bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP73 Integrating Valid Recommendations In The Clinical Practice Guidelines Updating Process Using GRADE Methodology
Authors: Sabalete-Moya Trinidad , Blasco-Amaro Juan Antonio , Gracia-San Román Francisco Javier , Engelhardt-Pintiado Ruth 
Published: January 2025

IntroductionThe development of clinical practical guidelines (CPGs) has been evolving towards a standard methodology based on GRADE. While reviewing CPGs, we found valid recommendations and no evidence to update. Including these initial recommendations in addition to new recommendations as part of the scope can improve understanding of the issue.MethodsTo develop a standardized approach to the writing of recommendations when updating a CPG, we consulted several methodological handbooks: Scottish Intercollegiate Guidelines Network (SIGN) (2011 and 2019 version), National Institute for Health and Care Excellence (NICE) last update (2024), New Zealand Guidelines Group (NZGG) grading system, and Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence 2. We compared the wording and specific symbols used to express strength of recommendations and quality of evidence with those used by GRADE, as described in the methodology handbook for developing clinical practice guidelines in the Spanish National Health System (SNS).ResultsA table was developed to express the equivalence of wording and symbols of quality of evidence and grading of recommendations to align the expression of SIGN, NICE, OCEBM, and NZGG methods with GRADE terminology. SIGN and NICE methodologies did not utilize specific symbols to express strength of recommendations; SIGN did not utilize the GRADE approach to assess the quality of evidence. The NZGG system applied its own classification for quality assessment and grading of recommendations. Oxford OCEBM keeps the terminology of level of evidence and grading of recommendations.ConclusionsUsing wording and symbols equivalence to standardize the recommendations of different methods to GRADE could assist the process of updating CPGs with the GRADE-Adolopment approach. Recommendations that are still valid and have been developed rigorously could be integrated in an updated CPG avoiding the duplication of efforts, but this generates uncertainty, especially when the quality assessment is focused on the studies designs.
PP77 Cost-Effectiveness Of The Dengue Vaccine (TAK-003) In Brazil
Authors: Fernandes Ricardo , da Costa Márcia Gisele , Tura Bernardo , Barros Bruno , Santos Marisa 
Published: January 2025

IntroductionDengue is an arbovirus that causes an acute febrile illness transmitted by the Aedes aegypti mosquito. The TAK-003 vaccine produced with Vero cells using recombinant DNA technology from the live and attenuated virus was approved by the Brazilian regulatory agency for preventing dengue infection, regardless of previous infection.MethodsA cost-effectiveness assessment comparing vaccinating specific age groups versus not vaccinating was conducted through a microsimulation model that tracked all epidemic rates over 20 years. Transitions between five health states (susceptible, asymptomatic, ambulatory, hospitalized, and death) were considered. Direct costs included vaccine costs and dengue healthcare (inpatient and outpatient). Quality-adjusted life years (QALY) were the primary outcome. Deterministic and probabilistic analyses explored key model uncertainties.ResultsAt a price of USD34.00 per dose, the average incremental cost-effectiveness ratio (ICER) was USD11,724.40/QALY. In the probabilistic analysis, no simulation was below the threshold of USD8,000.00/QALY. In an alternative scenario, in which the price of the vaccine would not be subject to taxes in the case of direct import, the average ICER was USD10,378,09/QALY, with one percent of the simulations below the standard cost-effectiveness threshold.ConclusionsAt both price scenarios, dengue vaccine did not prove to be a cost-effective technology to be funded for patients between four and 60 years old. Sensitivity analyses showed that vaccine price is the most sensitive variable. This study can support price negotiations to improve access to the vaccine.
PP101 A Review Of Health State Utility Values Associated With Herpes Zoster
Authors: Bergin Aoife , O’Donnell Helen , Ahern Susan , Quigley Joan , Harrington Patricia , Teljeur Conor , Ryan Máirín 
Published: January 2025

IntroductionHerpes zoster and post-herpetic neuralgia (PHN) can cause significant pain and morbidity, impacting on the health-related quality of life of those affected. This research aimed to identify primary studies that elicited health state utility values (HSUVs) relating to both acute herpes zoster and PHN, and to assess their suitability for an economic model of herpes zoster vaccination.MethodsCost-effectiveness analyses of herpes zoster vaccination were identified from (i) a recently published systematic review of economic evaluations of herpes zoster vaccination and (ii) an independently conducted rapid review that sought to update the results of the identified systematic review. The evaluations were hand-searched to identify original studies that elicited HSUVs of interest. Narrative synthesis of the original study characteristics was conducted and possible sources of variation in the studies identified. Appraisal of the methodological quality of the studies was undertaken using a published open response tool that outlined key quality assessment criteria for HSUV studies.ResultsTwenty-one studies that elicited HSUVs were identified. Values related either to changes in utility resulting from increased pain severity, or to changes with time since disease onset. Heterogeneity was observed, potentially caused by differences in population size and characteristics, methods of elicitation, and preference weights used to value utility. Methodological quality varied across studies, with concerns around low sample sizes for populations with PHN, and poor reporting of both missing data and uncertainty around the HSUVs obtained. Differences in study population, time of participant recruitment, and methods of measuring utility could limit the applicability of HSUV study data.ConclusionsThis study highlights both the heterogeneity in HSUVs obtained for herpes zoster and the challenges associated with selecting HSUV data suitable for an economic model. An evidence base from which to select values for an economic evaluation has been created, though poor methodological quality and reporting of the primary studies may compromise the validity of point estimates obtained.
PP102 Sustaining Ghana’s National Health Insurance Scheme: Leveraging The Role Of Priority-Setting Tools In Benefit Package Reviews
Authors: Mensah Annan Ruby Aileen , Heupink Lieke Fleur , Owusu Richmond , Frønsdal Katrine , Aryeetey Genevieve , Chola Lumbwe , Akweongo Patricia 
Published: January 2025

IntroductionEnsuring the National Health Insurance Scheme’s (NHIS) sustainability is essential to achieve Universal Health Coverage in Ghana. However, numerous addition requests to the Benefit Package (BP) places the scheme in precarious situations, necessitating evidence-based prioritization. Our objective is to conduct a situational analysis on the role of health technology assessment and priority-setting within the National Health Insurance Authority (NHIA).MethodsQualitative methods were used to assess the current NHIS BP review process. Desk reviews of policy documents and key informant interviews to establish the mandate of the NHIA in BP reviews were conducted. Finally, a mapping of the alignment of evidence from HTAs conducted by the Ministry of Health (MOH) with recent BP review and inclusion decisions of the NHIA was carried out.ResultsFindings validate the legal mandate of the NHIA to carry out BP reviews with processes spelled out in operating guidelines. Actuarial analysis determines the scheme’s capability to fund additional service, but no explicit priority-setting criteria are used. This leaves the NHIA open to external pressures for inclusion and presents risks to the financial sustainability of the scheme. An HTA on antihypertensive treatments in 2017 influenced reimbursement pathways of the NHIA. Similarly, the cost-effectiveness of extending existing medications on the NHIS Medicines List to cover Burkitt lymphoma corroborated the decision of the NHIA to cover childhood cancer in 2021.ConclusionsThe NHIA uses actuarial evidence in BP inclusion decisions. It, however, lacks an explicit priority-setting criteria to guide decisions on coverage. HTA evidence has been leveraged for sustainable coverage decisions. The development of an explicit priority-setting framework for reviews can guide inclusion decisions as well as clarify how the NHIA aligns with the HTA generation body.
PP106 Links Between Accuracy And Effectiveness Of Laboratory Diagnostic Tests: Health Technology Assessment Of Two Analytical Approaches For Glycated Hemoglobin
Authors: Di Resta Chiara , Sacco Chiara , Trbos Mladen , Locatelli Massimo , Tomaiuolo Rossella , Banfi Giuseppe 
Published: January 2025

IntroductionIn the field of laboratory medicine, the evolution of knowledge and the innovation of technologies are the basis of analytic and diagnostic progress, leading to the development of new solutions based on innovative technologies. However, these advances must be accompanied by evidence of appropriateness, diagnostic effectiveness, and efficiency of organizational aspects, considering the impact of the test on patient outcomes.MethodsThis study is an exemplificative case of the application of health technology assessment (HTA), exploiting the EUnetHTA core model, on two analyzers able to determine the glycated hemoglobin (hemoglobin A1c, HbA1c), the Capillarys 2 Flex Piercing analyzer (by Sebia, Lisses, France), and the HLC-723G11 analyzer (by Tosoh Corporation, Shunan, Yamaguchi, Japan) in the Laboratory Medicine Service of the IRCCS San Raffaele Hospital (Milan, Italy).ResultsThe nine domains of the EUnetHTA model are assessed, comparing the two technologies of interest and highlighting their pros and cons. As described below, the main aspect to be considered is the impact of the testing results on the clinical effectiveness evidence, due to the two different detection methods while both analyzers respond equally to the clinical and organizational needs of the San Raffaele laboratory.ConclusionsThis study demonstrates how HTA can aid decision-makers in evaluating health technologies to achieve specific objectives of diagnosis, treatment, and prevention.
PD04 A Systematic Review Of Decision Analytical Modeling Studies Of Medicines In The Middle East
Authors: Abdali Zainab , Avsar Tuba Saygin , Jowett Sue , Syed Muslim Abbas , Elmusharaf Khalifa , Jackson Louise 
Published: January 2025

IntroductionEconomic evaluation using decision analytical models (DAMs) plays a limited role in shaping healthcare resource optimization and reimbursement decisions in the Middle East. This review aimed to systematically examine economic evaluation studies focusing on DAMs of medicines in the Middle East, defining methodological characteristics and appraising the quality of the identified models.Methods
Six databases were searched (MEDLINE, Embase, EconLit, Web of Science, the Global Health Cost-Effectiveness Analysis Registry, and the Global Index Medicus) from 1998 to September 2023 to identify published DAMs of medicines in the Middle East. Studies meeting the inclusion criteria—full economic evaluations of medicines using a model-based method in the Middle East—were included. Data were extracted and tabulated to include study characteristics and methodological specifications. The results were analyzed narratively. The Philips checklist was used to assess the quality of the studies.ResultsSixty-two DAM studies of medicines were identified from nine Middle Eastern countries, the majority of which (76%) were conducted in Iran, Turkey, and Saudi Arabia. The cost effectiveness of medications for non-communicable diseases was explored in 70 percent of the models. Cost-effectiveness thresholds based on gross domestic product were commonly used. International sources provided data on intervention effectiveness and health outcomes, while national sources were mainly used for the costs of resource use. Most models incorporated an assessment of parameter uncertainty, whereas other types of uncertainty were not explored. Studies from high-income countries were generally of higher quality than those from middle-income countries.ConclusionsThe number of published DAMs was low considering the available medicines and disease burden. Key aspects of high quality DAMs regarding model structure, input sources, and uncertainty assessment were not consistently fulfilled. Recommendations for future studies and policies included strengthening existing health economic capacities, establishing country-specific health technology assessment systems, and initiating collaborations to generate national cost and outcome data.
PD10 Cost Effectiveness Analysis Of Etranacogene Dezaparvovec Versus Factor IX Prophylaxis In Adult Men With Hemophilia B From Brazil
Authors: Silva Mendes Ana Clara , Camelo Ricardo Mesquita , Alvares-Teodoro Juliana 
Published: January 2025

IntroductionHemophilia B (HB) is a rare bleeding disorder caused by clotting factor IX (FIX) deficiency. Regular FIX replacement (prophylaxis) is the mainstream treatment for preventing bleeding in people with HB. Etranacogene dezaparvovec, also known as AMT-061, is a new gene therapy approved in many countries for people with HB. This study evaluated the cost effectiveness of conventional FIX prophylaxis compared with AMT-061 for people with HB.Methods
A cost-effectiveness decision tree was constructed based on current literature and national guidelines on HB treatment. The model was based on a Brazilian Ministry of Health perspective, assumed that people with severe HB were 18 years or older, and used a time horizon of three years. The Brazilian Ministry of Health distributes plasma-derived FIX (pdFIX) for prophylaxis. The cost of pdFIX was obtained from data on public purchases and AMT-061 cost was based on the price of a currently approved gene therapy in Brazil. Sensitivity analyses were performed to assess uncertainty and to identify which variables most affected the incremental costs.ResultsThe cost of prophylaxis with pdFIX for three years was BRL233,309 (USD41,236) with an annualized bleeding rate (ABR) of 10.95, while the cost of gene therapy for three years was BRL10,379,041 (USD1,834,466) with an ABR of 2.86. This resulted in an incremental cost-effectiveness ratio (ICER) of BRL1,253,674 (USD221,583) per bleeding episode. Compared with pdFIX, AMT-061 was not cost effective since there was a threshold of BRL30,000 (USD5,302) per bleeding episode avoided. In the deterministic sensitivity analysis, treatment time had a major impact on the ICER, followed by AMT-061
cost.ConclusionsIn this model, AMT-061 was not cost effective compared with pdFIX prophylaxis. In the long term or with a lower AMT-061 cost, gene therapy may be cost effective. AMT-061 demonstrated better clinical results, but its economic viability must be considered in terms of access and sustainability in the Brazilian public healthcare system.
PD11 Cost-Effectiveness Analysis Of Inclisiran For Treating Primary Hypercholesterolemia And Mixed Dyslipidemia In Singapore
Authors: Lim Yan Ling , Tan Ru San , Poh Kian Keong , Wang Xiao Jun 
Published: January 2025

IntroductionInclisiran is approved in Singapore as an add-on to maximally tolerated statins for the treatment of primary hypercholesterolemia or mixed dyslipidemia. This study evaluated the cost effectiveness of inclisiran compared with standard care (SC), evolocumab, or alirocumab to treat primary hypercholesterolemia and mixed dyslipidemia.MethodsA lifetime Markov model was used to evaluate the cost effectiveness of inclisiran as an add-on to SC (inclisiran+SC) versus SC alone, evolocumab+SC, or alirocumab+SC in four subpopulations: atherosclerotic cardiovascular disease (ASCVD), secondary prevention of heterozygous familial hypercholesterolemia (HeFH), primary prevention of HeFH, and primary prevention in patients with an elevated risk of ASCVD Baseline cardiovascular event risks were estimated from databases and published literature from the Netherlands and the UK. Efficacy data were obtained from the ORION trials and other comparative trials. Costs were obtained from public healthcare institutions and local publications. A willingness-to-pay (WTP) threshold of SGD45,000 (USD33,280) per quality-adjusted life-year (QALY) was selected, and a one-way deterministic sensitivity analysis (DSA) was performed.ResultsInclisiran+SC resulted in higher QALYs and higher total costs than SC alone in all four subpopulations, with incremental cost-effectiveness ratios (ICERs) ranging from SGD34,654 to SGD163,158 (USD25,630 to USD120,673) per QALY gained. At the selected WTP threshold, inclisiran+SC was cost effective, compared with SC, in patients with ASCVD and for secondary prevention of HeFH. Compared with evolocumab+SC and alirocumab+SC, inclisiran+SC achieved higher total QALYs at a lower total cost in all four subpopulations. The ICER was most sensitive to the price and efficacy of inclisiran and the rate ratios translating reductions in low-density lipoprotein cholesterol levels to the risk of cardiovascular death.ConclusionsInclisiran+SC resulted in greater QALYs and higher costs, compared with SC alone, and higher QALYs at lower costs, compared with evolocumab+SC and alirocumab+SC, in adults with primary hypercholesterolemia and mixed dyslipidemia. At the selected WTP threshold, inclisiran+SC was cost effective, compared with SC alone, in patients with ASCVD and for secondary prevention of HeFH. These findings can help inform future funding decisions in Singapore.
PD29 Using Different Parametric Distributions In Partitioned Survival Analysis: Impact On Incremental Cost-Utility Ratio In A Proportional Hazards Model
Authors: Gargano Ludmila , Oliveira Layssa , De Oliveira Junior Haliton Alves , Lucchetta Rosa 
Published: January 2025

IntroductionPartitioned survival analysis (PtSA) is a useful modeling technique, especially in oncology, in which different parametric distributions can be used to extrapolate survival data. Many studies lack justification for their chosen distributions, neglecting exploration of uncertainty in extrapolated estimates. We evaluated how different distributions impact the incremental cost-utility ratio (ICUR) for docetaxel, compared with abiraterone plus docetaxel (AA+DTX), for prostate cancer.MethodsA three-state PtSA was constructed using overall survival (OS) and progression-free survival (PFS) curves from a docetaxel trial extrapolated over a 20-year horizon with exponential, Weibull, and Gompertz distributions. Log-normal, log-logistic, and generalized gamma were not considered because they are not compatible with the proportional hazards assumption. Curves for AA+DTX were adjusted using hazard ratios (HRs) from indirect comparisons for OS (HR 0.75, 95% confidence interval [CI]: 0.59, 0.95) and PFS (HR 0.50, 95% CI: 0.35, 0.72). Assessment included visual inspection, clinical plausibility, and Akaike and Bayesian information criterion (AIC/BIC) statistics. Utility values, medication costs, and disease monitoring costs were considered based on health state (pre- or post-progression).ResultsFor docetaxel PFS, visual inspection showed no significant differences between the three distributions used for the proportional hazards model, while the exponential model showed the longest tail for OS. When choosing by the lowest AIC/BIC (OS: Weibull; PFS: exponential), cost-effectiveness analysis resulted in an ICUR of BRL79,224 (USD16,139) per quality-adjusted life-year (QALY). The maximum and minimum ICUR was BRL81,559 (USD16,615) (OS: Gompertz; PFS: Weibull) and BRL70,136 (USD14,288) (OS: exponential; PFS: Weibull), respectively, which represented an important variation in the base case scenario (AIC/BIC) ICUR.ConclusionsUsing the Brazilian cost-effectiveness threshold (BRL120,000 [USD24,446] per QALY gained) and choosing any of the three distributions of the proportional hazards model, AA+DTX would be considered cost effective, which would not change the direction of the recommendation. However, despite the few recommendations in the literature regarding the adoption of parametric models for economic analyses in health, it is important to explore scenarios with different distributions.
PD43 Single-Arm Studies In Literature Reviews: Trials Versus Case Series
Authors: Chappell Mary , Fitzgerald Anita , Sanderson Alice , Watkins Deborah , Miller Paul , di Ruffano Lavinia Ferrante , Edwards Mary , McCool Rachael 
Published: January 2025

IntroductionSingle-arm studies, particularly single-arm trials (SATs), are increasingly being used in submissions for marketing authorization and health technology assessment. As reviewers of evidence, we sought to better understand the validity of SATs, compared with observational single-arm studies (case series), and how to assess them in our reviews.Methods
We conducted a highly pragmatic literature review to create a convenience sample of recent systematic reviews published from January to July 2023 to establish the following: (i) what single-arm study designs are included; (ii) what quality assessment tools are used; and (iii) whether there is a difference in effect size and variability among different study designs. A single reviewer identified reviews of interventions that included single-arm studies and extracted information on the numbers of included SATs and case series, and the quality assessment tools used. Any misclassifications by review authors were identified. For meta-analyses, outcome data were extracted and a subgroup analysis comparing SATs and case series was conducted.ResultsWork is still underway to complete this investigation. So far, it appears that a large proportion of systematic reviews misclassify SATs and case series studies and few use appropriate quality assessment tools. There is not yet any evidence of a systematic difference between SATs and case series in terms of effect size.Conclusions
Findings suggest that there is poor understanding of SATs in the review community. There are limited specific quality assessment tools for SATs and review authors frequently use inappropriate tools to assess them. More research is likely to be needed to investigate the relative validity of SATs and single-arm observational studies.