of €9,515 per life-year gained, an ICUR of €11,345 per QALY gained, and an INMB of €12,104. In scenario analyses, considering maximum selling prices for all other drugs, ICUR decreased to €11,311 per QALY and €7,498 per QALY when a 10% and 20% discount, respectively, was applied to the olaparib official price, and the INMB increased to €12,186 and €21,366, respectively. DSA found that the model results were most sensitive to the proportion of patients with relapsing disease in response to platinum-based chemotherapy, time receiving olaparib first-line maintenance treatment, and subsequent treatments price. According to PSAresults, olaparib was associated with a probability of being cost-effective at a €16,372 per QALY WTP threshold ranging from 70% to 100% in the scenarios examined.ImplicationsOur analysis indicates that olaparib maintenance therapy may deliver a significant health benefit with a contained upfront cost during a 50-year time horizon, from the Italian NHS perspective, providing value in a setting with curative intent.     

Cost-effectiveness of Dabigatran Compared With Rivaroxaban for Prevention of Stroke and Systemic Embolism in Patients With Atrial Fibrillation in China

PurposeIn China, dabigatran and rivaroxaban are the only approved non–vitamin K antagonist oral anticoagulants for the treatment of atrial fibrillation (AF). The goal of this article was to assess the cost-effectiveness of dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in Chinese patients with AF from the perspective of the Chinese health care system.MethodsA Markov model was constructed to estimate the cost-effectiveness of dabigatran versus rivaroxaban. Clinical events were modeled for a lifetime horizon, based on clinical efficacy data from indirect treatment comparisons. The weighted average of the most recent prices of these 2 drugs was used as the drug acquisition cost. Other costs, including follow-up costs and event costs, were collected by using a survey from a panel of local experts. Utility inputs (health state utilities, clinical event disutilities, and event history utility) were obtained from published literature. Sensitivity analyses that included scenario analyses and a probabilistic sensitivity analysis were conducted to examine the robustness of the economic model.FindingsOver a lifetime, patients treated with dabigatran experienced fewer ischemic strokes (2.14 dabigatran vs 2.61 rivaroxaban) and fewer intracranial hemorrhage (0.48 vs 0.94) per 100 patient-years. In the base case analysis, dabigatran had an incremental cost of ¥28,128 but with higher life years (10.38 vs 10.14) and quality-adjusted life years (QALYs) (7.95 vs 7.70). The resulting incremental cost-effectiveness ratio of ¥112,910 per QALY gained and net monetary benefit of ¥12,214 versus rivaroxaban showed that dabigatran was a cost-effective alternative to rivaroxaban. Extensive sensitivity analyses indicated that the results were robust over a wide range of inputs. The probabilistic sensitivity analysis indicated that dabigatran was cost-effective in 84.2% of the 10,000 Monte Carlo simulations compared with rivaroxaban.ImplicationsDabigatran reduced the occurrence of clinical events and increased QALYs compared with rivaroxaban. The use of dabigatran for the prevention of stroke and systemic embolism is a cost-effective option compared with rivaroxaban among patients with AF in China.     

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease

PurposeClinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer’s disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD.MethodsWe developed a Markov state–transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD. AD states included MCI due to AD, mild AD, moderate AD, severe AD, and death. A hypothetical DMT was assumed to confer a 30% reduction in progression from MCI and mild AD. The base case annual drug acquisition cost was assumed to be $56,000. Other medical and indirect costs were obtained from published literature or list prices. Utilities for patients and caregivers were obtained from the published literature and varied by AD state and care setting (community care or long-term care). We considered 3 DMT treatment strategies: (1) treatment administered until patients reached severe AD (continuous strategy), (2) treatment administered for a maximum duration of 18 months or when patients reached severe AD (fixed-duration strategy), and (3) 40% of patients discontinuing treatment at 6 months because of amyloid plaque clearance and the remaining patients continuing treatment until 18 months or until they reached severe AD (test-and-discontinue strategy). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost per quality-adjusted life-year (QALY) gained.FindingsFrom the health care sector perspective, continuous treatment with a hypothetical DMT versus BSC resulted in an ICER of $612,354 per QALY gained. The ICER decreased to $157,288 per QALY gained in the fixed-duration strategy, driven by large reductions in treatment costs. With 40% of patients discontinuing treatment at 6 months (test-and-discontinue strategy), the ICER was $125,631 per QALY gained. In sensitivity and scenario analyses, the ICER was the most sensitive to changes in treatment efficacy, treatment cost, and the initial population AD state distribution. From the modified societal perspective, ICERs were 6.3%, 20.4%, and 25.1% lower than those from the health care sector perspective for the continuous, fixed-duration, and test-and-discontinue strategies, respectively.ImplicationsUnder a set of assumptions for annual treatment costs and the magnitude and duration of treatment efficacy, DMTs used for a limited duration may deliver value consistent with accepted US cost-effectiveness thresholds.     

Economic Evaluation of Adding Daratumumab to a Regimen of Bortezomib + Dexamethasone in Relapsed or Refractory Multiple Myeloma: Based on the Latest Updated Analysis of CASTOR

PurposeAdding daratumumab to a regimen of bortezomib + dexamethasone (Vd) has been reported to provide a benefit of longer progression-free survival in patients with relapsed or refractory multiple myeloma (RRMM). However, it is still unclear whether the addition of daratumumab is cost-effective in RRMM. Based on the latest updated analysis of data from the CASTOR trial, this study performed an economic evaluation of the addition of daratumumab to Vd in patients with RRMM.MethodsA Markov decision model was used for estimating the long-term costs and efficacy of Vd with or without daratumumab in patients with RRMM. Data on efficacy were taken from the CASTOR trial to compare Vd + daratumumab with Vd. Costs were taken from the US Centers for Medicare & Medicaid Services and from the literature. A series of sensitivity analyses were performed to address the robustness of the model. Variations in the price of daratumumab and subgroup analyses were conducted.FindingsThe base-case analysis showed that adding daratumumab to Vd provided an additional 1.256 quality-adjusted life-years (QALYs) or 1.645 life-years (LYs), with incremental 213,164 USD (163,184 USD) per QALY (LY) gained. Univariate sensitivity analyses suggested that the subsequent treatment cost of DVd and the price of daratumumab had the greatest effect on the incremental cost-effectiveness ratio. According to the variations analysis of the price of daratumumab, the addition of daratumumab would be cost-effective when daratumumab was priced at 70% (30%) of the current price at a willingness-to-pay threshold of 200,000 USD/QALY (150,000 USD/QALY). Subgroup analysis indicated that adding daratumumab to Vd was most cost-effective in patients with 1 prior line of therapy.ImplicationsFrom a US-payer perspective, daratumumab added to Vd in RRMM is likely to exceed the common accepted values of cost-effectiveness     

Cost-effectiveness of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary artery disease in Germany

Background

Recent studies have demonstrated a superior diagnostic accuracy of cardiovascular magnetic resonance (CMR) for the detection of coronary artery disease (CAD). We aimed to determine the comparative cost-effectiveness of CMR versus single-photon emission computed tomography (SPECT).

Methods

Based on Bayes’ theorem, a mathematical model was developed to compare the cost-effectiveness and utility of CMR with SPECT in patients with suspected CAD. Invasive coronary angiography served as the standard of reference. Effectiveness was defined as the accurate detection of CAD, and utility as the number of quality-adjusted life-years (QALYs) gained. Model input parameters were derived from the literature, and the cost analysis was conducted from a German health care payer’s perspective. Extensive sensitivity analyses were performed.

Results

Reimbursement fees represented only a minor fraction of the total costs incurred by a diagnostic strategy. Increases in the prevalence of CAD were generally associated with improved cost-effectiveness and decreased costs per utility unit (ΔQALY). By comparison, CMR was consistently more cost-effective than SPECT, and showed lower costs per QALY gained. Given a CAD prevalence of 0.50, CMR was associated with total costs of €6,120 for one patient correctly diagnosed as having CAD and with €2,246 per ΔQALY gained versus €7,065 and €2,931 for SPECT, respectively. Above a threshold value of CAD prevalence of 0.60, proceeding directly to invasive angiography was the most cost-effective approach.

Conclusions

In patients with low to intermediate CAD probabilities, CMR is more cost-effective than SPECT. Moreover, lower costs per utility unit indicate a superior clinical utility of CMR.     

Cost-effectiveness of Community-Based Depression Interventions for Rural and Urban Adults With Type 2 Diabetes: Projections From Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II

OBJECTIVEWe estimated the cost-effectiveness of the Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II community-based exercise (EXER), cognitive behavioral therapy (CBT), and EXER+CBT interventions in adults with type 2 diabetes and depression relative to usual care (UC) and each other.RESEARCH DESIGN AND METHODSData were integrated into the Michigan Model for Diabetes to estimate cost and health outcomes over a 10-year simulation time horizon from the health care sector and societal perspectives, discounting costs and benefits at 3% annually. Primary outcome was cost per quality-adjusted life-year (QALY) gained.RESULTSFrom the health care sector perspective, the EXER intervention strategy saved $313 (USD) per patient and produced 0.38 more QALY (cost saving), the CBT intervention strategy cost $596 more and gained 0.29 more QALY ($2,058/QALY), and the EXER+CBT intervention strategy cost $403 more and gained 0.69 more QALY ($585/QALY) compared with UC. Both EXER and EXER+CBT interventions dominated the CBT intervention. Compared with EXER, the EXER+CBT intervention strategy cost $716 more and gained 0.31 more QALY ($2,323/QALY). From the societal perspective, compared with UC, the EXER intervention strategy saved $126 (cost saving), the CBT intervention strategy cost $2,838/QALY, and the EXER+CBT intervention strategy cost $1,167/QALY. Both EXER and EXER+CBT interventions still dominated the CBT intervention. In comparison with EXER, the EXER+CBT intervention strategy cost $3,021/QALY. Results were robust in sensitivity analyses.CONCLUSIONSAll three Program ACTIVE II interventions represented a good value for money compared with UC. The EXER+CBT intervention was highly cost-effective or cost saving compared with the CBT or EXER interventions.     

First-line Daratumumab in Addition to Chemotherapy for Newly Diagnosed Multiple Myeloma Patients Who are Transplant Ineligible: A Cost-Effectiveness Analysis

PurposeDaratumumab is a standard-of-care treatment for newly diagnosed multiple myeloma (NDMM). According to the ALCYONE trial, the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) provides significantly longer overall survival and progression-free survival than bortezomib, melphalan, and prednisone (VMP) in patients with NDMM. However, considering the high price of daratumumab, it is necessary to conduct further research on its efficacy and cost. This study evaluated the cost-effectiveness, from the US payer perspective, of D-VMP vs VMP in the first-line setting for patients with NDMM who are not eligible for autologous stem cell transplantation.MethodsA Markov model was developed to estimate the lifetime cost and effectiveness of VMP with or without daratumumab as the first-line therapy for patients with NDMM. Univariable sensitivity analysis and probabilistic sensitivity analysis were performed to address the model robustness and uncertainty. Expected value of perfect information analysis was conducted to explore the uncertainty of decision-making and future costs.FindingsD-VMP provides an additional 2.417 quality-adjusted life years (QALYs), at a cost of $30,893 per QALY. Sensitivity analysis revealed that the transition probability of progression-free survival in D-VMP strategy, the price of daratumumab, and body weight of the patient influenced the model results most strongly. Probabilistic sensitivity analysis showed that D-VMP versus VMP has a 90.8% probability of being cost-effective at the $150,000/QALY willingness-to-pay (WTP) threshold. The population expected value of perfect information was $2150 million at a WTP threshold of $50,000/QALY and $1481 million at $100,000/QALY.ImplicationsIn this study, D-VMP was estimated to be cost-effective compared with VMP for patients with NDMM at a WTP threshold of $150,000/QALY.     

Cost-effectiveness Analysis of Prophylaxis Versus On-demand Treatment for Children With Hemophilia B Without Inhibitors in China

PurposeHemophilia B (HB) is a hereditary bleeding disorder caused by a deficiency of coagulation factor IX (FIX), which represents 15% to 20% of all patients with hemophilia. Clinical studies have found significant benefits of prophylaxis treatment with FIX versus on-demand (OD) treatment. However, these benefits are associated with an increase in FIX consumption and a considerable increase in cost. Most Chinese children with HB receive OD treatment. Only a small proportion of patients with HB receive prophylaxis treatment in China. The patients with inhibitors could result in more complicated bleeding events, joint status, or treatment patterns. The objective of this study is to assess the cost-effectiveness of prophylaxis compared with OD treatment in children with HB without inhibitors from the Chinese health care perspective.MethodsA Markov model was used to analyze cost-effectiveness by comparing prophylaxis with OD treatment. The model uses a 17-year time horizon with a yearly cycle. Transition probabilities and utility weights were estimated using published studies. The cost data for patients with HB were collected from Beijing Children's Hospital and Capital Medical University. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the results.FindingsThe model projects that prophylaxis has an incremental 1.23 quality-adjusted life-years (QALYs). The incremental cost per QALY gained for individuals with HB receiving prophylaxis was ¥155,709.80 ($23,530.36) compared with the OD group, which is under the willingness-to-pay threshold (3 times the gross domestic product per capital according to the World Health Organization recommendations) in China of ¥193,932 ($29,306.37). Moreover, 1-way sensitivity analysis found that the results were sensitive to the utility of nonarticular bleeding. The lower this parameter is, the higher the probability is of the incremental cost-effectiveness ratio for prophylaxis not being cost-effective. This finding infers that when the patients have a better QALY (higher utility) at the beginning, the cost for benefit from prophylaxis treatment is lower. The results of the probabilistic sensitivity analyses indicate that the probability of prophylaxis being cost-effective is 89.3%.ImplicationsAlthough prophylaxis is a costly treatment, the results of this study indicate that it is cost-effective compared with OD treatment for children with HB in China.     

Cost-effectiveness and Net Monetary Benefit of Durvalumab Consolidation Therapy Versus No Consolidation Therapy After Chemoradiotherapy in Stage III Non–small Cell Lung Cancer in the Italian National Health Service

PurposeThe aim of this study was to evaluate the cost-effectiveness and net monetary benefit of durvalumab consolidation therapy compared with no consolidation therapy after chemoradiotherapy in patients with stage III non–small cell lung cancer with programmed cell death 1 ligand 1 expression ≥1% from the Italian National Health Service perspective.MethodsWe developed a 12-month decision tree combined with a lifetime cohort Markov model in which patients were assigned to receive durvalumab consolidation therapy or active follow-up (Italian standard of care) after chemoradiotherapy to compare cost-effectiveness and net monetary benefit of the two strategies during a 40-year period. Clinical outcomes data were obtained from the respective clinical trials and extrapolated using survival analysis; cost data were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio, incremental cost-utility ratio, and incremental net monetary benefit were computed and compared against a 16,372 € per quality-adjusted life-year (QALY) willingness-to-pay threshold. We performed deterministic sensitivity analysis and probabilistic sensitivity analysis to assess how uncertainty affected results; we also performed scenario analyses to compare results under different pricing settings.FindingsIn the base-case scenario, during a 40-year period, the total costs for patients treated with durvalumab consolidation therapy and active follow-up were €59,860 and €49,840 respectively; life-years gained were 3.47 and 3.31, respectively; and QALYs gained were 2.73 and 2.50, respectively, with an incremental cost-effectiveness ratio of €62,131 per life-year, an incremental cost-utility ratio of €42,322 per QALY, and an incremental net monetary benefit of €−6,144. We found that durvalumab was cost-effective (incremental net monetary benefit = 0) when a discount of 13% and 30% on its official price was applied, considering all other drugs priced according to official or maximum selling prices, respectively. Results were most sensitive to the progression-free survival rate for durvalumab and active follow-up, health utility in progression-free state, and price of subsequent treatments.ImplicationsOur analysis indicates that durvalumab consolidation is cost-effective when a discount is applied on its official price. These results suggest that durvalumab may deliver an incremental health benefit with a contained upfront cost during a 40-year period, from the Italian National Health Service perspective, providing added value in a potentially curative care setting.     

Cost-effectiveness of Osimertinib vs Docetaxel-bevacizumab in Third-line Treatment in EGFR T790M Resistance Mutation Advanced Non–Small Cell Lung Cancer in China

PurposeThis study aimed to evaluate the cost-effectiveness of osimertinib vs docetaxel and bevacizumab in third-line treatment in EGFR T790M resistance mutation advanced non–small cell lung cancer in China from the perspective of the health care system.MethodsTo explore modeling uncertainty, 2 different model methods (a Markov model and a partitioned survival [PS] model) were developed to simulate costs and health outcomes during a lifetime. Both models consisted of 3 health states: progression-free survival, postprogression survival, and death. Efficacy and safety data of osimertinib vs docetaxel and bevacizumab in patients who had acquired EGFR T790M resistance mutation were derived from a key head-to-head clinical trial. Cost and utility values were derived from local charges, the literature, the China Drug Bidding Database, and patients’ health care documents. Two scenario analyses and sensitivity analyses were performed to explore the robustness of the results.FindingsIn the Markov model, compared with docetaxel and bevacizumab, osimertinib yielded 0.69 additional quality-adjusted life-years (QALYs) at an additional cost (in US dollars) of $17,311 for an incremental cost-utility ratio (ICUR) of $25,463 per QALY. In the PS model, osimertinib yielded an additional 0.69 QALYs with an incremental cost of $17,827 for an ICUR of $25,951 per QALY. From the Markov model, the ICUR was $29,416 per QALY in scenario 1 and $25,543 per QALY in scenario 2. From the PS model, the ICUR was $30,264 per QALY and $25,947 per QALY for scenarios 1 and 2, respectively. In the probabilistic sensitivity analysis, osimertinib treatment had a 21%–63% probability of being cost-effective at a willingness-to-pay threshold of $9777 to $29,330 per QALY (1–3 times the gross domestic product per capita).ImplicationsThe findings from the present analysis suggest that osimertinib could be cost-effective vs docetaxel and bevacizumab in third-line treatment in EGFR T790M resistance mutation advanced non–small cell lung cancer in China.     

Cost-Effectiveness Analysis of Adding Palbociclib as a Second-Line Endocrine Therapy for HR+/HER2– Metastatic Breast Cancer From the US and Chinese Perspectives

PurposeAs a second-line endocrine therapy for hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR⁺/HER2^–) metastatic breast cancer, palbociclib has demonstrated significant efficacy in prolonging progression-free survival when added to a regimen containing fulvestrant. The objective of this study was to evaluate the cost-effectiveness of palbociclib from the perspectives of the United States and China.MethodsWe developed a Markov model to estimate lifetime costs, overall life-years gained, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed to predict the uncertainty of the model developed. The time horizon was 10 years, and the perspective was that of the payer.FindingsWithin a 10-year time horizon, the palbociclib-containing strategy provided an additional 0.568 QALY, with an ICER of 88,854 USD/QALY, in the United States. When palbociclib cost 30%, 20%, and 10% of the current price, the ICERs were 185,526, 42,193, and 98,860 USD/QALY, respectively. In China, the ICER was 182,779 USD/QALY. When palbociclib cost 30%, 20%, and 10% of the current price, the ICERs were 79,558, 64,812, and 50,066 USD/QALY, respectively. In order to meet 50% probability of cost-effectiveness, the estimated price would have to be 32.52 USD/100 mg at a willingness-to-pay threshold of 58,480 USD/QALY (3 × per-capita domestic product of Beijing, China).ImplicationsAdding palbociclib to a regimen of fulvestrant is unlikely to be cost-effective as a second-line endocrine therapy for HR⁺/HER2^– metastatic breast cancer (MBC) with at the current price in the United States and China. For widely meeting the treatment demands of patients, it may be a better option to decrease the price or provide more patients with a financial assistance program for palbociclib both in the United States and in China.     

Cost-effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the united states

Background: Prophylaxis with granulocyte colony-stimulating factor reduces the risk for febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy.Objective: We estimated the incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 of chemotherapy) with pegfilgrastim versus filgrastim in women with early-stage breast cancer receiving myelosuppressive chemotherapy in the United States.Methods: A decision-analytic model was constructed from a health payer's perspective with a lifetime study horizon. The model considered direct medical costs and outcomes related to reduced FN and potential survival benefits due to reduced FN-related mortality and on-time receipt of full-dose chemotherapy. Sensitivity analyses were conducted.Results: Pegfilgrastim was cost-saving and more effective (ie, dominant strategy) than 11-day filgrastim. The incremental cost-effectiveness ratio (ICER) for pegfilgrastim versus 6-day filgrastim was $12,904 per FN episode avoided. Adding the survival benefit due to reduced FN mortality and receipt of optimal chemotherapy dose yielded an ICER of $31,511 per quality-adjusted life year (QALY) gained and $14,415 per QALY gained, respectively. The most influential factors included inpatient FN case-fatality rate, cost of pegfilgrastim and filgrastim, baseline probability of FN, relative risk for FN between filgrastim and pegfil-grastim, and cost of administration of filgrastim.Conclusion: Pegfilgrastim was cost-saving compared with 11-day filgrastim and cost-effective compared with 6-day filgrastim from a health payer's perspective for the primary prophylaxis of FN in these women with early-stage breast cancer receiving myelosuppressive chemotherapy.     

Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia,Including Ventilator-associated Pneumonia,in Italy

PurposeCeftazidime/avibactam (CAZ-AVI) is a fixed-dose combination antibiotic approved in Europe and the United States for patients with hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP). The economic benefits of a new drug such as CAZ-AVI are required to be assessed against those of available comparators, from the perspective of health care providers and payers, through cost-effectiveness and cost-utility analyses. The objective of this analysis was to compare the cost-effectiveness of CAZ-AVI versus meropenem in the empirical treatment of appropriate hospitalized patients with HAP/VAP caused by gram-negative pathogens, from the perspective of publicly funded health care in Italy (third-party perspective, based on the data from the REPROVE (Ceftazidime-Avibactam Versus Meropenem In Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia) clinical study; ClinicalTrials.gov NCT01808092).MethodsA patient-level, sequential simulation model of the HAP/VAP clinical course was developed using spreadsheet software. The analysis focused on direct medical costs. The time horizon of the model selected was 5 years, with an annual discount rate of 3% on costs and quality-adjusted life-years (QALYs). Clinical inputs for treatment comparisons were mainly obtained from the REPROVE clinical study data. In addition to clinical outcomes observed in the trial, the model incorporated impact of resistance pathogens, based on data from published studies and expert opinion. Certain assumptions were made for some model parameters due to a lack of data.FindingsThe analysis demonstrated that the intervention sequence (CAZ-AVI followed by colistin + high-dose meropenem) versus the comparator sequence (meropenem followed by colistin + high-dose meropenem) provided a better clinical cure rate (+13.52%), which led to a shorter hospital stay (−0.40 days per patient), and gains in the number of life-years (+0.195) and QALYs (+0.350) per patient. The intervention sequence had an estimated net incremental total cost of €1254 ($1401) per patient, and the estimated incremental cost-effectiveness ratio was €3581 ($4000) per QALY gained, well below the willingness-to-pay threshold of €30,000 ($33,507) per QALY in Italy.ImplicationsThe model results showed that CAZ-AVI is expected to provide clinical benefits in hospitalized patients with HAP/VAP in Italy at an acceptable cost compared to meropenem.