Quality-adjusted Life Expectancy Research Articles

Estimating Taiwan's QALY league table for catastrophic illnesses: Providing real-world evidence to integrate prevention with treatment for resources allocation

Background/purposeCurative technologies improve patient's survival and/or quality of life but increase financial burdens. Effective prevention benefits all three. We summarize estimation methods and provide examples of how much money is spent per quality-adjusted life year (QALY) or life year (LY) on treating a catastrophic illness under a lifetime horizon and how many QALYs/LYs and lifetime medical costs (LMC) could be potentially saved by prevention. MethodsWe established cohorts by interlinkages of Taiwan's nation-wide databases including National Health Insurance. We developed methods to estimate lifetime survival functions, which were multiplied with the medical costs and/or quality of life and summed up to estimate LMC, quality-adjusted life expectancy (QALE) and lifetime average cost per QALY/LY for catastrophic illnesses. By comparing with the age-, sex-, and calendar year-matched referents simulated from vital statistics, we obtained the loss-of-QALE and loss-of-life expectancy (LE). ResultsThe lifetime cost-effectiveness ratios of ventilator-dependent comatose patients, dialysis, spinal cord injury, major trauma, and cancers were US$ 96,800, 16,200–20,000, 5500–5,900, 3400–3,600, and 2900–11,900 per QALY or LY, respectively. The successful prevention of lung, liver, oral, esophagus, stomach, nasopharynx, or ovary cancer would potentially save US$ 28,000–97,000 and > 10 QALYs; whereas those for end-stage kidney disease, stroke, spinal injury, or major trauma would be US$ 55,000–300,000 and 10–14 QALYs. Loss-of-QALE and loss-of-LE were less confounded indicators for comparing the lifetime health benefits of different technologies estimated from real-world data. ConclusionsIntegration of prevention with treatment for resources allocation seems feasible and would improve equity and efficiency.

Modelling long-term outcomes and mortality risk in patients with post-stroke spasticity during abobotulinum toxin injections as part of rehabilitation

To date, there are no Russian or international studies investigating the long-term efficacy of botulinum therapy (abobotulinum toxin injections – AboBTX) during rehabilitation in patients with post-stroke spasticity in terms of its impact on the risk of death from all causes and the development of cardiovascular complications. A 10-year study conducted in the United Kingdom analyzed the effects of AboBTX injections in patients with post-stroke spasticity on long-term clinical (all-cause mortality, cardiovascular events, length and quality of life) and economic (direct medical costs) outcomes. For the first time ever, a model was developed to evaluate the clinical (quality-adjusted life expectancy) and economic benefits of AboBTX injections in the structure of rehabilitation compared to rehabilitation without botulinum therapy in patients with post-stroke spasticity. It was shown that the inclusion of regular injections of AboBTX in the rehabilitation process resulted in an 8.8% reduction in the risk of death from all causes, a 13% increase in life expectancy (and by 59% in quality-adjusted terms compared to rehabilitation without botulinum therapy) and proved to be cost-effective. The use of AboBTX injections in patients with post-stroke spasticity as part of rehabilitation is cost-effective in the long term and improves long-term outcomes, including post-stroke survival.

Antivirals to prepare for surges in influenza cases: an economic evaluation of baloxavir marboxil for the Netherlands.

We perform a cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of baloxavir marboxil compared to current care in the Netherlands for patients at risk of influenza-related complications, including patients with comorbidities and the elderly. In the CEA, a decision tree model was developed to assess the cost-effectiveness of baloxavir marboxil for a cohort of 52-year-olds from a societal perspective. A lifetime horizon was taken by incorporating the quality-adjusted life expectancy. The BIA included different epidemiological scenarios, estimating different plausible epidemiological scenarios for seasonal influenza considering the whole Dutch population with an increased risk of influenza complications. The base-case ICER was estimated to be €8,300 per QALY. At the willingness-to-pay threshold of €20,000 per QALY, the probability of being cost effective was 58%. The base-case expected budget impact was €5.7 million on average per year, ranging from €1.5 million to €10.5 million based on the severity of the influenza epidemic and vaccine effectiveness. In the Netherlands, baloxavir is a cost-effective treatment option for seasonal influenza, with a base-case ICER of €8,300 per QALY for the population aged 60years and over and patients at high risk of influenza-related complications. For a large part, this ICER is driven by the reduction of the illness duration of influenza and productivity gains in the working population.

Estimating quality-adjusted life expectancy (QALE) for local authorities in Great Britain and its association with indicators of the inclusive economy: a cross-sectional study

ObjectivesQuantifying area-level inequalities in population health can help to inform policy responses. We describe an approach for estimating quality-adjusted life expectancy (QALE), a comprehensive health expectancy measure, for local authorities...

Tirzepatide 10 and 15 mg vs semaglutide 2.0 mg: A long-term cost-effectiveness analysis in patients with type 2 diabetes in the United States.

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes (T2D) treatment. To compare the long-term cost-effectiveness of tirzepatide 10 mg and 15 mg vs semaglutide 2.0 mg, an injectable glucagon-like peptide-1 receptor agonist, in patients with T2D from a US health care payer perspective. The PRIME T2D Model was used to project clinical and cost outcomes over a 50-year time horizon. Baseline cohort characteristics and treatment effects were sourced from a published adjusted indirect treatment comparison that used data from the SURPASS-2 and SUSTAIN FORTE trials. Patients were assumed to intensify to insulin therapy at a hemoglobin A1c of greater than 7.5%. Costs and health state utilities were derived from published sources. Future costs and clinical benefits were discounted at 3% annually. Tirzepatide 10 mg and 15 mg were associated with improved quality-adjusted life-expectancy (10 mg: 0.085 quality-adjusted life-years [QALYs], 15 mg: 0.121 QALYs), higher direct costs (10 mg: USD 5,990, 15 mg: USD 6,617), and incremental cost-effectiveness ratios of USD 70,147 and 54,699 per QALY gained, respectively, vs semaglutide 2.0 mg. Both doses of tirzepatide remained cost-effective vs semaglutide 2.0 mg over a range of sensitivity analyses. Long-term projections using the PRIME T2D model and based on treatment effects from an adjusted indirect treatment comparison indicate that tirzepatide 10 mg and 15 mg are likely to be cost-effective vs semaglutide 2.0 mg for the treatment of T2D in the United States.

Cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anemia in England

Aims Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous iron is the preferred ID anemia (IDA) treatment where oral iron is contraindicated, ineffective or not tolerated, or where ID correction is urgent. The objective was to evaluate the cost-utility of ferric derisomaltose (FDI) versus ferric carboxymaltose (FCM) in patients with IBD and IDA in England, in whom IV iron treatment is preferred. Materials and methods A patient-level simulation model was developed, capturing quality of life (QoL) differences based on SF-36v2 data from the PHOSPHARE-IBD randomized controlled trial, monitoring and incidence of post-infusion hypophosphatemia, and number of iron infusions required. Analyses were conducted over a five-year time horizon from the Department of Health and Social Care (DHSC) perspective, with healthcare provider and societal perspectives adopted in separate analyses. Future costs and effects were discounted at 3.5% per annum and one-way and probabilistic sensitivity analyses were performed. Results FDI increased quality-adjusted life expectancy by 0.075 QALYs versus FCM from 2.57 QALYs to 2.65 QALYs per patient. Patients receiving FDI required 1.63 fewer iron infusions over the five-year time horizon, driving infusion-related cost savings of GBP 496 per patient (GBP 2,188 versus GBP 1,692) from the DHSC perspective. Costs of monitoring and treating hypophosphatemia after FCM were GBP 226, yielding total savings of GBP 722 per patient (GBP 2,414 versus GBP 1,692) over the five-year time horizon. FDI also led to reduced costs versus FCM in the societal and provider analyses and was therefore the dominant intervention across all three perspectives. Limitations The analysis did not capture patient adherence, hypophosphatemic osteomalacia, or fractures. Conclusions Results showed that FDI improved patient QoL and reduced direct healthcare expenditure versus FCM in patients with IBD and IDA in England.

EQ-5D-5L Population Norms and Quality-Adjusted Life Expectancy by Sociodemographic Characteristics and Modifiable Risk Factors for Adults in Queensland, Australia

ObjectivesOver half of Australia’s disease burden is due to morbidity, predominantly chronic conditions. Health-related quality of life instruments provide measures of morbidity and health status across different dimensions with EQ-5D being one of the most widely used. This study reports EQ-5D-5L general population norms for Queensland, Australia using the recently published Australian value set. MethodsPopulation survey results from cross-sectional computer-assisted telephone interviews for Queensland adults in 2022 and 2023 were analyzed. EQ-5D-5L, as well as modifiable risk factors and sociodemographic data were collected. Using the recently published final Australian EQ-5D-5L value set, mean utility scores were calculated for Queensland, as well as by sociodemographic characteristics, including remoteness and socioeconomic area-based measures, and modifiable risk factors, such as smoking and body mass index. Results were combined with life tables to estimate quality-adjusted life expectancy (QALE) for subgroups with different lifestyles. ResultsThe EQ-5D utility score for the Queensland adult population was 0.916. Smoking daily, being obese or older in age, or living in the most disadvantaged socioeconomic area were associated with lower mean scores. QALE was 6.1 and 7.9 years shorter than the life expectancy for Queensland males and females, respectively, but generally, those who reported having healthier lifestyles had higher mean utility scores and thus longer QALE. ConclusionsIn addition to reporting Queensland EQ-5D-5L general population norms, these results demonstrate potential QALE gains in people following healthier lifestyles. The results support investment in prevention and may motivate further studies in this important area.

Abstract 12: Association Between Socioeconomic Deprivation, Stroke Incidence and Long-Term Outcome: 10-year Follow-Up From a Population-Based Cohort Study of All Strokes in Oxfordshire, UK

Background: Socioeconomic deprivation is associated with an increased risk of stroke. However, there is scant evidence on its impact on long-term stroke outcomes. We investigate its long-term impact on stroke incidence, mortality, functional outcome, quality-of-life and life-expectancy. Methods: In a prospective population-based cohort, deprivation (based on residential postcode and stratified into quartiles using the national cut-points for England) was related to incident stroke, 10-year mortality, disability (modified Rankin Scale>2), institutionalisation in long-term care facilities, quality of life (Euroqol-5Dimensions), and life expectancy (including disability-free and quality-adjusted) after first-ever stroke. Cox, logistic and ordinary least squares regression were used to adjust for age, sex, urban-rural mix, previous comorbidity/disability, risk factors, stroke severity and type. Findings: Out of a population of 94,567 people (~1.5 million people years), 2,429 had a first-ever stroke. Higher deprivation was associated with stroke risk in those aged 55 to 74. Compared to the most affluent (quartile 1), stroke risk was higher in those living in quartile 2 (incidence rate ratio: 1.28, p=0.0019), quartile 3 (1.37, p=0.005) and quartile 4 (1.81, p=0.001). Mean follow-up after stroke was 5.2 (S.D. 4.0) years. After multivariable adjustment, increasing deprivation was associated with mortality (p=0.046), disability (p=0.013) and reduced quality of life (p=0.028), but not with institutionalisation (p=0.23). 10-year quality-adjusted life-expectancy was 4.85 (95%CI: 4.67 to 4.04 years) in stroke patients in quartile 1, with life expectancy reducing by 0.46 (-0.75 to -0.16) in quartile 2, 1.10 (-1.58 to -0.67) in quartile 3 and 1.25 (-2.06 to -0.48) years in quartile 4. Interpretation: We show that incidence of stroke, as well as 10-year health outcomes, are worsened with increasing deprivation. Consequently there remains considerable scope for improvements in at risk deprived communities.

Cost-utility of real-time continuous glucose monitoring versus self-monitoring of blood glucose in people with insulin-treated Type II diabetes in France.

Aim: Clinical trials and real-world data for Type II diabetes both show that glycated hemoglobin (HbA1c) levels and hypoglycemia occurrence can be reduced by real-time continuous glucose monitoring (rt-CGM) versus self-monitoring of blood glucose (SMBG). The present cost-utility study investigated the long-term health economic outcomes associated with using rt-CGM versus SMBG in people with insulin-treated Type II diabetes in France. Materials & methods: Effectiveness data were obtained from a real-world study, which showed rt-CGM reduced HbA1c by 0.56% (6.1mmol/mol) versus sustained SMBG. Analyses were conducted using the IQVIA Core Diabetes Model. A French payer perspective was adopted over a lifetime horizon for a cohort aged 64.5years with baseline HbA1c of 8.3% (67mmol/mol). A willingness-to-pay threshold of €147,093 was used, and future costs and outcomes were discounted at 4% annually. Results: The analysis projected quality-adjusted life expectancy was 8.50 quality-adjusted life years (QALYs) for rt-CGM versus 8.03QALYs for SMBG (difference: 0.47QALYs), while total mean lifetime costs were €93,978 for rt-CGM versus €82,834 for SMBG (difference: €11,144). This yielded an incremental cost-utility ratio (ICUR) of €23,772 per QALY gained for rt-CGM versus SMBG. Results were particularly sensitive to changes in the treatment effect (i.e., change in HbA1c), annual price and quality of life benefit associated with rt-CGM, SMBG frequency, baseline patient ageand complication costs. Conclusion: The use of rt-CGM is likely to be cost-effective versus SMBG for people with insulin-treated Type II diabetes in France.

Dynamic changes and lifetime effect of functional disability profiles for stroke patients: real-world evidence from South Korea.

This work aimed to investigate the long-term dynamic changes of functional disabilities and estimate lifetime outcomes of different functional disabilities after a stroke, using real-world data from a nationally representative South Korean cohort. Patients aged 18 and above with ischemic and hemorrhagic strokes were identified from the Korea Health Panel (KHP) data (2008-2018). Functional disabilities were repeatedly measured for patients aged 55 and over for the prevalence of disabilities associated with activities of daily living (ADL), and kernel smoothing means were estimated for each item. The lifetime survival function of stroke patients in Korea was adopted from another study utilizing the National Health Insurance Service of Korea's national sample cohort. By multiplying the disability-free proportion with the survival function throughout life, disability-free life expectancy (DFLE) for each ADL item was estimated. The loss-of-DFLE was calculated by subtracting the DFLE from age-, sex-, and calendar year-matched referents simulated from Korean life tables. The KHP dataset included 466 stroke patients. The overall functional disability needs increased over time after stroke diagnosis. DFLE was lowest for bathing (10.1 years for ischemic stroke and 12.8 years for hemorrhagic stroke), followed by those for dressing and washing. Loss-of-DFLE was highest for bathing for ischemic and hemorrhagic strokes (7.2 and 10.7 years, respectively), indicating that this task required the most assistance for stroke patients compared with the other tasks. DFLEs were slightly lower than the quality-adjusted life expectancy of stroke patients. Our findings provide valuable insights for resource allocation and policy decisions in long-term stroke care, potentially enhancing the quality of life for stroke survivors and caregivers.

Decreasing alloimmunization-specific mortality in sickle cell disease in the United States: Cost-effectiveness of a shared transfusion resource.

Red blood cell alloimmunization and consequent delayed hemolytic transfusion reaction (DHTR) incidence and mortality in patients with sickle cell disease (SCD) are high. A shared transfusion resource has decreased both in other countries, while in the United States cost concerns persist. We conducted a Markov cohort simulation of a birth cohort of alloimmunized patients with SCD to estimate lifetime DHTR incidence, DHTR-specific mortality, quality-adjusted life expectancy (QALE), and costs with the implementation of a shared transfusion resource to identify antibody history versus without (i.e., status quo). We conducted our analysis using a lifetime analytic time horizon and from a United States health system perspective. Implementation of shared transfusion resource projects to decrease cumulative DHTR-specific mortality by 26% for alloimmunized patients with SCD in the United States, relative to the status quo. For an average patient population of 32 000, this intervention would generate a discounted increment of 4000 QALYs at an incremental discounted cost of $0.3 billion, resulting in an incremental cost-effectiveness ratio of $75 600/QALY [95% credible interval $70 200-81 400/QALY]. The results are most sensitive to the baseline lifetime medical expenditure of patients with SCD. Alloantibody data exchange is cost-effective in 100% of 10 000 Monte Carlo simulations. The resource would theoretically need a minimum patient population of 1819 patients or cost no more than $5.29 million annually to be cost-effective. By reducing DHTR-specific mortality, a shared transfusion resource in the United States projects to be a life-saving and cost-effective intervention for patients with SCD in the United States.

P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in Finland

Abstract Background Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland. Methods A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects. Results Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention. Conclusion Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.

Quantifying the Value of Reduced Health Disparities: Low-Dose Computed Tomography Lung Cancer Screening of High-Risk Individuals Within the United States

ObjectiveThis study aimed to measure the value of increasing lung cancer screening rates for high-risk individuals and its impact on health disparities. MethodsThe model estimated changes in health economic outcomes if low-dose computed tomography screening increased from current to 100% compliance, following clinical guidelines. Current low-dose computed tomography screening rates were estimated by income, education, and race, using 2017-2019 Behavioral Risk Factor Surveillance System data. The model contained a decision tree module to segment the population by screening outcomes and a Markov chain module to estimate cancer progression over time. Model parameters included information on survival, quality of life, and costs related to cancer diagnosis, treatment, and adverse events. Distributional cost-effectiveness analysis estimated the net monetary value from reduced health disparities—measured using quality-adjusted life expectancy—across income, education, and race groups. Outcomes were assessed over 30 years. ResultsLung cancer screening eligibility using US Preventive Services Task Force guidelines was higher for individuals with income <$15 000 (47.2%) and without a high-school education (46.1%) than individuals with income >$50 000 (16.6%) and with a college degree (13.5%), respectively. Increasing lung cancer screening to 100% compliance was cost-effective ($64 654 per quality-adjusted life-year) and produced economic value by up to $560 per person ($182.1 billion for United States overall). Up to 32.2% of the value was due to reductions in health disparities. ConclusionsSignificant value in increasing lung cancer screening rates derived from reducing health disparities. Policy makers and clinicians may not be appropriately prioritizing cancer screening if value from reducing health disparities is unconsidered.

Survival-weighted quality of life profiles in patients treated for laryngeal and hypopharyngeal cancers.

Objectives: This study assessed functional outcomes and quality of life (QoL) in the long term in individuals treated for laryngohypopharyngeal cancer (LHC) by estimating their life expectancy (LE), survival-weighted psychometric scores (SWPSs), and quality-adjusted LE (QALE). Materials and methods: To estimate survival outcomes, we retrospectively reviewed the data of 1576 patients treated for primary LHC between January 2010 and December 2018 and followed them until death or December 2020. We also prospectively collected QoL and functional data between October 2013 and November 2022 from 232 patients by administering the Taiwanese Chinese versions of the QoL Questionnaire Core 30, Head and Neck 35, and EQ-5D-3L. To estimate LE, we employed linear extrapolation of a logit-transformed curve. We calculated QALE and SWPSs by combining the QoL data with the LE results. Results: We estimated the LE of the patients with LHC to be 7.8 years and their loss of LE to be 15.7 years. The estimated QALE was 7.0 QALYs, with a loss of QALE of 16.5 QALYs. Lifetime impairment durations were estimated for cognitive (4.9 years), physical (4.2 years), emotional (3.4 years), social (3.4 years), and role functions (2.7 years). We estimated the durations of problems related to swallowing, speech, and teeth to be 6.2, 5.6, and 4.8 years, respectively. The patients were expected to be dependent on feeding tubes for 1.2 years. Conclusions: Patients with LHC experience significant reductions in both LE and QALE. SWPSs may constitute a valuable tool for obtaining subjective information regarding how LHC affects multifaceted QoL outcomes.

Early HIV diagnosis enhances quality-adjusted life expectancy of men who have sex with men living with HIV: A population-based cohort study in Taiwan

BackgroundWhether early HIV diagnosis is beneficial for HIV patients themselves remains uncertain, given the stigma and social discrimination associated with an HIV diagnosis. This study aimed to measure the impact of early HIV diagnosis on quality-adjusted life expectancy (QALE) in comparison with late HIV diagnosis, from real-world data in Taiwan under universal access to antiretroviral therapy (ART). MethodsThis population-based cohort study included 14,570 men who have sex with men (MSM) in the national HIV registry and a quasi-random sample (n = 127) of MSM patients to measure quality of life using the EQ-5D health utility instrument. We integrated quality of life data into the extrapolated cohort survival curve to estimate the QALE in patients with early versus late HIV diagnosis (≤30 days before AIDS diagnosis). Loss-of-QALE were estimated by comparing the cohort with age-, sex-, and calendar-year-matched referents simulated from vital statistics. Difference-in-differences was estimated to quantify the effect of early HIV diagnosis. ResultsEarly HIV diagnosis is associated with a loss-of-life expectancy of 3.11 years, with an average health utility of 0.95, in contrast to those diagnosed late (loss-of-life expectancy 8.47 years, with an average health utility of 0.86). After integration of survival and life quality, early HIV diagnosis results in a reduction of loss-of-QALE by 8.28 quality-adjusted life years among MSM living with HIV. ConclusionsUnder universal access to ART, early HIV diagnosis is highly beneficial for people living with HIV themselves, with a net gain of 8.28 healthy life years compared with those diagnosed late.

Second-Line Therapy Sequencing in Primary Warm Autoimmune Hemolytic Anemia: Splenectomy-Rituximab Versus Rituximab-Splenectomy

Introduction: Primary warm autoimmune hemolytic anemia (wAIHA) is a hematologic condition that affects approximately 1 in 8000 people and occurs when IgG antibodies directed against self-erythrocytes cause hemolysis and exceed the bone marrow's ability to compensate. First-line treatment with glucocorticoids yields sustained remission in less than 30% of individuals. For patients requiring second-line treatment, splenectomy was the preferred treatment for over 50 years, being recommended over rituximab by leading experts as recently as 2010. In the last decade this practice shifted due to concerns of tripartite risk of splenectomy with rates of infection, thrombosis, and perioperative mortality, juxtaposed against the increased experience with rituximab. These risks are outdated as they predate the modern-day vaccination, thromboprophylaxis, and laparoscopic splenectomy era, respectively. Summarily, the 2017 British guidelines dropped splenectomy from second- to third-line for patients with primary wAIHA, consistent with expert opinion in the United States in 2023. Over these same twenty years, the mortality and morbidity of splenectomy has greatly decreased, owing to updated preoperative vaccination standards, prevention of thrombosis, and widespread use of the laparoscopic (i.e., rather than open) technique. Despite these advancements, splenectomy is now used in fewer than 10% of patients with wAIHA. In the absence of a clinical trial randomizing patients to splenectomy versus rituximab, we conducted the first simulation of second-line therapeutic sequencing for adult patients with primary wAIHA with a focus on short-run and long-run effectiveness results. Methods: We constructed a Markov simulation of adult patients with primary wAIHA and requiring second-line therapy to compare the effectiveness of strategy #1: splenectomy followed by rituximab, if necessary, versus strategy #2: rituximab followed by splenectomy, if necessary. Transition probabilities for initial response and time-variant relapse risk with rituximab and with splenectomy were drawn from retrospective primary-wAIHA-specific literature. For rituximab, we assumed that 1) patients maintained in remission for three years following treatment with a rituximab cycle would remain in remission and 2) all patients who relapse more than a year after receiving rituximab, would be retreated with rituximab. Costs were sourced from the Centers for Medicare &amp; Medicaid Services and the Centers for Disease Control and Prevention. Utility values for patients with wAIHA were specific to the reported patient disease status, whether in relapse, partial remission (defined as hemoglobin &amp;gt;10g/dL) or complete remission (defined as hemoglobin &amp;gt;12g/dL). These were sourced from the Global Burden of Disease Study and weighted for the degree of anemia corresponding with each status. Effectiveness was calculated in quality-adjusted life-years (QALYs). The primary outcomes were lifetime discounted costs, QALYs, and net monetary benefits across accepted willingness-to-pay thresholds over short- and long-runs at 5 years and lifetime, respectively. Probabilistic sensitivity analysis was employed to vary all parameters across their uncertainty intervals simultaneously over 10,000 Monte Carlo iterations. Results: In the short-run, strategies #1 and #2 cost $39,700 and $47,100 and accrued 5.21 and 5.26 QALYs (Table 1). In the long run, costs were $909,000 and $912,000 while accruing 22.0 and 22.1 QALYs. Net monetary benefit point estimates were similar across the accepted range of WTP thresholds in both the short- and long-runs. Conclusion: The balance of costs and quality-adjusted life expectancy appears to be comparatively tightly balanced in the sequencing of second-line therapies in primary wAIHA with splenectomy-rituximab versus rituximab-splenectomy. The absence of a clear rituximab-early advantage on a population level may be driven by advancements in vaccination, thromboprophylaxis, and laparoscopic surgical techniques for splenectomy over the last 20 years. Value-of-information analysis would help identify parameters whose uncertainty reduction with future study in the real world would yield a treatment strategy with a definitive advantage. In the meantime, patients whose values and preferences align with splenectomy should not be dissuaded from pursuing it due to perceived risk.

Equitable Care for Severe Hemophilia_A: Distributional Cost-Effectiveness of Prophylactic Weekly Efanesoctocog Alfa Versus Standard-Care Factor VIII in Patients with Severe Hemophilia_A in the United States

Introduction: Prophylactic coagulation factor replacement is crucial to decrease bleeding episodes and improve quality-adjusted life expectancy (QALE) for patients with severe hemophilia A. Even with prophylactic treatment (i.e., at three to four times weekly) patients remain at risk of bleeding events and still develop chronic arthropathy across their lifetimes. The additional economic burden associated with lifelong prophylactic treatment is a major equity concern for patients with hemophilia A and their families. Efanesoctocog alfa is a recently developed extended half-life agent for hemophilia A prophylaxis and management, supporting the possibility of once-weekly prophylaxis. An open-label multicenter study (XTEND-1) showed that once-weekly dosing of efanesoctocog alfa improves the annualized bleeding rate (ABR) by 77% versus prophylaxis with standard-care factor VIII in patients with severe hemophilia A. We sought to evaluate, both for the first time, the conventional and distributional cost-effectiveness of prophylaxis with efanesoctocog alfa versus with standard-care factor VIII for patients with severe hemophilia A in the United States. Methods: For this independent analysis free of industry influence, we built a Markov model to examine the conventional cost-effectiveness of prophylaxis with efanesoctocog alfa versus standard-care factor VIII for patients with severe hemophilia A. Transition probabilities for ABRs and product utilization were informed by phase 3 study data and supplemented with FDA package insert information. Within ABRs, we accounted for treated bleeding severity and bleeding event types, inclusive of hemarthrosis, intracranial hemorrhage, in addition to assuming the prevalence of chronic arthropathy with SHL (i.e., due to silent bleed burden) is eliminated by efanesoctocog alfa. Costs for the base-case were sourced from the Centers for Medicare &amp; Medicaid Services with negotiated (i.e., lower) cost of efanesoctocog alfa supplied from the Veterans Affairs Federal Supply Schedule Service (VA-FSS). Age-, sex- and disease-specific background mortality were employed. Utilities for severe hemophilia A and disutilities for bleed events and hospitalizations were informed by extensive literature specific to severe hemophilia A. The primary outcome was the incremental cost-effectiveness ratio (ICER) in USD/QALY, at a willingness-to-pay threshold of $150,000/quality-adjusted life-year (QALY). The secondary outcome was a threshold analysis for the maximum efanesoctocog alfa price that renders efanesoctocog alfa prophylaxis cost-effective. To account for health inequities in the care of patients with hemophilia A we then conducted a distributional cost-effectiveness analysis (DCEA) to derive an equity weight threshold (i.e., inequality aversion parameter) for the decision of prophylaxis with efanesoctocog alfa versus with standard-care factor VIII. This threshold was then compared to prior estimates for commonly used equity weights in the United States (range 0.5-3.0). Results: In the base-case, prophylaxis with efanesoctocog alfa versus with standard-care factor VIII accrued 19.4 and 15.4 QALYs at mean costs of $17.3 and $9.7 million. The ICER for efanesoctocog alfa was $1,890,000/QALY (95% credible interval 1,190,000-3,330,000). Threshold analysis showed that prophylaxis with efanesoctocog alfa became cost-effective when the price of efanesoctocog alfa decreased by at least 59%. In deterministic sensitivity analysis, the model was most sensitive to the costs of efanesoctocog alfa and factor VIII. In probabilistic sensitivity analysis, standard-care factor VIII was favored over efanesoctocog alfa in 100% of 10,000 Monte Carlo simulations. The equity weight threshold for the treatment decision of prophylaxis with efanesoctocotog alfa versus with standard-care factor VIII was 7.4, higher than commonly used equity weights in the US. This implies a threshold that is higher than what has previously been used in the United States, per DCEA standards. Conclusion: As compared to standard-care factor VIII and at VA-FSS pricing, efanesoctocog alfa prophylaxis is conventionally cost-ineffective for patients with severe hemophilia A. Prophylaxis with efanesoctocog alfa does not meet commonly used distributive equity standards in the United States at this time.

Longitudinal Systemic Bevacizumab Therapy Produces Cost Savings and Improves Quality-Adjusted Life Expectancy in the Care of Patients with Hereditary Hemorrhagic Telangiectasia with Moderate-to-Severe Bleeding

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is the second-most-common hereditary bleeding disorder worldwide, afflicting 1 in 5000 or 1.4 million persons. Unlike peer disorders hemophilia and von Willebrand disease, there are no FDA or EMA-approved therapies. The current standard-of-care (SOC) consists of red blood cell (RBC) transfusion, IV iron supplementation, and local hemostatic procedures (i.e., nasal, gastrointestinal). However, bleeding pathophysiology is amenable to vascular endothelial growth factor inhibition, and IV bevacizumab has shown great promise as a disease-modifying therapeutic. The multisite, international InHIBIT-Bleed study employed a pre- versus post-bevacizumab design and was the largest clinical study of HHT (n=238). InHIBIT-Bleed demonstrated that longitudinal systemic bevacizumab significantly improved clinical symptoms, raised hemoglobin levels, and nearly abrogated IV iron infusion and RBC transfusion need for patients with HHT. Although bevacizumab is an expensive biologic agent with a financial barrier to access, we hypothesized that reduction in health resource utilization and improvement in transfusion dependence will improve quality-of-life for patients with HHT at costs commensurate with added clinical value. Accordingly, we conducted the first cost-effectiveness analysis of bevacizumab therapy in HHT. Methods: For this independent analysis free of industry influence, we built a Markov simulation of adult patients with HHT to examine the cost-effectiveness of bevacizumab added to SOC versus SOC alone, over a lifetime time-horizon and across accepted willingness-to-pay (WTP) thresholds. Costs were assessed in 2023 US dollars. We employed study data for pre- and post-bevacizumab that included descriptive statistics for 1) hemostatic procedures, 2) hospitalizations, 3) emergency department visits, 4) RBC transfusions, and 5) iron infusions. Treatment-specific patient time and lost wages were also accounted for across IV infusions, emergency department visits, hospitalizations, and hemostatic procedures. Probabilities of RBC- and iron-related adverse events were sourced from hemovigilance reports, the 2015 National Blood Collection and Utilization Survey and 2008-2017 World Health Organization's VigiBase. Ferric carboxymaltose was used as the base-case iron supplement, and a scenario analysis examined ferumoxytol. Effectiveness was calculated in QALYs, and employed age-adjusted utilities derived using HHT-specific EQ-5D index values, with the 2019 Global Burden of Disease Study used to account for the degree of anemia improvement reported with bevacizumab. The primary outcome was the incremental cost-effectiveness ratio (ICER), or incremental net monetary benefit (iNMB) if intervention was found to be cost-saving. The secondary outcome was the aggregated patient time spent receiving HHT-specific care. We concluded by conducting deterministic and probabilistic sensitivity analyses, capturing uncertainty in all parameters simultaneously over 10,000 Monte Carlo iterations. Results: In the base-case, bevacizumab versus SOC cost $959,000 and $1,533,000 while accruing 24.1 and 21.8 QALYs, respectively. The iNMB with bevacizumab was $916,000 [95% credible interval $454,000-$1,994,000] and $1,004,000 [95% CI $473,000-$2,237,000] from the US health system and societal perspectives, respectively, at a WTP of $150,000/QALY. Bevacizumab also saves patients 125 hours per year lived. Deterministic sensitivity analysis revealed that no parameter variance changes the model result. In probabilistic sensitivity analysis bevacizumab was favored in 100.0% of 10,000 Monte Carlo iterations: saving cost with increased QALYs in 99.6% and cost-effective in the remaining 0.4% of iterations (Figure 1). Similar cost-savings were found in the scenario analysis with ferumoxytol. Conclusion: By reducing the need for hemostatic procedures, hospitalizations, emergency visits, RBC transfusions, and iron infusions, bevacizumab is, unusually, a cost-saving intervention that also improves the quality-adjusted life expectancy of patients with HHT. Bevacizumab also saves patient time spent on receiving HHT-specific care. Collecting long-term follow-up data to evaluate continued response to bevacizumab will help assess its value versus future advances in the care of patients with HHT.

Allotransplantation and Gene Therapy Equity for Children with Sickle Cell Disease: Distributional Cost-Effectiveness of Allotransplantation Vs Gene Therapy Vs Standard-of-Care in Pediatric Patients with Sickle Cell Disease in the United States

Introduction: Patients with sickle cell disease (SCD) have reduced quality-adjusted life expectancy due to substantial mortality risks and decreased quality-of-life for every year lived with the disease. Allotransplantation was the first treatment with curative potential, but it carries concomitant risks of transplant-related mortality and graft-versus-host disease (GVHD). Once approved, gene therapy would be the second treatment with the possibility of lifelong cure but unlike allotransplantation, it may do so without the concomitant risks. Prior research has shown that even if gene therapy is conventionally cost-ineffective versus the standard-of-care (SOC), it can be a justifiable treatment option for a historically marginalized patient population in the United States, as demonstrated by equity-weighted cost-effectiveness. For allotransplantation and gene therapy, neither conventional nor distributional (i.e., equity-weighted) cost-effectiveness is known. Accordingly, we conducted the first conventional and distributional cost-effectiveness analyses of allotransplantation therapy for pediatric patients with SCD in the United States. Methods: We built a Markov model of pediatric patients with sickle cell disease to examine the cost-effectiveness of allotransplantation vs gene therapy vs SOC and determine equity weight thresholds. Sex-, age-, and disease-severity-specific annual costs and transition probabilities across disease severities for SOC were informed by 11 years of data from US commercially insured patients with SCD (2007-2017; Optum). Disease severity was defined based on annual number of hospitalizations for vaso-occlusive crises, as defined in clinical trials. SOC included hydroxyurea, opioid therapy, antibiotics, vaccinations, and blood transfusions. Allotransplantation- and GVHD-specific transition probabilities and costs were informed by prior literature and health resource utilization data, originally reported from the Center for International Blood and Marrow Transplant Research and the Pediatric Health Information System. Quality-adjusted life-years (QALYs) were informed by published lifetime simulations of patients living with SCD and matched controls, derived initially from a polynomial fit linking Euroqual-5 Dimensions to the visual analog scale for pain in patients with SCD in several studies. Age-, sex- and disease-specific background mortality probabilities were employed. Conventional cost-effectiveness was quantified using an incremental cost-effectiveness ratio (ICER), at a willingness-to-pay threshold of $100,000/QALY. Given expert clinical experience with optimizing allotransplantation outcomes in SCD, we employed a maximum patient starting age of 12 and assumed that gene therapy cost $2.45 million and was 100% effective. To account for health inequities in SCD, we then conducted a distributional cost-effectiveness analysis (DCEA), which applies an inequality aversion parameter (i.e., how much weight one puts on reducing disparities), to the distribution of outcomes across relevant sub-groups for allotransplantation to be favored over SOC and justify funding per DCEA standards. These were compared to prior estimates for commonly used equity weights in the United States (range 0.5-3.0). Results: In the base-case, allotransplantation, gene therapy, and SOC accrued 22.1, 25.5, 15.7 discounted lifetime QALYs at costs of $1.9, $2.8, $1.0 million, respectively, with all therapies on the cost-effectiveness frontier (Table 1). The ICERs and equity weight thresholds were $138,000/QALY and 0.5, and $253,000/QALY and 4.5, for allotransplantation (vs SOC) and gene therapy (vs allotransplantation), respectively. Conclusion: Similar to findings for gene therapy versus SOC in the first published DCEA in sickle cell disease, allotransplantation also appears to be an equitable therapeutic option for pediatric patients with sickle cell disease, regardless of conventional cost-ineffectiveness and as compared to SOC. The consideration of patient-population-specific equity offers an important opportunity to derive transparent benchmarks for intertwined equity- and value-informed decision making. Quantitative consideration of equity in the context of conventional cost-ineffectiveness can be an important tipping point in justification of funding.

Cost-Effectiveness of Rapid Hemosil Versus in-House and Send-out ADAMTS13 Activity Testing in the Care of Patients with Immune Thrombotic Thrombocytopenic Purpura

INTRODUCTION Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy requiring immediate treatment when the pretest probability is intermediate or high, a probability determined with the use of the PLASMIC and/or French clinical scores. Ruling out iTTP with a biomarker ADAMTS13 activity level can take several days at most hospital systems in the United States, all the while empiric treatment for iTTP accrues risks and costs. The newly developed rapid turnaround and fully automated, chemiluminescent immunoassay (HemosIL) reveals high concordance with chromogenic ELISA and FRET-based assays, the diagnostic standard-of-care. Unlike rapid in-house testing requiring technical expertise, the HemosIL assay can abrogate the cost and risk exposure associated with treating patients for iTTP whose biomarker activity level later rules out this diagnosis. Despite existing concerns of testing cost, we hypothesized that rapid and fully automated diagnostic testing would be cost-saving with similar quality-adjusted life-expectancy, as compared to both in-house FRET-based evaluation and send-out FRET-based evaluation. We further posited that this effect would be greater in the context of 1) intermediate- versus high-probability PLASMIC scores, and 2) patients treated with caplacizumab versus without. We sought to fill these gaps by conducting the first cost-effectiveness evaluation of the HemosIL assay in patients treated with and without caplacizumab. METHODS For this independent analysis free of industry influence, we built a Markov simulation of patients with intermediate- (PLASMIC score =5) or high- (PLASMIC score 6-7) pretest probability for iTTP empirically treated while awaiting results under three testing strategies: 1) HemosIL rapid turnaround (&amp;lt;1 hour), 2) 24-hour in-house, FRET-based evaluation, and 3) 72-hour send-out, FRET-based evaluation. For transition probabilities, our model was informed by extensive literature published on test characteristics, as well as derivation and validation cohorts for the PLASMIC score. Adverse events for therapeutic plasma exchange (TPE) and caplacizumab were informed from clinical trial data and real-world data, with costs in 2023 US dollars sourced from the Centers for Medicare and Medicaid Services. Utilities were informed by literature on critically ill adults hospitalized in the medical intensive care unit and were originally derived with validated EuroQol methodology. Age- and sex-adjusted background mortality were employed. The primary outcome was the incremental cost-effectiveness ratio (ICER) or, the incremental net monetary benefit (iNMB) if the intervention (HemosIL) was found to be cost-saving, reported over a 3-day time-horizon and across accepted willingness-to-pay thresholds in USD per quality-adjusted life-year (QALY). Four scenario analyses were examined: 1) PLASMIC 5 with caplacizumab, 2) PLASMIC 5 without caplacizumab, 3) PLASMIC 6-7 with caplacizumab, 4) 6-7 PLASMIC without caplacizumab. We concluded by executing deterministic and probabilistic sensitivity analyses, varying all parameter estimates +/-50% and capturing uncertainty in all parameters simultaneously over 10,000 Monte Carlo simulations. RESULTS Across all scenario analyses, testing with HemosIL was cost saving and accrued the same amount of QALYs (Table 1). These savings with HemosIL ranged from $2,900 (PLASMIC 6-7, without caplacizumab) through $44,700 (PLASMIC 5, with caplacizumab) per-patient-tested versus send-out, and from $800 to $19,800 versus in-house testing. No parameter variation changed the outcome of any scenario to favoring a non-HemosIL testing strategy in deterministic sensitivity analysis. In probabilistic sensitivity analyses across accepted willingness-to-pay thresholds in the United States, HemosIL was favored in 100% of iterations in the PLASMIC 5 context (with and without caplacizumab), and 99.9% and 98.6% in the PLASMIC 6-7 context with and without caplacizumab use, respectively (Table 2). CONCLUSION Despite cost concerns, HemosIL testing for patients with intermediate- or high-risk PLASMIC score produces significant cost savings for each patient tested and empirically treated. This is achieved by reducing the costs associated with unnecessary therapeutic plasma exchange and caplacizumab therapy.