bluuebunny/crossref_metadata_2025 huggingface dataset:
Professional Supervision for Principals
Authors: Hunter Mary Ann , Broughton Geoffrey
Published: January 2025

School leaders work in increasingly complex systems. Alongside leading learning, they daily navigate the needs and expectations of educational departments, teachers, students, parents, society, and themselves. Leadership can therefore be a dynamic vocational calling, but studies show that principals' professional agency, career sustainability, and wellbeing are diminishing. This Element brings a fresh perspective to how educational leaders can be better served and supported by collaborative, co-agentic partnerships at this time. It makes the case for professional supervision, a practice commonplace in clinical and pastoral professions that offers facilitated, action-oriented attention to the interplay of role, 'soul', and context. As a practice-based primer, this Element reclaims supervision against outdated associations with performance management by drawing on interdisciplinary research and the authors' own experience as supervisor partners with principals. It proposes a new schema of professional supervision in education informed by curiosity, unlearning, resonance, and attunement in a rapidly changing world.
Agatha Christie and Gothic Horror
Authors: Richards Stuart
Published: January 2025

Agatha Christie's work has been adapted extensively resulting in transformations that are both textual and cultural. While many adaptations are best known for being quaint murder mysteries, there are many adaptations of her work that draw on horror aesthetics. This book will look at how the growth of Agatha Christie adaptations have grown increasingly darker. Of key relevance to this study is the work of Sarah Phelps, whose 'Witness for the Prosecution', 'And Then There Were None', 'Ordeal by Innocence', 'The ABC Murders' and 'The Pale Horse' all are darker than their precedents. Born out of their contemporary screen contexts, they use entrenched literary and filmic codes of Gothic horror as central reference points for audiences. Drawing on adaptation scholarship, where adapters are interpreters as well as creators, this study will look at how Agatha Christie is closer to Gothic horror than what we realise.
The Issue of Dark Patterns in Digital Platforms: The Challenge for Indonesia’s Consumer Protection Law
Authors: Hayati Adis Nur
Published: January 2025

Dark patterns have become a pervasive issue around the world. However, Indonesia has not taken any action to deal with the situation. This article aims to analyse the issue of dark patterns in digital platforms from Indonesia’s consumer protection law perspective. It contends that Indonesia’s consumer protection law is not adequate in overcoming the issue of dark patterns in digital platforms. Several laws regulate basic principles and provisions that indirectly prohibit dark patterns, but these regulations can only be applied to certain forms of dark patterns and are difficult to implement. The article suggests that Indonesia must specifically regulate the prohibition of the practices of dark patterns in its current law. The regulations do not have to define the term “dark patterns” directly; however, they should expressly regulate prohibitions against the practice of using design interfaces in a way that subverts or impairs consumers’ autonomy and/or exploits consumers’ behavioural biases.
Limitarianism and Relative Thresholds
Authors: Harel Ben Shahar Tammy
Published: January 2025

In her groundbreaking paper “Having too much” Ingrid Robeyns introduces the principle of “limitarianism,” arguing that it is morally impermissible to have more resources than needed for leading a maximally flourishing life. This paper focuses on one component of limitarian theory, namely the nature of the riches threshold, and critiques Robeyns’ absolute threshold, that limits wealth above what is needed for satiating human flourishing. The paper then suggests an alternative, relative threshold for determining excessive wealth, and also argues that limitarianism is best understood as a set of wealth-limiting principles, each with its own threshold, justifications, and conditions for operation.
Evidencing terrorism: Juridical truth-making in terrorism trials
Authors: Chukwuma Kodili Henry
Published: January 2025

This article explores the construction of terrorism via evidentiary practices, through the examination of terrorism trials in Nigeria. By conceptualising legal evidence – or evidencing – as a juridical practice of truth-making, the article contributes to the growing stream of critical literature on terrorism trials, and pre-emptive security more broadly, by examining the production of terrorism knowledge in light of the dominant pre-crime rationality that typically underpins counte-terrorism practice. The article highlights the complex processes and practices involved in the making of juridical truth in court and criminal justice processes, and how this enables the production and contestation of terrorism.

The article utilises important works on truth-making, alongside the contemporary literature on terrorism trials, to develop its theoretical and methodological approach. The empirical data for this study include court documents of terrorism cases in Nigeria, including those from the so-called Kainji trials, which emerged from fieldwork conducted in Abuja, Nigeria in 2020. The article demonstrates the productivity of legal evidence in the context of terrorism trials, involving different truth-makers, narratives, techniques, temporalities, and rationalities. In doing so, the article therefore contributes to the problematisation of terrorism and related issues of pre-emption, as well as the discussion on truth-making, by illustrating how the production of legal truth is shaped by different narratives, material practices, and logics in terrorism trials.
Global variation in the assessment of psychological trauma in pregnancy
Authors: Wall Kathryn , Penner Francesca , Wallace Goldman Lindsey , Shin Jin Young , Novak Eloise , Lowell Amanda , Day Michèle , Papa Lea , Wright Drew , Givrad Soudabeh , Rutherford Helena J. V.
Published: January 2025

A history of psychologically traumatic experiences can impact health outcomes for pregnant people and their infants. The perception and prevalence of traumatic experiences during pregnancy may differ by geographical region. To better understand trends in how and what kinds of psychological trauma are assessed globally, we conducted a secondary analysis on a larger systematic review examining psychological trauma measurement in pregnancy. Through a systematic literature review conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, completed between July 2021 and September 2023 using Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, PsycInfo and Cochrane, we identified 576 research studies assessing psychological trauma during pregnancy that were conducted across nine geopolitical regions. Most of these studies took place in North America, followed by sub-Saharan Africa, Europe, Asia, the Middle East or Northern Africa, Oceania, South America, and Central America. The fewest number of studies was conducted across multiple regions. We found that most studies measuring psychological trauma in pregnancy across the nine geopolitical regions assessed interpersonal trauma, and the fewest number of studies assessed healthcare trauma. Moreover, for each type of psychological trauma assessed, the greatest number of studies was conducted in North America. We also found that Central America, Oceania, sub-Saharan Africa, Asia, Middle East or Northern Africa, Europe, and studies conducted across multiple regions had one-third or more studies that only used in-house assessments, rather than previously validated assessments of psychological trauma. The results of this review emphasize the need for regionally specific and culturally appropriate measures of psychological trauma for pregnant people, which prioritize the types of psychological trauma that are most common in a given region. Newly developed measures can be used for screening and treatment of patients using trauma-informed obstetric care.
Is the European Parliament a Key to Success for (All) Right-Wing Populist Parties? Two Different Pathways to Engaging with the EP
Authors: Hwang Injeong
Published: January 2025

This study examines the intra-party mechanism that links right-wing populist parties' electoral performance in European elections and their persistence on the national political stage. Nationally marginalized right-wing populist parties have benefited from the second-order character of European elections since the introduction of the direct election in 1979. However, not every right-wing populist party has been able to turn its European victory into a national success. The most similar system comparison of right-wing populist parties in France and the UK shows that only parties that have strategically utilized the resources provided by the European Parliament have persisted in the national political arena.
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

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

This 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

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

Introduction

High-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.

Methods

The 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.

Results

Annual 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.

Conclusions

Our 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

Introduction

Multiple 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.

Methods

We 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.

Results

Ciltacabtagene 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.

Conclusions

Ciltacabtagene 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

Introduction

In 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.

Methods

A 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.

Conclusions

Although 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.

Results

IDegLira 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.

Conclusions

Based 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

Introduction

The 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).

Methods

A 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.

Conclusions

RWE 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

Introduction

Ranked 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.

Methods

The 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.

Results

The 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.

Conclusions

The 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

Introduction

Time 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.

Methods

The 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.

Results

Of 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).

Conclusions

Data 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

Introduction

Several 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.

Methods

Primary 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.

Results

NMA 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.

Conclusions

RRMS 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

Introduction

The 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.

Methods

Using 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.

Results

Of 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.

Conclusions

The 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.
OP54 Different Perceptions Of Additional Benefit By Payers And Providers: Discrepant Voting Within G-BA’s Benefit Appraisals
Authors: Rasch Andrej , Julian Elaine , Ruof Jörg
Published: January 2025

Introduction

Appraisal decisions on additional benefit of new medicines within the German health technology assessment (HTA) body Gemeinsamer Bundesausschuss (G-BA) are made by voting among the member of the G-BA plenary. We identified and analyzed key characteristics of decisions that were not reached by consensus.

Methods

G-BA’s homepage was used to identify AMNOG (German Medicines Market Reorganization Act) procedures that started after January 2011 and were finalized before November 2023. Appraisal voting is conducted publicly, and results are documented in the data source of the German Association of Research-Based Pharmaceutical Companies (vfa). Both the payer (National Association of Statutory Health Insurance [GKV-SV]) and provider (National Association of Statutory Health Insurance Physicians, Dentists and the German Hospital Federation) “benches” have an equal number of votes with the independent chair of the G-BA acting as swing vote in case of discrepant decisions. Discrepant voting instances were extracted and analyzed.

Results

From January 2011 to November 2023, G-BA conducted 908 appraisals of medicines. In 66 appraisals, (7.3%) decisions were not reached by consensus. Discrepant voting was related to oncological (n=28), metabolic (n=15), infectious (n=12), neurologic (n=3), cardiovascular (n=2), psychiatric (n=2), dermatologic (n=2), musculoskeletal (n=1) and urogenital conditions (n=1) conditions. Fourteen discrepant voting instances related to orphan medicines. The best benefit category reached in the 66 discrepant decisions were: major (n=2), considerable (n=16), minor (n=19), non-quantifiable (n=13), and no benefit (n=16). In all discrepant voting decisions, the provider bench favored a better scoring versus the payer bench.

Conclusions

Appraisal decisions within G-BA are reached by voting. The appraisals are a key element within the subsequent price negotiations. In all discrepant decisions, the payer bench suggests less benefit (strength of benefit, respectively) versus the provider bench, indicating a procedural challenge with the GKV-SV being involved in both the voting on the additional benefit and the negotiation of price.
OP67 “Black Box Bottleneck” Paradigm And Transparency Issues On Artificial-Intelligence-Based Tools In Health Technology Assessment: 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

Introduction

One of the pillars of health technology assessment (HTA) is transparency, which guarantees reproducibility and accountability. Due to the “black-boxness” of artificial intelligence (AI) models, the use of AI-based tools adds new layers of complexity for transparency issues. The aim of this scoping review is to map AI-based tools applied in HTA processes, regarding human supervision and “open-sourceness” aspects.

Methods

A search strategy using the terms “AI,” “HTA,” and correlated terms was performed in nine specialized databases (health and informatics) in February 2022. Inclusion criteria were publications testing AI models applied in HTA. Selection of studies was performed by two independent researchers. No filter was applied. Variables of interest included a subset of AI models (e.g., machine learning [ML], neural network), learning methods (e.g., supervised, unsupervised, or semi-supervised learning), and code availability (e.g., open source, closed source). Data were analyzed exploratorily as frequency statistics.

Results

ML with one layer of hidden nodes was applied in 48 (78.6 %) studies, while deep learning (DL) (two-plus layers) were applied in eight (13.1 %). ML models that used supervised learning accounted only for half of the reported models, while half used unsupervised learning. Considering supervision methods in DL models, seven used unsupervised learning, and one used supervision. Four studies did not report the AI model, and 14 studies did not report the supervision paradigm. It was not possible to assess “open-sourceness” in 31 studies. Among the identified software, seven models were not open source, and 13 were open source.

Conclusions

Transparency and accountability are of utmost importance to HTA. Complexity of AI models may introduce trustworthiness issues in HTA. Transparency provided by open-source code becomes essential in building trust in the automation of HTA processes, as does quality of report. Although progress has been observed in transparency and quality, the lack of a methodological framework still poses challenges in the field.
OP68 Adaptation Of Processes For HTA Of Digital Health Technologies Based On Artificial Intelligence
Authors: Moltó-Puigmartí Carolina , Segur-Ferrer Joan , Herrera Didier Domínguez , Trias Susanna Aussó , Vivanco-Hidalgo Rosa Maria
Published: January 2025

Introduction

The advent of artificial intelligence (AI) in digital health technologies (DHT) requires a comprehensive health technology assessment (HTA) to ensure safety and effectiveness and to demonstrate the value of these technologies in healthcare systems. Recognizing the unique requirements posed by AI-based DHT, our agency has undertaken several initiatives to tailor and adapt our processes for effective HTA.

Methods

We started by identifying the processes that were not working optimally and planned a list of actions needed to improve them. These actions were: (i) to develop a new evaluation framework for the assessment of DHT, including those based on AI; (ii) to increase our activity on early HTA; (iii) to seek collaboration with an organization for technical assessment of AI, with a particular emphasis on trustworthy AI requirements; (iv) to adapt our HTA report templates; (v) to create new forms to request information from the technology developers; and (vi) to set up a working group on HTA of AI-based
DHT.

Results

We have now an evaluation framework that informs on the relevant aspects for HTA of AI-based DHT and the evidence that developers need to generate in order to proof the value of their technology. We designed a circuit to identify promising technologies and increased our early HTA work for timely advice. The evaluation team now involves an additional partner for the technical assessment domain. In addition, we have new templates for early HTA reports, which explain those AI-specific elements to be addressed, as well as industry information request forms that enable collecting specific information like algorithm type and population used for clinical validation.

Conclusions

Tailoring HTA processes to AI-based DHT is crucial in today’s fast-paced health technology landscape. Our new evaluation framework, the involvement of new partners in the assessment team, the creation of new templates, and enhanced early HTA work helps to evaluate these technologies optimally. We are also setting up a working group to ensure homogeneous evaluation within Spain.
OP72 Patient Organization Submissions Made To A National Health Technology Assessment Agency In Ireland
Authors: O’Callaghan Joan , Tilson Lesley , Adams Roisin , McCullagh Laura
Published: January 2025

Introduction

The National Centre for Pharmacoeconomics (NCPE) has a Patient Organisation Submission Process (POSP) enabling patients to communicate their experiences to the drug-reimbursement decision-maker. The NCPE proactively invites and supports patient organizations to make submissions to the decision-maker for ongoing health technology assessments (HTAs). We evaluate uptake of the POSP and determine whether submission trends differ by drug type.

Methods

We reviewed all HTAs completed by the NCPE since 2016 (when the POSP was first introduced) to present (data cut-off date 22 November 2023). Time trends in the proportions of HTAs for which a patient organization submission had been made to the NCPE were analyzed descriptively. We also compared the proportions of HTAs for which a patient organization submission had been made for (i) orphan versus non-orphan drugs and (ii) oncology versus non-oncology drugs.

Results

The number of patient organization submissions made to the NCPE has increased over time. In 2016, 24 percent (6/25) of completed HTAs were associated with a patient organization submission compared with 50 percent (11/22) in 2023. The proportions of completed HTAs associated with a patient organization submission are comparable between orphan (38%; 24/64) and non-orphan drugs (29%; 34/117) (Chi²; p=0.245). The proportion of completed HTAs for which a patient organization submission had been made was lower for oncology drugs (14%; 14/97) versus non-oncology drugs (52%; 44/84) (Chi²; p<0.001).

Conclusions

Patient organization submissions to the NCPE have increased over time. The proportions of HTAs for which patient organization submissions have been made are comparable between orphan and non-orphan drugs. However, the proportion of patient organization submissions for oncology drugs is lower than the proportion for non-oncology drugs. The NCPE will continue to liaise with patient organizations to increase engagement with the POSP.
OP74 A Comprehensive Health Technology Assessment Framework For Omics Technologies In The Spanish Setting
Authors: Garcia-Sanz Patricia Julia , Aguilera-Cobos Lorena , Rosario Lozano María Piedad , Blasco-Amaro Juan Antonio
Published: January 2025

Introduction

Personalized precision medicine (PPM) is an innovative approach to disease diagnosis, prognosis, and treatment of individual or group characteristics using diverse data sources. While omics technologies are integral to PPM, they pose challenges. Therefore, developing an appropriate methodology to assess these technologies is crucial for patient safety, resource efficiency, and clinical decision-making within the Spanish National Health System.

Methods

This health technology assessment (HTA) methodology procedure was developed by combining three different approaches: a systematic review (SR); a survey targeting experts in omics technology, ranging from basic science researchers to clinicians, and patient associations; and, finally, a consensus method (RAND Appropriateness Method [RAM]).

Results

Through data extraction and evidence synthesis of the 38 studies included in SR, 30 existing frameworks for evaluating omics technologies were identified, as well as the elements needed to assess these technologies, leading to the first version of the framework. Two surveys were performed to integrate the perspectives of omics technology experts and patients. Subsequently, this framework version was further developed by a RAM consensus panel of experts from HTA agencies to ensure a rigorous evaluation of gathered data. The final framework was categorized into 94 elements divided into sections, categories, domains, and subdomains.

Conclusions

A methodological guide, including the assessment framework, was developed for the Spanish HTA network. The framework is divided into several sections addressing evidence-gathering, provision models, organizational elements, economic evaluation, and ethical and social implications. Compared to other available frameworks, our proposal included aspects such as bioinformatics, technological maturity level, and the patient perspective with the personal utility domain.
OP76 Cost-Effectiveness Of Offering Human Papillomavirus Self-Sampling To Non-Attendees Of Organized Primary Cervical Cancer Screening In Germany
Authors: Sroczynski Gaby , Hallsson Lára R. , Muehler Milena , Hillemanns Peter , Jentschke Matthias , Siebert Uwe
Published: January 2025

Introduction

In Germany, organized cervical cancer screening with annual Papanicolaou (Pap) cytology for women age 20 to 34 years and three-yearly co-testing with human papillomavirus (HPV) and Pap for women as of age 35 years is standard. However, about 30 percent of women eligible for screening remain un/under-screened. We systematically evaluated benefits, risks, and cost-effectiveness of offering additional HPV self-sampling (HPV-SS) to non-attendees.

Methods

A validated Markov model for the German context was used to evaluate different HPV-SS screening strategies compared to standard clinician-based screening: HPV-SS for non-attendees age 25 to 65, 30 to 65 or 35 to 65 years, every five years with regular invitation, either opt-in (invitation with link to order the test), or send-to-all (test sent with invitation). German clinical, epidemiological, and economic data (index year 2022/23), along with test accuracy and HPV-SS-attendance data from international meta-analyses and trials were incorporated. Outcomes included undiscounted life years gained (LYG) compared to standard screening without HPV-SS in non-attendees, and the incremental cost-effectiveness ratio (ICER; in EUR/LYG). Comprehensive sensitivity analyses were performed.

Results

Incremental undiscounted effectiveness (compared to standard screening without HPV-SS) and discounted ICERs (compared to next effective) for non-dominated HPV-SS screening strategies were 0.00090 LYG (EUR22,700/LYG) for offering with five-yearly screening invitation an HPV-SS (opt-in) to non-attendees age 35 to 65, 0.00166 LYG (EUR25,900/LYG) for HPV-SS (send-to-all) age 35 to 65, 0.00167 (EUR726,000/LYG) for HPV-SS (send-to-all) age 30 to 65, and 0.00167 LYG (EUR1.78 million/LYG) for HPV-SS (send-to-all) age 25 to 65 years. Other opt-in strategies were dominated. Results were robust over a wide range of parameter variations.

Conclusions

Offering HPV-SS (send-to-all) to non-attendees every five years as an additional strategy within the organized cervical cancer screening program is effective and cost effective in the German context. The results can be used to inform decision-makers and clinical guideline developers regarding incorporation of the specific version of HPV self-sampling into the established organized cervical cancer screening program in Germany.