Five-year Time Horizon Research Articles

Evaluating cost-effectiveness of PFO management strategies: closure with Cardioform vs. Amplatzer, and treatment with medical therapy alone, for secondary stroke prevention

Aim The aim of this study was to evaluate the cost-effectiveness of patent foramen ovale (PFO) closure using CARDIOFORM Septal Occluders versus AMPLATZER Septal Occluders, as well as compared to Medical Therapy Alone, from a payor perspective in the United States. Methods An economic evaluation compared the value of CARDIOFORM, AMPLATZER, and Medical Therapy Alone. A Markov model simulated a cohort of 1,000 individuals with PFO and a history of cryptogenic stroke, with baseline demographic and clinical characteristics reflecting individuals enrolled in the REDUCE and RESPECT trials over a five-year time horizon. The costs and health consequences associated with complications and adverse events, including recurrent stroke, were compared over a time horizon of 5 years. Results PFO closure using CARDIOFORM was economically dominant, providing both cost-savings and improved effectiveness compared to closure with AMPLATZER. It resulted in an estimated savings of over $1.3 million, an additional 24.8 quality-adjusted life-years (QALYs) gained, and 28 strokes avoided in a cohort of 1,000 patients. When compared to Medical Therapy Alone, closure with CARDIOFORM was found to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of $36,697 per QALY gained. Sensitivity and scenario analysis showed the model findings to be highly robust across reasonable changes to baseline input values and assumptions. Conclusions The results of this analysis suggest that PFO closure using the CARDIOFORM Septal Occluder is the most cost-effective treatment strategy for patients with a PFO-associated stroke, particularly compared to AMPLATZER where it resulted in both cost-saving and improved patient outcomes.

Cost-Effectiveness Analysis of Current Treatment Options for Eosinophilic Esophagitis.

The management strategies for eosinophilic esophagitis (EoE) include proton pump inhibitors (PPI), swallowed topical steroids (tCS), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treament. We performed cost-effectiveness analyses to compare these approaches of first-line therapy. A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for EoE, including PPI, tCS, and six-food elimination diet (SFED), with.crossover in treatments for primary and secondary non-response. The primary outcome was incremental cost-effectiveness ratio (ICER) at two- and five-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab to tCS and PPI. In the base-case scenario (five-year time horizon), the average costs were SFED:$15,296.81, PPI:$16,153.77, and tCS:$20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a two-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both two- and five-year time horizons. Amongst pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions. SFED was the most effective/least costly first-line therapy from payer perspective, while PPI was more cost-effective from societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy.

Out-of-Pocket Cost Modeling of Adjuvant Antiestrogen and Radiation Therapy After Lumpectomy for Early-Stage Breast Cancer Across Medicaid and Medicare Plans

The optimal adjuvant therapy (antiestrogen therapy [ET] + radiation therapy or ET alone, or in some reports radiation therapy alone) in older women with early-stage breast cancer has been highly debated. However, granular details on the role of insurance in the out-of-pocket cost for patients receiving ET with or without radiation therapy are lacking. This project disaggregates out-of-pocket costs by insurance plans to increase treatment cost transparency. Several radiation therapy schedules are accepted standards as per the National Comprehensive Cancer Network guidelines. For our financial estimate model, we used the 5-fraction and 15-fraction radiation therapy and ET prescribed over a 5-year duration. The total aggregate out-of-pocket costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plans. The model assumes a Medicare- and/or Medicaid-eligible patient ≥70 years of age with node-negative, early-stage estrogen-receptor-positive breast cancer. Patient out-of-pocket costs were estimated from publicly available insurance data from plan-specific benefit coverage materials using a 5-year time horizon. Original Medicare beneficiaries face a total out-of-pocket treatment charge of $2738.52 for ET alone, $2221.26 for 5-fraction radiation therapy alone, $2573.92 for 15-fraction radiation therapy alone, $3361.26 for combined ET+ 5-fraction radiation therapy, and $3713.92 for combined ET + 15-fraction radiation therapy. Medigap Plan G beneficiaries have an out-of-pocket charge of $1130.00 with radiation therapy alone and face an out-of-pocket of $2270.00 for ET alone and combined ET+ radiation therapy. For Medicaid beneficiaries, all treatments approved by Medicaid are covered without limit, resulting in no out-of-pocket expense for either adjuvant treatment option. This model (based on actual cost estimates per insurance plan rather than claims data), by estimating expenses within Medicare and Medicaid plans, provides a level of transparency to patient cost. With knowledge of the costs borne by patients themselves, treatment decisions informed by patients' individual priorities and preferences may be further enhanced.

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.

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.

Remembrances of things past: evidence from a twenty-year Kerala panel

ABSTRACTWe construct a panel of 242 households from five consecutive Kerala Migration Surveys that span 20 years at five-year intervals to study the fundamental determinants of the decision to migrate abroad as well as the decision to remit. Accounting for time-invariant unobservables and allowing migration and remittance behavior to depend upon previous choices clarifies our understanding of both decisions. Migration and remittance behavior display positive serial correlation over a five-year time horizon and the presence of a return migrant in the household increases the likelihood of migration by 13% and remittances by 4%. Migration is 1% more likely in female-headed households, 4% less likely when the household head is employed, increases by 0.4% for each additional year of the household head's age and is 6% more likely in households that are asset-poor. Remittances are between 20% and 70% more likely to obtain when the migrant was married at the time of migration and 3% less likely when the household head is employed, the latter suggesting either an old-age security or a co-insurance motive. Evidence in favor of a very strong inheritance competition motive is found in that each additional male heir increases the likelihood of remittances by between 8% and 31%. Based on our econometric evidence, and in particular our findings pertaining to serial correlation and the presence of a return migrant in the household, it is likely that both migration from and remittances to Kerala will quickly rebound to their pre-pandemic levels.

PP61 Cost-Effectiveness Analysis Of Trastuzumab Deruxtecan Versus Chemotherapy For Previously Treated HER2-Positive Gastric Cancer In Singapore

IntroductionThe phase two DESTINY-Gastric-01 trial demonstrated that trastuzumab deruxtecan (T-DXd) improved overall survival in Asian patients with human epidermal growth factor receptor 2 (HER2)-positive, advanced gastric or gastroesophageal adenocarcinoma that had progressed following two or more treatments, compared with chemotherapy (irinotecan or paclitaxel monotherapy). Considering the high cost of T-DXd, we assessed the cost-effectiveness of T-DXd versus chemotherapy from the Singapore healthcare system’s perspective.MethodsA partitioned survival model with three health states (progression-free, progressed disease and death) was developed, with a five-year time horizon. Survival curves from DESTINY-Gastric-01 were extrapolated beyond the trial duration using parametric functions. Health state utilities were obtained from published literature and direct costs were sourced from public healthcare institutions in Singapore. Utility decrements for adverse events such as interstitial lung disease was incorporated into the model for the differences in safety profiles. A discount rate of three percent was applied to costs and outcomes. One-way deterministic sensitivity analyses (OWSA) and scenario analyses were conducted to assess parameter and model uncertainties.ResultsTreatment with T-Dxd, compared to chemotherapy, had a high base case incremental cost-effectiveness ratio (ICER) of over SGD450,000 (USD334,900) per quality-adjusted life-year gained. The cost of T-DXd greatly influenced the results according to OWSA. Seventy-three percent of the total costs accrued in the T-DXd arm was due to the cost of the drug, compared to seven percent in the chemotherapy arm. The ICER was also sensitive to the assumptions around extrapolation of the survival curves, but when tested across all scenario analyses, the results remained unfavorable.ConclusionsAt the current cost, T-DXd does not represent good value compared to chemotherapy for previously treated HER2-positive gastric cancer in Singapore. The findings from our cost-effectiveness analysis, alongside other considerations, will be useful to inform policy makers on funding decisions.

OP128 Uncertainties In The Cost-Effectiveness Analysis Of Onasemnogene Abeparvovec For Spinal Muscular Atrophy Type 1

IntroductionNusinersen and risdiplam are available in the Brazilian Unified Health System (SUS) for the treatment of spinal muscular atrophy (SMA) type 1. Onasemnogene abeparvovec, a promising gene therapy, was approved in 2020 in Brazil. Given the high cost of this therapy and its promise of a lifetime effect, the objective of this study was to evaluate the cost effectiveness of onasemnogene abeparvovec, compared with nusinersen and risdiplam, in the treatment of SMA type 1 from the perspective of SUS in different scenarios.MethodsA Markov model was adapted from one originally developed for the USA that considers five states of health. Short-term data were obtained from pivotal clinical trials and long-term survival curves were extracted from published reports from the USA. Maintenance of motor function milestones achieved at the end of follow up in clinical trials was considered until death. Costs and quality-adjusted life-years (QALYs) were discounted at five percent per year over a baseline lifetime time horizon. Alternative scenarios were evaluated for horizons of five and ten years, with and without a discount.ResultsOnasemnogene abeparvovec resulted in an incremental cost of BRL742,890 (USD297,156) per QALY and an increase of 3.32 QALYs in relation to the alternatives over a lifetime time horizon. In the same time horizon, but without the discount, onasemnogene abeparvovec resulted in an incremental cost-effectiveness ratio (ICER) of BRL166,539 (USD66,615) per QALY. In a five-year time horizon, considering the discount rate, the therapy resulted in an ICER of BRL12,527,667 (USD5,011,066); in ten years the ICER was BRL3,384,793 (USD1,353,917).ConclusionsSince the benefits of onasemnogene abeparvovec mainly occur in the long term, decision makers need to consider the uncertainty of assumptions of sustained effectiveness in view of the high initial cost of the technology.

Budget impact of introducing oral semaglutide to the public healthcare benefit package in Saudi Arabia

BackgroundThe Kingdom of Saudi Arabia (KSA) has embarked on a Health Sector Transformation Program as part of the Kingdom’s Vision 2030 initiatives with the facilitation of access to healthcare services for the millions in KSA with diabetes an essential part of the Program. Decision-making tools, such as budget impact models, are required to consider the addition of new medications like oral semaglutide that have multifaceted health benefits and address barriers related to therapeutic inertia to reduce diabetes-related complications.ObjectiveTo determine the financial impact of the introduction of oral semaglutide as a treatment option for people with type 2 diabetes mellitus (T2DM) in KSA.MethodsFrom the public payer’s perspective, the budget impact model estimates the costs before and after the introduction of oral semaglutide over a 5-year time horizon. The budget impact of introducing oral semaglutide (primary comparator) compared with three different classes of diabetes medicines: glucagon-like peptide-1 receptor agonists (GLP-1), sodium-glucose transport protein 2 inhibitors (SGLT 2i) and dipeptidyl peptidase 4 inhibitors (DDP-4i) have been calculated based on the projected market shares. The model includes the cost of care through the incorporation of health outcomes that have an impact on the national payer’s budget in Saudi Riyals (SAR).ResultsThe budget impact over the five-year time horizon indicates a medication cost increase (17,424,788 SAR), and cost offsets which include a difference in diabetes management costs (-3,625,287 SAR), CV complications costs (-810,733 SAR) and weight loss savings of 453,936 SAR. The cumulative total cost difference is 12,427,858 SAR (0.66%).ConclusionThe introduction of oral semaglutide 14 mg as a second-line treatment option after metformin is indicated as budget-neutral to slightly budget-inflating for the public pharmaceutical formulary of KSA. The price difference is offset by positive health outcomes and costs. This conclusion was confirmed through a probabilistic sensitivity analysis.

Transarterial therapies in patients with hepatocellular carcinoma eligible for transarterial embolization: a US cost-effectiveness analysis

ObjectivesTo assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC).DesignA cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a “watch and wait” state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature.ResultsAt five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained.ConclusionsTARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators.

Hybrid cardiac telerehabilitation for coronary artery disease in Australia: a cost-effectiveness analysis

BackgroundTraditional cardiac rehabilitation programs are centre-based and clinically supervised, with their safety and effectiveness well established. Notwithstanding the established benefits, cardiac rehabilitation remains underutilised. A possible alternative would be a hybrid approach where both centre-based and tele-based methods are combined to deliver cardiac rehabilitation to eligible patients. The objective of this study was to determine the long-term cost-effectiveness of a hybrid cardiac telerehabilitation and if it should be recommended to be implemented in the Australian context.MethodsFollowing a comprehensive literature search, we chose the Telerehab III trial intervention that investigated the effectiveness of a long-term hybrid cardiac telerehabilitation program. We developed a decision analytic model to estimate the cost-effectiveness of the Telerehab III trial using a Markov process. The model included stable cardiac disease and hospitalisation health states and simulations were run using one-month cycles over a five-year time horizon. The threshold for cost-effectiveness was set at $AU 28,000 per quality-adjusted life-year (QALY). For the base analysis, we assumed that 80% completed the programme. We tested the robustness of the results using probabilistic sensitivity and scenario analyses.ResultsTelerehab III intervention was more effective but more costly and was not cost-effective, at a threshold of $28,000 per QALY. For every 1,000 patients who undergo cardiac rehabilitation, employing the telerehabilitation intervention would cost $650,000 more, and 5.7 QALYs would be gained, over five years, compared to current practice. Under probabilistic sensitivity analysis, the intervention was cost-effective in only 18% of simulations. Similarly, if the intervention compliance was increased to 90%, it was still unlikely to be cost-effective.ConclusionHybrid cardiac telerehabilitation is highly unlikely to be cost-effective compared to the current practice in Australia. Exploration of alternative models of delivering cardiac telerehabilitation is still required. The results presented in this study are useful for policymakers wanting to make informed decisions about investment in hybrid cardiac telerehabilitation programs.

Cost-effectiveness analysis and budgetary impact of anidulafungin treatment for patients with candidemia and other forms of invasive candidiasis in Brazil.

Candidemia and other forms of invasive candidiasis (C/IC) are serious conditions, especially for immunosuppressed individuals with prolonged hospitalization in intensive care units (ICU). This study analyzed the incremental cost-effectiveness and budgetary impact (BI) of treatment for IC with anidulafungin compared to amphotericin B lipid complex (ABLC) and amphotericin B deoxycholate (ABD) or conventional amphotericin B (CAB), in the Brazilian Unified Health System (SUS). A decision model was conducted with a time horizon of two weeks from the perspective of SUS. The primary effectiveness endpoints were survival and treatment response rate. All patients were followed up until successful therapy or death. BI analysis was performed based on the measured demand method. A five-year time horizon was adopted based on the number of hospitalizations (per 1,000 hospitalizations). For effectiveness measured in the successful response rate (SRR), anidulafungin dominated the ABLC and ABD formulations. In the results of the analysis with the effectiveness measured according to survival, anidulafungin had a better cost-effectiveness ratio (R$988.26/survival) compared to ABD (R$16,359.50/survival). The BI estimate related to the incorporation of anidulafungin suggests savings of approximately 148 million reais in 5 years when comparing it to ABD. The economic evaluation of anidulafungin and its comparators found it to be cost-effective. The consensus of international scientific societies recommends it as a first-line drug for IC, and its incorporation by SUS would be important.

Clinical and economic impact of ferric carboxymaltose treatment for iron deficiency in patients stabilized following acute heart failure: a multinational study

ObjectiveTo estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF) <50% in the UK, Switzerland and Italy.MethodsA decision analytic cost-offset model was developed to evaluate the costs associated with introducing FCM for all eligible patients in three countries compared to a world without FCM, over a five-year time horizon. Data from AFFIRM-AHF clinical trial were used to model clinical outcomes, using an established cohort state-transition Markov model. Country-specific prevalence estimates were derived using data from real-world studies to extrapolate number of events and consequent cost totals to the population at risk on a national scale.ResultsThe cost-offset modeling demonstrated that FCM is projected to be a cost-saving intervention in all three country settings over a five-year time horizon. Savings were driven primarily by reduced hospitalizations and avoided cardiovascular deaths, with net cost savings of −£14,008,238, −CHF25,456,455 and −€105,295,146 incurred to the UK, Switzerland and Italy, respectively.LimitationsAlthough AFFIRM-AHF was a multinational trial, efficacy data per country was not sufficiently large to enable country-specific analysis, therefore overall clinical parameters have been assumed to apply to all countries.ConclusionsThis study provides further evidence of the potential cost savings achievable by treating ID with FCM at discharge in patients hospitalized for AHF with LVEF <50%. The value of FCM treatment within the healthcare systems of the UK, Switzerland and Italy was demonstrated even within a limited time frame of one year, with consistent cost savings indicated over a longer term.

PP59 Multidimensional Evaluation Of The Reducer Device In Patients With Refractory Angina

IntroductionTreatments for coronary heart disease patients have had major developments in recent decades, both in the pharmacological and interventional fields, and this has helped to prolong the survival of these patients. However, the growing number of patients who show persistent and disabling symptoms of angina proves that at the same time their quality of life has not been equally improved.MethodsWe conducted a multidimensional assessment coherent with health technology assessment methodology on the Coronary Sinus Reducer System (CSRS). CSRS is the latest line of therapy for patients with coronary artery disease who are ineligible for revascularization, demonstrate reversible ischemia, and have refractory angina pectoris (AP) despite optimal standard medical therapy. We performed a literature review in order to gather evidence on efficacy and safety of the device and on the economic and organizational impact of the procedure. In the economic domain we developed a cost-utility model based on a decision tree and a five-year time horizon budget impact model.ResultsSeveral studies in the literature have shown that this therapy is related to an increase in quality of life and an improvement in symptoms of refractory angina. The economic evaluations conducted show how the therapy, despite an increase in the resources absorbed in the first years of implementation, reaches a cost saving profile in the medium term due to positive outcomes, while leading to an increase in the quality of life in patients suffering from refractory angina.ConclusionsThe treatment of refractory angina remains a challenge for today’s medicine. Patients suffering from this condition are often described as “no option” patients. Thus, despite there is a need of further evidence to establish even more robustly the economic sustainability of the device, especially on its effectiveness in the medium-long term, the device should be taking into account in those patients who could benefit from it in terms of relieving the symptoms of angina and improving their quality of life.

Machine learning based multi-modal prediction of future decline toward Alzheimer's disease: An empirical study.

Alzheimer's disease (AD) is a neurodegenerative condition that progresses over decades. Early detection of individuals at high risk of future progression toward AD is likely to be of critical significance for the successful treatment and/or prevention of this devastating disease. In this paper, we present an empirical study to characterize how predictable an individual subjects' future AD trajectory is, several years in advance, based on rich multi-modal data, and using modern deep learning methods. Crucially, the machine learning strategy we propose can handle different future time horizons and can be trained with heterogeneous data that exhibit missingness and non-uniform follow-up visit times. Our experiments demonstrate that our strategy yields predictions that are more accurate than a model trained on a single time horizon (e.g. 3 years), which is common practice in prior literature. We also provide a comparison between linear and nonlinear models, verifying the well-established insight that the latter can offer a boost in performance. Our results also confirm that predicting future decline for cognitively normal (CN) individuals is more challenging than for individuals with mild cognitive impairment (MCI). Intriguingly, however, we discover that prediction accuracy decreases with increasing time horizon for CN subjects, but the trend is in the opposite direction for MCI subjects. Additionally, we quantify the contribution of different data types in prediction, which yields novel insights into the utility of different biomarkers. We find that molecular biomarkers are not as helpful for CN individuals as they are for MCI individuals, whereas magnetic resonance imaging biomarkers (hippocampus volume, specifically) offer a significant boost in prediction accuracy for CN individuals. Finally, we show how our model's prediction reveals the evolution of individual-level progression risk over a five-year time horizon. Our code is available at https://github.com/batuhankmkaraman/mlbasedad.

Ziconotide for the Management of Cancer Pain: A Budget Impact Analysis

ObjectivesRecent recommendations on starting dose, smaller dose increments, and longer intervals between dose increase have the potential to increase the safety of ziconotide administration in addition to improving its value for money. Ziconotide is not routinely commissioned in England, with one of the concerns being whether it represents the best use of resources. The aim of this project is to conduct a budget impact analysis to estimate the costs or savings associated with the changes in ziconotide dosage in addition to its use in combination with morphine for the management of cancer pain. Materials and MethodsAn open, Markov-like cohort decision analytic model was developed to estimate the budget impact of ziconotide in combination with morphine (ziconotide combination therapy) vs morphine monotherapy through intrathecal drug delivery (ITDD) for the management of cancer pain. The perspective adopted was that of the UK National Health Service, with a five-year time horizon. Sensitivity analyses were conducted to evaluate different scenarios. ResultsZiconotide combination therapy was more expensive than treatment with morphine monotherapy. The total costs of ziconotide combination therapy and morphine monotherapy for the first year were £395,748 and £136,628 respectively. The estimated five-year cumulative budget impact of treatment with ziconotide combination therapy for the five-year time horizon was £2,487,539, whereas that of morphine monotherapy was £913,804. The additional costs in any of the first five years are below the resource impact significance level of £1 million for medical technologies in England. ConclusionsThe results of this budget impact analysis suggest that although a combination of intrathecal ziconotide in combination with morphine is associated with higher costs to the health care system in England, the incremental costs are not significant. Routine commissioning of ziconotide alone or in combination with morphine would provide an alternative for a population with limited ITDD treatment options.

Cost-effectiveness of transcatheter aortic valve implantation in patients with severe symptomatic aortic stenosis of intermediate surgical risk in Singapore

ObjectiveThe objective was to assess the cost-effectiveness of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis with intermediate surgical risk in Singapore.MethodsA de novo Markov model with three health states – stroke with long-term sequelae, no stroke, and death – was developed and simulated using Monte Carlo simulations with 10,000 iterations over a five-year time horizon from the Singapore healthcare system perspective. A 3% annual discount rate for costs and outcomes and monthly cycle lengths were used. By applying the longest available published clinical evidence, simulated patients received either TAVI or surgical aortic valve replacement (SAVR) and were at risk of adverse events (AEs) such as moderate-to-severe paravalvular aortic regurgitation (PAR).ResultsWhen five-year PARTNER 2A data was applied, base-case analyses showed that the incremental cost-effectiveness ratio (ICER) for TAVI compared to SAVR was US$315,760 per quality-adjusted life year (QALY) gained. The high ICER was due to high incremental implantation and procedure costs of TAVI compared to SAVR, and marginal improvement of 0.10 QALYs as simulated mortality of TAVI exceeded SAVR at 3.75 years post-implantation. One-way sensitivity analysis showed that the ICERs were most sensitive to cost of PAR, utility values of SAVR patients, and cost of TAVI and SAVR implants and procedures. When disutilities for AEs were additionally applied, the ICER decreased to US$300,070 per QALY gained. TAVI was dominated by SAVR when the time horizon increased to 20 years. Clinical outcomes projected from one-year PARTNER S3i data further reduced the ICER to US$86,337 per QALY gained for TAVI, assuming early all-cause mortality benefits from TAVI continued to persist. This assumption was undermined when longer term data showed that TAVI’s early mortality benefits diminished at five years.Limitations and conclusionTAVI is unlikely to be cost-effective in intermediate surgical-risk patients compared to SAVR in Singapore.

Does the Choice of Health Metric, DALY or QALY, Influence Conclusions of Health Economic Evaluation? A Case Study of Rotavirus Vaccine in Burundi.

Two metrics, quality-adjusted life-year (QALY) and disability-adjusted life-year (DALY), have been commonly used to measure health benefits associated with health interventions. This study aimed to explore the effect of the choice of health metric (DALY or QALY) on economic evaluation conclusion. A previous published model for a cost-utility analysis (CUA) of rotavirus vaccine was adapted to estimate the QALYs gained and DALYs averted from four rotavirus vaccines: Rotarix, RotaTeq, Rotavac, and Rotasiil. The study was conducted in both Burundi provider and societal perspectives over a five-year time horizon. Disability weights (DW) were derived from the Global Burden of Disease (GBD) study. Scenario analysis was performed to evaluate the impact of age weights and source of utility weight. In base-case analysis, the QALYs gained ranged from 46 to 78% of the DALYs averted. The incremental cost-effectiveness ratios (ICER) per QALY gained were higher than ICER per DALY averted by 28 to 113%, leading to less favorable cost effectiveness. The QALYs gained from using 1-DW as utility weight were slightly higher than those using EQ-5D utility weight obtained from previous literature, yet less likely to alter CUA conclusions. When age-weighting was incorporated in the DALY calculation, the ICERs per DALY averted were reduced leading to more favorable cost effectiveness. In case of rotavirus diarrhea, in which mortality burden is considered larger than morbidity due to short duration of disease, although the use of DALY consistently led to more favorable cost-effective result than the use of QALY such effects were considered small and less likely to affect the EE conclusion under current CET of 1 GDP per capita.

POSA46 Cost Analysis of Lurasidone for the Treatment of Schizophrenia in Adults within the United Kingdom

An economic model was built to establish the incremental costs of lurasidone, a second-generation atypical antipsychotic, when introduced as a first-line adult schizophrenia treatment in the UK. The incremental cost of the following treatment sequences was estimated: lurasidone, cariprazine, brexpiprazole, clozapine versus cariprazine, brexpiprazole, lurasidone and clozapine. The costs of either lurasidone or cariprazine were compared as first-line options because there are currently no restrictions on treatment lines of schizophrenia therapy. A Markov model incorporating the following health states was developed: stable (receiving, or temporarily discontinued from, treatment) and relapse. Patient movement between health states was dependent on six-weekly probabilities of relapse and discontinuation due to intolerable side effects or any other reasons. All efficacy data were obtained from network meta-analyses. A six-week cycle length was used and a 3.5% discount rate was applied to costs over a five-year time horizon. Resource use and unit costs were reflective of the NHS and were obtained from published literature. Costs included treatment, outpatient, adverse events, primary and residential care. An increased mortality risk associated with schizophrenia was applied to all patients. Deterministic sensitivity analysis was undertaken to assess the uncertainty of the economic Results: The treatment sequence containing lurasidone as a first-line treatment resulted in a cost-saving of £816 per patient. First-line lurasidone was associated with increased treatment, stable health state and adverse event costs (£570, £107 and £6 per patient respectively). However, these costs were outweighed by the cost-savings within the relapse health state (savings of £1,499 per patient). Deterministic sensitivity analysis demonstrated the results were most sensitive to discontinuation rates, relapse rates and relapse residential costs. However, no variation in inputs caused first-line lurasidone to become cost-incurring. Lurasidone is a cost-saving intervention for the treatment of schizophrenia in adults when received first-line in a UK setting.

Rethinking companies’ culture through knowledge management lens during Industry 5.0 transition

Purpose Through the human resources (HR) and knowledge management (KM) perspective as human-centric processes, the aim of this study is to explore how companies’ engagement in diversity (DIV), inclusion (INC) and people empowerment (PEMP) policies influences companies’ organizational performance, to support organizations in the shift to the Industry 5.0 framework. Design/methodology/approach Combining the HR management and the KM-driven organizational culture, a conceptual model is proposed for explaining companies’ higher organizational performance. Proposed hypotheses are tested with reference to a set of listed international companies traced by Refinitiv on a five-year time horizon (2016–2020) through 24,196 firm-year observations. Findings This research shows that companies engaged in DIV policies, INC practices and PEMP through education have higher profitability and are more valued by capital markets’ investors. Originality/value This paper draws attention to the need to overcome the reductionist view of HR and rethink KM architecture to cope with the growing challenge of HR integration according to the Industry 5.0 paradigm.