bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP93 The Impact Of Using Different EQ-5D Scoring Methods On Cost-Utility Outcomes: A Simulation Study
Authors: Ben Ângela J , van Dongen Johanna M , Finch Aureliano P , Alili Mohamed El , Bosmans Judith E 
Published: December 2022

IntroductionPatients’ EQ-5D health states are preferably valued using country-specific value sets. If value sets are not available, crosswalks may be used to estimate utility values. However, up until now the impact of using crosswalks instead of value sets on cost-utility outcomes remains unclear.MethodsTrial-based cost-utility data were simulated for four conditions (depression, low back pain, osteoarthritis, and cancer), three levels of disease severity (mild, moderate, and severe), and three treatment effect sizes (small, medium, and large), resulting in 36 scenarios. For all scenarios, utility values were estimated using four scoring methods (EQ-5D-3L value set, EQ-5D-5L value set, 3L-to-5L crosswalk, and 5L-to-3L crosswalk) for three countries (the Netherlands, the United States, and Japan). Mean utility values, quality-adjusted life years (QALYs), incremental QALYs, and cost-utility outcomes (incremental cost-effectiveness ratios [ICER], probabilities of cost-effectiveness at willingness-to-pay [WTP] thresholds) were compared between value sets and crosswalks.ResultsDifferences between value sets and crosswalks ranged from -0.33 to 0.13 for mean utility values, from -0.18 to 0.13 for QALYs, and from -0.01 to 0.08 for incremental QALYs. Because of the small differences in incremental QALYs, ICERs between scoring methods were considerably different. For small effect sizes, at a WTP of EUR 20,000/QALY gained, the largest difference in the probability of cost-effectiveness was found for moderate cancer between the 5L value set and 3L-to-5L crosswalk (difference 0.63) using Japanese valuations. For medium effect sizes, the largest difference was found for mild cancer between the 3L value set and the 5L-to-3L crosswalk (difference 0.06) using Japanese valuations. For large effect sizes, the largest difference was found for mild osteoarthritis between the 3L value set and 5L-to-3L crosswalk (difference 0.08) using Japanese valuations.ConclusionsOur findings indicate that reimbursement decisions may change depending on the use of crosswalks. Crosswalks are justifiable in absence of country-specific value sets but should not be considered a sustainable alternative for value sets.
PP94 Exploring The Relationship Between Price And Outcome Of The Health-Economic Assessment In Japan
Authors: Song Xirong , Sejpal Nehal , Konar Rangaraja , Patil Saurabh , Gusain Sapana , Sonigra Preksha , Tikone Rutuja 
Published: December 2022

IntroductionThis study reviewed all publicly available Japanese cost-effectiveness appraisals delivered by the Center for Outcomes Research and Economic Evaluation for Health (C2H) from the national institute of public health (NIPH) and analyzed the relationship between the outcomes of the health-economic assessments and the final price adjustment decisions made by the Ministry of Health, Labour and Welfare (MHLW).MethodsData were extracted from all official health-economic assessments published by C2H website for the analysis. The extractions were structured based on the following items: indication, assessment methodology, appropriate comparators, health-economic outcomes, and key uncertainties identified by C2H. The analysis was performed on 29th November 2021. A threshold of 5 million JPY per Quality Adjusted Life Year gained (JPY/QALY) was used for the incremental cost-effectiveness ratio (ICER) analysis cut-off.ResultsUp to the time of this analysis, six health-economic assessments had been conducted for five products: three assessments performed cost-effectiveness analysis, one performed cost-minimization analysis and two performed cost-effectiveness and cost-minimization analysis for different comparators and different patient subgroups respectively. Among the five assessments’ reported ICER values, four of them are under the 5 million JPY/QALY threshold, ranging from 328,585 JPY/QALY to 483,056 JPY/QALY. However, price adjustments were still implemented on three out of the four products which were deemed to be cost-effective, ranging from -0.5 percent to -4.3 percent (mean: -3.0%). For the only product deemed to be not cost-effective, a price adjustment of -4.3 percent was implemented.ConclusionsA price discount could be implemented regardless of whether the ICER value falls under the 5 million JPY/QALY threshold. However, a lower magnitude of price discount is likely to be applied by MHLW for more cost effective treatments. The outcome of this analysis may be limited by the small sample size and continuous monitoring of further HTA publications in Japan is needed.
PP102 Selecting The Sequence Of Diagnostic Tests For Leprosy In Brazil
Authors: Barros Bruno , Magliano Carlos Alberto , Santos Marisa 
Published: December 2022

IntroductionHansen’s disease, or leprosy, is a chronic bacterial infection that affects the nerves, skin, eyes, and nose lining. In 2019, there were 202,256 new cases reported globally, and nearly 28,000 new cases are diagnosed each year in Brazil. The best way to prevent the spread of Hansen’s disease is early diagnosis and treatment of infected individuals. Most diagnoses are done clinically, but only the microscopic analysis of slit-skin smears is funded in Brazil. Serologic and polymerase chain reaction (PCR) tests have also been developed to aid in the diagnosis. The goal of this study was to identify the most cost-effective strategy for increasing the diagnosis of Hansen’s disease in Brazil.MethodsWe examined the impact of the following four strategies using a decision tree model: (i) slit-skin smear only; (ii) PCR test only; (iii) serologic testing followed by slit-skin smear for positive samples; and (iv) serologic testing followed by slit-skin smear for positive samples and PCR test for negative serologic tests and negative slit-skin smears. The accuracy of the tests was determined using a systematic review and meta-analysis and validated by experts. The costs were calculated from the Brazilian health system perspective. Univariate and probabilistic analyses were also conducted.ResultsSerologic testing or PCR followed by slit-skin smear was dominated in the economic model (more false-negative samples and more costly). The addition of serologic testing and PCR to the diagnostic sequence made the strategy more expensive than slit-skin smears alone, but it significantly reduced the percentage of false negative results (from 7.3 to 2.9%) at an estimated cost of USD 533.61 per incremental diagnosis. Disease prevalence was the most important variable in the sensitivity analysis.ConclusionsThis is the first cost-effectiveness model undertaken for Hansen’s disease. The results indicate that incorporating serology and PCR testing into the Brazilian health system could be an appealing option for reducing the spread of Hansen’s disease in Brazil.
PP109 Efficacy And Safety Of High-Intensity Focused Ultrasound In Parkinson’s Disease
Authors: Arias-Pacheco Amparo , del Mar Polo-de-Santos María , Luengo-Matos Setefilla , Hijas-Gómez Ana Isabel , Rodríguez-Ortiz-de-Salazar Begoña , Sánchez-Gómez Luis María 
Published: December 2022

IntroductionParkinson’s disease (PD) is the second most common neurodegenerative disease in the world. High-intensity focused ultrasound (HIFU) is a new non-invasive therapeutic option for treating the motor symptoms of PD. HIFU is an imaging-guided procedure for therapeutic brain ablation that has been used for patients with essential tremor and neuropathic pain. It is indicated for patients older than 22 years of age who have PD that is refractory to drug treatment and are ineligible for surgery. The objective of this study was to conduct an early assessment of HIFU subthalamotomy for the treatment of motor symptoms in patients with PD.MethodsHIFU was identified by the early awareness and alert system, SINTESIS- nuevas tecnologías, of the Agencia de Evaluación de Tecnologías Sanitarias at the Instituto de Salud Carlos III. Relevant literature published to October 2021 was identified by searching PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Library.ResultsOne prospective study and one randomized controlled trial (RCT) were found that assessed the efficacy and safety of HIFU subthalamotomy for treating the motor symptoms of PD. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) was used to measure changes in symptoms (>30% change from baseline was considered clinically relevant). Both studies reported a reduction of symptoms in the intervention group. The MDS-UPDRS III score changed from 16.6 to 7.5 six months after treatment in the prospective study and from 19.9 to 9.9 four months after treatment in the RCT (a decrease of 11.6 points was observed after 12 months). The main adverse events reported were dyskinesia, speech and gait disturbances, and weakness, all of which resolved without treatment.ConclusionsThe results regarding the efficacy and safety of HIFU for treating the motor symptoms of PD are promising. HIFU is a non-invasive procedure that eliminates the risks associated with surgery. Although rapid diffusion of this technology is expected, further studies and economic evaluation are needed.
PP119 Results And Lessons Learned From The Cyclic Appropriate Care Program From National Health Care Institute Of The Netherlands
Authors: Maagdenberg Hedy , Stam Mariska , Vreugdenhil Tjitske , Böcker Koen , Groeneveld Iris 
Published: December 2022

IntroductionSince 2013, the National Health Care Institute in the Netherlands has systematically analyzed the appropriateness of care provided under public health insurance. Here we present the method used, the results up to now, and what we have learned from it.MethodsThe appropriate care program consists of four phases: screening, in-depth analysis, implementation, and evaluation. Stakeholder involvement is a central part of the process. For every ICD-10 area, a screening took place to select care trajectories for in-depth analysis with a potential for wiser choices and more appropriate care. The in-depth analysis indicates which improvements can be made to reach more appropriate care, by assessing guideline adherence. During the implementation phase, which is primarily carried out by clinicians, patients and health insurers, actions are taken to improve care on the identified points. In the evaluation phase, we examine to what extent improvements have been achieved.ResultsCurrently, all ICD-10 areas have been screened and 29 selected care trajectories have been subjected to in-depth analyses. The analyses resulted in the identification of more than a hundred areas for potential improvement of the appropriateness of care. For most topics implementation of changes is currently taking place. The four most important impact-enhancing lessons learned by applying the working method are: (i) ICD-10 areas as a starting point for screening are not the most efficient method to reach the biggest impact. (ii) The screening should take a societal perspective. (iii) All public and private parties involved should fulfill their role and take responsibility. (iv) To fulfill our own role better, the working method should be more connected to health technology assessment for reimbursement decisions.ConclusionsThe program has resulted in the identification of many valuable points for improvement which could lead to more appropriate care in the coming years. The impact of the program could be increased through priority setting from a societal perspective and improving the connection to our other health technology assessment processes.
PP120 Fluorescent In Situ Hybridization (FISH) Vs Conventional Cytogenetic (CC) For Detecting High-Risk Genetic Mutations In Multiple Myeloma
Authors: Komoda Denis Satoshi , Visacri Marilia Berlofa , Correa Carlos Roberto , Santos Daniela , Maia Flavia , Ribeiro Mayra 
Published: December 2022

IntroductionThe Revised International Staging System (R-ISS) International Myeloma Working Group (IMWG) recommends a minimal panel to detect high-risk cytogenetics (del17p, t[4;14], t[14;16]) for patients with multiple myeloma (MM). In the Brazilian Public Health System, the use of FISH is currently authorized for rare diseases only, not including MM. In 2021, the Brazilian National Committee for Health Technology Incorporation, with the purpose of broadening the use of FISH to MM patients, requested a review to be undertaken by the Health Technology Assessment Center of University of Campinas’ Teaching Hospital. This study presents the results of a meta-analysis comparing FISH vs CC to the detection of the above-mentioned aberrations in MM patients.MethodsOn 25 June 2021, a pre-structured search on four databases (Embase, MEDLINE, Cochrane and LILACS) was performed to identify studies comparing FISH and CC results in MM patients for the detection of high-risk cytogenetics (del17p, t[4;14], and t[14;16]) in MM patients’ bone marrow samples. Study selection, risk of bias assessment, data extraction (frequency of positive tests) and quality of evidence assessment were performed by two independent researchers. Conflicts were solved in agreement meetings with a third researcher. Meta-analysis was performed using frequency of positives to obtain Risk Difference (RD), a surrogate measure of the surplus positive tests between FISH and CC.ResultsFrom a total of 1346 rendered entries, 11 studies were selected. Only observational studies were available. These studies presented an overall high risk of bias (QUADAS-2). A total of 781 patients were assessed (653 evaluated by FISH and 719 by CC). Meta-analysis results showed that, for t(4;14) FISH detected 12 percent more samples (RD:0.12 [95% confidence interval (CI):0.06-0.19]). For t(14;16), FISH detected 0.42 percent more samples (RD:0.00 [95%CI:-0.01-0.02]). And for del17p, FISH detected 1.6 percent more samples (RD:0.12 [95%CI:0.04-0.20]).ConclusionsFISH appears to be more effective than CC on the detection of t(4;414) and del17p aberrations, and can be a useful tool in hematology practice. The results of t(14;16) presented non-superiority, probably due to the low frequency of this aberration.
PP125 Economic Evaluation Of Molecular Diagnostics – A Review And Future Directions
Authors: Bouttell Janet , Heggie Robert , Oien Karin , Romaniuk Amy , VanSteenhouse Harper , von Delft Stephan 
Published: December 2022

IntroductionIt has been suggested that health economists need to adapt their methods in order to meet the challenges of evaluating molecular diagnostics. The aim of this review is to categorize and critically examine the challenges and methodological developments identified from the literature and to suggest how such challenges may be addressed.MethodsWe identified challenges and suggested methodological improvements using a systematic rapid review of the literature. We categorized challenges into those common to all economic evaluations, those common to all diagnostic technologies and those relevant to molecular diagnostics. We assessed whether development in the methods of economic evaluation or alternative action was required.ResultsWe found forty-one papers which identified twelve challenges. Choice of perspective and time-horizon were challenges common to all economic evaluations. Five challenges were relevant for all diagnostic technologies: complexity of analysis; range of costs; under-developed evidence base; behavioral aspects; and choice of outcome metrics. The final five challenges were specific to molecular diagnostics: heterogeneity of tests and platforms; increasing stratification; capturing personal utility; incidental findings and spill-over effects. The final five challenges may require methodological development. For example, although methods exist to capture the value of a diagnostic test over and above any health gain captured in a quality adjusted life year (‘personal utility’), there is currently no agreed method of incorporating this into a cost-utility analysis. For the other challenges development of evaluation processes is key. In particular, the weak evidence base for diagnostic technologies may require processes to evolve.ConclusionsCurrent methods of economic evaluation are generally able to cope with molecular diagnostics although a renewed focus on specific decision-makers’ needs and a willingness to move away from cost-utility analysis may be required. A key issue is the under-developed evidence-base and it may be necessary to rethink translation processes to ensure sufficient, relevant evidence is available to support economic evaluation and adoption of molecular diagnostics.
PP126 Direct Patient Involvement In HTA In Canada And Brazil: The Patients’ Perspectives
Authors: Silva Aline Silveira , Orecklin Paula , Ferrite Silvia 
Published: December 2022

IntroductionSince 2019, Canada’s Drug and Health Technology Agency (CADTH) has worked directly with patients through its Patient and Community Advisory Committee (PCAC). In Brazil, Conitec has worked directly with patients since 2021 through testimonials in its committee meetings for all assessed technologies. In this study we explored patients’ perspectives about their participation in these processes.MethodsTwo patients directly involved with both CADTH and Conitec were invited to share their perspectives about the strengths and weaknesses of the patient engagement processes.ResultsFor CADTH, the strengths were as follows: PCAC focuses on the whole organization, including the patient engagement strategy and strategic plan, and is on the same level as other professional committees; PCAC members are compensated; the ‘Learning Sessions’ show CADTH staff the ramifications of their work in people’s lives; and there is increased patient engagement on other committees throughout CADTH. The weaknesses identified with the CADTH process were that PCAC is an advisory body with no decision-making authority and that the diversity of people on the PCAC could be increased. In addition, while CADTH informs and consults patients, the PCAC is not involved in individual HTAs.The strengths of Conitec’s process were that the volunteer is selected by patients; there are opportunities to consolidate direct patient involvement and promote it in other instances; and the technical support is excellent. On the downside, there was a lack of information about this opportunity; the testimonials last only ten minutes and patients are frequently not questioned; only one patient can participate; there is a lack of transparency about testimonial analysis and its role; and being the only representative during a discussion that culminates in a decision can cause anxiety about performance.ConclusionsPatients felt heard in the engagement processes and stated that the PCAC embeds patient perspectives throughout CADTH, not just in particular HTAs. One patient felt that her participation was essential for the committees to understand patients’ lived experiences.
PP127 Impact Of Brazilian Patient Testimonials On Medical Devices And Public Confidence In The Healthcare Decision-Making
Authors: Toscas Sra Fotini , de Morais Oliveira Vivian Cardoso , Silva Aline Silveira 
Published: December 2022

IntroductionSince October 2020, Conitec has made public calls (PCs) to invite patients and family members to express perspectives during committee meetings. This study seeks to reflect about the impact of the newest patient and public involvement (PPI) Conitec strategy and how it can contribute to increase patient direct involvement and public confidence regarding Brazilian health decisions in medical devices.MethodsWe conducted a document analysis after searching for PCs addressed to medical devices in the section “Patient Perspectives” on Conitec´s website until Aug 31, 2021.ResultsFrom 64 PCs, five were related to medical devices. Rotational thromboelastometry for transfusion controls: Ended upon applicant request. Transcatheter aortic valve implantation (TAVI): One patient gave his testimonial, explaining how it impacted his quality of life and daily activities, besides answering questions from the committee. The testimonial was not included in the recommendation report. After the public consultation, the initial recommendation changed from non-reimbursement to reimbursement. Botton™ probe for gastrotomy: Eleven people volunteered and a family member was selected. She expressed the importance of the device in her son’s quality of life, making ordinary activities more accessible, helping in the physiotherapy sessions, reducing hospitalizations, and supporting her son’s socialization. The initial recommendation was to reimburse it. iStent Inject Trabecular Micro-Bypass System™ (glaucoma treatment): No patients volunteered. The final recommendation report informed that Conitec received 55 comments through public consultation, including experiences and opinions about the technology. After the public consultation, there was a change from the initial to the final recommendation, from non-incorporation to incorporation. Non-invasive ventilation (cystic fibrosis treatment): There were five volunteers and a mother of twins, both with cystic fibrosis, gave her testimonial. She expressed the importance of this device in her kids’ quality of life, allowing them to sleep better, eat and study, control the symptoms, and reduce hospitalizations and antibiotic usage.ConclusionsAspects such as documenting this participation, communicating and offering support to the public and patients, analysis and transparency are essential for evaluating and improving this strategy.
PP131 European Market Access Landscape Analysis Of Reimbursement Drivers In Pompe Disease: Results From 26 Payer Interviews
Authors: MacCulloch Alasdair , Raza Syed , Shohet Simon , Schammel Nico , Net Pierre 
Published: December 2022

IntroductionPompe disease (PD) is a rare, progressive neuromuscular disease that severely affects motor and respiratory functions. Late onset PD (LOPD) is the most common phenotype. Current treatment involves enzyme replacement therapy (ERT) with alglucosidase alfa, which was first approved in 2006. In Europe, the treatment landscape is changing as two new ERTs have been filed for regulatory approval: avalglucosidase alfa and cipaglucosidase alfa plus miglustat. We analyzed how health technology assessment (HTA) and reimbursement criteria may be applied to ERTs in key countries for patients with PD.MethodsEighteen different factors were identified from the pivotal trials (LOTS, COMET, and PROPEL) for the three recombinant enzymes. These covered the categories of trial design, endpoints, quality of life, and other product characteristics. Twenty-six HTA experts and health economists from Denmark, England, France, Germany, Italy, the Netherlands, Spain, and Sweden with rare disease experience were interviewed during the period from July to September 2021. In structured discussions, each participant was asked to rate (from one to seven) the factors in terms of their importance and impact on the HTA evaluation and reimbursement of treatments for adults with PD.ResultsThe following factors were highly rated: a well-defined PD trial population; use of an active trial comparator; efficacy in both treatment naïve and experienced subpopulations; a superiority study design; and payer-relevant endpoints and quality of life improvements. The five lowest rated factors were open-label data, biomarkers, innovation, ease of administration, and mode of action. While the results were mostly consistent across countries, the HTA expert viewpoints varied depending on the country. For example, HTA experts in Italy, the Netherlands, and Sweden rated innovation and biomarkers more highly than German experts.ConclusionsAs new ERTs become licensed, achieving reimbursement and successful HTA of them will require a clear exposition of payer-relevant evidence for the LOPD population in the target country, including comparative randomized controlled trial data, benefits for experienced and treatment naïve subgroups, and payer-relevant endpoints and quality of life gains.