bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP36 Real-world Effectiveness Of Umeclidinium And Umeclidinium/Vilanterol For Chronic Obstructive Pulmonary Disease: A Singapore Database Study
Authors: Ng Shannon , Ong Benjamin , Ng Kwong 
Published: January 2025

IntroductionLong-acting muscarinic antagonist (LAMA) monotherapy and LAMA in combination with a long-acting beta2 agonist are preferred over inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) therapy for Global Initiative for Chronic Obstructive Lung Disease (COPD) Group B and C patients. This study assesses impact of the subsidy decision of umeclidinium (umec) and umeclidinium/vilanterol (umec/vil) on Singapore’s healthcare system.MethodsA retrospective cohort study was conducted using national health record databases. Maintenance-naive COPD patients, with no concurrent asthma, initiated on umec, umec/vil, or ICS/LABA from 2016 to 2020, were included. Patient demographics, comorbidities, and clinical characteristics were balanced using propensity score matching. Primary outcomes measured were the rate of severe or moderate COPD exacerbation and pneumonia hospitalization within one-year follow-up. Effect size was estimated using incidence rate ratio (IRR) with 95% confidence intervals (CIs) from Poisson regression. Markov model extrapolated the number of exacerbations and pneumonia hospitalizations avoided arising from the initiation of umec or umec/vil over ICS/LABA.ResultsPatients initiated on umec (n=1,019) were less likely to experience severe (IRR 0.649; 95% CI: 0.438, 0.961) and moderate exacerbations (IRR 0.713; 95% CI: 0.569, 0.892) than ICS/LABA. Similarly, umec/vil-treated patients (n=1,206) had lower rates of severe (IRR 0.713; 95% CI: 0.517, 0.985) and moderate exacerbation (IRR 0.778; 95% CI: 0.642, 0.942). Both therapies were safer than ICS/LABA, with fewer pneumonia hospitalizations for umec (IRR 0.719; 95% CI: 0.532, 0.973) and umec/vil (IRR 0.781; 95% CI: 0.623, 0.980). Coupled with reduced drug cost from value-based pricing, subsidy potentially resulted in SGD53 million (USD39 million) cost savings over 10 years.ConclusionsAs the largest real-world study conducted among COPD patients in Singapore, our findings contribute to the limited real-world evidence in the region. Compared to ICS/LABA, umec or umec/vil were associated with better COPD control and reduced rates of pneumonia hospitalization. This confirms the importance of appropriate prescribing of COPD therapies and validates the subsidy decision.
PP40 The Use Of “Softer” Outcomes In The NICE Health Technology Assessment Process: The Case Of Multiple Sclerosis
Authors: Kritikou Persefoni , Rose Alison 
Published: January 2025

IntroductionMultiple sclerosis (MS) is characterized by a significant humanistic burden, as this is a chronic progressive disease associated with high levels of disability and need for caregiver support. Our objective was to explore to what extent “softer” outcome measures are considered as part of the health technology assessment (HTA) process of medications evaluated for the management of MS.MethodsWe performed a review of all Technology Appraisal Guidance (TAs) available at the National Institute for Health and Care Excellence (NICE) website, relating to the management of MS, in order to identify outcomes used either by the manufacturer or discussed by the Committee, that were beyond the typical ones around the clinical evidence, side effects, and costs associated with each technology under evaluation. The review focused on outcomes relating to the caregiver burden, the ease of use of the medication under evaluation, and the fatigue reported by patients.ResultsFifteen TAs were identified. Eight (53%) of the TAs included information on the caregiver burden, where the manufacturers applied caregiver disutilities in the cost-effectiveness analyses, which were deemed appropriate by the Committee. Six (40%) of the TAs further included a discussion on the ease of use for specific medications where the Committee concluded that the benefits of the mode of administration may not have been captured in the cost-effectiveness analysis. Fatigue was discussed in two TAs; the Committee provided conflicting conclusions around this measure, but in the most recent TA, it recognized that fatigue was an important outcome measure.ConclusionsBased on the above findings, it appears that “softer” outcome measures are deemed relevant in the HTA process for treatments aimed for MS, on top of the measures typically used in the HTA process; this highlights the importance of recording the humanistic burden of disease in a holistic way.
PP49 Prescribing Trends And Economic Impact Of Somatostatin Analogues In Acromegaly: A Threat To Brazil’s Public Health System Sustainability
Authors: Porto Dantas Lara Benigno , Mendes de Farias Fellipe Miguel , de Sousa Alves da Silva Thizzah Cecília , Naves Luciana Ansaneli , Zimmermann Ivan Ricardo 
Published: January 2025

Introduction
First-generation somatostatin analogues (SSA) are indicated as a first-line medical treatment for acromegaly in patients with persistent disease after surgery or who are not eligible for surgery. These drugs are the largest contributor to the direct medical cost of acromegaly management worldwide. We analyze the patterns of prescription and costs of SSA for the treatment of acromegaly in Brazil.MethodsThe first-generation SSA, octreotide LAR (OCT-LAR) and lanreotide autogel (LAN-ATG), are available in Brazil to treat acromegaly through the Specialized Component of Pharmaceutical Assistance policy. The public records of the nationwide database (DATASUS) were accessed to identify the drug use patterns during the year 2022. The current values of the drug acquisition costs of each medication in 2022 were consulted at the national prices database (BPS). Results were converted in purchase power parity (PPP) dollars according to the World Bank rates.ResultsThe acquisition cost of each octreotide (OCT-LAR) ampoule was USD492.33 (10 mg), USD537.04 (20 mg), and USD703.79 (30 mg); for lanreotide (LAN-ATG), each ampoule was USD394.74 for the 60 mg dosage, and USD418.48 for the 90 mg and 120 mg dosages. The average annual cost of a monthly 30 mg dosage of OCT-LAR would be estimated as USD8,445,48 against an average annual cost of USD5,021.76 for a monthly 120 mg dosage of LAN-ATG. Thus, we estimate that USD15,520,747.59 was spent on first-generation SSA to treat acromegaly in Brazil’s Unified Health System (SUS) in the year 2022; of this, 79 percent was attributed to OCT-LAR.ConclusionsLife-long treatment with SSA is related with a high economic burden in Brazil. There is a predominance of OCT-LAR prescription, where expanding the use of LAN-ATG may help reduce costs to the SUS. Nevertheless, studies and investments in other treatments, such as pituitary surgery and radiotherapy access, at a national level are also essential to improve acromegaly treatment costs.
PP52 Pharmaceutical Innovativeness Index – FDA-Approved Prostate Cancer Medications (2011 To 2021): A Case Study
Authors: André Ariane , Gargano Ludmila , Freitas Isabela , de Assis Acurcio Francisco , Alvares-Teodoro Juliana , Guerra Augusto 
Published: January 2025

IntroductionProstate cancer (PC) constitutes 13.5% of all cancer cases globally. Treatment is individualized and depends on various factors. In recent years, there has been an increase in the approval of drugs for the disease by the U.S. Food and Drug Administration (FDA). The study aimed to assess the innovativeness of FDA-approved drugs for PC treatment from 2011 to 2021.MethodsA search was conducted in the FDA database to identify medications approved from 2011 to 2021 and their supporting studies for approval. The assessment of the value of innovations was performed through the Pharmaceutical Innovativeness Index (PII), a methodology that quantitatively evaluates innovations in four domains: Therapeutic Need and Added Therapeutic Value of the new medication (graded on five levels from important to absent), and Study Design and Methodological Quality (graded on three levels) of the pivotal studies used as a data source for evaluation. Medications are assessed for a specific clinical indication and compared to available therapeutic alternatives.ResultsSeven medications were identified for the treatment of PC, targeting different stages of the disease. The drugs were evaluated with a score ranging from 0 to 100, measuring the degree of innovativeness across the four assessed domains. Five (70%) medications scored above 50.0. The majority of the medications addressed a significant Therapeutic Need (n=4; 56%). The Added Therapeutic Value was assessed based on the survival gain compared to the comparator, with five medications considered poor (70%) and two moderate (30%). Regarding the quality of evidence, most studies showed a low risk of bias and a partially adequate design.ConclusionsIn recent years, there has been an increase in the development of drugs for prostate cancer. However, the Added Therapeutic Value shows a small to moderate increase in survival compared to existing treatments. Many studies used a placebo instead of comparing new medications with available therapies. The PII indicates that, despite advancements, new technologies are needed to improve patient survival.
PP53 Potential Cost-Effectiveness And Innovation Headroom Of A More Accurate Companion Diagnostic For PD-L1 In Non-Small-Cell Lung Cancer
Authors: Akinsoji Toluwase , Dragojlovic Nick , Darviot Cécile , Meunier Michel , Lynd Larry D. 
Published: January 2025

IntroductionWhile targeted therapies have substantially improved survival rates for non-small-cell lung cancer (NSCLC), it remains the leading cause of cancer mortality in the US. Companion diagnostics (CDx) measuring programmed death-ligand 1 (PD-L1) expression help inform NSCLC treatment but have limited accuracy. We assessed the potential value of a more accurate PD-L1 CDx for multiple stakeholders.MethodsWe developed decision tree models to assess the potential cost-effectiveness of a hypothetical new CDx for atezolizumab, a PD-L1 inhibitor used as a first-line therapy for metastatic NSCLC and as an adjuvant therapy for stage II–IIIa NSCLC patients. The sensitivity and specificity of current PD-L1 assays as well as cost and health payoffs were estimated based on data extracted from the scientific literature. We calculated incremental cost-effectiveness ratios (ICERs) for both indications, conducted headroom and threshold analyses, and used model outputs to estimate the size of the US serviceable addressable market (SAM) for a new PD-L1 CDx in the adjuvant indication.ResultsApproximately five percent of metastatic and seven percent of stage II–IIIa NSCLC patients currently tested for PD-L1 expression receive false negative results. An equivalently priced 100 percent accurate PD-L1 CDx would add an average of 0.04 quality-adjusted life years (QALYs) and cost USD6,069 more per metastatic NSCLC patient (ICER: USD144,512/QALY gained; 95% confidence interval [CI]: USD74,178, USD206,937). It would add 0.08 QALYs and cost USD3,682 more for stage II–IIIa NSCLC patients (ICER: USD49,031/QALY gained; 95% CI: USD47,104, USD50,064). The maximum value-based price in stage II–IIIa NSCLC (assuming a USD100,000/QALY willingness-to-pay threshold) would be ˜USD4,000/patient. At a USD500 price per unit, the SAM would be ˜USD6.5M/year.ConclusionsBecause existing PD-L1 assays for NSCLC are optimized for specificity, the cost-effectiveness of a more accurate CDx reflects that of the immunotherapy drug it is paired with. Stage II–IIIa NSCLC has much greater innovation headroom for a new PD-L1 CDx than metastatic NSCLC. Early cost-effectiveness modeling can identify CDx use cases with higher value headroom and help inform market sizing.
PP56 National Immunization Technical Advisory Groups Are Essential For Successful Implementation Of The European Health Technology Assessment Regulation
Authors: Wolters Sharon , Marapin Ramesh , Beekman Jasmijn , Gurgel Gabriel , Viceré Anna 
Published: January 2025

IntroductionStarting from 2030, vaccines in the European Union (EU) require joint clinical assessments (JCAs), and joint scientific consultations (JSCs) can be requested from 2025. Involvement of national immunization technical advisory groups (NITAGs) is crucial to address vaccine specificities. However, NITAGs are currently not considered in the EU health technology assessment (HTA) framework. This study highlights potential risks for non-applicability of vaccine JCA reports nationally.MethodsThis study examined where in the JCA and JSC implementation process NITAGs could play an important role and highlighted the practical challenges of incorporating vaccine JCA reports into already very heterogeneous and complex vaccine access pathways across EU Member States. The EU HTA Regulation process was tested for three countries with different vaccine market access characteristics. This study was conducted using JCA guidance documents, NITAG vaccine assessment guidelines, and communications with the respective decision-making bodies.Results
The EU HTA Regulation framework requires adjustments for vaccine-specific considerations. NITAGs across the EU vary in experience, resources, expertise, and influence on decision-making regarding vaccine assessment and inclusion in the national immunization program. In addition to JCA and JSC, the EU HTA framework also covers horizon scanning, which several NITAGs are currently involved with at national level.. However, the EU HTA framework currently lacks explicit requirements for NITAG input in horizon scanning, JSC, and JCA processes. This could lead to unnecessary duplication of work, further complexity of the processes, and lengthening of population time to access to new vaccines.ConclusionsThe EU HTA framework of vaccines aims to avoid duplicate efforts and enhance patient access, but current processes that will be introduced may not achieve this optimally. Early and systematic inclusion of NITAGs in the horizon scanning, JSC, and JCA processes is pivotal to mitigate the risk of non-applicability and to successfully realize the objectives of the EU HTA framework.
PP84 Developing The Network For The Future Of Healthcare Through Telemedicine-Driven Diagnostic Innovation
Authors: Galvan Pedro , Ortellado José , Rivas Ronald , Grossling Benicio , Hilario Enrique 
Published: January 2025

IntroductionThe healthcare digital landscape has evolved and is crucial in shaping strategies for fortifying the health system, specifically in building a network for the future of health services. There is also considerable interest in digital health to facilitate innovation and access to health services in underserved hospitals. This study has evaluated the results of a telemedicine-driven diagnostic network in remote Paraguayan hospitals.MethodsThis is a descriptive study, where the results using a digital telemedicine-driven diagnosis innovation in remote public hospitals were evaluated as a tool to improve equity and accessibility of specialized diagnostic services countrywide. For these purposes, the type and frequency of diagnosis performed through a digital telemedicine platform was determined.ResultsDuring the study, a futuristic telemedicine-driven diagnostic innovation was implemented in 67 hospitals countrywide. The digital telediagnosis network facilitated tele-electrocardiography (ECG), teletomography, tele-electroencephalography (EEG), tele-Holter and tele-ABPM (ambulatory blood pressure monitoring). The implemented digital telemedicine network has performed 828,073 tests in total between 2013 and 2023. The most performed diagnoses were ECG (543,815 tests) followed by teletomography (266,750 tests), EEG (17,418 tests), Holter (43 tests), and ABPM (28 tests).ConclusionsAccording to our results, the telemedicine-driven diagnostic innovation network facilitates faster and more equitable access to tertiary-level diagnostic services for patients in remote underserved public hospitals in Paraguay. A widespread use-assessment is necessary before this platform is implemented.
PP92 Enhancing Patient Engagement In Health Technology Assessment: Identification Of Barriers, Facilitators, And Proposals For Improvement
Authors: Triñanes Yolanda , Gómez-Salgado Patricia , Molina-Linde Máximo , Cantero-Muñoz Paula , Martín-Gómez Carmen , Granja-Domínguez Anabel , Toledo-Chávarri Ana 
Published: January 2025

IntroductionPatient engagement in the health technology assessment (HTA) field is crucial but faces significant challenges. This study focuses on identifying the barriers and facilitators surrounding the incorporation of patients in HTA while proposing solutions from the perspective of the Patient Interest Group (GIP) within the Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS).MethodsAn ad hoc questionnaire with four open-ended questions about barriers, facilitators, and proposals was developed and distributed among the GIP members through an email survey methodology. The obtained results were discussed in an open in-person meeting, and a thematic analysis of the data was conducted.Results
Fifteen people answered the questionnaire (at least one HTA researcher from each agency), and forty people participated in the face-to-face discussion. Main barriers included the perception of a lack of institutional support, insufficient participative culture, lack of time and experience, and difficulties in planning. Facilitators included activities organized within the GIP and methodological procedures and documents published. The main proposals for improvement were focused on the training and capacity building of HTA researchers and patients, institutional commitment to patient involvement, promotion of forums and activities with patient entities, and improvement of communication channels with patients and dissemination.ConclusionsDespite current challenges in patient involvement, this study highlights facilitators and proposals for improvement. Specialized training and education, along with the promotion of a participative culture, emerge as relevant strategies.
PP96 Evaluating The Quality-Of-Life Impact Of Erythropoiesis-Stimulating Agents For Lower Risk (Low To Intermediate-1) Myelodysplastic Syndrome Patients
Authors: Bennett Alastair , Manca Andrea 
Published: January 2025

Introduction
Patients diagnosed with low- to intermediate-1-risk myelodysplastic syndrome (LR-MDS) encounter symptom burden that diminishes their health-related quality of life (HRQoL). Erythropoiesis-stimulating agents (ESAs) remain an option to alleviate anemia-related symptoms. However, existing HRQoL studies show limited evidential support. This study assesses the impact of ESAs on LR-MDS patients’ EuroQol 5-dimension questionnaire (EQ-5D) scores compared to not using ESA as initial therapy.Methods
The European MDS Registry (EUMDS) collects information including ESA usage, covariates, and EQ-5D scores at six-month intervals. Estimating average treatment effect (ATE) from observational data requires adjusting for several sources of bias. Our study controls for baseline and time-varying confounding by using inverse probability of treatment weights. Employing a methodology based on marginal structural models, we are able to estimate robust ATEs. A two-part mixed-effects beta model was used to calculate ATE during a four-year follow-up period. We compare ESA therapy every six months versus clinical management not involving the use of ESAs.ResultsOur results show an overall positive ESA effect on EQ-5D over the four-year follow-up period. The majority of time points have a positive ESA effect after adjustment, though a few time points show no effect. The estimated ATE at four years is small: 0.046 (−0.031, 0.114).ConclusionsWe found that use of ESAs over a four-year follow-up period produces mostly positive treatment effect estimates after adjusting for time-varying variables and confounders. Our robust results can be used to inform more reliable treatment decision-making.
PP109 Which Review Is Right For You? Choosing A Review Methodology
Authors: Edwards Mary , di Ruffano Lavinia Ferrante 
Published: January 2025

IntroductionWhile systematic reviews (SRs) are regarded as the gold standard in healthcare evidence reviewing (and a requirement of many health technology assessments [(HTAs)]), other types of review also play an important role throughout a product’s lifecycle. Drawing on more than thirty years’ experience in conducting reviews, we present key points to consider when deciding which review type might be required.MethodsSRs are recommended when a comprehensive search and synthesis approach is required, for example HTAs. They have highly structured methods, emphasizing bias minimization, transparency, and replicability. “Rapid,” “pragmatic,” or “targeted” reviews are increasingly popular due to their accelerated timelines and reduced costs, with methodological shortcuts possible at various stages. Scoping reviews explore what is known about a topic and typically have a broad research question. “Reviews of reviews” or “overviews” identify existing SRs on an established topic. Finally, “living reviews” follow the same process as an SR or rapid review but incorporate new evidence on a continual or regular basis.ResultsRapid reviews may be appropriate when flexibility exists regarding the scope and review methods. Any limitations due to methodological shortcuts must be acknowledged in a transparent manner. Scoping reviews are useful for pioneering research ahead of an SR, or early in a product’s development phase, when an overall understanding of the evidence base is required. Reviews of reviews are particularly useful when the size of the primary study literature means that a review of primary studies would be unfeasible. Living reviews are best suited to topics where the evidence base is changing rapidly, or the best information is needed quickly.ConclusionsWhen considering conducting or commissioning a review, organizations should consider the intended audience for the review, the resources, time, and budget available, and the size of the existing literature. Although SRs remain the gold standard, a rapid review, scoping review, or review of reviews may offer a more suitable way to approach a given research question.