Quality-adjusted Life-years Benefit Research Articles

The long-term cost-effectiveness of once-weekly semaglutide versus sitagliptin for the treatment of type 2 diabetes in China

BackgroundTo estimate the long-term cost-effectiveness of once-weekly semaglutide versus sitagliptin as an add-on therapy for type 2 diabetes patients inadequately controlled on metformin in China, to better inform healthcare decision making.MethodsThe Cardiff diabetes model which is a Monte Carlo micro-simulation model was used to project short-term effects of once-weekly semaglutide versus sitagliptin into long-term outcomes. Short-term data of patient profiles and treatment effects were derived from the 30-week SUSTAIN China trial, in which 868 type 2 diabetes patients with a mean age of 53.1 years inadequately controlled on metformin were randomized to receive once-weekly semaglutide 0.5 mg, once-weekly semaglutide 1 mg, or sitagliptin 100 mg. Costs and quality-adjusted life years (QALYs) were estimated from a healthcare system perspective at a discount rate of 5%. Univariate sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis were conducted to test the uncertainty.ResultsOver patients’ lifetime projections, patients in both once-weekly semaglutide 0.5 mg and 1 mg arms predicted less incidences of most vascular complications, mortality, and hypoglycemia, and lower total costs compared with those in sitagliptin arm. For an individual patient, compared with sitagliptin, once-weekly semaglutide 0.5 mg conferred a small QALY improvement of 0.08 and a lower cost of $5173, while once-weekly semaglutide 1 mg generated an incremental QALY benefit of 0.12 and a lower cost of $7142, as an add-on to metformin. Therefore, both doses of once-weekly semaglutide were considered dominant versus sitagliptin with more QALY benefits at lower costs.ConclusionOnce-weekly semaglutide may represent a cost-effective add-on therapy alternative to sitagliptin for type 2 diabetes patients inadequately controlled on metformin in China.

Cost-Effectiveness Modeling of Prostate-Specific Membrane Antigen Positron Emission Tomography with Piflufolastat F18 for the Initial Diagnosis of Patients with Prostate Cancer in the United States.

Piflufolastat F18 is a novel prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer that is superior to standard of care (SOC) imaging for the initial staging of prostate cancer and the detection of biochemical recurrence. As piflufolastat F18 has been approved in the United States (US) for this indication, this modeling study assessed the cost effectiveness of piflufolastat F18 versus fluciclovine F-18, gallium68-PSMA-11 (PSMA11), and SOC imaging (a mix of bone scans, computed tomography, and magnetic resonance imaging) for the diagnosis and staging of prostate cancer from a US healthcare system perspective. A US third-party payer perspective was used, which for this population reflects a mix of commercial and Medicare, considering only direct healthcare costs. This study utilized a tertiary healthcare setting. A decision tree was used to map the diagnostic/treatment pathway, consisting of the proportion of patients with local, regional, distant, or no disease; prostate-specific antigen (PSA) ≤1.0 or >1.0; and accuracy of imaging modalities. A Markov model predicted the long-term outcomes of disease progression according to treatment decisions. Inputs to the model were informed by data from the OSPREY and CONDOR clinical trials, public data, and the literature. Treatment mix included active surveillance, radiation therapy, prostatectomy, androgen deprivation therapy (ADT), and radiation therapy + ADT, informed by expert opinion. Outcomes included life-years (LY), quality-adjusted life-years (QALY), and the incremental cost-effectiveness ratio (ICER). All costs were reported in 2021 US dollars, using the US Bureau of Labor Statistics Consumer Price Index. A willingness-to-pay (WTP) threshold of $150,000 was considered cost effective, consistent with the upper range used as the standard for price benchmarks by the Institute for Clinical and Economic Review. The robustness of the base-case results was assessed in deterministic and probabilistic sensitivity analyses. Over a lifetime horizon, piflufolastat F18 had the greatest effectiveness in terms of LYs (6.80) and QALYs (5.33); for the comparators, LYs ranged from 6.58 (SOC) to 6.76 (PSMA11) and QALYs ranged from 5.12 (SOC) and 5.30 (PSMA11). Piflufolastat F18 was more cost effective compared with fluciclovine F18, PSMA11, and SOC, with ICERs of $21,122, $55,836, and $124,330 per QALY gained, respectively. Piflufolastat F18 was associated with the greatest net monetary benefit ($627,918) compared with the other options at a WTP threshold of $150,000. The results of the deterministic and probabilistic sensitivity analyses supported the robustness of the base-case results. This study suggests that piflufolastat F18 is a cost-effective diagnostic option for men with prostate cancer in the US, with higher associated LY, QALY, and greater net monetary benefit than fluciclovine F18, PSMA11, and SOC imaging.

992-P: Coronary Artery Calcium Scoring to Improve Statin Use in Adults with Type 2 Diabetes Not on Statin Therapy—Anticipated Cost Utility

Background: Statin use in adults with diabetes is sub-optimal. Coronary artery calcium (CAC) scoring can provide a visual quantification of CV risk and may improve statin initiation and long-term use. Objective: Estimate the cost-utility of CAC scoring compared to traditional CV risk counselling only, for improving statin use in adults with diabetes who have not previously had a CV event, and are not on statin therapy. Methods: Probabilistic Markov model from a health system perspective, over a 10-year time horizon. The effectiveness of CAC scoring was obtained from the EISNER trial. Outcomes included acute coronary syndrome (ACS), stroke, heart failure, mortality, and radiation-induced cancer. Outcome rates and costs were obtained from an analysis of Alberta administrative data, and from publicly available sources. The base population modeled was men age 60, with additional analyses for other age, sex-groups and scenarios. Results: CAC scoring increased statin use to 44% vs 25% with traditional CV risk counselling only. There were 8.4 fewer ACS, 5.5 fewer strokes, and 1.6 fewer deaths / 1000 individuals. Costs were slightly lower (-$14, 95% CI [-$402-(+$208)]) (CAD), for a small benefit in quality-adjusted life years (+0.01, [0.00-0.02]), with mean ICER of $7,132 (-$27,828-(+$65,513)) / QALY. At a willingness-to-pay of $50,000 / QALY, CAC was cost-effective in 95% of trials. CAC scoring was not cost-effective in younger men or in women, but could be cost-effective or cost savings in men (age ≥ 40) and older women (age ≥ 60) who refuse statin therapy, but would be persuaded by personalized evidence of coronary artery disease (CAC score > 10). Conclusion: CAC scoring may be cost-effective in older men not receiving statins, and in men or older women who agree to use statins if shown personalized evidence of coronary artery disease. Disclosure D.Lau: None. G.J.Pearson: Advisory Panel; HLS Therapeutics Inc., Novartis Pharmaceuticals Corporation, Pharmacience, Consultant; Trimedic Therapeutics. P.Raggi: None. S.Klarenbach: Research Support; Bayer Inc., Allergan, GlaxoSmithKline plc., CSL Behring, Lundbeck, University Hospital Foundation (University of Alberta), Purdue Canada.

407 Anterior Cervical Discectomy and Fusion in Ambulatory Surgery Center Versus Hospital Setting: One-Year Cost Utility and Cost Benefit Analysis

INTRODUCTION: Outpatient anterior cervical discectomy and fusion (ACDF) has recently gained popularity due to improved care and reduced costs. Cost-utility studies for ambulatory vs. inpatient ACDF are largely limited to small series, precluding an accurate assessment of cost-effectiveness. METHODS: A 6,504, ASA 1-3, patient sample (520 ASC, 5,984 inpatient) was used to propensity-match 748 patients (374/cohort) undergoing 1-2-level ACDF. Data was queried from the National Quality Outcomes Database (QOD). Medical resource utilization, missed work, and quality adjusted life years (QALYs) were assessed. Direct cost (one-year resource use x unit costs based on Medicare national allowable payment amounts) and indirect cost (missed workdays x average US daily wage) were recorded and incremental cost-effectiveness ratio was calculated. RESULTS: Estimated blood loss, length of surgery, and hospitalization were less for ASC vs. inpatient ACDF (p < 0.001). ASC vs. inpatient ACDF demonstrated similar improvement in patient reported outcomes. ASC vs. inpatient ACDF was associated with lower total one-year cost of $5,879.46 for Medicare patients and $12,873.97 for private payers (p < 0.001), with similar QALYs gained. Hospital vs ASC had a highly cost ineffective ICER of $3,674,662.50/QALY-gained and $8,046,231.25/QALY for Medicare and private payer patients, respectively. CONCLUSIONS: 1-2-level ACDF in the hospital vs ASC is associated with increased mean costs, without a QALY, safety, or outcome benefit. Hence, health economics strongly favor the ASC setting to the hospital for ACDF.

Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving reldesemtiv or placebo in FORTITUDE-ALS

AimsTo estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS.Materials and methodsWe performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated reldesemtiv in patients with ALS. Health utilities from the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L) were estimated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores collected during the trial. QALYs were estimated using the area under the curve method.ResultsThe full analysis set consisted of 456 patients (reldesemtiv n = 342, placebo n = 114), who received at least one dose of the double-blind study drug, and had ALSFRS-R assessed at baseline and at least one post-baseline assessment. The difference in EQ-5D-5L utility least-squares (LS) mean change from baseline to week 12 for reldesemtiv versus placebo, adjusted for baseline values, was statistically significant (0.03, 95% confidence interval [CI]: 0.01, 0.05; p = .0008). The incremental QALY of reldesemtiv versus placebo adjusted for baseline utility values showed a modest, but statistically significant, difference (0.004, 95% CI: 0.001, 0.007; p = .0058).ConclusionsThis post hoc analysis of FORTITUDE-ALS suggests that reldesemtiv showed a modest but significant benefit in health utilities and QALYs compared with placebo. Future long-term studies that include direct collection of EQ-5D-5L data will be needed to confirm our findings. ClinicalTrials.gov identifierNCT03160898

Cost-Utility and Cost-effectiveness of MoodSwings 2.0, an Internet-Based Self-management Program for Bipolar Disorder: Economic Evaluation Alongside a Randomized Controlled Trial.

Internet-delivered psychosocial interventions can overcome barriers to face-to-face psychosocial care, but limited evidence supports their cost-effectiveness for people with bipolar disorders (BDs). This study aimed to conduct within-trial cost-effectiveness and cost-utility analyses of an internet-based intervention for people with BD, MoodSwings 2.0, from an Australian health sector perspective. MoodSwings 2.0 included an economic evaluation alongside an international, parallel, and individually stratified randomized controlled trial comparing an internet-based discussion forum (control; group 1), a discussion forum plus internet-based psychoeducation (group 2), and a discussion forum plus psychoeducation and cognitive behavioral tools (group 3). The trial enrolled adults (aged 21 to 65 years) with a diagnosis of BD assessed by telephone using a structured clinical interview. Health sector costs included intervention delivery and additional health care resources used by participants over the 12-month trial follow-up. Outcomes included depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS; the trial primary outcome) and quality-adjusted life years (QALYs) calculated using the short-form 6-dimension instrument derived from the 12-item version of the short-form health survey. Average incremental cost-effectiveness (cost per MADRS score) and cost-utility (cost per QALY) ratios were calculated using estimated mean differences between intervention and control groups from linear mixed effects models in the base case. In total, 304 participants were randomized. Average health sector cost was lowest for group 2 (Aus $9431, SD Aus $8540; Aus $1=US $0.7058) compared with the control group (Aus $15,175, SD Aus $17,206) and group 3 (Aus $15,518, SD Aus $30,523), but none was statistically significantly different. The average QALYs were not significantly different among the groups (group 1: 0.627, SD 0.062; group 2: 0.618, SD 0.094; and group 3: 0.622, SD 0.087). The MADRS scores were previously shown to differ significantly between group 2 and the control group at all follow-up time points (P<.05). Group 2 was dominant (lower costs and greater effects) compared with the control group for average incremental cost per point decrease in MADRS score over 12 months (95% CI dominated to Aus $331). Average cost per point change in MADRS score for group 3 versus the control group was dominant (95% CI dominant to Aus $22,585). Group 2 was dominant (95% CI Aus $43,000 to dominant) over the control group based on lower average health sector cost and average QALY benefit of 0.012 (95% CI -0.009 to 0.033). Group 3, compared with the control group, had an average incremental cost-effectiveness ratio of dominant (95% CI dominated to Aus $19,978). Web-based psychoeducation through MoodSwings 2.0 has the potential to be a cost-effective intervention for people with BD. Additional research is needed to understand the lack of effectiveness for the addition of cognitive behavioral tools with the group 3 intervention.

Anterior Cervical Discectomy and Fusion in the Ambulatory Surgery Center Versus Inpatient Setting: One-Year Cost-Utility Analysis.

Retrospective analysis of prospectively collected data. Assess the cost-utility of anterior cervical discectomy and fusion (ACDF) performed in the ambulatory surgery center (ASC) versus inpatient hospital setting for Medicare and privately insured patients at one-year follow-up. Outpatient ACDF has gained popularity due to improved safety and reduced costs. Formal cost-utility studies for ambulatory versus inpatient ACDF are lacking, precluding an accurate assessment of cost-effectiveness. A total of 6504 patients enrolled in the Quality Outcomes Database (QOD) undergoing one-level to two-level ACDF at a single ASC (520) or the inpatient hospital setting (5984) were compared. Propensity matching generated 748 patients for analysis (374 per cohort). Demographic data, resource utilization, patient-reported outcome measures, and quality-adjusted life-years (QALYs) were assessed. Direct costs (1-year resource use×unit costs based on Medicare national allowable payment amounts) and indirect costs (missed workdays×average US daily wage) were recorded. Incremental cost-effectiveness ratios were calculated. Complication rates and improvements in patient-reported outcome measures and QALYs were similar between groups. Ambulatory ACDF was associated with significantly lower total costs at 1 year for Medicare ($5879.46) and privately insured ($12,873.97) patients, respectively. The incremental cost-effectiveness ratios for inpatient ACDF was $3,674,662 and $8,046,231 for Medicare and privately insured patients, respectively, reflecting unacceptably poor cost-utility. Inpatient ACDF is associated with significant increases in total costs compared to the ASC setting without a safety, outcome, or QALY benefit. The ASC setting is a dominant option from a health economy perspective for first-time one-l to two-level ACDF in select patients compared to the inpatient hospital setting.

Benefit accrual with cardiovascular disease prevention and effects of discontinuation: a modelling study

Abstract Background Statin therapy reduces rates of heart attacks and strokes and improves survival in people at increased cardiovascular disease (CVD) risk. However, there is some uncertainty when to start and how long to persist with statin therapy so as to optimise benefits. Purpose To project the accrual of benefit with statin therapy in population groups by age at therapy initiation using a newly developed micro-simulation model. Methods Participants without previous CVD (N=44,412) and with previous CVD (N=13,061) at entry were randomly selected from the UK Biobank cohort, ensuring sufficient representation in respective categories by age, LDL cholesterol, diabetes and 10-year CVD risk categories (QRISK3 score, for those without previous CVD only). The CTT-UKB model, a CVD micro-simulation model [1], was used to predict subsequent survival and quality-adjusted life years (QALYs) of the participants using their characteristics at entry. Treatment with atorvastatin 40mg daily was used as an example to illustrate the effect of the therapy compared to no such therapy. Scenarios include: (1) lifelong preventive therapy, (2) preventive therapy stopped at 80 years of age, and (3) delayed initiation of preventive therapy by 5 years in participants under 45 years of age. Results Statin treatment benefits, measured in QALYs gained, accrue over lifetime. The majority of benefits accrue later in life. Men accumulate larger benefits and earlier than women (Figure 1A). The pattern of benefits accrual is similar for participants with and without previous CVD (data not shown). The higher the participants' CVD risk, the larger and earlier the benefits, with younger participants accruing larger benefits (Figure 1B). Compared with lifelong prevention, stopping treatment at 80 years of age leads to large reductions in overall benefits, especially in women and those at lower CVD risk. For example, compared to lifelong therapy, people without previous CVD who initiate therapy in their 50s, would lose 47% of QALYs benefit (if men), 66% (if women), 73% (if with CVD risk &amp;lt;5%), and 35% (if with CVD risk ≥20%), respectively, if they stop treatment when they reach 80 years of age. Five-year delay of statin therapy initiation in people under 45 years of age reduces their benefits by about 4% on average, though the loss is somewhat larger in people at higher CVD risk (Figure 2). Conclusion Benefits from lifelong cardiovascular prevention accrue over peoples' lifespan with large share of benefits accruing at older age. Stopping treatment earlier substantially reduces benefits. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK NationalInstitute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, UK Medical Research Council (MRC), and British Heart Foundation

Optimising breathlessness triggered services for older people with advanced diseases: a multicentre economic study (OPTBreathe)

BackgroundIn advanced disease, breathlessness becomes severe, increasing health services use. Breathlessness triggered services demonstrate effectiveness in trials and meta-analyses but lack health economic assessment.MethodsOur economic study included a discrete choice...

Clinical and economic impact of molecular testing for BRAF fusion in pediatric low-grade Glioma

BackgroundTreatment personalization via tumor molecular testing holds promise for improving outcomes for patients with pediatric low-grade glioma (PLGG). We evaluate the health economic impact of employing tumor molecular testing to guide treatment for patients diagnosed with PLGG, particularly the avoidance of radiation therapy (RT) for patients with BRAF-fusion.MethodsWe performed a model-based cost-utility analysis comparing two strategies: molecular testing to determine BRAF fusion status at diagnosis against no molecular testing. We developed a microsimulation to model the lifetime health and cost outcomes (in quality-adjusted life years (QALYs) and 2018 CAD, respectively) for a simulated cohort of 100,000 patients newly diagnosed with PLGG after their initial surgery.ResultsThe life expectancy after diagnosis for individuals who did not receive molecular testing was 39.01 (95% Confidence Intervals (CI): 32.94;44.38) years and 40.08 (95% CI: 33.19;45.76) years for those who received testing. Our findings indicate that patients who received molecular testing at diagnosis experienced a 0.38 (95% CI: 0.08;0.77) gain in QALYs and $1384 (95% CI: $-3486; $1204) reduction in costs over their lifetime. Cost and QALY benefits were driven primarily by the avoidance of long-term adverse events (stroke, secondary neoplasms) associated with unnecessary use of radiation.ConclusionsWe demonstrate the clinical benefit and cost-effectiveness of molecular testing in guiding the decision to provide RT in PLGG. While our results do not consider the impact of targeted therapies, this work is an example of the value of simulation modeling in assessing the long-term costs and benefits of precision oncology interventions for childhood cancer, which can aid decision-making about health system reimbursement.

Better Breathlessness Services for Older People with Advanced Diseases: A Multicentre Discrete Choice Experiment and Economic Modelling (OPRBreathe)

Background: In advanced respiratory disease, breathlessness becomes severe, increasing health services use. Breathlessness Services (BSs) demonstrate effectiveness in trials and meta-analyses but lack health economic assessment and modelling of their impacts on care services. Methods: We conducted a discrete choice experiment (DCE), followed by cost-effectiveness analysis modelling. The DCE comprised face to face interviews with older patients with chronic breathlessness and their carers across eight UK centres. Regression analysis of DCE data determined the preferences (or not, indicated by negative β coefficients) of service attributes for patients. Economic modelling estimated costs and quality adjusted life years (QALYs) over five years. Findings: We recruited 190 patients, 68 carers. Offering BSs from GP surgeries was not preferred (β =-0.30, 95% CI -0.40 to -0.21); hospital outpatient clinics (0.16, 0.06 to 0.25) or via home visits (0.15, 0.06 to 0.24) were preferred. BSs with comprehensive treatment review (0.15, 0.07 to 0.21) and holistic support (0.19, 0.07 to 0.31) were preferred to usual services. Cost-effectiveness analysis found the most and the least preferred models of BSs were cost-effective compared to usual care. The most preferred BSs had £5,719 lower costs and 0.004 QALY benefit per patient. Uptake was higher when attributes were tailored to individual preferences (86% versus 40%). Interpretation: BSs are cost-effective compared to usual care for health and social care, giving cost savings and better quality of life. Uptake of BSs is higher when service attributes are individually tailored. Funding: This study was funding by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0815-20026). Declaration of Interest: All authors have nothing to disclose. Ethical Approval: This study received ethical approval from the West of Scotland Research Ethics Service (Ref. 17/WS/0083).

PCN92 Cost Effectiveness of Obinutuzumab PLUS Chemotherapy Followed By Obinutuzumab Maintenance for Patient with Previously Untreated Advanced-STAGE Follicular Lymphoma in French Setting

Obinutuzumab with chemotherapy plus obinutuzumab maintenance ( G-chemo+G) is reimbursed in France for the treatment of patient with previously untreated advanced-stage follicular lymphoma. Here, we evaluate the cost effectiveness of G-chemo+G over rituximab with chemotherapy plus R maintenance (R-chemo+R). A Markov model was developed over a 30 years time horizon including four health state: ‘PFS (on/off treatment)’, ‘Early progression within 24 months, ‘Late progressive disease in subsequent months’ and ‘Death’. Patient characteristics and clinical data were retrieved from GALLIUM study, except for death probabilities in late progressive diseases state which was based on PRIMA study. We adopted a payer perspective for costs. Frequency of resources used were based on expert opinion. We estimated the benefit in quality-adjusted life years (QALYs) according to age-adjusted EQ-5D-3L utility scores from GALLIUM and to disutilities for grade 3-4 AEs. Costs and outcomes were discounted at 2,5%. Sensitivity analysis were performed. Compared R-chemo+R, G-chemo+G was associated with a gain of 0.622 (11.999 versus 11.377) (QALYs) and an incremental cost of €28,367 mostly driven by treatment costs. The incremental cost-utility ratio (ICUR) was €45,610/QALY. Progression cost (including follow-up cost and 2nd line treatment cost) were lower in the G-chemo plus G arm with a difference of - 7,350€ (€39,175 versus €46,525) due the reduced number of patients progressing within 24 months. We demonstrate that G-chemo plus G maintenance is a cost effective option compared to R-chemo plus R maintenance. The PFS gain with G-chemo+G in patient with previously untreated advanced-stage follicular lymphoma bring a substantial health benefit to the patients at an acceptable additional cost in France.

Is Protocolised Weaning that Includes Early Extubation Onto Non-Invasive Ventilation More Cost Effective Than Protocolised Weaning Without Non-Invasive Ventilation? Findings from the Breathe Study.

BackgroundOptimising techniques to wean patients from invasive mechanical ventilation (IMV) remains a key goal of intensive care practice. The use of non-invasive ventilation (NIV) as a weaning strategy (transitioning patients who are difficult to wean to early NIV) may reduce mortality, ventilator-associated pneumonia and intensive care unit (ICU) length of stay.ObjectivesOur objectives were to determine the cost effectiveness of protocolised weaning, including early extubation onto NIV, compared with weaning without NIV in a UK National Health Service setting.MethodsWe conducted an economic evaluation alongside a multicentre randomised controlled trial. Patients were randomised to either protocol-directed weaning from mechanical ventilation or ongoing IMV with daily spontaneous breathing trials. The primary efficacy outcome was time to liberation from ventilation. Bivariate regression of costs and quality-adjusted life-years (QALYs) provided estimates of the incremental cost per QALY and incremental net monetary benefit (INMB) overall and for subgroups [presence/absence of chronic obstructive pulmonary disease (COPD) and operative status]. Long-term cost effectiveness was determined through extrapolation of survival curves using flexible parametric modelling.ResultsNIV was associated with a mean INMB of £620 ($US885) (cost-effectiveness threshold of £20,000 per QALY) with a corresponding probability of 58% that NIV is cost effective. The probability that NIV is cost effective was higher for those with COPD (84%). NIV was cost effective over 5 years, with an estimated incremental cost-effectiveness ratio of £4618 ($US6594 per QALY gained).ConclusionsThe probability of NIV being cost effective relative to weaning without NIV ranged between 57 and 59% overall and between 82 and 87% for the COPD subgroup.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00210-1) contains supplementary material, which is available to authorized users.

Comparative cost-effectiveness analysis of avelumab plus axitinib versus pembrolizumab plus axitinib, ipilimumab plus nivolumab, and sunitnib for advanced renal cell carcinoma in the U.K. Perspective.

689 Background: Avelulmab plus axitinib showed to improve clinical outcomes for patients with advanced renal cell carcinoma (aRCC) in the JAVELIN RENAL 101 trial. Several other immunocheckpints inihibitos (ICIs) options acquired a main role in the aRCC treatment, such as nivolumab plus ipilimumab and pembrolizumab plus axitinib. Our aim is to evaluate the cost effectiveness of avelumab/axitinib versus other FDA approved options for previously untreated patients with aRCC. Methods: A Markov model was used to estimate the costs and health outcomes of treatment of aRCC with sunitinib, or avelumab plus axitinib. Univariable and probabilistic sensitivity analyses were performed to determine the robustness of the model outcomes. The primary outputs of the model included the total cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Results: Avelumab plus axitinib provided and 4.77 additional QALY benefit. Total cost per patient was US$ 174,725 for avelumab/axitinib, US$ 178,725 for pembrolizumab/axitinib, US$ 169,390 for ipilimumab/nivolumab and US$ 97,846 for sunitnib. Avelumab/axitinib showed to be more cost-effective (ICER US$ 28,011/QALY) when compared to pembrolizumab/axitinib (ICER US$ 47,916/QALY) and ipilumumab/nivolumab (ICER US$ 95,392/QALY). Conclusions: Avelumab/axitinib is likely to be more cost-effective than ipilimumab/nivolumab, pembrolizumab/axitinib and sunitinib in the UK perspective. However further models, market discounts and stakeholders price negotiations could lead to variations of this scenario across the globe.

Anticoagulation in pulmonary arterial hypertension: a decision analysis.

Systemic anticoagulation may be beneficial in pulmonary arterial hypertension, but there is no randomized clinical trial data to guide therapeutic decision making, and current guidelines do not account for patient preferences or quality of life. Decision analytic models to evaluate the potential risks and benefits of systemic anticoagulation in pulmonary arterial hypertension patients, focusing on the benefit in quality-adjusted life years, may be helpful in clarifying this uncertainty. We constructed a 31-state Markov decision analytic model to explore anticoagulation and no anticoagulation strategies. Modeled patient characteristics included gender, use of central catheter-based pulmonary arterial hypertension therapy, type of pulmonary arterial hypertension (idiopathic, idiopathic pulmonary arterial hypertension, or connective-tissue associated, connective tissue disease-pulmonary arterial hypertension), and use of oral contraceptive medication by females. Modeled events included mortality, thromboembolic complications, atrial fibrillation, stroke, and anticoagulation bleeding. Deterministic and probabilistic sensitivity analyses were performed. Anticoagulation was favored in all idiopathic pulmonary arterial hypertension cases, with a gain of 0.43–0.51 quality-adjusted life years, and detrimental in all connective tissue disease-pulmonary arterial hypertension cases, with a loss of 0.66–1.89 quality-adjusted life years. Anticoagulation would need to demonstrate a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better to be favored. In our model, idiopathic pulmonary arterial hypertension patients benefit from anticoagulation in terms of quality-adjusted life years, and connective tissue disease-pulmonary arterial hypertension patients were harmed, with a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better being required to favorably impact quality-adjusted life years. These results suggest that anticoagulation significantly improves quality adjusted life years and should be offered to all idiopathic pulmonary arterial hypertension patients. Shared decision models based on these results may help clarify therapeutic decision-making uncertainty in pulmonary arterial hypertension patients.

PMU9 DO NICE APPRAISAL PROCESSES REWARD INNOVATIVE AND CURATIVE THERAPIES? AN ASSESSMENT OF CURRENT AND POTENTIAL FUTURE TECHNOLOGY APPRAISALS FOR RARE DISEASES

To assess NICE processes for rare diseases: Highly Specialised Technologies (HST) committee appraisal, weightings of quality-adjusted life years (QALY), and differential discounting. We assessed current and proposed HST and Single Technology Assessment (STA) evaluated technologies for adherence to the HST qualification criteria, eligible patient population/prevalence, undiscounted survival benefit and application of the QALY weighting. We also assessed a targeted selection of pipeline therapies with the potential for substantial survival and quality of life gain. Using published literature, we identified which therapies might qualify for the HST evaluation and, of those, which qualify for the QALY weighting and/or differential discounting. We simulated the impact of these processes on a hypothetical drug with a large survival benefit in a rare disease. To date, eight therapies have been recommended out of 20 referred to the NICE HST committee. Of those recommended, only one qualified for QALY weighting. For the others, the expected QALY benefit did not exceed the 10 QALY threshold. Of 11 selected pipeline therapies, only three (27%) would be expected to meet HST criteria and zero would meet thresholds for QALY weighting. In a hypothetical scenario where a drug for a rare condition improved survival by 20 years with an average utility score of 0.6, failure to qualify for QALY weighting/HST process would reduce the cost-effective price by more than £1M. NICE HST approaches are intended to make allowance for rare, debilitating conditions where treatments may not meet traditional cost-effectiveness thresholds. In practice, however, these allowances are ambiguous and evaluated technologies rarely qualify. Future innovative therapies may deliver substantial benefits, however, access may be limited if traditional thresholds are applied. Over time, this may signal to industry that without extreme survival benefit, treatments for rare disease are unattractive investments.

Quality-adjusted life years assessment using cabozantinib for patients with advanced hepatocellular carcinoma (aHCC) in the CELESTIAL trial.

207 Background: In patients previously treated for aHCC, cabozantinib (cabo) led to longer overall survival and progression-free survival vs placebo (pbo) in the randomized, phase 3 CELESTIAL trial (NCT01908426; N = 707). CELESTIAL was stopped early for benefit at the second interim analysis. This post hoc analysis estimated the incremental quality-adjusted life years (QALYs) accrued in CELESTIAL. Methods: Health utility was elicited at each study visit using the EQ-5D-5L quality of life questionnaire. (completed by 82–100% of patients overall). UK crosswalk tariffs were applied for health states. Cumulative QALYs by patient were calculated by linear interpolation; for patients who were censored (31% of patients; including 9% within 100 days of randomization), the last observed utility value was carried forward to study end. The difference in restricted mean QALYs was calculated using generalized linear models, accounting for baseline utility, and with 0.06–0.08 QALYs considered the minimal important difference. Results: At day 50 after randomization (acute treatment phase), cabo was associated with a small reduction in mean total QALYs vs pbo (difference −0.003; 95% CI −0.005 to −0.002; p ≤ 0.001; n = 601 [cabo, n = 389; pbo, n = 212]). At day 100, there was a numerical benefit in mean total QALYs for cabo (difference +0.007; 95% CI −0.001 to 0.015; p = 0.103; n = 627 [cabo, n = 410; pbo, n = 217]), and at day 150 the difference was +0.032 QALYs (95% CI 0.017 to 0.047; p ≤ 0.001; n = 629 [cabo, n = 412; pbo, n = 217]) in favor of cabo. Over the entire follow-up, patients randomized to cabo accrued a mean of +0.092 (95% CI 0.016 to 0.169; p = 0.018; n = 700 [cabo, n = 465; pbo, n = 235]) additional QALYs compared with those receiving pbo. Using alternative Devlin weights for health states, the mean accrued QALYs with cabo was +0.115 vs pbo (95% CI 0.032 to 0.198; p = 0.007). Conclusions: Cabo was associated with an initial, small reduction in health utility. However, with continued treatment, health utility increased and at the end of the study there was a clinically and statistically significant benefit in mean QALYs in favor of cabo. Clinical trial information: NCT01908426.

PIN68 - COST-EFFECTIVENESS ANALYSIS OF ISAVUCONAZOLE FOR THE TREATMENT OF INVASIVE ASPERGILLOSIS IN THE CZECH REPUBLIC

To assess cost-effectiveness (CE) of isavuconazole for the treatment of possible invasive aspergillosis (IA) in Czech adult patients when, at the point of treatment initiation, a differential diagnosis between IA and mucormycosis has not been achieved. Isavuconazole was compared to the standard of care (SoC, i.e. voriconazole) which is ineffective against mucormycosis, and thus leads to increased mortality. A decision tree model (DT) was created to assess CE. The DT modelled presence of either IA or mucormycosis. However, given the difficulties in achieving a prompt differential diagnosis, antifungal treatment must be initiated before pathogen information becomes available. The model projects quality-adjusted life-years (QALYs) and costs from healthcare payers’ perspective. Costs were based on list prices and reimbursement tariffs as of February 2018. Treatment efficacy, short-term mortality and adverse events data were derived from clinical trials. Results were extrapolated to a lifetime horizon using average life expectancy and quality of life relevant to the underlying health condition of patients treated for invasive mould disease (i.e. acute myeloid leukaemia). Costs and outcomes were discounted by 3%. One-way sensitivity analysis (OWSA) accompanied by scenario analysis (SA) were performed. Probabilistic sensitivity analysis (PSA; 1000 iterations) was performed using an implicit willingness-to-pay (WTP) threshold of €47,000/QALY. Over a lifetime horizon, isavuconazole yields additional 0.30 QALYs (7.80 vs. 7.50) at the additional total cost of €3059 (€18,664 vs. €15,605) compared with SoC, with the incremental cost-effectiveness ratio of €10,251 per QALY. PSA showed that probability of isavuconazole to be cost-effective is 75% at the WTP threshold. OWSA and SA confirmed the robustness of the base-case result while the most influential parameters were mortality and prevalence of mucormycosis. The model suggests that compared to voriconazole, isavuconazole may provide a benefit in quality-adjusted life-years and may be cost-effective using the Czech implicit willingness-to-pay threshold.

Cost-Effectiveness of Patent Foramen Ovale Closure Versus Medical Therapy for Secondary Stroke Prevention

Percutaneous transcatheter closure of patent foramen ovale (PFO closure) plus antiplatelet therapy has been shown to reduce the risk of recurrent stroke compared with medical therapy alone in carefully selected patients after cryptogenic stroke presumed to be from paradoxical embolism. Our objective was to determine the cost-effectiveness of PFO closure after cryptogenic stroke compared with conservative medical management from a US healthcare payer perspective. A decision analytic Markov model estimated the 15-year cost and outcomes associated with the additional benefit of PFO closure compared with medical management alone. Model inputs were obtained from published literature, national databases, and a meta-analysis of 5 published randomized clinical trials on PFO closure. Health outcomes were measured in quality-adjusted life years (QALY). Cost-effectiveness used the incremental cost per QALY gained, whereas the net monetary benefit assumed a willingness to pay of $150 000/QALY. One-way and probabilistic sensitivity analyses estimated the uncertainty of model results. At 15 years, PFO closure compared with medical therapy alone improved QALY by 0.33 at a cost saving of $3568, representing an incremental net monetary benefit of $52 761 (95% interval -$8284 to $158 910). When the meta-analysis hazard ratio for stroke was increased to the 95% interval's upper bound of 0.77, one-way sensitivity analyses suggested that PFO closure's cost-effectiveness was $458 558 per additional QALY. Probabilistic sensitivity analysis suggested cost-effectiveness in 90% of simulation runs. PFO closure for cryptogenic strokes in the right setting is cost-effective, producing benefit in QALYs gained and potential cost savings. However, patient selection remains vitally important as marginal declines in treatment effectiveness can dramatically affect cost-effectiveness.

Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases

BackgroundThe aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. MethodsPatients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. ResultsNo statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700–31,200 GBP. ConclusionThe HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.