Lifetime Time Horizon Research Articles

Universal Health Coverage of Opioid Agonist Treatment in Norway: An Equity-Adjusted Economic Evaluation.

Detailed information on the efficiency of health services targeting opioid use disorder (OUD) and treatment with opioid agonist treatment (OAT) is sparse. Many countries, including Norway, are still falling short of universal health coverage (UHC) of OAT. This study aims to evaluate the incremental lifetime costs and effects of treating OUD with OAT as compared to no OAT in Norway and scaling up the treatment to a universal coverage level using equity-adjusted health economic evaluations. We conducted cost-utility and budget impact analyses and constructed a two-state Markov model to compare the lifetime costs and outcomes among patients with OUD with and without OAT. Model inputs were derived from routine health information systems and the literature, with costs reported in 2023 Norwegian Kroner (NOK). The analyses were conducted from a Norwegian extended health-service and societal perspectives, with a lifetime time horizon. Quality-adjusted life years (QALYs) was the metric of health benefits. Outcomes were reported as incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was equity-adjusted according to the future prognostic healthy life year loss method in Norway (severity of disease criterion), which is sensitive to the size of future undiscounted healthy life year loss due to the affected conditions. The WTP threshold is NOK 825,000 per QALY gained in Norwegian policy for conditions with undiscounted future QALY loss > 20. Uncertainty in the parameters and robustness of the results were assessed with one-way and probabilistic sensitivity analyses and scenario analyses. The mean results from probabilistic sensitivity analysis estimated that OAT was associated with 3.03 additional discounted QALYs gain and incremental lifetime discounted cost of NOK 1.45 million, leading to an ICER of NOK 479,099 per QALY gained when compared with not providing OAT, with the extended health-service perspective. From a societal perspective, OAT was cost-saving, i.e. OAT produced greater health benefits while resulting in lower overall societal costs compared to no OAT. The mean undiscounted future health loss was estimated to be 21.34 QALYs for the Norwegian patient group with OUD. A total 5-year budget increase of NOK 1.208 billion was estimated if OAT was going to be scaled up from the current coverage level of 70% to UHC. Compared with the current coverage, 100% coverage of OAT was associated with an additional lifetime cost of NOK 4.332 billion but also an additional 6760 QALYs gained. Our analysis suggests that OAT is cost-effective in Norway and has the potential to be cost-saving from a societal perspective. Therefore, Norwegian policy should consider scaling up treatment to extend the coverage of OAT.

US cost-utility model of lenacapavir plus optimized background regimen (OBR) vs fostemsavir plus OBR and ibalizumab plus OBR for people with HIV with multidrug resistance.

Heavily treatment-experienced (HTE) people with HIV (PWH) have limited treatment options owing to multidrug resistance (MDR). Lenacapavir (LEN) is indicated, in combination with other antiretrovirals, for the treatment of adults with MDR HIV-1 experiencing failure of their current antiretroviral regimen because of resistance, intolerance, or safety considerations. To evaluate the cost-utility of LEN in combination with an optimized background regimen (OBR) vs alternative recently approved treatments for HTE PWH, fostemsavir (FTR)+OBR and ibalizumab (IBA)+OBR, for the treatment of PWH with MDR, from a mixed US health care payer perspective. A Markov state-transition model with a lifetime time horizon was developed. Transition probabilities between viral load categories were based on individual participant data from the CAPELLA trial for LEN+OBR and on relative efficacy parameters obtained from indirect treatment comparisons for comparators. Health state utilities were sourced from the literature. Costs included drug acquisition costs, drug administration costs, disease management costs, adverse event costs, AIDS-related event costs, and treatment switching costs and were sourced from red book costs, Medicare and Medicaid fees, and the literature. Costs and outcomes were discounted at 3% annually. The model was used to estimate total and incremental costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A deterministic and a probabilistic sensitivity analysis, as well as scenario analyses, were performed to address elements of uncertainty in the model and to explore the robustness of the results. Over a lifetime time horizon, LEN+OBR was associated with the highest absolute QALYs (9.41) and the greatest number of LYs (12.09) compared with FTR+OBR (QALYs: 8.75; LYs: 11.26) and IBA+OBR (QALYs: 8.36; LYs: 10.78). LEN+OBR was also associated with the lowest total lifetime costs of the 3 interventions (LEN+OBR: $1,441,122 [US dollars]; FTR+OBR: $1,504,986; IBA+OBR: $1,524,396) and therefore was dominant over both comparators in the base case. LEN+OBR remained dominant vs FTR+OBR and IBA+OBR across the range of scenarios tested and LEN+OBR had a 99% probability of being cost-effective compared with FTR+OBR and IBA+OBR in the probabilistic sensitivity analysis at a willingness-to-pay threshold of $50,000/QALY. This economic evaluation demonstrated that LEN+OBR provides meaningful increases in QALYs and LYs, and is dominant over a lifetime time horizon, compared with FTR+OBR and IBA+OBR for the treatment of PWH with MDR in the United States.

Cost-Effectiveness of Baloxavir Marboxil Versus Oseltamivir or no Treatment for the Management of Influenza in the United States.

This study sought to evaluate the cost-effectiveness of baloxavir marboxil compared with oseltamivir or no antiviral treatment from a US payer perspective using data from a real-world US administrative claims study. Given baloxavir's ability to rapidly stop viral shedding, the potential health economic implications of a baloxavir-induced population-level reduction in viral transmission was also explored. A decision tree cost-effectiveness model was developed for seasonal influenza (2018-2020) using a lifetime time horizon with 3.0% discounting for costs and quality-adjusted life-years (QALYs). Patients aged≥12years could receive baloxavir, oseltamivir or no antiviral treatment. Patient characteristics, complications, and costs were derived from the Merative™ MarketScan® Research Databases including US commercial claims and Medicare and Medicaid Supplemental databases. A scenario analysis explored the impact of reduced viral transmission with baloxavir. In the base case analysis, baloxavir was cost-effective within a willingness-to-pay threshold of US$100,000/QALY compared with oseltamivir [incremental cost-effectiveness ratio (ICER), $6813/QALY gained] or no antiviral treatment (ICER, $669/QALY gained). The net monetary benefit (NMB) of baloxavir was $1180 and $6208 compared with oseltamivir and no treatment, respectively. The NMB of baloxavir increased linearly with reductions in viral transmission, where a 5% transmission reduction yielded an NMB of $2592 versus oseltamivir and $7621 versus no treatment. Baloxavir became dominant (more effective and less costly, with ICERs<0) starting with a 12.0% reduction in viral transmission versus oseltamivir and 6.0% versus no antiviral treatment. Baloxavir was cost-effective compared with oseltamivir or no antiviral treatment. The potential of baloxavir to reduce viral transmission offers a substantial economic benefit from a US payer perspective.

Cost-Effectiveness Analysis of Newborn Screening for Spinal Muscular Atrophy in Italy.

A decision-analytic model assessed the cost effectiveness of newborn screening from the National Health Service perspective in 400,000 newborns. Newborn screening enabling early identification and presymptomatic treatment of SMA was compared with no newborn screening, symptomatic diagnosis, and treatment. Transition probabilities between health states were estimated from clinical trial data. Higher-functioning health states were associated with increased survival, higher utility values, and lower costs. Long-term survival and utilities were extrapolated from scientific literature. Health care costs were collected from official Italian sources. A lifetime time horizon was applied, and costs and outcomes were discounted at an annual rate of 3%. Deterministic and probabilistic sensitivity analyses were conducted. Newborn screening followed by presymptomatic treatment yielded 324 incremental life-years, 390 incremental quality-adjusted life-years, and reduced costs by €1,513,375 over a lifetime time horizon compared with no newborn screening. Thus, newborn screening was less costly and more effective than no newborn screening. Newborn screening has a 100% probability of being cost effective, assuming a willingness-to-pay threshold of >€40,000. Newborn screening followed by presymptomatic SMA treatment is cost effective from the Italian National Health Service perspective.

Osteochondroplasty with or without labral repair is more cost-effective than arthroscopic lavage with or without labral repair for treatment of young adults with femoroacetabular impingement: A cost-utility analysis based on data from a randomized controlled trial

ObjectivesThe objective of this study was to conduct a cost–utility analysis of osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair for femoroacetabular impingement (FAI) from a Canadian public payer perspective. MethodsA Markov model was constructed to compare the lifetime quality-adjusted life years (QALYs) and costs of the two treatment strategies. The target population was surgical FAI patients aged 36 years. The primary data source was patient-level data from the Femoroacetabular Impingement Randomised Controlled Trial, which evaluated the efficacy of the surgical correction of FAI via arthroscopic osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair in Canada. Long-term data were extrapolated using a generalized gamma model. The primary outcome was the incremental cost-effectiveness ratio, calculated by dividing the difference in costs by the difference in QALYs between osteochondroplasty and lavage, with or without labral repair. Probabilistic sensitivity analyses and one-way sensitivity analyses were used to characterize uncertainty of model parameters and assumptions. ResultsOver a lifetime horizon, osteochondroplasty, with or without labral repair, had a greater expected benefit (0.63 QALYs gained per patient) and lower costs ($955.89 saved per patient), as compared with lavage with or without labral repair. Probabilistic sensitivity analyses demonstrated that the probability of osteochondroplasty, with or without labral repair, being cost-effective was 90.5% at a commonly used willingness-to-pay threshold of $50,000/QALY in Canada. Across all one-way sensitivity analyses, osteochondroplasty with or without labral repair remained a cost-effective option. ConclusionOver a lifetime time horizon, osteochondroplasty, with or without labral repair, is a cost-effective treatment strategy for young adults with FAI. Future research involving real-word data is needed to further validate these findings. Level of evidenceIII.

Long-Term Health Economic Evaluation of Intermittently Scanned Glucose Monitoring Compared with Self-Monitoring Blood Glucose in a Real-World Setting in Finnish Adult Individuals with Type 1 Diabetes.

Background and Aims: There has been an evolving trend in the use of intermittently scanned continuous glucose monitoring (isCGM) among individuals with type 1 diabetes. Although isCGM is proven to be beneficial in the treatment of individuals with type 1 diabetes, its use leads to increasing device costs. This study aimed to investigate the long-term cost-effectiveness of isCGM. Methods: Long-term clinical outcomes and costs were projected using the IQVIA Core Diabetes Model (v10.0) based on the observed real-world outcomes of isCGM. The clinical input data for the analysis were sourced from a real-world patient cohort from Eastern Finland, including 877 adult individuals with type 1 diabetes with isCGM (i.e., Freestyle Libre 1 and 2). At the baseline, the patients' mean age was 48 years, and the mean duration of diabetes was 25.8 years. The mean baseline HbA1c was 8.6%, and the mean 12-month change from baseline in HbA1c was -0.37% after the initiation of isCGM. The cost-effectiveness analysis was performed over a lifetime time horizon. A discount rate of 3% was used for the future costs and health outcomes. Results: The projected use of isCGM was associated with improved quality-adjusted life year (QALY) expectancy of 0.84 QALYs after the start of isCGM. The direct lifetime costs were 7861 EUR higher with the use of isCGM, which resulted in an incremental cost-effectiveness ratio of 9396 EUR per QALY gained. Conclusions: According to the present analysis, the use of isCGM is considered cost-effective in adult individuals with type 1 diabetes in a real-world setting in Finland.

Cost-Effectiveness of Plasma Microbial Cell-Free DNA Sequencing When Added to Usual Care Diagnostic Testing for Immunocompromised Host Pneumonia.

Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value. The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients. A semi-Markov model was utilized from the US third-party payer's perspective such that only direct costs were included, using a lifetime time horizon with discount rates of 3% for costs and benefits. Three comparators were considered: (1) All UC, which included non-invasive (NI) and invasive testing and early bronchoscopy; (2) All UC & mcfDNA; and (3) NI UC & mcfDNA & conditional UC Bronch (later bronchoscopy if the initial tests are negative). The model considered whether a probable causative infectious etiology was identified and if the patient received appropriate antimicrobial treatment through expert adjudication, and if the patient died in-hospital. The primary endpoints were total costs, life-years (LYs), equal value life-years (evLYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio per QALY. Extensive scenario and probabilistic sensitivity analyses (PSA) were conducted. At a price of $2000 (2023 USD) for the plasma mcfDNA, All UC & mcfDNA was more costly ($165,247 vs $153,642) but more effective (13.39 vs 12.47 LYs gained; 10.20 vs 9.42 evLYs gained; 10.11 vs 9.42 QALYs gained) compared to All UC alone, giving a cost/QALY of $16,761. NI UC & mcfDNA & conditional UC Bronch was also more costly ($162,655 vs $153,642) and more effective (13.19 vs 12.47 LYs gained; 9.96 vs 9.42 evLYs gained; 9.96 vs 9.42 QALYs gained) compared to All UC alone, with a cost/QALY of $16,729. The PSA showed that above a willingness-to-pay threshold of $50,000/QALY, All UC & mcfDNA was the preferred scenario on cost-effectiveness grounds (as it provides the most QALYs gained). Further scenario analyses found that All UC & mcfDNA always improved patient outcomes but was not cost saving, even when the price of mcfDNA was set to $0. Based on the evidence available at the time of this analysis, this CEA suggests that mcfDNA may be cost-effective when added to All UC, as well as in a scenario using conditional bronchoscopy when NI testing fails to identify a probable infectious etiology for ICHP. Adding mcfDNA testing to UC diagnostic testing should allow more patients to receive appropriate therapy earlier and improve patient outcomes.

Long-term cost-effectiveness analysis of rugby fans in training–New Zealand: a body weight reduction programme for males

ObjectivesWe sought to extrapolate the long-term costs and clinical impacts attributed to the rugby fans in training–New Zealand (RUFIT-NZ) trial in Aotearoa, New Zealand.DesignA modelled cost-effectiveness analysis using efficacy data...

The Cost-Effectiveness of Germline BReast CAncer Gene Testing in Metastatic Prostate Cancer Followed by Cascade Testing of First-Degree Relatives of Mutation Carriers

ObjectivesPatients with metastatic prostate cancer (mPCa) with BReast CAncer gene (BRCA) mutations benefit from targeted treatments (eg, olaparib). In addition, family members of affected patients have increased risk of hereditary cancers and benefit from early detection and prevention. International guidelines recommend genetic testing in mPCa; however, the value for money of testing patients with mPCa and cascade testing of blood-related family members has not been assessed. In this context, we evaluated the cost-effectiveness of germline BRCA testing in patients with mPCa followed by cascade testing of first-degree relatives (FDRs) of mutation carriers. MethodsWe conducted a cost-utility analysis of germline BRCA testing using 2 scenarios: (1) testing patients with mPCa only and (2) testing patients with mPCa and FDRs of those who test positive. A semi-Markov multi–health-state transition model was constructed using a lifetime time horizon. The analyses were performed from an Australian payer perspective. Decision uncertainty was characterized using probabilistic analyses. ResultsCompared with no testing, BRCA testing in mPCa was associated with an incremental cost of AU$3731 and a gain of 0.014 quality-adjusted life-years (QALYs), resulting in an incremental cost-effectiveness ratio of AU$265 942/QALY. Extending testing to FDRs of variant-positive patients resulted in an incremental cost-effectiveness ratio of AU$16 392/QALY. Probability of cost-effectiveness at a willingness-to-pay of AU$75 000/QALY was 0% in the standalone mPCa analysis and 100% in the cascade testing analysis. ConclusionBRCA testing when performed as a standalone strategy in patients with mPCa may not be cost-effective but demonstrates significant value for money after the inclusion of cascade testing of FDRs of mutation carriers.

Cost-effectiveness of eculizumab and efgartigimod for the treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost. To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively. A Markov model with 4 health states was developed, evaluating costs and utility with a 4-week cycle length and lifetime time horizon from a health care system perspective and a modified societal perspective including productivity losses from patients and caregiver burden. Model inputs were informed by key clinical trials and relevant publications identified from targeted literature reviews, and drug costs were identified from Micromedex Red Book. Costs and outcomes were discounted at 3% per year. Incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life-year [QALY] gained) were calculated for each comparison. Among the corresponding populations, lifetime costs and QALYs, respectively, for eculizumab were $5,515,000 and 11.85, and for conventional therapy, $308,000 and 10.29, resulting in an ICER of $3,338,000/QALY gained. For efgartigimod, lifetime costs and QALYs, respectively, were $6,773,000 and 13.22, and for conventional therapy, $322,000 and 9.98, yielding an ICER of $1,987,000/QALY gained. After applying indirect costs in a modified societal perspective, the ICERs were reduced to $3,310,000/QALY gained for eculizumab and $1,959,000/QALY gained for efgartigimod. Eculizumab and efgartigimod are rapidly acting and effective treatments for myasthenia gravis. However, at their current price, both therapies greatly exceeded common cost-effectiveness thresholds, likely limiting patient access to these therapies.

Changes in the cost-effectiveness of pneumococcal vaccination and of programs to increase its uptake in U.S. older adults.

Multiple factors, such as less complex U.S. adult pneumococcal recommendations that could increase vaccination rates, childhood pneumococcal vaccination indirect effects that decrease adult vaccination impact, and increased vaccine hesitancy (particularly in underserved minorities), could diminish the cost-effectiveness of programs to increase pneumococcal vaccination in older adults. Prior analyses supported the economic favorability of these programs. A Markov model compared no vaccination and current recommendations (either 20-valent pneumococcal conjugate vaccine [PCV20] alone or 15-valent pneumococcal conjugate vaccine plus the 23-valent pneumococcal polysaccharide vaccine [PCV15/PPSV23]) without or with programs to increase vaccine uptake in Black and non-Black 65-year-old cohorts. Pre-pandemic population- and serotype-specific pneumococcal disease risk and illness/vaccine costs came from U.S. Program costs were $2.19 per vaccine-eligible person and increased absolute vaccination likelihood by 7.5%. Delphi panel estimates and trial data informed vaccine effectiveness values. Analyses took a healthcare perspective, discounting at 3%/year over a lifetime time horizon. Uptake programs decreased pneumococcal disease overall. In Black cohorts, PCV20 without program cost $216,805 per quality-adjusted life year (QALY) gained compared with no vaccination; incremental cost-effectiveness was $245,546/QALY for PCV20 with program and $425,264/QALY for PCV15/PPSV23 with program. In non-Black cohorts, all strategies cost >$200,000/QALY gained. When considering the potential indirect effects from childhood vaccination, all strategies became less economically attractive. Increased vaccination with less complex strategies had negligible effects. In probabilistic sensitivity analyses, current recommendations with or without programs were unlikely to be favored at thresholds <$200,000/QALY gained. Current U.S. pneumococcal vaccination recommendations for older adults were unlikely to be economically reasonable with or without programs to increase vaccine uptake. Alternatives to current pneumococcal vaccines that include pneumococcal serotypes associated with adult disease should be considered.

Cost effectiveness analysis of nadofaragene firadenovec for the treatment of high-risk, bacillus Calmette-Guerin–unresponsive, non-muscle invasive bladder cancer from a US third-party payer perspective.

4598 Retraction The abstract by Yang et al entitled, “Cost effectiveness analysis of nadofaragene firadenovec for the treatment of high-risk, bacillus Calmette-Guerin–unresponsive, non-muscle invasive bladder cancer from a US third-party payer perspective,” ( Journal of Clinical Oncology 42, no. 16_suppl 4598; DOI 10.1200/JCO.2024.42.16_suppl.4598) published on May 29, 2024, has been retracted. The authors wish to retract this article as it is undergoing additional review and further updates are expected. They could not rule out that the current results may be incorrect, inaccurate, or misleading. It is important to provide the best estimate of nadofaragene’s cost effectiveness vs pembrolizumab in this space for healthcare decision making whereas uncertainty remains at this time. The authors are no longer able to endorse the work. This abstract was retracted on August 26, 2024. Background: Bladder cancer is the second most common cancer in the urinary tract in the United States (US), with 75% restricted to the superficial layers of the bladder and termed as non-muscle invasive bladder cancer (NMIBC). Bacillus Calmette-Guerin (BCG) is the standard of care for high risk NMIBC patients; however, bladder preserving treatments are limited after BCG failure. Nadofaragene firadenovec, an interferon-alfa-2b encoding gene therapy, is approved for the treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors (CIS ± Ta/T1). This study assessed cost-effectiveness of nadofaragene firadenovec compared to pembrolizumab from a US third-party payer perspective. Methods: A Markov model was developed to estimate total costs, quality-adjusted life-years (QALYs), and corresponding incremental cost per QALY ratios (ICER) over a lifetime time horizon for patients treated with nadofaragene firadenovec or pembrolizumab. In the absence of head-to-head data comparing nadofaragene firadenovec to pembrolizumab, the model population was based on Phase 3 trial for nadofaragene firadenovec (NCT02773849, data cut: July 8, 2019) and included adult patients (mean age of 71.0 years; 11.7% female) with high-risk, BCG unresponsive NMIBC with CIS ± Ta/T1. Pembrolizumab data was informed by the published KeyNote-057 trial (NCT02625961, data-cut: May 25, 2020). The model consisted of 7 mutually exclusive health states with a three-month model cycle: NMIBC disease-free, NMIBC recurrence, MIBC, metastatic disease, cystectomy, post-cystectomy, and death. Drug costs, adverse events (AEs) costs, and health state associated medical costs were included and discounted at 3% annually. The nadofaragene firadenovec and pembrolizumab prices were informed by 2023 U.S. pricing compendia. Sensitivity analyses were performed. Results: Compared to pembrolizumab, nadofaragene firadenovec resulted in an ICER of $123,725 per QALY gained. The incremental cost was $24,194 (nadofaragene firadenovec: $374,280; pembrolizumab: $350,086) and the incremental QALYs were 0.196 (nadofaragene firadenovec: 4.560; pembrolizumab: 4.364). The cumulative drug acquisition and administration costs for nadofaragene firadenovec and pembrolizumab were $181,134 and $141,954 respectively, and AE costs were $248 and $2,749 and medical costs associated with health states were $192,898 and $205,382, respectively. The ICERs for nadofaragene firadenovec remained cost-effective across a majority of the sensitivity analyses and simulations. Conclusions: The analysis suggests that nadofaragene firadenovec is cost-effective compared to pembrolizumab for the treatment of high-risk, BCG unresponsive NMIBC with CIS ± Ta/T1 at a willingness to pay of $150,000/QALY.

An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a Danish healthcare perspective

Abstract Background As demonstrated in three randomized clinical trials (RCTs), initial rhythm control with first-line pulmonary vein isolation (PVI) using cryoballoon ablation decreases atrial arrhythmia recurrence compared to antiarrhythmic drug (AAD) therapy in patients with symptomatic paroxysmal atrial fibrillation (PAF). Purpose To assess the cost-effectiveness of first-line cryoablation versus first-line AADs in a Danish healthcare setting. Methods Data from 703 participants with symptomatic PAF enrolled into Cryo-FIRST, STOP AF First and EARLY-AF RCTs were used to estimate risk equations (rate of ablation, AF recurrence and resolution, AF-related hospital attendance in addition to health-related quality-of-life (HRQoL) utilities). These were then incorporated into a cost-effectiveness model (CEM) . The Danish cost data was derived from published Danish literature, DRG tariffs and pharmaceutical list prices in Denmark. Where parameters could not be derived, inputs were sourced from published literature or expert opinion. The CEM consisted of a decision tree (one-year time horizon) and a Markov model (three-month cycle length) hybrid, with a lifetime (40 years) time horizon. The CEM is from the perspective of the Danish healthcare system. Health benefits were expressed in quality-adjusted life-years (QALYs), and all costs and benefits were discounted at 3%. As there is no official cost-effectiveness threshold in Denmark, the UK threshold of £20,000 (~€23,200) was assumed. Input uncertainty within the CEM was explored using probabilistic sensitivity analysis. The results presented include data from the initial 12-week blanking period for all studies. Results The three-monthly rate of AF symptom recurrence had a reduction, on average, of 46.7% (p&amp;lt;0.001) in those treated with cryoablation. In addition, the cryoablation arm had a 72.8% (p&amp;lt;0.001) reduction in the monthly rate of receiving an ablation following initial treatment. The average cryoablation patient was also associated with a 4.3% (p=0.025) increase in their HRQoL. Finally, there was no difference in the rate of AF symptom resolution in those who failed initial treatment. Base case results per patient are presented in Table 1. Cryoablation was shown to be dominant when compared to AADs (0.159 more QALYs and €2,519 less costly), with a 99.96% probability of being cost-effective at a willingness-to-pay threshold of ~€23,200 per QALY gained. Individuals in both arms of the model were also expected to receive ~1.2 ablations over a lifetime horizon. Nonetheless, there was a 45% relative reduction in time spent in symptomatic AF states for individuals who were initially treated with cryoablation. Scenario analysis results are presented in Table 2. Cryoablation remained cost-effective over AADs in all scenarios conducted. Conclusions Initial rhythm control with cryoballoon ablation is cost-effective (dominant) when compared to AADs in the Danish healthcare system.Table 1:Key results (per patient)Table 2.Deterministic scenario analysis

The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7). Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia. To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy. A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023. No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers. Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios. HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations. The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Cost-Effectiveness of Lovotibeglogene Autotemcel (Lovo-Cel) Gene Therapy for Patients with Sickle Cell Disease and Recurrent Vaso-Occlusive Events in the United States.

Gene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥12years with ≥4 vaso-occlusive events (VOEs) in the past 24months. We developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses. Patients treated with lovo-cel were predicted to survive 23.84years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs. Our analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden.

Cost-Effectiveness Analysis of Fluocinolone Acetonide Intravitreal (FAI) Implant for Chronic Noninfectious Uveitis Affecting the Posterior Segment of the Eye (NIU-PS) in China.

Chronic non-infectious uveitis affecting the posterior segment (NIU-PS), which can be recurrent and persistent for numerous years, mainly affects people of working age and significantly increases the risk of visual impairment. This study aimed to investigate the cost-effectiveness of fluocinolone acetonide intravitreal (FAI) implant in the treatment of patients with chronic NIU-PS from the Chinese healthcare perspective. A Markov model with a 2-week cycle was constructed from the perspective of the Chinese healthcare system over a lifetime time horizon. The model consists of four health states: on-treatment, treatment failure, blindness, and death. The outcomes for effectiveness were based on the Chinese real-world study (RWS). Utilities and mortality rates were derived from published literature and standard sources. Costs were determined from the MENET website, prices of medical service items at local providers, published literature, and expert surveys. Outcomes were measured in quality-adjusted life years (QALYs). Sensitivity analyses were performed to account for the impact of uncertainty. It was estimated that in the base case, the FAI implant provided 0.43 incremental QALYs compared with the limited current practice (LCP) at an additional cost of $7503.72 (¥50,575.05), resulting in an incremental cost-effectiveness ratio (ICER) of $17,373.49 (¥117,097.33) per QALY gained. Parameters related to utility emerged as the primary influencers on the outcomes. In probabilistic sensitivity analysis (PSA), considering the willingness-to-pay (WTP) threshold of $19,072 (¥128,547) and $38,145 (¥257,094), the FAI implant had 67.70% and 99.50% probability of being cost-effective, respectively. As demonstrated in the scenario analysis, if the FAI implant aligns its price reduction with the average rate from the 2023 negotiation of the National Reimbursement Drug List (NRDL), it would result in lower costs and represent an absolute advantage. The FAI implant, which can effectively reduce the recurrence rate and maintain the incremental costs within the WTP limit, is likely to be cost-effective in treating chronic NIU-PS in China.

Rituximab or cyclosporine a for the treatment of membranous nephropathy: Economic evaluation of the MENTOR trial.

The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health care payers. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health care payer with a life-time time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced cost biosimilar rituximab. Rituximab for the treatment of membranous nephropathy was cost-effective (assuming a willingness-to-pay threshold of ${\$}$50000 per quality adjusted life year (QALY) gained; ${\$}$US 2021) compared with cyclosporine, with an ICER of ${\$}$8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was ${\$}$28007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favourable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Cost-effectiveness of bevacizumab therapy in the care of patients with hereditary hemorrhagic telangiectasia

AbstractNo US Food and Drug Administration- or European Medicines Agency-approved therapies exist for bleeding due to hereditary hemorrhagic telangiectasia (HHT), the second-most common inherited bleeding disorder worldwide. The current standard of care (SOC) includes iron and red cell supplementation, alongside the necessary hemostatic procedures, none of which target underlying disease pathogenesis. Recent evidence has demonstrated that bleeding pathophysiology is amenable to systemic antiangiogenic therapy with the anti-vascular endothelial growth factor bevacizumab. Despite its high cost, the addition of longitudinal bevacizumab to the current SOC may reduce overall health care resource use and improve patient quality of life. We conducted, to our knowledge, the first cost-effectiveness analysis of IV bevacizumab in patients with HHT with the moderate-to-severe phenotype, comparing bevacizumab added to SOC vs SOC alone. The primary outcome was the incremental net monetary benefit (iNMB) reported over a lifetime time horizon and across accepted willingness-to-pay thresholds, in US dollar per quality-adjusted life year (QALY). Bevacizumab therapy accrued 9.3 QALYs while generating $428 000 in costs, compared with 8.3 QALYs and $699 000 in costs accrued in the SOC strategy. The iNMB of bevacizumab therapy vs the SOC was $433 000. No parameter variation and no scenario analysis, including choice of iron supplementation product, changed the outcome of bevacizumab being a cost-saving strategy. Bevacizumab therapy also saved patients an average of 133 hours spent receiving HHT-specific care per year of life. In probabilistic sensitivity analysis, bevacizumab was favored in 100% of all 10 000 Monte Carlo iterations across base-case and all scenario analyses. Bevacizumab should be considered for more favorable formulary placement in the care of patients with moderate-to-severe HHT.

Cost-utility analysis of TAVI compared with surgery in patients with severe aortic stenosis at low risk of surgical mortality in the Netherlands

BackgroundThere is growing evidence to support the benefits of transcatheter aortic valve implantation (TAVI) over surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis (sSAS) who are at high- or intermediate-risk of surgical mortality. The PARTNER 3 trial showed clinical benefits with SAPIEN 3 TAVI compared with SAVR in patients at low risk of surgical mortality. Whether TAVI is also cost-effective compared with SAVR for low-risk patients in the Dutch healthcare system remains uncertain. This article presents an analysis using PARTNER 3 outcomes and costs data from the Netherlands to inform a cost-utility model and examine cost implications of TAVI over SAVR in a Dutch low-risk population.MethodsA two-stage cost-utility analysis was performed using a published and validated health economic model based on adverse events with both TAVI and SAVR interventions from a published randomized low risk trial dataset, and a Markov model that captured lifetime healthcare costs and patient outcomes post-intervention. The model was adapted using Netherlands-specific cost data to assess the cost-effectiveness of TAVI and SAVR. Uncertainty was addressed using deterministic and probabilistic sensitivity analyses.ResultsTAVI generated 0.89 additional quality-adjusted life years (QALYs) at a €4742 increase in costs per patient compared with SAVR over a lifetime time horizon, representing an incremental cost-effectiveness ratio (ICER) of €5346 per QALY gained. Sensitivity analyses confirm robust results, with TAVI remaining cost-effective across several sensitivity analyses.ConclusionsBased on the model results, compared with SAVR, TAVI with SAPIEN 3 appears cost-effective for the treatment of Dutch patients with sSAS who are at low risk of surgical mortality. Qualitative data suggest broader societal benefits are likely and these findings could be used to optimize appropriate intervention selection for this patient population.