bluuebunny/crossref_metadata_2025_split huggingface dataset:
Half-kilowatt high-energy third-harmonic conversion to 50 J @ 10 Hz at 343 nm
Authors: Pilar Jan , Divoky Martin , Phillips Jonathan , Hanus Martin , Navratil Petr , Denk Ondrej , Severova Patricie , Paliesek Tomas , Clarke Danielle , Smrz Martin , Butcher Thomas , Edwards Chris , Mocek Tomas 
Published: January 2025

Abstract
We present results of frequency tripling experiments performed at the Hilase facility on a cryogenically gas cooled multi-slab ytterbium-doped yttrium aluminum garnet laser system, Bivoj/DiPOLE. The laser produces high-energy ns pulses at 10 Hz repetition rate, which are frequency doubled using a type-I phase-matched lithium triborate (LBO) crystal and consequently frequency summed using a type-II phase-matched LBO crystal. We demonstrated a stable frequency conversion to 343 nm at 50 J energy and 10 Hz repetition rate with conversion efficiency of 53%.
Welfare regime typologies: The six worlds of social inclusion
Authors: Brown C. Taylor , Brik Anis Ben 
Published: January 2025

AbstractThis study bridges the study of social inclusion with welfare regime theory. By linking social inclusion with welfare regimes, we establish a novel analytical framework for assessing global trends and national divergences in social inclusion based on a multidimensional view of the concept. While scholars have developed typologies for social inclusion and welfare regimes independent of each other, limited insights exist on how social inclusion relates to welfare regime typologies. We develop a social inclusion index for 225 countries using principal component analysis with 10 measures of social inclusion from the United Nations’ Sustainable Development Goals Indicators Database. We then employ clustering algorithms to inductively group countries based on the index. We find six “worlds” of social inclusion based on the index and other social factors – the Low, Mid, and High Social Inclusion regimes and the Low, Mid, and High Social Exclusion regimes.
The Decolonial Aesthetics of Failure in Ali Hatami's Haji Washington (1982)
Authors: Vafa Amirhossein 
Published: January 2025

Abstract
Based freely on the writings of Hoseyn Qoli Khān Nuri, Persia's first ambassador to the United States (1888–1889), Haji Washington (1982) was Ali Hatami's first feature film following the Islamic Revolution. This article explores Hatami's departure from historical record in light of his aesthetic and political appropriation of Nuri's image as a failure. Viewing the film through a methodology that recasts failure as decolonial praxis beyond post/colonial mastery, I argue that Haji's embrace of failure, and his ultimate adoption of relationality as a mode of worldliness, constitute a “decolonial aesthetics of failure” with broad implications for both the world of the narrative and the moment of the film's production in postrevolutionary Iran.
OP01 Impact Of Cost Heterogeneity On Assessing The Value Of Gene Therapies
Authors: Zemplenyi Antal , Leonard Jim , DiStefano Michael , Anderson Kelly , Wright Garth , Mendola Nick , Nair Kavita , Mcqueen Robert 
Published: January 2025

IntroductionHigh-cost gene therapies strain the sustainability of healthcare budgets. Despite the potential long-term savings promised by certain gene therapies, realizing these savings faces challenges due to uncertainties regarding the treatment’s durability and a lesser-discussed factor: the true potential for cost offset. Our study aims to assess the cost-offset uncertainty for US Medicaid regarding recently approved gene therapies in hemophilia A and B.MethodsThe analysis used 2018 to 2022 Colorado Department of Health Care Policy & Financing data to determine direct costs of standard of care (factor replacement therapy or emicizumab). Cost-simulation models over five- and ten-year time horizons estimated Colorado Medicaid costs if patients switched to gene therapy (valoctocogene roxaparvovec or etranacogene dezaparvovec) versus maintaining standard of care. Patients were included if aged 18 and over with ICD-10-CM codes D66 (hemophilia A) and D67 (hemophilia B). In the base case, severe hemophilia A was defined as requiring greater than or equal to six yearly factor VIII or emicizumab claims and moderate/severe hemophilia B requiring greater than or equal to four factor IX replacement therapy claims annually.ResultsAnnual standard-of-care costs were USD426,000 (SD USD353,000) for hemophilia A and USD546,000 (SD USD542,000) for hemophilia B. Valoctocogene roxaparvovec (hemophilia A) had incremental costs of USD880,000 at five years and −USD481,000 at 10 years. Sensitivity analysis revealed a 23 percent chance of break-even within five years and 48 percent within 10 years. Etranacogene dezaparvovec (hemophilia B) showed incremental costs of USD429,000 at five years and −USD2,490,000 at 10 years. Simulation indicated a 32 percent chance of break-even within five years and 59 percent within 10 years. Varying eligibility (≥4 to ≥15 standard-of-care claims) notably affected break-even; for example, valoctocogene roxaparvovec: 40 percent to 77 percent chance of break-even in 10 years.ConclusionsOur study highlights significant cost variation in the standard of care of patients eligible for gene therapies, adding to the uncertainty surrounding cost estimation and highlighting the importance of addressing this factor in risk-sharing agreements. The impact of varying eligibility criteria on cost offsets emphasizes the importance of carefully defining eligibility when using real-world data in the context of health technology assessment.
OP05 Efficiency Frontier Analysis Of Ciltacabtagene Autoleucel For Relapsed/Refractory Multiple Myeloma In Brazil
Authors: Borin Marcus Carvalho , Álex Brunno do Nascimento Martins Ludmila Gargano , Alvernaz dos Santos Bárbara Rodrigues , Freitas Isabela , de Assis Acurcio Francisco , Alvares-Teodoro Juliana , Guerra Augusto 
Published: January 2025

IntroductionMultiple myeloma (MM) is a challenging hematological malignancy, primarily treated with autologous stem cell transplantation (ASCT). However, relapse or refractoriness is inevitable, necessitating alternative treatments. This study evaluates ciltacabtagene autoleucel (Carvykti®), a novel therapy, against a second ASCT, using an efficiency frontier approach to assess its therapeutic value and cost-effectiveness.MethodsWe conducted a comparative analysis using data from CARTITUDE-1 clinical trials and a Brazilian real-world cohort (2002 to 2015) of MM patients treated under SUS (Brazilian Healthcare System). We estimated survival curves and area under the curve (AUC) for both interventions over 48 months and projected the curves for a 10-year horizon using parametric distributions. Cost-effectiveness was assessed by calculating the incremental cost per month of survival. Efficiency frontier methodology was employed to determine a proportional price for ciltacabtagene autoleucel, based on the cost and median survival benefits compared to the second ASCT.ResultsCiltacabtagene autoleucel demonstrated a 7.27 percent increase in AUC for overall survival over 48 months compared to the second ASCT. The incremental cost was BRL54,219.15 (USD11,133.30) per month of survival. Over a 10-year horizon, the estimated cost for ciltacabtagene autoleucel was significantly higher than that for the second ASCT. Using the efficiency frontier approach, the cost of ciltacabtagene autoleucel should not exceed BRL228,226.42 (USD46,863.74), considering its survival benefit and cost of production.ConclusionsCiltacabtagene autoleucel demonstrates significant anti-tumor activity in relapsed/refractory MM, with a notable survival advantage. Efficiency frontier analysis suggests a maximum justified cost, providing a framework for pricing decisions. This study highlights the importance of balancing innovation with cost-effectiveness in healthcare decision-making.
OP07 Technical Aspects Of Artificial-Intelligence-Based Tools Applied In Health Technology Assessment Processes: A Scoping Review
Authors: Komoda Denis Satoshi , de Almeida Cardoso Marilia Mastrocolla , Lima Ana Renata , Visacri Marília Berlofa , Silveira Correa Carlos Roberto , Fernandes Brígida Dias 
Published: January 2025

IntroductionIn the last decade, artificial intelligence (AI) has been increasingly applied in health technology assessment (HTA) to accelerate evidence synthesis, optimize resources allocation, and guarantee timely delivery of trustworthy technologies in health. The aim of the present scoping review is to map AI models applied in HTA, and technical characteristics of AI-based automation and semi-automation applied in HTA.MethodsA search strategy containing core expressions “AI” and “HTA” and correlated terms was conducted in nine specialized databases (health and informatics) in February 2022. Inclusion criteria were publications testing AI models applied in HTA. Study selection was performed by independent pairs, with consensus meetings. No filters were applied. Data on year and country of publication, HTA phase, subsets of AI (e.g., machine learning [ML], neural networks), type of algorithm (e.g., support vector machine [SVM], K-nearest neighbors), and performance scale were extracted. Data were analyzed as descriptive frequency statistics. Used metrics will be presented narratively.Results
Sixty-one publications were included. The first study identified was published in 2006, and since then the number of publications has been consistently growing, with 11 publications in the year 2021. Canada, USA, and the UK concentrate 72 percent of publications (44 in 61) equally distributed. The most common HTA phase was the evidence synthesis, with 59 studies (96%). The main task performed was study screening/selection (66.6%). The majority of ML models (80.9%) contained two learning nodes or fewer, and applied SVM and decision-tree-based algorithms. Inter-rater agreement, accuracy, and 95 percent recall were the most common scales observed.ConclusionsAlthough recent developments in AI applied to HTA show increasing potentiality, studies are concentrated in the study selection phase of evidence synthesis. Many areas need further development, such as horizon scanning and policymaking processes. Additionally, studies reporting time gain and economic gain outcomes are scarce and should be considered for the development of future studies in the field.
OP21 Long-Term Cost-Effectiveness Of IDegLira Versus Basal-Bolus Insulin Therapy In Patients With Type 2 Diabetes In Chinese Setting
Authors: Weng Junling , Xiao Dunming , Chen Yingyao 
Published: January 2025

Introduction
IDegLira is a fixed-ratio combination (FRC) comprising insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, used for treating uncontrolled type 2 diabetes mellitus (T2DM) patients. We aimed to compare the long-term clinical and cost outcomes between IDegLira and basal-bolus insulin therapy by analyzing data from the Chinese healthcare system.Methods
The IQVIA Core Diabetes Model was employed to compare the two treatments. Cohort characteristics were derived from DUAL II China in patients with uncontrolled T2DM on basal insulin. Efficacy data were sourced from a published indirect comparative analysis. Utilities, medication, and complications costs were taken from publications. All costs were calculated in Chinese yuan (CNY) and discounted to 2022. The long-term outcomes estimated by the model spanned 40 years and encompassed life years (LY), quality-adjusted life years (QALY), cumulative incidence of diabetes-related complications, time alive and free of complication, costs, incremental cost-effectiveness ratio (ICER), and a probabilistic sensitivity analysis.ResultsIDegLira was associated with increased LY (12.46 vs 12.413), increased QALY (10.946 vs 10.669), and reduced costs (CNY408,580.94 [USD56,407.22] vs CNY586,937.81 [USD81,030.54]) compared to basal-bolus insulin therapy. IDegLira was dominant compared to basal-bolus insulin therapy and exhibited a reduction in the cumulative incidence of diabetes-related complications. Additionally, IDegLira extended the time alive and free of complications. The probabilistic sensitivity analysis showed with 100 percent accuracy that IDegLira is more cost effective as compared to basal-bolus insulin therapy.ConclusionsBased on this analysis, IDegLira can be fully regarded as a dominant treatment compared to basal-bolus insulin therapy in Chinese patients with uncontrolled T2DM on basal insulin.
OP24 How Does Robotic-Assisted Surgery Real-World Evidence Complement Randomized Controlled Trials Evidence? A Systematic Literature Review And Meta-Analysis
Authors: Patel Neera , Yankovsky Ana , Hebert April , Kreaden Usha 
Published: January 2025

IntroductionThe use of real-world evidence (RWE) by health technology assessments to evaluate emerging technologies has increased. Although traditionally recognized as the gold standard of evidence, randomized controlled trials (RCTs) may be challenging to conduct, especially in surgical settings. The aim of this analysis is to synthesize and compare results from RWE with those from RCTs for robotic-assisted surgery (RAS).MethodsA systematic review was performed according to PRISMA methods. RWE and RCT studies published between 1 January 2010 and 31 December 2022 and comparing RAS, laparoscopic, or open surgery across seven procedures were included. Perioperative outcomes of interest were operative time, length of stay (LOS), conversion to an open procedure, estimated blood loss (EBL), blood transfusions, readmissions, reoperations, postoperative complications, and mortality. A meta-analysis was performed using R software.Results
Thirty-three RCTs and 121 RWE studies were included. For RAS versus laparoscopy, RCTs and RWE were concordant for conversions (RCT:OR=0.56 [0.42, 0.74], p<0.01; RWE:OR = 0.41 [0.36, 0.47], p<0.01) and LOS in favor of RAS (RCT:WMD = −0.66 [−1.12, −0.20], p<0.01; RWE:WMD = −0.50 [−0.63, −0.36], p<0.01), while operative time was longer for RAS (RCT:WMD = 27.89 [12.66, 43.12], p<0.01; RWE:WMD = 28.89 [15.56, 42.22], p<0.01). RWE complemented RCTs on blood transfusions and mortality, showing RAS favored over laparoscopy. For RAS versus open surgery, RCTs and RWE agreed RAS had significantly lower EBL (RCT:WMD = −260.42 [−515.16, −5.67], p = 0.05; RWE: WMD = −328.27 [−474.08, −182.47], p<0.01), lower postoperative complications (RCT:OR = 0.70 [0.50, 0.97], p = 0.03; RWE:OR = 0.56 [0.50, 0.62], p<0.01), shorter LOS (RCT:WMD = −1.88 [−3.12, −0.64], p<0.01; RWE:WMD = −1.95 [−2.20, −1.70], p<0.01), and longer operative time (RCT:WMD = 35.38 [2.14, 68.61], p=0.04; RWE:WMD = 38.80 [24.62, 52.97], p<0.01). For the remaining outcomes, RCTs showed no difference, while RWE provided complementary results in favor of RAS.ConclusionsRWE confirmed many of the results shown in RCTs and complemented findings for perioperative outcomes. Based on these results, RWE can supplement the findings from RCTs in the literature, provide more generalizability, and offer a more comprehensive landscape of the evidence on robotic-assisted surgery.
OP25 Rapid Molecular Tests For Detecting Multidrug-Resistant Microorganisms: An Overview Of Systematic Reviews Within A Living Evidence Project
Authors: Imeshtari Valentin , Roteta Nora Ibargoyen , Arrate Gaizka Benguria , Cordero Lorea Galnares , Rojas Maria X. , Gutierrez-Ibarluzea Iñaki 
Published: January 2025

IntroductionRanked among the top 10 global health threats, antimicrobial resistance (AMR) prompts concern. Embracing a living evidence synthesis (LES), we address this concern by informing health decision-makers about molecular tests for swift detection of multidrug-resistant organisms (MDROs). This updated HTA report for the Spanish National Health System prioritizes decisions based on the most current evidence, adapting to emerging technologies and evidence.MethodsThe LES commenced with a baseline synthesis, shaping the initial HTA report regarding rapid molecular test impact on safety, efficacy, effectiveness, and patient outcomes in suspected infection cases. Based on this, on 12 July 2023, we initiated a 12-month evidence monitoring process. Utilizing the Living Evidence to Inform Health Decisions (LE-IHD) framework and interactive tools, we conducted ongoing baseline synthesis and evidence tracking. Artificial intelligence (AI) and the Living Overview of Evidence (L.OVE) platform aided in continual evidence identification. Tri-monthly scans of trial registries unveiled ongoing studies. New eligible studies were rigorously assessed. Updates in HTA conclusions were in line with this synthesis.ResultsThe baseline synthesis identified 25 systematic reviews that suggested that the use of rapid molecular test for the identification of pulmonary tuberculosis showed good performance, but less evidence or low-quality evidence was available for other medical conditions or on patient outcomes. During the conference, we will report on 11 months of monitoring and regular updates, including key messages on changes in the evidence synthesis conclusions whenever there are substantial updates of the HTA report.ConclusionsThe living evidence approach enables timely updates of conclusions for HTA reports relying on low- and very low-quality evidence, enhancing their significance in decision-making. The LE-IHD framework streamlines tasks for HTA developers in planning and executing LES to inform health decisions.
OP34 Implications Of The New EU Regulation For Orphan Drug Health Technology Assessments In Ireland
Authors: Usher Cara , McCullagh Laura , Barry Michael , Adams Roisin , Fogarty Emer , Tilson Lesley 
Published: January 2025

IntroductionTime to reimbursement has been described as a hurdle to availability of new medicines to European patients, with assessment and decision-making processes frequently quoted as taking the majority of time. In light of the upcoming Regulation (EU) 2021/2282 on health technology assessment (HTAR), the aim was to examine timelines and health technology assessment (HTA) recommendations for orphan drugs in Ireland.MethodsThe study reviewed all orphan drug submissions to the National Centre for Pharmacoeconomics (NCPE) from January 2020 to December 2023 inclusive. The number of days from marketing authorization to rapid review (RR) commissioning was calculated. The RR and HTA recommendations were identified for all medicines. The timelines for the RR and HTA process were evaluated.ResultsOf the 66 submissions identified, 38 percent were made prior to marketing authorization (MA), eight percent were made within 30 days of MA, and 79 percent were made 30 days post MA. RRs were completed within 32 days (mean). Full HTA was recommended in 62 percent (n=41). Price negotiations were recommended in 38 percent (50% of which have been reimbursed to date). Where a full HTA was recommended (n=41), 20 have been completed to date (price negotiations were recommended in 90%). For those 20 HTAs completed, 11 have been reimbursed to date; a decision is pending for the remainder. HTAs were completed within 200 days (mean).ConclusionsData shows that the majority of submissions were made 30 days post MA. A pragmatic approach may have to be taken nationally to accommodate the HTAR post 2024 and those submissions that are made prior to publication of a joint clinical assessment. The majority of orphan drug HTA recommendations lead to reimbursement recommendations.
OP39 Efficiency Frontier For Relapsing-Remitting Multiple Sclerosis In Brazil: An Approach To System Sustainability
Authors: Barros Bruno , Correia Marcelo , Tura Bernardo , Magliano Carlos 
Published: January 2025

IntroductionSeveral drugs are licensed for the treatment of relapsing-remitting multiple sclerosis (RRMS) in Brazil. The technological horizon of the disease introduces some additional therapies not yet approved in the country. The objective of this study was to establish an efficiency frontier for medicines used for RRMS, to guide the entry of new therapies into the market.MethodsPrimary data on the annualized relapse rate (ARR) and sustained disability progression for six months (CDP6), from 15 different therapies approved in Brazil, were obtained from the literature. Two network meta-analyses (NMA) were conducted comparing multiple treatments based on ARR and CDP6. A Markov model with transition states based on the Expanded Disability Status Scale (EDSS), with an annual cycle and a lifetime time horizon, was built to carry out the cost–utility assessment with an efficiency frontier.ResultsNMA results for ARR and CDP6 were used as inputs for the economic model. In the cost–utility analysis, all strategies were dominated by the lowest-cost medication (teriflunomide) and the most effective one (alemtuzumab). In the deterministic sensitivity analysis, alemtuzumab was the dominant drug in 78 percent of simulations. In probabilistic analysis, most medications had an incremental cost-effectiveness ratio (ICER) below the Brazilian cost-effectiveness threshold in over 90 percent of simulations (approximately USD8,000/quality-adjusted life years [QALY]). An efficiency frontier was established between teriflunomide and alemtuzumab, with an ICER of USD11,141/QALY.ConclusionsRRMS presents a scenario where several therapies compete for the Brazilian market, but only two of these drugs remained within the established efficiency frontier: alemtuzumab and teriflunomide. For the sustainability of public and private health systems, the efficiency frontier could serve as a cost-effectiveness benchmark, requiring new therapies considering entering the market to adapt to the set parameters.
OP49 Are Propensity-Score-Based Adjusted Indirect Comparisons Feasible For All European Joint Clinical Assessments Based On Non-Randomized Data?
Authors: Krüger Robert , Cantoni Chiara , Engen Anke Van 
Published: January 2025

IntroductionThe EU HTA member state coordination group has finalized methodological guidance on indirect comparisons that states that propensity score (PS) methods should generally be used for indirect comparisons of non-randomized data in joint clinical assessments (JCAs). Half of new oncology approvals by the European Medicines Agency (EMA) between 2020 and 2023 were based on non-randomized data. This study aimed to identify how many of these were able to submit PS-based comparisons.MethodsUsing IQVIA’s Market Access Insights (MAI) database of HTAs and regulatory approvals, we characterized evidence packages submitted to EMA and HTA agencies of EU member states according to the use of PS-based comparisons and access to individual patient data (IPD) from comparator studies.ResultsOf the 56 oncology approvals between 2020 and 2023, 30 (54%) were based on non-randomized data, of which 23 (23%) submitted PS-based indirect comparisons to EMA (15 therapies) or to HTA agencies (23 therapies). Electronic health record (EHR) or chart reviews were the most common source of comparative RWE, but agencies only took this evidence into account in fewer than half of HTAs where it was available. Use of PS-based methods also did not lead to more positive HTA outcomes than the alternative unanchored matching-adjusted indirect comparisons (MAICs) to aggregated data.ConclusionsThe prevalence of oncology approvals based on single-arm trials is expected to be a key challenge to the success of JCA. Unanchored comparisons will be required, but IPD was not necessarily shown to reduce uncertainty in HTAs analyzed in this research, and in about half of cases, comparisons to aggregate data were preferred due to applicability and heterogeneity concerns. Thus, the source of comparator data appears more relevant than the comparison method in HTAs, which contrasts with the available EU HTA coordination group guidance that focuses mainly on methodological aspects.