bluuebunny/crossref_metadata_2025 huggingface dataset:
PP55 Health Technology Assessment Scoping Definition For Health Regulation
Authors: Oliveira Margarete , Ramos Maira , Camargo Erika , Silva Erica , Elias Flávia Tavares
Published: January 2025

Introduction

The first phase of a health technology assessment (HTA) is to define the scope of the assessment and choose the appropriate type of studies. The HTA in Regulation has been produced in cooperation with the Oswaldo Cruz Foundation (Brasilia) and the Brazilian Health Regulatory Agency (Anvisa). This work reports the Brazilian experience with HTA priority-setting within the time period 2022 to 2023.

Methods

Focusing on Anvisa’s 2022 to 2030 research themes, a workgroup developed a priority-setting cycle addressing the following four steps: (i) survey application to define problems and topics (August to October 2022); (ii) data compilation and exploratory searches by topic; (iii) workshops with technical areas (March to June 2023), aiming to refine themes, define research questions, and determine what types of studies will be conducted); and (iv) presentation of prioritized themes.

Results

Forty-six topics at the intersection of HTA and health regulation were prioritized. Macro-agendas for medical devices and medicines were the most frequent. The studies (39 scoping reviews, nine rapid HTAs, and four technical reports) aimed at post-market surveillance, definition of regulatory problems, selection of the best regulatory options, and identification of the legal basis for the selected problem. These studies will be used to assess the impact of the proposed solutions on stakeholders and identify any potential risks associated with them. Lastly, the studies will provide recommendations for decision-making regarding health regulatory measures.

Conclusions

By establishing technical cooperation between stakeholders to gather the best available evidence for regulatory decision-making processes through HTA studies, scoping definition based on the real needs of decision-makers has taken place. In this collaboration, experts were mobilized to expand response capacity and technical-scientific knowledge to support decision-making in health regulation.
PP64 Impact Of The Cost-Effectiveness Threshold On Drug Funding Recommendations: The Case Of Rare Diseases In Brazil
Authors: Oliveira Eduardo , Xavier Luciana , Louly Priscila , Prado Clementina , Bonan Luciene
Published: January 2025

Introduction

In 2022, the Brazilian public health system has adopted an explicit cost-effectiveness threshold of USD24,232.91 per quality-adjusted life years (QALY) for evaluating technologies intended for rare diseases treatment. Although regarded as a strategy for increasing efficiency, the National Committee for Health Technology Incorporation (Conitec) has recommended that the threshold should not be used as a knockout parameter.

Methods

A retrospective analysis of Conitec’s recommendations regarding technologies for rare diseases issued between January and October 2023 was conducted. The following data were extracted from Conitec’s reports: (i) disease (rare or ultra-rare); (ii) health technology evaluated; (iii) scientific evidence regarding efficacy, effectiveness, and safety of the technology; (iv) incremental cost-effectiveness ratio (ICER); (v) recommendation issued; and (vi) rationale for recommendation. Identified technologies will be divided into two groups according to the recommendation issued (positive or negative). The rationale for each recommendation, along with other information, will be reviewed to look for explicit threshold utilization and its impact on decision-making.

Results

Twelve technologies for nine rare diseases evaluated in 2023 were retrieved and eleven were included in the analysis. Six drugs have received a positive recommendation for funding. The ICERs estimated varied between ‒USD5,278,362.06 for emicizumab for hemophilia A and USD116,407.47 for elexacaftor/tezacaftor/ivacaftor for cystic fibrosis. Two of them have received a positive recommendation despite their associated ICER exceeding the explicit threshold. All negative recommendations were associated with ICERs higher than the threshold, which varied between USD52,456.32 and USD847,942.97. For two, the threshold was specifically mentioned as the rationale for the negative.

Conclusions

After the adoption of an explicit cost-effectiveness threshold in 2023, Conitec has issued two positive funding recommendations for rare diseases technologies despite their associated ICER exceeding the threshold: agalsidase alpha for Fabry disease and elexacaftor/tezacaftor/ivacaftor for cystic fibrosis. For both recommendations, the drug’s favorable impact on the natural history of the disease was considered decisive.
PP65 How Does The Spanish Health Technology Assessment Network Assess The Value Of Robotic Surgical Platforms? A Review Of Challenges Faced
Authors: Vercher Beatriz Pellicer , Orozco María Álvarez , Morales Carlos Mansilla
Published: January 2025

Introduction

The value assessment of robotic surgical platforms poses several challenges on existing health technology assessment (HTA) frameworks of robotic-assisted surgery (RAS). Following widely RAS adoption, this work aimed to assess current RAS evaluation from the Spanish HTA network perspective taking into consideration, in the absence of local guidance, the principles published by Erskine J et al. in 2023.

Methods

A review of the HTA reports comparing RAS versus open surgery (OS) and laparoscopic surgery (LPS) conducted by the Spanish HTA network and published between 2017 and 2023 was performed and compared against the consensus statement on RAS evaluation set out around seven key themes (i.e., evidence inclusion and exclusion, patient- and clinician-reported outcomes [PRO, CRO, respectively]), the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits].

Results

Four HTA reports, developed by AQuAS (Agència de Qualitat i Avaluació Sanitàries de Catalunya), assessing RAS versus OS and LPS were identified and reviewed in depth. Seven groups of indications and 57 outcomes were retrieved and classified according to the principles set out in the paper. Our findings show there is a strong lack of compliance with the consensus statement: real-world evidence studies are deprioritized or considered insufficient, and none of the reports provides either an economic evaluation or an assessment on the robotics ecosystem. Only PROs comply fully or partially, except for one report.

Conclusions

Spanish HTA evaluation of robotic surgical platforms diverges significantly from the consensus. Discrepancies were observed across crucial domains, notably in evidence-selection criteria, economic evaluations, and holistic robotic ecosystem assessment, despite occasional compliance with PROs. Capturing specific, relevant outcomes to enable a comprehensive HTA beyond the context of therapy is key to informing decision-making and enhancing reliability of future evaluations.
PP70 Comparison Of Approval Dates Of New Substances Between The U.S. Food And Drug Administration And The European Medicines Agency
Authors: Batscheider Ariane , Shlaen Evgeniya , Weiß Katharina , Schnauffer Darya , Greiner Roger-Axel , Wagner Peter , Bonduelle Doreen
Published: January 2025

Introduction

Early access to innovative medications is a key factor for the quality of medical care. We investigated differences in approval dates of new active substances between the U.S. and Europe and a potential connection with company headquarter location.

Methods

Data of new active substances (no generics, biosimilars, and hybrids) approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) from 1 January 2018 to 29 November 2023 were retrieved from FDA and EMA websites. We calculated the time difference between the drug approval dates between the agencies. We also retrieved the location of the headquarters of pharmaceutical companies.

Results

Since 2018, 390 medicines were approved by FDA or EMA: 113 (29.0%) only by FDA versus 40 (10.3%) only by EMA, and 237 (60.8%) by both. Approval of 32.1 percent of medicines occurred within six months. Fifty-seven percent were approved more than six months earlier by FDA and 11.0 percent more than six months earlier by EMA. Overall, 45.6 percent of the headquarters are in Europe and 44.1 percent are in North America. For medicines approved by FDA only, 63.7 percent of headquarters are in North America and 26.5 percent are in Europe. This is reversed for medicines approved by EMA only. For substances approved by both, 50.6 percent of headquarters are in Europe and 39.2 percent are in North America.

Conclusions

Almost 30 percent of new medicines approved by FDA within the last five years are not yet approved in Europe whereas only 10 percent are approved by EMA only. There is a tendency for companies with headquarters in North America to seek approval from FDA first. For medicines with approval from both authorities, most companies are primarily located in Europe.
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

Introduction

The 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.

Methods

To 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).

Results

A 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.

Conclusions

Using 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

Introduction

Dengue 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.

Methods

A 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.

Results

At 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.

Conclusions

At 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

Introduction

Herpes 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.

Methods

Cost-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.

Results

Twenty-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.

Conclusions

This 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

Introduction

Ensuring 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).

Methods

Qualitative 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.

Results

Findings 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.

Conclusions

The 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

Introduction

In 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.

Methods

This 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).

Results

The 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.

Conclusions

This 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

Introduction

Economic 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.

Results

Sixty-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.

Conclusions

The 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

Introduction

Hemophilia 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.

Results

The 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.

Conclusions

In 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

Introduction

Inclisiran 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.

Methods

A 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.

Results

Inclisiran+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.

Conclusions

Inclisiran+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

Introduction

Partitioned 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.

Methods

A 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).

Results

For 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.

Conclusions

Using 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

Introduction

Single-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.

Results

Work 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.
PD51 Effectiveness And Safety Of Vitamin D For COVID-19: A Living Evidence Synthesis Informing A Health Technology Assessment Report
Authors: Blasco-Amaro Juan Antonio , Sabalete-Moya Trinidad , Rodríguez-López Rocío , Rojas Maria X.
Published: January 2025

Introduction

An evidence synthesis developed to inform decision-making on the use of vitamin D for preventing and treating COVID-19 showed that current available evidence is of low to very low quality. We set up a rigorous living evidence to inform health decisions (LE-IHD) approach to provide timely updates of this health technology assessment (HTA) report and aid decision-making.

Methods

Following the LE-IHD framework, we developed a baseline synthesis and evidence monitoring on the effects of high-dose vitamin D for the prevention and treatment of severe COVID-19 on all-cause mortality, COVID-19-related hospitalization, intensive care unit admission, length of hospital stay, quality of life, adverse events, and long COVID-19. The evidence identification, screening, and selection processes were supported by Epistemonikos technological enablers and the Living Overview of Evidence platform. We searched for ongoing studies in trial registries every three months. New eligible studies were assessed using a systematic and reproducible process to update the HTA report.

Results

For the baseline synthesis we identified nine randomized control trials (RCTs) assessing high dose vitamin D2, vitamin D3, and their metabolites, which provided very low quality evidence on all the outcomes of interest. Up to date evidence monitoring identified seven studies reporting on all-cause mortality and intensive care unit admission, eight studies reporting on length of hospital stay, and six studies reporting on adverse events. The living evidence synthesis has been updated twice. At the time of the conference, we will report on 10 months of monitoring results and any substantial updates to the HTA report.

Conclusions

For HTA reports based on low and very low quality evidence (uncertain results), the living evidence approach allows for timely updating of conclusions. The LE-IHD framework facilitates the planning and execution of living evidence syntheses to inform health decisions. This living evidence synthesis is being developed as part of a project to strengthen decision-making capacity in the Spanish health system.
PD55 Living Recommendations Within A Type 2 Diabetes Mellitus Guideline
Authors: De Val Soledad Isern , Benavent Patricia Gavin
Published: January 2025

Introduction

The Institute for Health Sciences of Aragon (IACS) has coordinated the development of a clinical practice guideline (CPG), funded by the Spanish Ministry of Health, for managing antidiabetic drugs in patients with type 2 diabetes mellitus. We conducted a living systematic review to provide a continuously updated evidence summary for formulating living recommendations on intensifying basal insulin therapy by comparing glucagon-like peptide-1 (GLP-1) receptor agonists with rapid-acting insulin.

Methods

In 2021, the IACS joined the Living Evidence to Inform Health Decisions (LE-IHD) project, which includes the use of technological tools to identify early emerging evidence on a defined topic. We conducted searches in the centralized Living Overview of Evidence (LOVE) and Epistemonikos databases. Specifically, the LOVE topic of interest from which the articles were selected was “glucagon-like peptide analogs and agonists for diabetes mellitus”. We applied the GRADE approach to rate the certainty of evidence and to develop clinical practice recommendations.

Results

The initial baseline report included six randomized controlled trials (RCTs). We have continuously monitored the evidence and performed a monthly screening. Only one RCT was identified in the first update. The Guideline Development Group (GDG) decided to formulate a strong recommendation in favor of GLP-1 receptor agonists. The GDG considered the reduction in the risk of severe hypoglycemia events among patients treated with GLP-1 receptor agonists, compared with rapid insulin, particularly significant as well as the greater improvement in patient quality of life. Since the guideline was formulated, no new evidence has been identified that would change the recommendation.

Conclusions

Adoption of the living systematic approach underscores the commitment to providing continuously updated recommendations within CPGs. Utilizing the GRADE approach, the Guideline Development Group decided to formulate a strong recommendation in favor of GLP-1 receptor agonists over rapid insulin. No new evidence has emerged to alter this recommendation. The living systematic review will remain active, ensuring continuous monitoring until the final draft CPG is disseminated.
PD57 Patient Involvement In The Development Of Clinical Practice Guidelines For Rare Diseases: A Systematic Literature Review
Authors: Dominguez Anabel Granja , Martín-Gómez Carmen , Rodríguez-López Rocío , Gonzalez-Bermudez Lourdes , Blasco-Amaro Juan Antonio
Published: January 2025

Introduction

One obstacle to the development of clinical practice guidelines (CPGs) for rare diseases (RDs) is the lack of scientific evidence. This can be partially overcome by involving patients in the development of CPGs. Our aim was to develop a process for involving patients with RDs in all stages of CPG development to ensure that their needs and expectations are addressed.

Methods

A literature search was conducted in the MEDLINE, Cochrane Library, and Embase databases and the websites of the European Organization for Rare Diseases, the National Organization for Rare Disorders, and INAHTA. Eligible articles reported methods for involving patients in CPGs, other clinical decision support tools, and research studies. A fit-for-purpose data extraction template was created to capture the following data: author, year, country, type of study, characteristics of the target population, and strategies for participation, engagement, and involvement of patients. Data were synthesized according to methods for recruiting, involving, or engaging patients and obtaining information from them. The entire process was performed by pairs of researchers.

Results

A total of 1,113 records were identified once duplicates were deleted. Of these, 55 were included. The review collected data on types of patients (patient representatives or patient experts) and their recruitment, which could be classified as open or nominated. The various involvement strategies included consultation, participation, and communication. Differences between involving and engaging patients in the CPGs development process were noted. Procedures for obtaining the opinion of patients included surveys, interviews, workshops, and focus groups, among others. The review also provided information on the importance of involving patients in the dissemination and implementation stages of CPG development and the methods for doing so.

Conclusions

When patients with RDs are actively involved in all phases of CPG development, they can contribute to the identification, prioritization, and inclusion of topics pertinent to RDs as questions to be addressed in the CPGs. These aspects might otherwise be overlooked by clinical experts and researchers. Therefore, involving patients with RDs is a promising approach to addressing gaps in the management of these diseases.
PD68 A Cross-Cultural Validation Study Of The German And English Versions Of The ICEpop CAPability measure for Adults (ICECAP-A)
Authors: Ubels Jasper , Schlander Michael
Published: January 2025

Introduction

Proponents of the capability approach argue that the effect of health technologies should be measured in terms of capabilities, that is, the freedom to live as desired. The ICECAP-A, initially developed in the UK, has been used internationally to measure capability wellbeing. This study examined whether participants from Australia, Canada, Germany, the UK, and the USA similarly interpret and respond to the ICECAP-A.

Methods

A multigroup confirmatory factor analysis was conducted. Four types of measurement invariance were tested: configural invariance, metric invariance, scalar invariance, and residual invariance. Measurement invariance was assessed by studying the comparative fit index (CFI) and the root mean square error of approximation (RMSEA) and standardized root mean squared residual (SRMR) fit indices. For this study, data from the multi-instrument comparison database were used to compare response patterns of participants from Australia (n=1,430), Canada (n=1,330), Germany (n=1,269), the UK (n=1,356), and the USA (n=1,460).

Results

The configural invariant model showed adequate fit (CFI 0.992, RMSEA 0.076, SRMR 0.016), and metric invariance was established (change in variables: CFI -0.002, RMSEA -0.014, SRMR 0.015). Scalar invariance (and consequently residual invariance) was not established (change in variables: CFI -0.036, RMSEA 0.046, SRMR 0.018). Post-hoc analysis indicated that full measurement invariance could be established by excluding the German sample, with improved fit index values for configural invariance (CFI 0.994, RMSEA 0.069, SRMR 0.015), metric invariance (change in variables: CFI-0.000, RMSEA -0.020, SRMR 0.006), scalar invariance (change in variables: CFI -0.007, RMSEA 0.011, SRMR 0.006), and residual invariance (change in variables: CFI -0.002, RMSEA 0.009, RMR 0.006).

Conclusions

Response patterns to the German and English versions of the ICECAP-A differed. Caution should be exercised when using these two versions in the same study. Further research is required to determine whether these differences are due to linguistic variations from translation, or whether they indicate fundamental differences in participant understanding and responses to the different versions of the ICECAP-A.
PD69 Road Map Of Health Equity Considerations In Health Technology Assessments: Identifying The Evidence From Epidemiology To Health Economics
Authors: Sarri Grammati , Radhakrishnan Amruta , Vinals Lydia
Published: January 2025

Introduction

Achieving health equity through access to new health technologies has not been consistently considered within the health technology assessment (HTA) remit. HTA bodies now recognize that achieving health equity (or reducing health inequities) is a distinct value element for new technologies beyond the restrictive focus on clinical benefits and costs, but they lack familiarity with methods to reliably measure such effects.

Methods

We conducted a targeted literature review in indexed databases (Embase and MEDLINE) to identify relevant literature on methods for measuring health equity in HTAs published in the English language within the last five years. We mapped the literature based on key HTA stages: topic selection (eligible patient population); scoping (description of pre-decision health equities); evidence synthesis (equity impacts on health outcomes from introducing the intervention); comparative clinical comparisons including indirect treatment comparisons and cost-effectiveness analyses (including assessment of equity and efficiency trade-offs); and re-assessment (for conditional marketing). Equity-informed HTA decision frameworks and checklists were separately summarized. A narrative synthesis was performed.

Results

The databases returned 2,800 unique publications. After screening 50 percent of the abstracts (30 publications) were found to be relevant. We applied additional selection criteria based on quality and information availability. Findings across the studies were grouped in a health equity methodological map as follows: understanding baseline epidemiological data in the targeted population; assessing diversity in trial populations and need for additional robust real-world evidence; effectiveness methods (subgroup analyses, incorporation of observational data with trials, simulation studies); and expanded economic modeling (distributional cost-effectiveness analysis, augmented cost-effectiveness analysis, extended cost-effectiveness analysis) or the use of multicriteria decision analysis. Two equity checklists and frameworks for HTA were also identified.

Conclusions

Greater familiarity with health equity methods will drive its routine implementation in HTA and decision-making. This road map provides a summary of available health equity methodologies across the full HTA cycle and can be used as a guide for future HTA case studies. Decision-makers should directly engage with patients to learn about the experiences of diverse and disadvantaged patient groups.
PD95 Enhancing Clinical Practice Guideline Development In Brazil: A Tutoring Program For Health Technology Assessment Centers
Authors: Falavigna Maicon , Araujo Cintia , Parahiba Suena , Dorneles Gilson , Stein Cinara
Published: January 2025

Introduction

This study outlines a tutoring program supported by the Brazilian Ministry of Health (MoH), which aimed to develop clinical practice guidelines (CPGs) through Health Technology Assessment Centers (Nuclei of Health Technology Assessment or NATS) for the Brazilian Unified Health System (SUS). It emphasizes the integration of CPGs into health technology assessment development processes, focusing on methodological rigor, reproducibility, and reliability.

Methods

The program combined face-to-face and virtual meetings and engaged MoH representatives, methodologists, and researchers. It focused on the MoH Methodological Guideline for Developing Clinical Guidelines, which follows the Guidelines International Network and United States Institute of Medicine recommendations. This approach facilitated planning and creation of CPGs across diverse NATS.

Results

Between 2021 and 2023, 60 professionals from 10 NATS participated, aiding in developing or updating 16 CPGs. These CPGs addressed 93 research questions. The CPG development phase averaged 317 days (interquartile range [IQR] 252 to 402), while the MoH assessment and public consultation took about 63 days (IQR 45 to 94). Additionally, nine Protocolos Clínicos e Diretrizes Terapêuticas (official guidelines from the Brazilian MoH) required technology assessments for SUS reimbursement, leading to 14 HTA reports. Eight technologies were favorably reviewed and recommended in the CPGs.

Conclusions

This tutoring program significantly improved the development of CPGs in Brazil, enhancing their methodological rigor and standardization. It also effectively integrated HTA into the CPG development process, addressing clinical needs and enriching public health decision-making.
PD117 Proposed Matrix For Efficient Reassessment Of Selective Benefits
Authors: Jang Jun , Choi Yoon-Jeong , Kim Myoung-Hwa
Published: January 2025

Introduction

To reduce the burden of medical expenses on patients, some noncovered medical technologies with proven safety but uncertain therapeutic effectiveness or cost effectiveness are incorporated into the “selective benefit (SB) system” and reassessed regularly to determine reimbursement scope. This study proposes a matrix based on the usage trends of new technologies (NTs) and alternative therapies (ATs) to facilitate efficient reassessment.

Methods

This study investigated the following five indices: (i) replacement of an NT by an AT; (ii) market shares of NTs; (iii) usage trends of NTs; (iv) usage trends of ATs before and after introduction of NTs; and (v) social demand for NTs. These were combined to generate an algorithm-based matrix that classified 139 NTs into 22 cases and five reimbursement scope categories. Health insurance data from 2009 to 2021 were analyzed to investigate market shares and usage trends. Social demand was evaluated using the last assessment results for each NT.

Results

Using the matrix, 139 NTs were classified as follows: (i) switch to an essential benefit (copayment 20%; n=11); (ii) stay as a SB (copayment 50%; n=19); (iii) stay as a SB (copayment 80%; n=30); (iv) stay as a SB (copayment 90%; n=8); and (v) convert to noncovered (copayment 100%; n=40). The remaining 31 with an insufficient analysis period were classified as a SB (copayment 80%) for further analysis. Excluding the latter 31 SBs, 57 of the 108 (53%) were classified as “stay as a SB” categories, suggesting that these technologies need to be monitored further.

Conclusions

The usage trend driven matrix may be useful for efficient reassessment of NTs. For example, NTs that have a high market share and an increasing usage trend and ATs with a decreasing usage trend after SB of an NT can potentially be switched to an essential benefit.