Total Quality-adjusted Life Years Research Articles

Economic evaluation of trastuzumab in HER2-positive early breast cancer in Indonesia: A cost-effectiveness analysis.

Trastuzumab has significantly enhanced the survival and prognosis of individuals diagnosed with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Considering its relatively high costs, we aimed to examine the cost-effectiveness of trastuzumab plus chemotherapy compared with chemotherapy alone in HER2-positive early breast cancer from an Indonesian healthcare payer's perspective. A Markov model was developed to project the lifetime health benefits and costs associated with trastuzumab treatment for a cohort of women with HER2-positive early breast cancer. Efficacy data and baseline characteristics in the base-case analysis were primarily derived from the 11-year results of the HERA trial. Costs were based on verified reimbursement data from Indonesia's Health and Social Security Agency (BPJS Kesehatan) of the year 2020. A scenario analysis was conducted with efficacy data based on the joint analysis from the NSABP B-31 and NCCTG N9831 trials, allowing for subgroup analysis by age at diagnosis. Univariate and probabilistic sensitivity analyses were conducted to assess the influence of parameter uncertainty. In the base-case analysis, the results indicated that the lifetime costs for trastuzumab plus chemotherapy and chemotherapy alone were US$33,744 and US$22,720, respectively, resulting in substantial incremental savings of US$11,024 per patient for the former. Trastuzumab plus chemotherapy also led to higher total quality-adjusted life years (QALYs) and life years gained (LYG), resulting in incremental cost-effectiveness ratios (ICERs) of US$6,842 per QALY and US$5,510 per LYG. In scenario analysis, the subgroup with an age at diagnosis <40 years old reflected the most cost-effective subgroup. Both the base-case and scenario analyses demonstrated cost-effectiveness with a willingness-to-pay threshold of three-times Gross Domestic Product (GDP). Sensitivity analyses confirmed the robustness of the findings and conclusions. In Indonesia, trastuzumab plus chemotherapy can be considered cost-effective compared to chemotherapy alone at a willingness-to-pay threshold of three times GDP, and it is likely most cost-effective in women <40 years of age.

Cost-Effectiveness of Recombinant FactorIX Fc Prophylaxis and Recombinant FactorIX On-Demand Treatment in Patients with HaemophiliaB Without Inhibitors.

Recombinant factor IX (rFIX) and recombinant FIX Fc fusion protein (rFIXFc) are standard half-life and extended half-life FIX replacement therapies, respectively, and represent established treatment options indicated for adults and children with haemophiliaB. These FIX replacement therapies can be administered as prophylaxis (to prevent bleeding) or 'on-demand' (to stop bleeding). This analysis aimed to estimate the cost-effectiveness of once-weekly prophylaxis with rFIXFc versus on-demand treatment with rFIX in patients with haemophiliaB without inhibitors in the Italian healthcare setting. A Markov model was developed to assess a hypothetical cohort of adolescent or adult male patients (≥ 12years) with haemophiliaB (FIX level of ≤ 2IU/dL) without inhibitors. Model inputs were derived from the pivotal phase3 clinical studies for rFIXFc and rFIX, published literature and assumptions when published data were unavailable. The model employed a lifelong time horizon with 6-monthly transitions between health states, and it estimated total costs, total quality-adjusted life years (QALYs), number of bleeds, number of surgeries and incremental cost-effectiveness ratio. rFIXFc prophylaxis was associated with lower total costs per patient (€5,308,625 versus €6,564,510) and greater total QALYs per patient (15.936 versus 11.943) compared with rFIX on-demand; rFIXFc prophylaxis was therefore the dominant treatment strategy. The model also demonstrated that rFIXFc prophylaxis was associated with fewer incremental bleeds (- 682.29) and surgeries (- 0.39) compared with rFIX on-demand. rFIXFc prophylaxis provides improved health outcomes and lower costs, and represents a cost-effective treatment option compared with rFIX on-demand for adolescent and adult male patients with haemophiliaB. This comparative assessment of cost-effectiveness should help to inform both clinicians and healthcare policy makers when making treatment decisions for patients with haemophiliaB.

Evaluating the health and economic outcomes of a PCV15 vaccination program for adults aged 65 years-and-above in Switzerland

ObjectiveTo assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland.Interventions: The three vaccination strategies examined were:1)Vaccination with PCV13.2)Vaccination with PCV15.3)No vaccination (do-nothing alternative).Target population: All adults aged 65 years-and-above.Perspective(s): Switzerland health care payer.Time horizon: 35 years.Discount rate: 3.0%.Costing year: 2023 Swiss Francs (CHF).Study design: A static Markov state-transition model.Data sources: Published literature and publicly available databases or reports. Outcome measuresPneumococcal diseases (PD) i.e., invasive pneumococcal diseases (IPD) and non-bacteremic pneumococcal pneumonia (NBPP); total quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (CHF/QALY gained). ResultsUsing an assumed coverage of 60%, the PCV15 strategy prevented a substantially higher number of cases/deaths than the PCV13 strategy when compared to the No vaccination strategy (1,078 IPD; 21,155 NBPP; 493 deaths). The overall total QALYs were 10,364,620 (PCV15), 10,364,070 (PCV13), and 10,362,490 (no vaccination). The associated overall total costs were CHF 741,949,814 (PCV15), CHF 756,051,954 (PCV13) and CHF 698,329,579 (no vaccination). Thus, the PCV13 strategy was strongly dominated by the PCV15 strategy. The ICER of the PCV15 strategy (vs. no vaccination) was CHF 20,479/QALY gained. In two scenario analyses where the vaccine effectiveness for serotype 3 were reduced (75% to 39.3% for IPD; 45% to 23.6% for NBPP) and NBPP incidence was increased (from 1,346 to 1,636/100,000), the resulting ICERs were CHF 29,432 and CHF 13,700/QALY gained, respectively. The deterministic and probabilistic sensitivity analyses demonstrated the robustness of the qualitative results—the estimated ICERs for the PCV15 strategy (vs. No vaccination) were all below CHF 30,000/QALYs gained. ConclusionsThese results demonstrate that using PCV15 among adults aged 65 years-and-above can prevent a substantial number of PD cases and deaths while remaining cost-effective over a range of inputs and scenarios.

Cost-Effectiveness of Artificial Intelligence–Based Opportunistic Compression Fracture Screening of Existing Radiographs

PurposeOsteoporotic vertebral compression fractures (OVCFs) are a highly prevalent source of morbidity and mortality, and preventive treatment has been demonstrated to be both effective and cost effective. To take advantage of the information available on existing chest and abdominal radiographs, the authors’ study group has developed software to access these radiographs for OVCFs with high sensitivity and specificity using an established artificial intelligence deep learning algorithm. The aim of this analysis was to assess the potential cost-effectiveness of implementing this software. MethodsA deterministic expected-value cost-utility model was created, combining a tree model and a Markov model, to compare the strategies of opportunistic screening for OVCFs against usual care. Total costs and total quality-adjusted life-years were calculated for each strategy. Screening and treatment costs were considered from a limited societal perspective, at 2022 prices. ResultsIn the base case, assuming a cost of software implantation of $10 per patient screened, the screening strategy dominated the nonscreening strategy: it resulted in lower cost and increased quality-adjusted life-years. The lower cost was due primarily to the decreased costs associated with fracture treatment and decreased probability of requiring long-term care in patients who received preventive treatment. The screening strategy was dominant up to a cost of $46 per patient screened. ConclusionsArtificial intelligence–based opportunistic screening for OVCFs on existing radiographs can be cost effective from a societal perspective.

Economic Evaluation of an Enhanced Post-Discharge Home-Based Care Program for Stroke Survivors

ObjectivesTo examine the cost-effectiveness of an enhanced postdischarge home-based care program for stroke survivors compared with usual care. MethodsThis was a trial-based economic evaluation study. One hundred and sixteen patients with ischemic stroke were recruited from neurology units in a Chinese hospital and randomized into intervention (n = 58) or usual care groups (n = 58). The intervention commenced with predischarge planning and transitioned to home follow-up postdischarge. Trained nurse case managers supported by an interdisciplinary team provided comprehensive assessment, individualized goal setting, and skill training to support home-based rehabilitation for intervention group participants. Standard care was provided to usual care group participants. Total cost and quality-adjusted life-years gained at 3-month (T1), 6-month (T2), and 12-month (T3) follow-ups were calculated. The incremental cost-effectiveness ratios between the groups were obtained. ResultsThe intervention group showed a significant increase in utility compared with the usual care group at T1 (P = .003), T2 (P = .007), and T3 (P < .001). The average total QALY gain from baseline for the intervention group was higher than for the usual care group at all time points. The likelihood of being cost-effective ranged from 61.9% to 67.2% from the provider perspective, and from 59.7% to 66.8% from the societal perspective. ConclusionsThe results showed that the intervention program was cost-effective with significantly higher quality-adjusted life-years for stroke survivors when compared with usual care. It provides economic evidence to support the development of home-based stroke rehabilitation program, especially in the low- and middle-income countries.

Cost-utility of tiotropium in patients with severe asthma

SummaryAdd-on therapy with tiotropium was cost-effective when added to usual care in patients who remain uncontrolled despite treatment with medium or high-dose ICS/LABA in a middle-income country.BackgroundA significant proportion of asthma patients remain uncontrolled despite inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, such as tiotropium bromide, have been recommended for this subgroup of patients. This study aimed to assess the cost-effectiveness of tiotropium as an add-on therapy to inhaled corticosteroids and long-acting b2 agonists for patients with severe asthma.MethodsA probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYs of two interventions include standard therapy with inhaled corticosteroids and long-acting bronchodilators versus add-on therapy with tiotropium. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $5180.ResultsThe expected incremental cost per QALY (ICER) is estimated at US$–2637.59. There is a probability of 0.77 that tiotropium + ICS + LABA is more cost-effective than ICS + LABA at a threshold of US$5180 per QALY. The strategy with the highest expected net benefit is Tiotropium, with an expected net benefit of US$800. Our base-case results were robust to parameter variations in the deterministic sensitivity analyses.ConclusionAdd-on therapy with tiotropium was cost-effective when added to usual care in patients who remain uncontrolled despite treatment with medium or high-dose inhaled corticosteroids and long-acting bronchodilators. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Evaluating the cost utility of estradiol plus dydrogesterone for the treatment of menopausal women in China

AimEvaluate the cost utility of menopausal hormone therapy for women in China.Materials and methodsA bespoke Markov cost utility model was developed to evaluate a cohort of symptomatic perimenopausal women (>45 years) with intact uterus in China in accordance with China’s Pharmacoeconomic guideline. Short (5-year) and long (10-year) treatment durations were evaluated over a lifetime model time horizon with 12-month cycle duration. Societal and healthcare payer perspectives were evaluated in the context of a primary care provider/prescriber, outpatient setting with inpatient care for patients with chronic conditions. Disease risk and mortality parameters were derived from focused literature searches, and China Diagnosis-related Group cost data was included. Comprehensive scenario, univariate and probabilistic sensitivity analysis were undertaken along with independent validation. This is the first model to include MHT-related disease risks.ResultsAccording to base case results, the total cost for MHT was 22,516$ (150,106¥) and total quality adjusted life years 12.32 versus total cost of no MHT 30,824$ (205,495¥) and total quality adjusted life years 11.16 resulting in a dominant incremental cost effectiveness ratio of −7,184$ (−47,898¥) per QALY. Results hold true over a range of univariate deterministic sensitivity and scenario analyses. Probabilistic analysis showed a 91% probability of being cost effective at a willingness to pay threshold of three times Gross Domestic Product per capita in China.ConclusionContingent on the structure and assumptions of the model, combination of estradiol plus dydrogesterone MHT is potentially cost saving in symptomatic women over the age of 45 years in China.

Cost-effectiveness of triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate compared with dual therapy for the treatment of chronic obstructive pulmonary disease (COPD) in Canada

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with significant economic and societal burden in Canada. For patients whose symptoms remain uncontrolled with dual therapies including long-acting muscarinic antagonists (LAMA)/long-acting beta2-adrenergic agonists (LABA) or inhaled corticosteroids (ICS)/LABA, step-up to triple-therapy with ICS/LAMA/LABA is recommended. Budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) is an ICS/LAMA/LABA therapy with demonstrated efficacy compared to dual therapies in pivotal phase 3 trials (ETHOS and KRONOS). OBJECTIVES The objectives of this study were to conduct a cost-utility analysis to compare BGF with dual therapies (ICS/LABA and LAMA/LABA) for patients with COPD requiring escalation to triple therapy. METHODS A Markov cohort-based cost-utility analysis was conducted over a 30-year time horizon from a public payer perspective, to compare costs and outcomes in patients with COPD requiring escalation from dual therapy to triple therapy. The analysis was based on data from the ETHOS trial, Canadian administrative data, and published sources. Health states were characterized by forced expiratory volume (FEV1) severity and exacerbations (none, moderate, severe). RESULTS Over a 30-year time horizon in probabilistic analysis across several scenario analyses, BGF was associated with modest but consistent benefits to overall costs ($40,406 total for BGF, $40,685 for LAMA/LABAs and $43,261 for ICS/LABAs), as well as life years and quality-adjusted life year (QALYs) gained compared to dual therapies (8.7 total QALYs for BGF triple therapy, 8.5 for LAMA/LABAs and 8.4 for ICS/LABAs). CONCLUSIONS From a Canadian public healthcare perspective, BGF is associated with both cost-savings and improved health benefits compared with dual therapies for maintenance treatment of COPD patients at risk of exacerbations. These results may help to inform optimal decision-making.

Cost-Effectiveness Analysis of Trastuzumab Deruxtecan Versus Trastuzumab Emtansine for Patients With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer in the United States

ObjectivesTo assess the cost-effectiveness of trastuzumab deruxtecan compared with trastuzumab emtansine as second-line therapy for patients with human epidermal growth factor receptor 2 positive metastatic breast cancer from a US healthcare sector perspective. MethodsA 3-state partitioned survival model was developed to estimate the cost-effectiveness of trastuzumab deruxtecan compared with trastuzumab emtansine. For both treatments, modeled patients were administered treatment intravenously every 3 weeks indefinitely or until disease progression. Transition parameters were principally derived from the updated DESTINY-Breast03 phase III randomized clinical trial. Costs include drug costs extracted from Centers for Medicare and Medicaid Services average sales price and administrative, adverse event, and third-line therapy costs derived from published literature, measured in 2022 US dollars. Health utilities for health states and disutilities for adverse events were sourced from published literature. Effects were measured in quality-adjusted life years (QALYs). We conducted both probabilistic sensitivity analysis and comprehensive scenario analysis to test model assumptions and robustness, while utilizing a lifetime horizon. ResultsIn our base-case analysis, total costs for trastuzumab deruxtecan were $1 266 945, compared with $820 082 for trastuzumab emtansine. Total QALYs for trastuzumab deruxtecan were 5.09, compared with 3.15 for trastuzumab emtansine. The base-case incremental cost-effectiveness ratio was $230 285/QALY. Probabilistic sensitivity analysis indicated that trastuzumab deruxtecan had an 11.1% probability of being cost-effective at a $100 000 per QALY willingness-to-pay threshold. ConclusionsDespite the higher efficacy of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer, our findings raise concern regarding its value at current prices.

Abstract 16635: Cost Effectiveness Analysis of the Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction REVIVED Trial Data

Introduction. Evidence on survival benefits of percutaneous coronary intervention (PCI) in patients with severe ischemic left ventricular systolic dysfunction (ILVD) is scant. The REVIVED trial showed that, compared to optimal medical therapy (OMT), revascularisation by PCI did not reduce the incidence of death from any cause or heart failure hospitalization (HF); it also failed to provide sustained improvements in health-related quality of life. REVIVED data are used to evaluate the economic consequences and health outcomes of PCI+OMT and OMT alone in HF patients in the UK. Methods. 700 patients with ILVD were randomised to either PCI+OMT or OMT. Healthcare resource use and patient-reported health outcomes data EuroQol on each patient were collected at baseline and over a period of 8 years post randomisation (median follow up of 3.5 years). Health resources were costed using publicly available national unit costs from the perspective of the UK health system. Within trial mean total costs and quality adjusted life years (QALYs) were estimated and incremental cost effectiveness was evaluated. Regression analysis on total costs and total QALYs was used to adjust for clinically relevant baseline covariables. Probabilistic sensitivity analysis was used to reflect parameter uncertainty. Results. Statistical modelling identified gender, BMI, hypertension, diabetes, NYHA grade and previous hospitalisation as the most relevant baseline predictors of costs and benefits. Over the 8 years of fu, patients undergoing PCI yielded, on average, similar health benefits (4.13 QALYs IC [4.10 - 4.16]) at higher costs (£14,674 IC[£14,334 - £15,014]), compared to OMT (4.16 QALYs [4.13 - 4.19]; £5154 IC [£5,034 - £5,273]). Conclusion. We found no difference in total QALYs between arms and PCI+OMT was not cost-effective compared to OMT, given its additional costs. Therefore, a strategy of routine PCI to treat ILVSD does not appear to be a justifiable use of healthcare resources.

Optimal timing of delivery for growth restricted fetuses with gastroschisis: A decision analysis.

Our objective was to determine the optimal timing of delivery of growth restricted fetuses with gastroschisis in the setting of normal umbilical artery (UA) Dopplers. We designed a decision analytic model using TreeAge software for a hypothetical cohort of 2000 fetuses with isolated gastroschisis, fetal growth restriction (FGR), and normal UA Dopplers across 34-39weeks of gestation. This model accounted for costs and quality adjusted life years (QALYs) for the pregnant individual and the neonate. Model outcomes included stillbirth, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), short gut syndrome (SGS), neonatal sepsis, neonatal death, and neurodevelopmental disability (NDD). We found 38weeks to be the optimal timing of delivery for minimizing overall perinatal mortality and leading to the highest total QALYs. Compared to 37weeks, delivery at 38weeks resulted in 367.98 more QALYs, 2.22 more cases of stillbirth, 2.41 fewer cases of RDS, 0.02 fewer cases of NEC, 1.65 fewer cases of IVH, 0.5 fewer cases of SGS, 2.04 fewer cases of sepsis, 11.8 fewer neonatal deaths and 3.37 fewer cases of NDD. However, 39weeks were the most cost-effective strategy with a savings of $1,053,471 compared to 38weeks. Monte Carlo analysis demonstrated that 38weeks was the optimal gestational age for delivery 51.70% of the time, 39weeks were optimal 47.40% of the time, and 37weeks was optimal 0.90% of the time. Taking into consideration a range of adverse perinatal outcomes and cost effectiveness, 38-39weeks gestation is ideal for the delivery of fetuses with gastroschisis, FGR, and normal UA Dopplers. However, there are unique details to consider for each case, and the timing of delivery should be individualized using shared multidisciplinary decision making.

Societal health and economic burden of cardiovascular diseases in the population with type 2 diabetes in Qatar. A 10-year forecasting model.

To predict the future health and economic burden of cardiovascular disease (CVD) in type 2 diabetes (T2D) in Qatar. A dynamic multistate model was designed to simulate the progression of fatal and non-fatal CVD events among people with T2D in Qatar aged 40-79 years. First CVD events [i.e. myocardial infarction (MI) and stroke] were calculated via the 2013 Pooled Cohort Equation, while recurrent CVD events were sourced from the REACH registry. Key model outcomes were fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years, total direct medical costs and total productivity loss costs. Utility and cost model inputs were drawn from published sources. The model adopted a Qatari societal perspective. Sensitivity analyses were performed to test the robustness of estimates. Over 10 years among people with T2D, model estimates 108 195 [95% uncertainty interval (UI) 104 249-112 172] non-fatal MIs, 62 366 (95% UI 60 283-65 520) non-fatal strokes and 14 612 (95% UI 14 472-14 744) CVD deaths. The T2D population accrued 4 786 605 (95% UI 4 743 454, 4 858 705) total years of life lived and 3 781 833 (95% UI 3 724 718-3 830 669) total quality-adjusted life years. Direct costs accounted for 57.85% of the total costs, with a projection of QAR41.60 billion (US$11.40 billion) [95% UI 7.53-147.40 billion (US$2.06-40.38 billion)], while the total indirect costs were expected to exceed QAR30.31 billion (US$8.30 billion) [95% UI 1.07-162.60 billion (US$292.05 million-44.55 billion)]. The findings suggest a significant economic and health burden of CVD among people with T2D in Qatar and highlight the need for more enhanced preventive strategies targeting this population group.

Cost-effectiveness analysis of baricitinib versus dupilumab for moderate to severe atopic dermatitis: an Italian healthcare system perspective

AimsTo assess, within the Italian healthcare system, the cost-effectiveness of baricitinib versus dupilumab, both in combination with topical corticosteroids (TCS), in adults with moderate to severe atopic dermatitis (AD) who are eligible for but have failed, have contraindications to, or cannot tolerate ciclosporin.Materials and methodsUsing the perspective of the Italian healthcare payer, direct medical costs associated with each intervention were estimated over a lifetime horizon. A Markov cohort model utilized the proportions of patients with ≥75% improvement Eczema Area and Severity Index obtained from clinical trials. Health outcomes were evaluated in quality-adjusted life years (QALYs) to assess the cost effectiveness of baricitinib against a willingness-to-pay threshold of €35,000 per QALY gained.ResultsIn the base case, with secondary censoring applied, patients treated with dupilumab or baricitinib, in combination with TCS, accumulated total costs of €135,780 or €129,586, and total QALYs of 18.172 or 18.133, respectively. The incremental cost-effectiveness ratio of dupilumab versus baricitinib was estimated at €160,905/QALY.LimitationsCore assumptions were needed to extrapolate available short-term clinical trial data to lifelong data, adding uncertainty. Benefits of baricitinib seen in clinical trials and not assessed in dupilumab clinical trials were not included. Discontinuation rates for each treatment were derived from different sources potentially introducing bias. Results may not be generalizable to other populations.ConclusionsThis cost-effectiveness analysis shows that, from the Italian healthcare payer perspective, in the treatment of patients with moderate to severe AD who have experienced failure on, are intolerant to, or have contraindication to ciclosporin, dupilumab cannot be considered cost-effective when compared with baricitinib. Given its oral administration, favorable risk/benefit profile and lower acquisition cost compared with dupilumab, baricitinib may offer a valuable, cost-effective treatment option—after failure on conventional systemic agents—for patients with moderate to severe AD in Italy.

A cost-effectiveness analysis of hypertrophic cardiomyopathy sudden cardiac death risk algorithms for implantable cardioverter defibrillator decision-making.

To conduct a contemporary cost-effectiveness analysis examining the use of implantable cardioverter defibrillators (ICD) for primary prevention in patients with hypertrophic cardiomyopathy (HCM). A discrete-time Markov model was used to determine the cost-effectiveness of different ICD decision-making rules for implantation. Several scenarios were investigated including the reference scenario of implantation rates according to observed real world practice. A 12-year time horizon with an annual cycle length was used. Transition probabilities used in the model were obtained using Bayesian analysis. The study has been reported according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Using a 5-year SCD risk threshold of 6% was cheaper than current practice and has marginally better total quality adjusted life years (QALYs). This is the most cost-effective of the options considered, with an incremental cost effectiveness ratio of £834 per QALY. Sensitivity analyses highlighted that this decision is largely driven by what health related quality of life (HRQL) is attributed to ICD patients and time horizon. We present a timely new perspective on HCM ICD cost-effectiveness, using methods reflecting real-world practice. While we have shown that a 6% 5-year SCD risk cut-off provides the best cohort stratification to aid ICD decision-making, this will also be influenced by the particular values of costs and HRQL for subgroups or at a local level. The process of explicitly demonstrating the main factors which drive conclusions from such an analysis will help to inform shared decision-making in this complex area for all stakeholders concerned.

Clinical outcomes and cost-effectiveness of manipulation under brachial plexus block versus physiotherapy for refractory frozen shoulder: a prospective observational study

Frozen shoulder (FS) is a pathological condition that involves a painful and stiff shoulder joint, most commonly in people aged 40-60 years. Most literature supports treatment with physical therapy (PT), although some studies have demonstrated years of continuing pain and functional deficits. Manipulation under anesthesia is effective at eliminating the contracture of intra-articular lesions for refractory FS. This study aimed to compare whether manipulation under anesthesia or PT is a more effective treatment in refractory FS. This study was a prospective observational study. A total of 102 patients with refractory FS were enrolled in this study in the medical records, all of whom had severe and multidirectional loss of motion and thickening of the joint capsule and coracohumeral ligament on magnetic resonance imaging. Fifty-one patients were in the manipulation under brachial plexus block (MUB) group (34 females, median age: 57 years), and 51 patients were in the PT group (34 females, median age: 59 years). The MUB procedure consisted of the conventional method with additional adduction manipulation, in which one examiner initially abducted the shoulder joint as much as possible. We recorded the visual analog scale, shoulder range of motion, and American Shoulder and Elbow Surgeons and Constant Scores at the initial baseline visit and at the 1-, 3-, 6-, and 12-month follow-ups. The total cost was calculated from the medical records, and cost-effectiveness was evaluated using quality-adjusted life year and incremental cost-effectiveness ratio. Visual analog scale (P<.001), range of motion (P<.001), and American Shoulder and Elbow Surgeons and Constant Scores (P<.001) in the MUB group were significantly superior to those in the PT group at 1, 3, 6, and 12 months after treatment. The median cost and total quality-adjusted life year in the MUB and PT groups were $1375 versus $2751 and 2.95 versus 2.68, respectively, and the cost-effectiveness ratio between the MUB and PT groups was calculated as -$560. The new MUB procedure provides a shorter treatment period, better clinical outcomes, and higher cost-effectiveness in patients with refractory FS compared to PT.

Cost-effectiveness model of trastuzumab deruxtecan as second-line treatment in HER2-positive unresectable and/or metastatic breast cancer in Finland.

Trastuzumab deruxtecan (T-DXd) was recently recommended by the Committee for Medicinal Products for Human Use as a treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, who had received a prior anti-HER2-based regimen. In our study, we evaluated the cost-effectiveness of T-DXd compared with ado-trastuzumab emtansine (T-DM1) for this indication in Finland. A three-state partitioned survival analysis model was developed with a payer's perspective. Time to event data from the DESTINY-Breast03 (DB-03) trial were extrapolated over a lifetime horizon either directly-for progression-free survival and time to treatment discontinuation-or using an alternative approach utilizing long-term T-DM1 survival data and DB-03 data-for overall survival. Discount rates of 3% were applied for costs and effects. Inputs were sourced from the Medicinal Products Database from Kela, Helsinki University Hospital service price list, Finnish Medicines Agency assessments, clinical experts, and DB-03. Sensitivity analyses were performed to characterize and demonstrate parameter uncertainties in the model. Total quality-adjusted life years (QALYs) and life years (LYs) gained for T-DXd compared with T-DM1 were 1.93 and 2.56, respectively. Incremental costs for T-DXd compared with T-DM1 were €106,800, resulting in an ICER of €55,360 per QALY gained and an ICER of €41,775 per LY gained. One-way sensitivity analysis showed the hazard ratio of T-DXd vs T-DM1 for OS was the most influential parameter. The probabilistic sensitivity analysis showed similar results to the base case. T-DXd is cost-effective based on surrogate WTP thresholds of €72,000 and €139,000 per QALY.

Integrating real-world data in cost-effectiveness analysis of universal HLA-B*15:02 screening in Malaysia.

Despite the availability of newer antiseizure medications, carbamazepine (CBZ) remains the gold standard. However, patients of Asian ancestry are susceptible to CBZ-related severe cutaneous adverse reactions. Universal HLA-B*15:02 screening is a promising intervention to address this. With the increasing recognition of integrating real-world evidence in economic evaluations, the cost-effectiveness of universal HLA-B*15:02 screening was assessed using available real-world data in Malaysia. A hybrid model of a decision tree and Markov model was developed to evaluate 3 strategies for treating newly diagnosed epilepsy among adults: (i) CBZ initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to CBZ initiation; and (iii) alternative prescribing without HLA-B*15:02 screening. The model was populated with real-world inputs derived from the Malaysian population. From a societal perspective, base-case analysis and sensitivity analyses estimated the costs and outcomes over a lifetime. Incremental cost-effectiveness ratios were calculated. In the base-cases analysis, universal HLA-B*15:02 screening yielded the lowest total costs and the highest total quality-adjusted life years (QALYs) gained. Compared with current practice, universal screening was less costly by USD100 and more effective by QALYs increase of 0.1306, while alternative prescribing resulted in 0.1383 QALYs loss at additional costs of USD332. The highest seizure remission rate (56%) was estimated for universal HLA-B*15:02 screening vs. current practice (54%) and alternative prescribing (48%). Our study suggests that universal HLA-B*15:02 screening is a cost-effective intervention in Malaysia. With the demonstrated value of real-world evidence in economic evaluations, more relevant standardization efforts should be emphasized to better inform decision-making.

The trade-off between COVID-19 and mental diseases burden during a lockdown: Mathematical modeling of control measures.

During the COVID-19 pandemic, many countries used lockdowns as a containment measure. While lockdowns successfully contributed to slowing down the contagion, the related mobility restrictions were reportedly associated with an increased risk of major depressive and anxiety disorders. We aimed to quantify the trade-off between the quality-adjusted life years (QALY) gain due to lower COVID-19 incidence as a result of a lockdown and QALY loss due to lockdown-induced mental disorders. We developed an agent-based model of COVID-19 epidemic and coupled mental disorder development in the population of a large city. We used data sources on the places of living, studying and working, public health and census surveys. Modeling of mental disorders was based on diathesis-stress concept. We quantified mental and physical health burden in terms of QALY taking into account major depressive and anxiety disorder episodes, lethal and non-lethal cases of COVID-19, and immunization. We evaluated the dynamics of new major depressive disorder (MDD) and anxiety disorder (AD) cases during the period between September 2020 and December 2021 in Moscow, Russia. We found that lockdown imposition increases the daily chances of getting MDD or ADD by a vulnerable person by 16.79% (95% CI [12.36%, 21.23%]). The QALY loss associated with COVID-19-induced and lockdown-induced mental disorders was estimated to be 18.93% (95% CI [16.94%, 19.73%]) of the total QALY loss caused by COVID-19, immunization, and all kinds of mental disorders. For a synthetic "strong" lockdown, it had been shown that QALY loss is minimized when about 70% of the population are isolated. The burden associated with mental disorders amounts to a considerable part of COVID-19-related losses. Our findings demonstrate that cost-benefit analysis of mobility restriction should include a forecast of mental disorder development in the population.

The estimated disease burden of COVID-19 in Japan from 2020 to 2021

BackgroundTo date, it is not fully understood to what extent COVID-19 has burdened society in Japan. This study aimed to estimate the total disease burden due to COVID-19 in Japan during 2020–2021. MethodsWe stratify disease burden estimates by age group and present it as absolute Quality Adjusted Life Years (QALYs) lost and QALYs lost per 100,000 persons. The total estimated value of QALYs lost consists of (1) QALYs lost brought by deaths due to COVID-19, (2) QALYs lost brought by inpatient cases, (3) QALYs lost brought by outpatient cases, and (4) QALYs lost brought by long-COVID. ResultsThe total QALYs lost due to COVID-19 was estimated as 286,782 for two years, 114.0 QALYs per 100,000 population per year. 71.3% of them were explained by the burden derived from deaths. Probabilistic sensitivity analysis showed that the burden of outpatient cases was the most sensitive factor. ConclusionsThe large part of disease burden due to COVID-19 in Japan from the beginning of 2020 to the end of 2021 was derived from Wave 3, 4, and 5 and the proportion of QALYs lost due to morbidity in the total burden increased gradually. The estimated disease burden was smaller than that in other high-income countries. It will be our future challenge to take other indirect factors into consideration.

Cost-effectiveness of tenecteplase versus alteplase for acute ischemic stroke.

Alteplase is widely used as an intravenous thrombolytic drug in acute ischemic stroke (AIS). Recently however, tenecteplase, a modified form of tissue plasminogen activator, has been shown to increase early recanalization rate and has proven to be non-inferior with a similar safety profile compared to alteplase. This study aims to evaluate the cost-effectiveness of 0.25 mg/kg tenecteplase versus 0.9 mg/kg alteplase for intravenous thrombolysis in AIS patients from the Dutch healthcare payer perspective. A Markov decision-analytic model was constructed to assess total costs, total quality-adjusted life year (QALY), an incremental cost-effectiveness ratio, and incremental net monetary benefit (INMB) of two treatments at willingness-to-pay (WTP) thresholds of €50,000/QALY and €80,000/QALY over a 10-year time horizon. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted to test the robustness of results. Clinical data were obtained from large randomized controlled trials and real-world data. Treatment with tenecteplase saved €21 per patient while gaining 0.05 QALYs, resulting in INMB of €2381, clearly rendering tenecteplase cost-effective compared to alteplase. Importantly, tenecteplase remained the cost-effective alternative in all scenarios, including AIS patients due to large vessel occlusion (LVO). Probabilistic sensitivity analysis proved tenecteplase to be cost-effective with a 71.0% probability at a WTP threshold of €50,000/QALY. Tenecteplase treatment was cost-effective for all AIS patients (including AIS patients with LVO) compared to alteplase. The finding supports the broader use of tenecteplase in acute stroke care, as health outcomes improve at acceptable costs while having practical advantages, and a similar safety profile.