AM23_OralAbstractBook_01

Oral Abstracts THE ROAD TO POLICY AND CLINICAL INTEGRATION June 24-28,2023 htai2023.org #HTAi2023Adelaide

Oral Presentation Number: OP01 Abstract Title: Causal Association Between Type 2 Diabetes Mellitus And Risk Of Cancer Author Names: Fabiola Lemus ([email protected]), Neil Hawkins, Kathleen A Boyd Introduction. Type 2 diabetes mellitus (T2DM) is a major public health problem. Evidence suggests an association between diabetes and cancer, but this may be distorted by confounding. This research aimed to identify and assess the evidence suggesting a causal association between T2DM and cancer. Methods. A systematic review was conducted in Pubmed, Embase, CINAHL, Web of Science, and the Cochrane Library for literature on the association between T2DM and cancer, from inception to 7 May 2021. Case-control and cohort studies published in any language were considered. Based on a targeted literature review, a directed acyclic graph for each type of cancer was developed to test whether the causal effects were adequately controlled for potential confounding. Results. A total of 131 studies with a low risk of bias were selected that reported 415 effect estimates of the association of T2DM with 57 types of cancer. Breast, colorectal, pancreas, prostate, and lung were the cancer sites with the highest number of studies. Causality was claimed in 57 studies, but only 34 percent of the outcomes were adequately controlled for confounders. Of the studies assessing a causal relationship for prostate and pancreatic cancer, 87 and 70 percent adequately controlled for confounding. In contrast, only 29 percent of lung cancer, 27 percent of colorectal cancer, and 17 percent of breast cancer results considered the minimal sufficient adjustment set. Lifestyle variables were identified as key potential confounders in more than 20 types of cancer, but they were not included in the analyses. Conclusions. Many studies simply reported an association between diabetes and cancer. The policy implications of such studies are unclear. Of the studies claiming a causal link between diabetes and cancer, a large proportion did not adequately control for confounding. It is critical that studies take a systematic approach to identifying potential confounding factors, such as targeted reviews and the development of directed acyclic graph approaches, to estimate causal effects that may be useful in informing health policy.

Oral Presentation Number: OP03 Abstract Title: Comparative Safety And Efficacy Of PD-L1 Inhibitors For Advanced Non-Squamous Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis Author Names: Yi Yang ([email protected]), Ying Tao, Dai Lian, Yingyao Chen Introduction. Multiple inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have been approved for the first-line treatment of advanced non-squamous non-small cell lung cancer (nsNSCLC) in China. This study aimed to compare the relative safety and efficacy of various PD-L1 inhibitors to identify the optimal PD-1/PD-L1 inhibitor regimen for patients with advanced nsNSCLC. Methods. We performed a systematic review and Bayesian network meta-analysis by retrieving relevant literature from PubMed, the Cochrane Library, Embase, ClinicalTrials.gov, Chinese databases, and major international conferences. We included published and gray sources of randomized controlled trials comparing immunotherapy combinations with other treatments as first-line therapy for patients with advanced nsNSCLC. This study was registered in PROSPERO (CRD42021275631) to ensure transparency. Results. We analyzed a total of 19 studies involving 9,263 patients and 15 immunotherapy combinations. Pembrolizumab plus chemotherapy was found to be comparable with sintilimab plus chemotherapy in providing the best overall survival benefit (hazard ratio 0.98, 95% confidence interval [CI]: 0.70, 1.36) and progression-free survival (hazard ratio 0.97, 95% CI: 0.71, 1.32). Furthermore, camrelizumab plus chemotherapy had the highest discontinuation rate due to adverse effects (odd ratio 0.18, 95% CI: 0.07, 0.42) and was the most likely to cause at least three adverse events (odds ratio 0.41, 95% CI: 0.27, 0.61). Chemotherapy was associated with relatively lower overall and progression-free survival relative to combined immunotherapy and chemotherapy. Conclusions. Our results suggest that PD-1/PD-L1 inhibitor combinations are associated with potentially better survival outcomes than chemotherapy for patients with nsNSCLC. Sintilimab plus chemotherapy and pembrolizumab plus chemotherapy regimens seem to be the superior first-line immunotherapy combinations for patients with advanced nsNSCLC. Moreover, the efficacy of China’s domestic immunotherapies was not inferior to international PD-1/PD-L1 inhibitors in the treatment of nsNSCLC

Oral Presentation Number: OP04 Abstract Title: The Efficacy Of Segmentectomy And Lobectomy For Non-Small Cell Lung Cancer: A Systematic Review And Meta-Analysis Author Names: Kai Zhao, Xinyu Xue, Jiajie Yu ([email protected]), Youping Li Introduction. The latest clinical practice guidelines for non-small cell lung cancer (NSCLC) published by the National Comprehensive Cancer Network in 2022 recommend that patients with NSCLC (>1 and ≤2 cm) should be diagnosed as T1b. Segmentectomy and lobectomy are equally effective in treating patients with NSCLC no bigger than 2 cm, and especially for tumors no bigger than 1 cm. However, the effectiveness of these treatments for NSCLC tumors between 1 and 2 cm is unknown. We conducted a systemic review and meta- analysis to assess the efficacy of these two surgical treatments in patients with T1b stage NSCLC. Methods. We searched for randomized controlled trials (RCTs) and cohort studies investigating the efficacy of lobectomy and segmentectomy for patients with T1b stage NSCLC. Study quality was assessed with the Cochrane Quality in Prognosis Studies tool. We used random effects models to analyze overall survival (OS) and lung cancer- specific survival (LCSS), expressed as hazard ratios (HR) and 95% confidence intervals (CIs). The effect of covariates was assessed using subgroup analysis. All procedures were performed according to the PRISMA guidelines. Results. We identified ten cohort studies that matched our selection criteria, with general low risk of quality, including a total of 37,691 patients. No publication bias was found. Compared to lobectomy, segmentectomy had lower OS (HR 1.31, 95% CI: 1.16, 1.47; p=0.026) and LCSS (HR 1.21, 95% CI: 1.03, 1.42, p=0.015) before Cox regression. After multivariable Cox regression, adjusted by age, sex, histological type, and lymph node section, segmentectomy had similar OS (HR 1.17, 95% CI: 1.00, 1.37; p=0.2) and LCSS (HR 1.10, 95% CI: 0.89, 1.36; p=0.8). Conclusions. Segmentectomy can be used to treat patients with T1b stage NSCLC. Patients who undergo segmentectomy have survival outcomes that are the same as those of patients who received lobectomy. This evidence-based observation provides a reference for surgical choice in the treatment of patients with T1b stage NSCLC, which should be further confirmed through RCTs.

Oral Presentation Number: OP06 Abstract Title: Development Of A Tool To Support The Collection Of Policy-Relevant, Stakeholder-Informed Clinical Evidence For Innovative Digital Health Technologies Author Names: Amy Von Huben ([email protected]), Martin Howell, Sarah Norris, Kirsten Howard Introduction. The number of studies on digital health technologies (DHTs) for remote treatment and patient self- management is increasing. Existing health technology assessment (HTA) frameworks for DHTs, which guide researchers in generating evidence suitable for HTA, do not cover all domains of the commonly used EUnetHTA Core Model, and DHT-specific considerations have not been informed by a large stakeholder preference study. Our aim was to develop a stakeholder prioritized, literature-informed checklist of DHT- specific considerations that aligns with the EUnetHTA model. Methods. We conducted two systematic reviews to identify: (i) DHT evaluation frameworks published to March 2020 for content; and (ii) primary research on DHTs published from 1 January 2015 to 20 March 2020. Stakeholder prioritization of issues was performed using a best-worst scaling preference study among a broad cross- section of patients, carers, health professionals, and the general population in Australia, Canada, New Zealand, and the UK. Systematic review issues were prioritized and adapted for use as a practical checklist. Results. DHT evaluation content was recommended by the 44 identified frameworks for 28 of the 145 issues in the EUnetHTA model and for 22 new DHT-specific issues. A coverage assessment of 112 clinical studies of remote treatment and self-management DHTs for patients with cardiovascular disease or diabetes revealed that less than half covered DHT-specific content in all but one domain, or traditional HTA content in clinical effectiveness and ethical analysis. The preference survey of 1,251 stakeholders identified broad agreement on the 12 most important DHT attributes, six of which were related to safety. The most important attribute was “helps health professionals respond quickly when changes in patient care are needed”, which is not a focus of existing DHT HTA frameworks. Conclusions. The review identified mismatches in the content generated by DHT clinical studies and that required for DHT- specific HTAs. These findings informed the development of an extended checklist comprising 22 stakeholder- prioritized DHT-specific considerations, which are aligned with the EUnetHTA model and will help ensure the planning of DHT-specific research generates evidence suitable for HTA

Oral Presentation Number: OP07 Abstract Title: Eleven Years Of Conitec: Advances And Challenges Of Patient And Public Involvement In The Brazilian Health Technology Assessment Process Authors Names: Andrea Brigida Souza, Adriana Prates, Andrija Almeida, Clarice Portugal ([email protected]), Luiza Losco, Mariana Fonseca, Melina Barros, Vania Canuto Introduction. Patient and public involvement (PPI) is a core element of the health technology assessment (HTA) process. Since its creation in 2011, the National Committee for Health Technology Incorporation (Conitec) has promoted initiatives to include stakeholders in HTA for the Brazilian Public Health System (SUS). This work aimed to present a report on the advances and challenges related to PPI in 11 years of Conitec. Methods. A retrospective analysis of PPI actions carried out at Conitec was conducted, based on an analysis of minutes and records of meetings and discussions held internally and documents published on Conitec´s website. Results. Events and meetings were held over the years with different actors interested in the HTA process. Since 2015, a plain-language version of the technical report has been made available to the public during public consultations for each HTA topic. Recently, a register of patients, specialists, and SUS managers was created to form a database and establish a network with the stakeholders. Since 2020, SUS users have been allocated time to speak at Conitec´s meetings. Qualitative analysis of public consultation documents started in 2021 and a pilot qualitative evidence synthesis was carried out in 2022. These initiatives, although not directly focused on PPI, increase the consideration of the perspectives of patients, family members, and caregivers in the HTA process. Conclusions. PPI actions implemented at Conitec have significantly promoted inclusiveness and exchanges among stakeholders, contributing to a greater transparency regarding Conitec's actions. Nonetheless, we have important challenges on our horizon, such as strengthening connections with primary healthcare managers and professionals and social movements. It is also strategic to expand the technical and scientific discussion on PPI and qualitative approaches with HTA researchers and the voting members of Conitec. Finally, another aim is to improve knowledge of HTA and public health policy among law professionals and the pharmaceutical industry in Brazil.

Oral Presentation Number: OP08 Abstract Title: International Benchmarking Of Health Technology Assessment Training Tools And Materials For Patients And Consumers Authors Names: Eunice Low ([email protected]), Joëlle André-Vert, Marc Guerrier, Gaëlle Fanelli, Margaret Galbraith Introduction. The objective was to conduct a benchmarking study of available online health technology assessment (HTA) training tools for patients, specifically those used by HTA agencies and major European and international patient and consumer groups (PCGs). We compared existing online training tools on this topic in order to develop in-house HTA training tools for French patients and consumers. Methods. A literature search and a scoping review of websites was conducted by including the websites of HTA agencies, European and international PCGs, and other bodies. This was supplemented with videoconference interviews with selected HTA agencies and patient groups. The inclusion criterion was the existence of content describing HTA and patient and public involvement (PPI) in HTA that PCGs could use (regardless of its format). Results. Eighty-two online training tools were selected according to the specified inclusion criterion. Sixteen international HTA bodies, nine European and international PCGs, and 13 other bodies provided online HTA training tools available for patients and consumers. No journal articles matching the inclusion criterion were found. Two broad categories of content were identified: the first relating to HTA and the second relating to PPI in HTA. Moreover, the formats of these tools ranged from interactive to non-interactive, with varying accessibility (freely available or with a paywall) and assessment methods. Conclusions. These results should be considered together with budget requirements, project time constraints, human resources, and the preferences of HAS and patients when developing HTA training tools to improve the participation of patients and consumers in the HTA process at HAS.

Oral Presentation Number: OP09 Abstract Title: Developing A Patient And Consumer Training Tool Explaining Health Technology Assessment And Patient/Consumer Participation: The French Experience Author Names: Eunice Low ([email protected]), Joëlle André-Vert, Marc Guerrier, Gaëlle Fanelli, Margaret Galbraith Introduction. The French National Authority for Health's (HAS) 2019-2024 strategic workplan called for \"making public involvement a priority.\" This project was designed within the roadmap validated in 2021; \"Strengthening public involvement in health technology assessment (HTA) at the HAS”, including an action of building a means of training patient organizations for their contribution. The project’s overall objective was to develop with patients and consumers a first training tool, representing an online knowledge base targeting French patients and consumers to explain the HAS HTA process and assist their participation in these assessments. Methods. Three stages were designed to meet this objective. Firstly, an international benchmark was performed of available online HTA training tools for patients and consumers, notably those used by HTA bodies and European and international patient and consumer groups (PCGs). Secondly, an internal HAS search for e- learning tools, was conducted to identify whether they could meet the training needs of French patients and consumers. Finally, the training tool was developed via a working group composed of patients and HAS scientific officers. Results. The benchmark identified 82 online training tools selected according to the specified inclusion criteria. Sixteen international HTA agencies, nine European and international PCGs and 13 other bodies provided online HTA training tools for patients and consumers during the research period, but no journal articles identified such tools. Eleven formats and 12 key themes, divided into two main categories were identified: important content related to HTA, and important content related to public involvement in HTA. The HAS search for e-learning tools resulted in internal e-learning tools offered for clinical experts not meeting the needs and preferences of patients and consumers. Finally, HAS based its training tool development on these preferences and needs to create a PowerPoint in two blocks of modules covering the two main categories above (six modules in total). Conclusions. French patients and consumers preferences and needs for a HTA training tool were inspired by the international benchmark, dividing key themes into two main categories: important content related to HTA, and important content related to public involvement in HTA. This resulted in HAS development of two blocks of modules in PowerPoint format covering these two categories.

Oral Presentation Number: OP10 Abstract Title Standardized Multilingual Reporting Of Health Technology Assessment And Stakeholder Involvement Author Names: Jack Nunn ([email protected]), Gillian Mason Introduction. There is currently no standardized way to share information about health technology assessment (HTA). Standardised Data on Initiatives (STARDIT) addresses current limitations and inconsistencies in sharing data about HTA processes by providing a way to report these data, including which stakeholders have been involved, their tasks, what methods and data sources were used, and any impacts or outcomes observed. Methods. STARDIT development began in 2019 and was guided by participatory action research paradigms. A multidisciplinary international team of over 100 citizens, experts, and data users was involved in co-creating STARDIT. These co-creators include cancer patients, people affected by rare diseases, Indigenous peoples from multiple countries, representatives involved in HTA processes, health researchers, environmental researchers, economists, librarians, and academic publishers. Methods of involving people included public events, online discussions, and a public consultation process. STARDIT is free to use, and data can be submitted by anyone. Report authors can be verified to improve trust and transparency, and data can be checked for quality. Results. STARDIT can help create high-quality standardized information about HTA processes that can be accessed and edited by anyone. STARDIT enables data reporting at all stages of the HTA process and works in multiple languages. This allows stakeholders involved in or affected by HTA processes (including patients, the public, Indigenous peoples, and people from industry) to appraise and edit information and to self-identify the labels and terminology used to describe them. Organizations such as the Cochrane Collaboration, Australian Genomics, and multiple universities have created STARDIT reports. A link to the working beta version can be found at scienceforall.world/STARDIT. Conclusions. STARDIT offers those conducting HTA access to standardized information that enables well-founded comparisons of the effectiveness of different HTA methods, including the most effective methods of involving stakeholders. STARDIT allows anyone to access data about HTA processes, which can support participatory ways of working and help improve the equity and quality of HTA processes worldwide.

Oral Presentation Number: OP11 Abstract Title: Cost-Effectiveness Of Atezolizumab Plus Chemotherapy As A First-Line Treatment For Metastatic Non-Squamous Non-Small Cell Lung Cancer. Author Names: Liu Liu, Yi Yang([email protected]), Dunming Xiao, Yingyao Chen Introduction. Treatment with atezolizumab plus standard chemotherapy can prolong the overall survival of patients with metastatic non-squamous non-small cell lung cancer (NSCLC). However, the economic value of this treatment regimen is unknown. This study aimed to estimate the cost effectiveness of atezolizumab plus chemotherapy in the first-line treatment of metastatic non-squamous NSCLC from a healthcare system perspective in China. Methods. A partitioned survival model consisting of three discrete health states was developed to estimate the cost and effectiveness of atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) versus carboplatin or cisplatin plus pemetrexed (PP) in the first-line treatment of metastatic non-squamous NSCLC over a 12-year lifetime horizon. Key clinical data were generated from the IMpower132 trial. Local direct medical and non- medical costs were used and health preference data were collected from patients with NSCLC in 13 tertiary hospitals across five provinces in China. Costs, quality-adjusted life-years (QALYs), and incremental cost- effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model. Results. Compared with the PP regimen, APP therapy yielded a gain of 0.21 QALYs at an increased cost of CNY145,602 (USD22,574), resulting in an ICER of CNY684,894 (USD106,185) per QALY gained. The ICER was significantly higher than three times the gross domestic product per capita for China in 2021 (USD37,663). One-way sensitivity analyses revealed that one of the most influential factors in this model was the cost of atezolizumab. Probabilistic sensitivity analysis showed that there was 14.7% probability that atezolizumab plus chemotherapy was cost effective at a willingness-to-pay value of CNY242,928 (USD37,663) per QALY gained. Conclusions. The APP regimen could prolong survival and improve health benefits over standard chemotherapy in the first- line treatment of patients with metastatic non-squamous NSCLC, but it is unlikely to be a cost-effective treatment option in China.

Oral Presentation Number: OP12 Abstract Title: Cost Effectiveness Comparison Of PD-L1 Inhibitors In First-Line Treatment Of Advanced Non- Squamous Non-Small Cell Lung Cancer In China Author Names: Yi Yang ([email protected]), Dunming Xiao, Fuming Li, Yu Xia, Yingyao Chen Introduction. In China, multiple programmed cell death ligand 1 (PD-L1) inhibitor drugs have been approved for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC). This study aimed to systematically compare the cost effectiveness of these PD-L1 inhibitors. Methods. A partitioned survival model was developed from a societal perspective to simulate the disease progression and cost effectiveness of various PD-L1 inhibitors for the first-line treatment of advanced non-squamous NSCLC over a lifetime horizon. The model consisted of three health states: alive with no progression, alive with progression, and dead. Key clinical inputs were based on Kaplan-Meier survival curves from relevant randomized controlled trials. Local direct medical and non-medical cost data were used. Utilities were obtained from questionnaires conducted in 13 tertiary hospitals from five provinces across China. Results. When compared with the regimen of pembrolizumab plus platinum doublet chemotherapy, the following results were obtained: • Atelelizumab combined with chemotherapy was more costly (USD88,446 versus USD62,182) and less effective in terms of quality-adjusted life-years (QALYs) (1.43 versus 1.85); • Camrelizumab plus chemotherapy was less costly (USD44,792 versus USD62,182) and less effective (1.59 versus 1.85 QALYs), with a base-case incremental cost-effectiveness ratio (ICER) of USD66,374 per QALY gained. This was greater than three times China's gross domestic product per capita in 2021 (USD 37,656); • Islelizumab plus chemotherapy was more costly (USD66,634 versus USD62,182) but had better effectiveness (2.14 versus 1.85 QALYs) and was a cost-effective option, with an ICER of USD15,458 per QALY gained; • Sintilimab combined with chemotherapy was less costly (USD53,978 versus USD62,182) and more effective (1.80 versus 1.85 QALYs), and was the dominant regimen. The results of sensitivity and scenario analyses further confirmed the robustness of the base-case outcomes. Conclusions. Compared with pembrolizumab and a standard chemotherapy regimen, sintilimab and tislelizumab regimens are cost effective, whereas atelelizumab and camrelizumab regimens are not.

Oral Presentation Number: OP13 Abstract Title: Cost-Effectiveness Analysis Of Sintilimab Plus Chemotherapy For The First-Line Treatment Of Non-Squamous Non-Small Cell Lung Cancer: Societal Perspective Author Names Fuming Li ([email protected]), Yi Yang, Dunming Xiao, Yingyao Chen Introduction. Sintilimab is an IgG4 anti-programmed cell death protein 1 (PD-1) antibody that has a high-affinity blocking interaction with PD-1 and its ligands. The updated ORIENT-11 study showed that sintilimab plus chemotherapy significantly prolonged progression-free and overall survival, compared with chemotherapy alone, in the first- line treatment of non-squamous non-small cell lung cancer (NSCLC). In China, it is uncertain whether sintilimab is a cost-effective alternative to standard immunotherapy. Methods. A partitioned survival model with three health states (including progression-free survival, disease progression, and death) was constructed from the Chinese societal perspective using a three-week cycle with a lifetime horizon (16 years). Individual patient data were captured from the updated ORIENT-11 study, and high-risk and clinically severe adverse events were specifically added to the states. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were the primary outcomes. Costs, health productivity losses, and utilities were derived from questionnaires and supplemented by expert opinion and literature review. All costs were expressed in 2021 USD, and costs and QALYs were discounted at an annual rate of five percent. Sensitivity analyses and scenario analyses considering the healthcare system perspective were performed to explore model uncertainty. Results. Patients receiving sintilimab plus chemotherapy incurred a mean total cost of USD67,727 and gained 2.5 QALYs during the lifetime period, compared with USD40,530 and 1.5 QALYs for patients receiving standard chemotherapy. The corresponding ICER was USD27,665 per QALY in China. At a willingness-to-pay threshold of three times the gross domestic product per capita in China (USD37,663), sintilimab plus chemotherapy was the optimal treatment in 84 percent of replications. Deterministic sensitivity analysis showed that the most significant driving determinant was the discount rate of costs and QALYs. An ICER of USD21,020 per QALY was obtained from the Chinese healthcare system, validating the robustness of the cost-effectiveness analysis. Conclusions. Compared with standard chemotherapy, sintilimab plus chemotherapy is a cost-effective treatment regimen for non-squamous NSCLC in China. Thus, sintilimab may benefit Chinese patients and should be promoted by decision makers.

Oral Presentation Number: OP14 Abstract Title: Cost-Utility Analysis Of Regorafenib For Patients With Hepatocellular Carcinoma Who Progressed On Sorafenib Treatment Author Names Ambrish Singh ([email protected]), Salman Hussain Introduction. In the RESORCE trial, regorafenib was shown to provide overall survival (OS) benefit for patients with hepatocellular carcinoma (HCC) that has progressed on sorafenib treatment. Subsequently, it was approved by the Therapeutic Goods Administration for the treatment of patients with HCC who were previously treated with sorafenib; however, regorafenib is still not recommended by the Pharmaceutical Benefits Advisory Committee in Australia. We aimed to assess the cost effectiveness of regorafenib as a second-line therapy for patients with HCC who progressed on sorafenib from an Australian healthcare perspective. Methods. We developed a Markov model to compare the cost effectiveness of regorafenib with best supportive care (BSC) as a second-line therapy for HCC after treatment with sorafenib. The health outcomes of life-years and quality-adjusted life-years (QALYs) were derived from the RESORCE trial. Survival benefits sourced from the RESORCE trial were fitted with the parametric model to estimate survival beyond the follow-up period. Drug costs and costs associated with adverse events (AEs) were sourced from published literature and the Independent Health and Aged Care Pricing Authority cost report. Model validity was verified using probabilistic sensitivity analyses. Results. The incremental monthly cost of treatment with regorafenib was AUD19,273 (USD13,374), with an incremental life-year gain of 0.38, compared with BSC. The incremental QALYs gained with regorafenib were 0.24, resulting in a base-case incremental cost-effectiveness ratio (ICER) of AUD80,511 (USD55,872) per QALY. In the probabilistic sensitivity analyses across scenarios, the ICER remained above the conventional threshold of AUD50,000 (USD34,698) per QALY, with a zero probability of being cost effective at this willingness-to-pay threshold. Conclusions. At the current price, second-line treatment with regorafenib in patients with HCC that has progressed on sorafenib was not cost effective at the conventional willingness-to-pay threshold from an Australian health- system perspective.

Oral Presentation Number: OP18 Abstract Title: Laying The Foundation For Sustainable Health Technology Assessment Training Program In Ukraine Author Names Wietske Kievit, Jip Janssen, Wija Oortwijn, Anton Voitenko, Oresta Piniazhko, Rabia Sucu ([email protected]) Introduction. Since 2017, health technology assessment (HTA) has been included in the Ukrainian Health Law fundamentals and its implementation has accelerated since it became mandatory in 2020. SAFEMed has been supporting the Ministry of Health in integrating HTA into the decision-making ecosystem and building capacity in HTA. In this 2022 to 2023 project, we aimed to create and conduct HTA training for doers, users, and trainers based on a developed model curriculum for an HTA master’s program, and to identify sets of criteria for successful training and training centers. Methods. First, we reviewed websites and documents of current academic HTA master’s and advanced programs worldwide. Second, we performed an assessment of the training needs of HTA doers, users, and trainers in Ukraine using an online survey that captured level of experience and knowledge gaps. Third, we reviewed the capacity and quality requirements of existing academic centers that provide HTA training. Results. We identified seven HTA master’s programs globally, which covered five HTA domains: (i) health problem and current use of the technology; (ii) description and technical characteristics; (iii) safety; (iv) clinical effectiveness; and (v) costs and economic evaluations. Other aspects of HTA, such as ethical, legal, social, and cultural aspects were also covered, but not in all programs. The needs assessment was completed by 40 doers (53%), users (43%), and potential trainers (5%) of HTA in Ukraine. Specific knowledge gaps included: comparative effectiveness, health economics, qualitative evidence synthesis, patient and public involvement, and ethical issues. The proposed program addresses these gaps and includes an introduction to HTA that is in line with the new HTA definition. We also generated a minimum set of quality assurance criteria to ensure successful training and to develop efficient training centers for delivering HTA programs. Conclusions. Our study provides a strong foundation for planning and conducting sustainable HTA training for current and future doers, users, and trainers in Ukraine, which can be an example for other countries wishing to increase HTA capacity.

Oral Presentation Number: OP19 Abstract Title: Exploring The Environment/Capacity Of South African Citizen Actors To Contribute To Health Technology Assessment Processes, Policy Development And Institutionalization Author Names Lauren Pretorius ([email protected]), Debjani Muller Introduction. Several overarching health policy reform processes are currently underway in South Africa (SA), providing an opportunity to establish health technology assessment (HTA) and value-based assessment (VBA) frameworks that foster patient and citizen involvement (PCI). A mapping of the capacity, knowledge, and skill of SA PCI advocacy actors and understanding of the ‘middle-ground’ and influencing relationships that influence advocacy strategies for PCI in HTA, will allow us to determine the needs of PCI actors to entrench PCI principles in the emerging institutionalization of HTA in SA. Methods. An analysis of national and international legislative and policy frameworks indicates current gaps and opportunities for PCI institutionalization in HTA in SA. A survey was conducted to determine SA patient and citizen advocacy actors’ capacity, knowledge, and skill across multiple disease areas. An analysis of decision maker’s opinions and positions about PCI in HTA and VBA policy, and their potential influence on the PCI process was undertaken. Results. The legislation and policy review indicate that engagement initiatives are positioned at the ‘involvement’ or ‘consultation’ stages of the engagement continuum, rather than higher-level engagement. Five percent of patient advocacy groups (PAGs) interviewed have formalized PCI HTA advocacy strategies. Few PAGs indicated employing processes to actively monitor the HTA and PCI-related activities of decision-makers. The majority of PAGs stated that collaborative efforts within larger networks would generate more success, if they engaged in PCI in HTA advocacy. Over eighty percent of civil society stakeholders face capacity constraints, such as lack of knowledge of the legislative framework and theory of HTA, funding and manpower to engage in PCI. The majority of HTA processes undertaken by funders in SA do not actively include PAGs or formalized PCI. Conclusions. Existing legislative and policy frameworks do not include PCI capacity-building strategies. This is impacted by the lack of coordination amongst patient and consumer groups, the willingness of existing HTA structures to formalize PCI, and the resources of the country’s PCI advocate actors to influence existing HTA processes.

Oral Presentation Number: OP21 Abstract Title: Patient Values Project (PVP): Patient Preferences For Cancer Treatments To Inform A Framework Incorporating Patient Values Into Health Technology Assessment Author Names Deborah A Marshall ([email protected]), Karen V MacDonald, Barry Stein Introduction. The methodology for explicitly incorporating patient preferences by expert committees engaged in deliberative health technology assessment (HTA) processes for drug reimbursement recommendations is a relatively unexplored area despite the growing emphasis on patient-reported outcomes and patient engagement. The Patient Values Project (PVP) aims to improve patient input to expert review committees and promote a better understanding of the patient perspective using quantitative data to support the rationale in assessing new cancer drugs. Using colorectal cancer as a starting point, the PVP aims to develop a framework to objectively incorporate quantitative patient values and preferences into Canada's cancer drug HTA decision- making process. We report on results from the first phase. Methods. In the first phase, we developed a bilingual survey informed by qualitative focus groups, literature review and feedback from clinicians, patients and experts. The survey includes background questions, general and cancer specific quality-of-life tools, two discrete choice experiments (DCE) and a best worst scaling (BWS) experiment. After pre-testing and pilot testing, the survey was administered across Canada to metastatic and non- metastatic colorectal cancer patients and caregivers, in addition to adults from the general population. In the next phases, we will use vignettes to explore how patient preferences could be incorporated explicitly into decision-making, and what approach to use in HTA submissions. Results. DCE1 survey results (~n=1,000) reflect trade-offs between health-related quality-of-life and survival; DCE2 results reflect trade-offs between treatment regimens, side effects and survival/risk of recurrence; BWS results ranked and weighted the tolerability of 25 possible side effects of treatment. We observed differences in preferences amongst the general population, patients with metastatic cancer, non-metastatic cancer and caregivers. Conclusions. Patients have unique perspectives and preferences about what is important and of value to them, which may impact patient adherence to treatment. In the next phases, we will explore how this evidence from patient preferences can be translated into values that could potentially be incorporated as an explicit element of the deliberative process for HTA decision-making.

Oral Presentation Number: OP22 Abstract Title: Benchmarking Of Population-Based Childhood Cancer Survival By Toronto Stage: Know The Differences To Propose Effective Interventions Author Names Rosalia Ragusa ([email protected]), Dott Fabio Didonè, Laura Botta, Antonina Torrisi, Maria Alessandra Bellia, Gemma Gatta, BENCHISTA Italy working group Introduction. Pediatric cancers are rare tumors, heterogeneous in location and biologically very different from adult cancers. Documented survival variation across European countries and Italian regions shows that there is still room for further improvement by reducing inequalities. We aim to understand why there are differences in survival. The BENCHISTA-ITA project (National Benchmarking of Childhood Cancer Survival by Stage at diagnosis), that is the Italian twin project of the International BENCHISTA, collects stage at diagnosis of solid pediatric tumors, according to the Toronto Guidelines. We will compare how far the cancer has spread at diagnosis and test if differences in tumor stage explain any survival differences between Italian regions Methods. The project study involved the stage distribution and the survival of 9 pediatric solid tumors diagnosed between 2013 and 2017 in Italy. All patients therefore had at least 3 years of follow-up in 2021 for life-stage definition. The study involves the identification of all new diagnoses of cancer, evaluation of the clinical documentation of cases eligible for research, and international classification and coding. Analyses of stage distribution and survival rates for each tumor type will be described. Results. Data from 35 population-based cancer registries from 18 out of 20 Italian regions were collected covering about 84 percent of the Italian child population. In particular, data on: imaging/examination performed before any treatment; source used for staging; primary treatment defined as given within one year from diagnosis; relapse/ recurrence/ progression; follow up and status of life. The study tested the applicability of the Toronto Guidelines as a tool to obtain population-level comparable stage information for childhood cancers. There were 1,343 cases collected (242 Neuroblastoma, 124 Wilms Tumour, 145 Medulloblastoma, 148 Osteosarcoma, 135 Ewing sarcoma, 115 Rhabdomyososarcoma, 54 Ependimoma, 47 Retinoblastoma, 333 Astrocytoma). Toronto stage could be assigned in more than 90 percent in the majority of tumours. Tumors in which it was more difficult to assign the stage using the Toronto staging guidelines were ependymoma, astrocytoma, and retinoblastoma. It was easier to retrieve data for patients in the 0-14 years of age than adolescents (14-18 years). Differences in stage distribution and survival differences between regional grouping were presented. Conclusions.

The Italian BENCHISTA project, improving the connection between pediatric cancer registries, aims to improve care of children with cancer across the nation, reducing possible disparities. The wide adoption of the Toronto Guidelines will facilitate international comparative incidence studies, strengthen the interpretation of survival data, and contribute to more appropriate solutions to improve childhood cancer outcomes.

Oral Presentation Number: OP23 Abstract Title: Early Detection Tools For Emotional Distress In Adult Cancer Patients In Spain: A Health Technology Assessment Report Author Names Patricia Gomez-Salgado ([email protected]), Yolanda Triñanes, Beatriz Casal- Acción, María José Faraldo-Vallés Introduction. Patient-reported outcome measures are being increasingly considered both in clinical practice and in the field of health technology assessment. Although emotional distress is currently recognized as the sixth vital sign in cancer care, its early detection and screening is not yet included in routine clinical practice in Spain. The main objective of this study was to assess the psychometric properties and diagnostic accuracy of validated tools for the early detection of distress among adults with cancer in the Spanish context, at the request of the Spanish National Health System (NHS) Cancer Strategy. Methods. A systematic review was carried out to analyze development and validation studies. The Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) was used for the risk of bias assessment, and a multicriteria global assessment was used for the tests. Ethical and organizational aspects were also addressed. Results. Fifteen validation studies were included, corresponding to seven tests. The tools considered were the Distress Thermometer (DT), the Brief Symptom Inventory-18 (BSI-18), the Edmonton Symptom Assessment System- revised (ESAS-r), the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale for Anxiety and Depression (VAS-AD), the Detection of Emotional Distress (DED) scale, and the Psychosocial and Spiritual Needs Evaluation (ENP-E) scale. Evidence of validity, reliability (internal consistency), and diagnostic accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve) were summarized. Three scales were rated as poor (VAS-AD, BSI-18, and ESAS-r), the ENP-E scale was rated as acceptable, and three scales were rated as moderate (DT, DED, and HADS). Conclusions. The DT (single-item measure) stands out as an appropriate tool for early detection of emotional distress in the Spanish NHS. The use of this scale could be considered a first stage, to be combined later with a longer scale to improve screening specificity. The HADS scale could be utilized for this purpose. The use of these tools should be framed within a structured screening program that ensures further evaluation and subsequent psychological care when needed.

Oral Presentation Number: OP24 Abstract Title: Preferences Of Depressed And Depression-Prone Groups With Regard To Antidepressants In China: A Best-Worst Scaling Survey Author Names Shimeng Liu ([email protected]), Yanfeng Ren, Jing Liu, Yan Wei, Yingyao Chen Introduction. Antidepressants are one of the main treatment approaches for depression, and previous evidence suggests that consideration of patient preferences can improve their adherence to medication regimens. The objective was, therefore, to evaluate the preferences of depressed and depression-prone groups in China with respect to antidepressant medications. Methods. An online survey with best-worst scaling choices was administered in depressed and depression-prone patients. The balanced independent block design generated 13 choice task profiles for each participant to answer, with each choice set consisting of four alternatives out of 13 antidepressant-specific attributes. Count analysis and a conditional logit model were used to estimate the relative importance of the 13 attributes and preference heterogeneity. Results. The analytical sample included 210 participants, comprising 49 individuals who had previous experience with depression and 161 who were depression prone. Participants in both groups preferred medications with a low risk of liver or kidney damage, headache or dizziness, and recurrence. There were significant differences in both groups regarding out-of-pocket costs and duration of medication. The K-means clustering further proved preference heterogeneity among the patients. Conclusions. Our study revealed patient preferences for antidepressant medication choices in China. Healthcare decision makers should consider and discuss patient preferences in the treatment decision-making process to improve patient adherence to and satisfaction with medications, and to ultimately improve patient outcomes.

Oral Presentation Number: OP25 Abstract Title: Increasing Harmonization Through Improving Uptake Of Core Outcome Sets In Clinical Trials And Systematic Reviews Author Names Paula Williamson ([email protected]), Sean Tunis Introduction. We reviewed what is known about the uptake of core outcome sets (COS) in research, where a COS is defined as an agreed standardized set of outcomes that should be measured and reported, at a minimum, in all clinical trials in a specific area of health or health care. We reviewed similarities between COS and outcomes recommended by relevant stakeholders in the evidence ecosystem, and described actions taken by those stakeholders to facilitate COS uptake. Methods. The Core Outcome Measures in Effectiveness Trials Initiative database was searched in May 2022 for publications classified as ‘COS methods research’, ‘COS uptake study’, or ‘systematic review of COS uptake studies’. We also added articles related to endorsement of COS and other references that were known to the authors. Evidence was classified according to the relevant stakeholder group as well as COS developers. Results. COS uptake was low in most research areas. Common facilitators related to increased trialist awareness and understanding of COS. Common barriers were not including all specialties who might use the COS in the development process and a lack of recommendations on how to measure the outcomes. Increasingly, COS developers are considering strategies for promoting uptake earlier in the process, with some including actions beyond traditional dissemination approaches. There was good overlap in outcomes between COS and those in regulatory documents and health technology assessments. An increasing number and variety of organizations are recommending that COS be considered. Conclusions. Greater emphasis on encouraging and facilitating COS uptake is essential to achieve greater harmonization and collaboration among decision makers. COS developers should collaborate with key organizations from the outset to identify uptake strategies. Stakeholders from many organizations and communities should do more to promote the uptake of COS, and research to identify and develop evidence-based strategies for increasing uptake amongst trialists is needed. This may include initiatives and interventions that can push and pull trialists towards considering COS for their studies.

Oral Presentation Number: OP27 Abstract Title: Impact Of Generic Entry Of Pharmaceuticals On Drug Prices In Australia Author Names Arun PG-Jones, Victoria Serra-Sastre, Hansoo Kim ([email protected]) Introduction. Policy makers are keen to introduce cost containment measures in medicine spending due to aging populations and fiscal pressure. A major price reform was applied to the Australian Pharmaceutical Benefits Scheme (PBS) in 2014. This aimed to stimulate price reductions by increasing competition among generics, amidst growing evidence at the time of unnecessarily high generic medicine prices in Australia. The aim of this study was to estimate the effect of patent expiration and generic competition on drug prices, while controlling for other determinants of drug prices in Australia. Methods. A dataset from publicly available sources was constructed using monthly data on the price of drugs listed on the PBS from October 2014 to July 2022. The information included the generic drug name, item code, date, approved ex-manufacturer price, dispensed price per maximum quantity, and brand names. This was supplemented with monthly government spending and number of prescriptions filled per item code. A fixed effects regression model was used to estimate the effect of patent expiration and generic competition on dispensed drug prices. Results. The model estimated that introducing generics in Australia led to an 18 percent decrease in prices, excluding further decreases resulting from other controlled variables. The price elasticity of total prescriptions filled was estimated to be -0.6, suggesting that a one percent increase in prescriptions filled resulted in drug prices being lowered by 0.6 percent. This reflects the fact that, on average, firms reacted by reducing prices to increase market share when faced with an increase in quantity demanded. Each extra competitor was estimated to result in a reduction in prices of roughly 1.8 percent. Conclusions. These results show that entry of generics into the Australian pharmaceutical market resulted in a significant reduction in drug prices. However, this alone does not provide empirical support for the effectiveness of these price reforms in generating savings by inducing generic competition, especially over other forms of pharmaceutical regulation.

Oral Presentation Number: OP29 Abstract Title: Impact Of New Drug Indications After Initial Registration By The Agência Nacional de Vigilância Sanitária (ANVISA) in Brazil Author Names Silvana Kelles ([email protected]), Camila Pereira, Carina Martins, Daniel Reis, Ernesto Azevedo, Geraldo Ribeiro, Karina Zocrato, Lélia Carvalho, Marcela Freitas, Maria Horta, Mariana Barbosa, Mariza Talim, Marcus Carvalho Borin Introduction. Most drugs have data only from clinical trials focused on a specific population at the time of first registration, so their indications for use are restricted to this population. In Brazil, the prices of new drugs for clinical conditions with no therapeutic alternatives are relatively high. When these drugs expand to other indications their prices are not reviewed, which can have a major financial impact. This study aimed to evaluate the financial impact of expanding the indication for trastuzumab deruxtecan. Methods. We calculated the annual cost to treat all Brazilian patients with the indications listed for trastuzumab deruxtecan at first registration, and then all additional indications. Populations were estimated from epidemiological data from National Committee for Health Technology Incorporation reimbursement documents and a clinical trial comparing trastuzumab deruxtecan with trastuzumab emtansine. Costs were calculated using the ANVISA Câmara de Regulação do Mercado de Medicamentos price value and a patient weight of 70 kg. Results. In January 2022, trastuzumab deruxtecan was introduced in Brazil for patients with human epidermal growth factor receptor (HER2) positive metastatic or unresectable breast cancer who had received two or more anti- HER2 treatment regimens. In June 2022, the indication was expanded to patients with HER2-positive metastatic or unresectable breast cancer who had received one anti-HER2 treatment regimen. In November 2022, the indication was further expanded to patients with metastatic or unresectable low-expression HER2 breast cancer who had received prior systemic therapy. The number of patients estimated to be eligible for the drug increased from 383 to 23,000, with an increased total cost from BRL467,970,786 (USD90,621,763) to BRL26,048,234,160 (USD5,044,197,164). Conclusions. The expansion of indications for trastuzumab deruxtecan may substantially increase its financial impact and compromise the sustainability of health systems. In Brazil, the lack of monitoring of drug prices means that the only change in prices occurs due to regulated annual inflation adjustments. Regulation is needed to reduce drug prices according to new indications, changes in therapeutic options for the same condition, and obsolescence.

Oral Presentation Number: OP31 Abstract Title: Societal Opportunity Costs: Incorporating Impacts That Fall Outside The Healthcare Sector Author Names Laura Edney ([email protected]), Laura Vallejo-Torres, Jonathan Karnon Introduction. Estimates of health opportunity costs provide an empirical basis for cost-effectiveness thresholds to support health technology funding decisions. Existing estimates reflect a healthcare system perspective. Many evaluations of new health technologies include a societal perspective, most commonly through incorporation of productivity losses. To inform cost-effectiveness thresholds from a societal perspective the societal opportunity costs of funding decisions should be estimated. The aim of this work is to (i) to empirically estimate the societal opportunity costs of health funding decisions based on the relationship between total healthcare spending and productivity; and (ii) to estimate if the relationship between health spending and productivity varies by disease category. Methods. A national panel dataset, including data on categories of healthcare spending by broad disease areas and measures of national productivity, such as lost productivity due to absenteeism, are being generated by geographic region and compiled from publicly available sources. Results. Fixed effects panel models will be used to estimate (i) the marginal effects of total health spending on productivity to generate an estimate of the reference societal incremental cost-effectiveness ratio (ICER) for Australia; and (ii) the marginal effects of alternative areas of health spending on productivity. The estimated societal opportunity costs and the effects by disease area will be interpreted in the context of the previously estimated health opportunity costs to describe potential consequences for health policy and funding decisions for new health technologies. Conclusions. The societal perspective is increasingly presented as a supplement to economic evaluations undertaken from a healthcare system perspective in funding submissions. This work represents an important extension to recent estimates of health opportunity costs and has important policy implications for interpretation of generated ICERs for new technologies and for funding recommendations. The methods also offer a framework for incorporation of additional impacts of health spending outside of the healthcare system such as those on the education and criminal justice systems.

Oral Presentation Number: OP33 Abstract Title: Child And Adolescent Mental Health Care Models: A Scoping Review Author Names Ingrid Zechmeister-Koss ([email protected]), Reinhard Jeindl, Viktoria Hofer Introduction. Mental illnesses are among the most common health problems in children and adolescents worldwide, and their prevalence has recently increased. At the same time, many countries face gaps in care and a shortage of services. To address these challenges, countries are developing child and adolescent mental health (CAMH) strategies and adopting their models of care. This paper aimed to give an international overview of these strategies and care models to support decision makers and stimulate mutual learning and improved CAMH care. Methods. We identified core topics within published CAMH strategies and care model documents from seven selected countries within the Global North, which represented different healthcare systems, geographical regions, and public health traditions to maximize variety. We systematically extracted data on the identified topics and summarized them narratively by applying qualitative content analyses. Results. The documents addressed the following core topics: awareness raising activities; prevention and promotion; detection; treatment; telemedicine; care pathways; transitional psychiatry; vulnerable patient groups; user participation; infrastructure; workforce development; implementation; digital tools for case management; and data acquisition and research. A stand-alone CAMH strategy exists in most countries. Recommendations on CAMH care often followed a public mental health approach and placed a high priority on mental health promotion and cross-sectional organization and funding of CAMH care services. Key principles of future CAMH care included: increased flexibility of care settings; early intervention; an open and non-judgmental attitude among staff; and strengths orientation instead of focusing on deficits and diagnoses. Conclusions. Reducing the prevalence of mental illness and current shortcomings in care requires action at the policy level (e.g., developing a CAMH strategy with a focus on mental health promotion and installing cross-sectoral governance), organizational level (e.g., reorganizing treatment settings and pathways of care), and individual level (e.g., strengthening user involvement and workforce development). Applying the recommended approaches in other countries will likely require redesign, ideally with a participatory approach and evaluation alongside piloting.

Oral Presentation Number: OP34 Abstract Title: Application Of A Case-Mix Analysis In COVID-19 Management At A University Hospital In Malaysia Author Names Amirah Azzeri ([email protected]), Mohd Hafiz Jaafar, Maznah Dahlui Introduction. The COVID-19 pandemic significantly affected healthcare systems. The most immediate effect was the increased demand for healthcare resources. This study aimed to conduct a case-mix analysis at one of the teaching hospitals in Malaysia to understand the economic implications of the pandemic. Methods. Admissions related to COVID-19, either as a primary or secondary diagnosis, were extracted and given ICD-10 codes for diagnosis and ICD9-CM codes for procedures. The combined ICD-10 and ICD9-CM codes were imported into a case-mix grouper to generate the case-mix codes. The codes used for COVID-19 were A-4-13-I, A-4-13-II, and A-4-13-III for mild, moderate, and severe disease, respectively. Clinical pathways were collected and healthcare resource utilization was estimated by combining top-down and bottom-up costing approaches. Discounting and inflation were based on guidelines and official rates. The cost data were reported in US dollars (price year 2021). Results. A total of 4,889 patients with a COVID-19 diagnosis were admitted to the hospital in 2021. Of these, 4,813 patients (98%) had a primary diagnosis of COVID-19. The remaining 76 patients (2%) were admitted for other medical reasons but were found to be positive for SARS-Cov-2 during admission. Therefore, for these patients, infection with the virus was considered a secondary diagnosis during the treatment episode. Among the 4,813 patients, 3,909 (81%) were admitted with mild COVID-19 (A-4-13-I), 630 (13%) had moderate COVID-19 (A-4- 13-II), and 274(6%) had severe disease (A-4-13-III). More than half (56%) of the patients with a secondary diagnosis of COVID-19 were admitted for elective procedures. The average length of hospital stay (LOS) for mild disease was 9 days, with cumulative hospital costs of USD1,543. The average LOS for both moderate and severe disease was 21 days, and the cumulative hospital costs were USD23,527 and USD26,731 respectively. The total costs incurred for COVID-19 were estimated at USD19,259,153. Conclusions. COVID-19 has considerable economic implications. This study provided information as part of a health technology assessment in the hospital to inform evidence-based healthcare decisions.

Oral Presentation Number: OP37 Abstract Title: Modelling The Effect Of Multi-Indication Treatment In Multimorbid Patients Using Population- Scale Linked Electronic Health Records For Healthcare Policy Author Names Rhiannon Owen ([email protected]), Jane Lyons, Ashley Akbari, Ronan Lyons, Keith Abrams Introduction. Healthcare decision-making has previously focused on developing recommendations for single conditions. However, standardized care for each chronic condition in isolation may be inappropriate for individuals living with multiple long-term conditions, known as multimorbidity, and may lead to unnecessary polypharmacy. This research aimed to develop a modeling framework to estimate the effect of a multi-indication treatment in multimorbid populations. Methods. Motivated by recent National Institute for Health and Care Excellence (NICE) recommendations on the use of a sodium-glucose cotransporter-2 (SGLT2) inhibitor in three commonly coexisting long-term conditions (type 2 diabetes mellitus [T2DM], chronic kidney disease [CKD], and heart failure [HF]), age-adjusted multistate models were used to estimate evolving temporal sequences of diseases and mortality. Baseline hazards were estimated using population-scale, individual-level, linked anonymized electronic health record (EHR) data for 613,195 individuals aged 55 to 85 years in Wales over a 20-year period (2000 to 2019). Hazard ratios for treatment effects were obtained from published randomized controlled trials and used in a patient-level simulation to estimate health-state transitions for different temporally ordered sequences of multimorbidity. Results. SGLT2 inhibitors increased the estimated mean life expectancy from 0.02 (95% confidence interval [CI]: -0.02, 0.05) to 1.44 (95% CI: 1.12, 1.74) years in multimorbid patients with T2DM, CKD, and HF. The largest gain occurred in individuals with HF, followed by T2DM. The estimated gain in life expectancy was less than 0.5 years for individuals with T2DM, CKD, and HF in different temporally ordered sequences. The estimated mean time to develop HF increased by 3.1 (95% CI: 3.00, 3.24) and 1.34 (95% CI: 1.12, 1.56) years in individuals with CKD, and in those with CKD followed by T2DM, respectively. Conclusions. There is an increasing need to appraise interventions in patients with multiple long-term conditions to identify optimal treatment strategies and reduce polypharmacy. Multistate models applied to linked EHRs allow for a more rigorous assessment of treatment effects in multimorbid patients for healthcare policy and decision- making.

Oral Presentation Number: OP38 Abstract Title: Evaluation Of A High-Cost Medicine For A Rare Disease: 16-Year Cohort Of Imiglucerase Use For Gaucher Disease In Brazil Author Names Marcus Carvalho Borin ([email protected]), Francisco de Assis Acúrcio, Juliana Alvares- Teodoro, Augusto Afonso Guerra Junior Introduction. Gaucher disease is a lysosomal storage disease of autosomal recessive inheritance that is caused by a deficiency of the enzyme glucocerebrosidase. This deficiency results in accumulation of the enzyme’s main substrate in the lysosomes of macrophages, mainly in the spleen, liver, and bone marrow. In more severe cases it can affect the lung, kidneys, and central nervous system. There are two main treatments available for patients with Gaucher disease: enzyme replacement therapy and inhibition of substrate synthesis. The main enzyme replacement therapy used in Brazil is imiglucerase, an analog of the human β-glucocerebrosidase enzyme. Imiglucerase is produced by recombinant DNA technology using a cell culture derived from the Chinese hamster ovary. It has 497 amino acids and differs from the endogenous enzyme by an amino acid at position 495, where histidine is replaced by arginine. The objective of the study was to analyze the survival of patients treated for Gaucher disease with imiglucerase in Brazil from 2000 to 2015. Methods. We constructed a retrospective cohort study of patients with Gaucher disease who received imiglucerase through the Brazilian National Health System from 2000 to 2015 using a national database created from the linkage of administrative databases. Results. A total of 1,241 patients who received imiglucerase were included. The overall survival rates at one, ten, and 15 years were 98.7 percent (95% confidence interval [CI]: 98.1, 99.4), 92.3 percent (95% CI: 90.2, 94.4), and 89.4 percent (95% CI: 85.6, 93.3), respectively. Conclusions. Our findings advance the understanding of the profile, survival, and risk factors of people with Gaucher disease, adding new data to the discussion regarding pharmaceutical therapies and patient care, and providing data for the development of new public health policies for the use of advanced, high-cost drugs for rare diseases.

Oral Presentation Number: OP39 Abstract Title: Real-World Evidence Of Pos-Incorporation Use Of Monoclonal Antibodies For Psoriasis In The Brazilian Public Health System Author Names Laís Lessa Neiva Pantuzza ([email protected]), Amanda Oliveira Lyrio, Felipe Ferré, Tacila Pires Mega, Ana Carolina de Freitas Lopes, Vania Cristina Canuto Santos, Stéfani Sousa Borges Introduction. Psoriasis is an immune-mediated chronic inflammatory disease that can affect the skin, joints, and nails. The treatment of the disease is offered by the Brazilian Public Health System (SUS) in accordance with the guidelines of the Ministry of Health. The aim of this study was to analyze real-world data (RWD) on the implementation and use of monoclonal antibodies (mAbs) for the treatment of psoriasis in the SUS. Methods. This is a descriptive study that used national administrative data on drug dispensing from the Open Room for Health Intelligence Situation (SABEIS-SUS) from October 2019 to December 2021. Adult individuals (≥18 years) with vulgar (L40.0), generalized pustular (L40.1), gutata (L40.4) and other (L40.8) psoriasis who used the mAbs adalimumab, etanercept, risankizumab, secukinumab and ustekinumab were included. Results. The year of implementation of mAbs for the treatment of psoriasis in the SUS was October 2019 (adalimumab, etanercept and secukinumab) and May 2020 (ustekinumab). Risankizumab was implemented in April 2022. The number of individuals using mAb grew from 366 in 2019 to 10,146 in 2021. In 2019, 2020 and 2021, the proportion of individuals using each mAbs was 62.3 percent, 46.2 percent and 35.4 percent (adalimumab), 7.9 percent, 3.3 percent and 2.7 percent (etanercept), 29.8 percent, 33.8 percent and 30.5 percent (secukinumab), 0 percent, 16.7 percent and 31.4 percent (ustekinumab), respectively. Conclusions. The number of mAbs users has greatly increased from 2019 to 2021, which may indicate a successful implementation of the psoriasis treatment in SUS. Most individuals used adalimumab in the year of the first implementation. However, the proportion of users of this mAb has greatly decreased after the implementation of ustekinumab. This reduction should not be so expressive since adalimumab and ustekinumab are recommended in different lines of treatment. The low proportion of etanercept use may be due the fact the medication is indicated for individuals up 18 years of age. This study provides important real- word evidence for monitoring the implementation of mAbs for psoriasis treatment in Brazil.

Oral Presentation Number: OP40 Abstract Title: An Initiative To Identify The Long-Term Effects Of COVID-19: Turkish Ministry Of Health (MoH) COVID-19 Follow-Up Centers Author Names Olgun Şener ([email protected]), Banu Ayar, Sultan Ogras Introduction. During COVID-19 pandemic Follow-up Centers were established by Turkish Ministry of Health (MoH) to detect possible complications in recovered COVID-19 patients at an early stage and make necessary interventions on time. It was aimed to reveal the short, medium and long-term effects of the disease by monitoring regularly. The Follow-up Center algorithms were designed by 10 clinicians of different branches with the support from United Nations Development Programme (UNDP). The follow-ups were made for one year in two pilot centers by using the health information systems infrastructure. In the dissemination process, follow-ups centers were established initially in 24 and subsequently in 81 provinces. Methods. In this study, the establishment, dissemination, operation and patient follow-up process of the COVID-19 Follow-up Centers were examined. The one-year (between 1 December 2021 and 1 December 2022) data obtained were analyzed. The patient follow-up; • was made at 0, 1, 3, 6 and 12 months for the first year, • planned to be made twice in the second year and the following years if needed. In the first year, people who received 3 follow-ups by using the forms and scales in the integrated information system modules were assumed to be followed up regularly. Results. Among the one-year data obtained from the COVID-19 follow-up centers, the total number of follow-ups, the distribution of follow-ups by date, gender and age groups and symptoms according to time were examined. In the first year; 11,288 people were included in the follow-ups and 18,328 follow-ups were made; 2,462 people were followed-up regularly. The followed up people consisted of 51.8% women; 48.3% of them were men. The incidence of symptoms decreased from 1,198 people in the first follow-up and to 180 people in the third follow-up. Conclusions. The establishment of Follow-up Centers is considered to be an important initiative to generate systematic data on the long-term effects of COVID-19. It was concluded that conducting studies using two-year data obtained from the follow-up centers, especially for complications, would be beneficial for management of the COVID-19 pandemic and in preparation for similar pandemics.

Oral Presentation Number: OP43 Abstract Title: Translating Cell And Gene Therapy HTA Into Practice - Building The Plane As We Fly It Author Names Paul Fennessy ([email protected]), Monica Ferrie Introduction. Assessing, funding, and implementing cell and gene therapies are usually based on limited evidence. This requires health technology assessment (HTA) agencies to develop new methodologies; payers to accept risk- based funding; industry to consider the right evidence and price; hospitals to consider if they have the necessary requirements; patients to consider their risk appetite for gene therapies; and health departments to consider all the above. Ensuring timely patient access to these therapies is challenging in Australia’s federated health system. To ensure stakeholders are aligned, all must come to the table and share their respective insights, experiences, and expertise to support planning, decision-making, funding, and commissioning of these therapies. It is time to develop a new consultative and decision-making paradigm to expedite HTAs, funding, commissioning, and timely patient access for cell and gene therapies. Methods. Australian federal, state, and territory government representatives agreed to develop a framework that clarifies processes around information sharing, HTA, funding, commissioning, and monitoring of highly specialized therapies and services (including cell and gene therapies). A draft national framework was developed that addresses assessment, funding, and implementation of high cost, highly specialized therapies and services (e.g., bone marrow transplants). However, it is unclear whether non-government stakeholders have been consulted. Results. The framework for assessing, funding, and implementing high cost, highly specialized therapies and services across Australia’s public hospital system is pending endorsement by each of the jurisdictional governments. High-level in nature, the framework’s primary audiences are industry and public hospitals. While not all processes are in place, the framework is forward-looking. A detailed implementation plan is warranted to better inform the roles and requirements of each stakeholder. Conclusions. The framework allows stakeholders to better understand government processes regarding assessment, funding, and implementation of high-cost therapies and services, thereby fostering a collaborative environment that supports timely patient access. Articulating process details in a follow-up implementation plan is essential to gain the trust of, and input from, industry, clinicians, and patient representatives.

Oral Presentation Number: OP44 Abstract Title: Exploring The Disconnect In Relevant Outcomes For Health Technology Assessment-Related Economic Evaluation Relative To Care Commissioning: Implications For Resource Allocation Author Names Matthew Franklin ([email protected]), Sebastian Hinde, Rachael Hunter, Gerry Richardson, William Whittaker Introduction. Outcome-based commissioning – a set of arrangements to define and pay for a service based on pre-agreed outcomes – has been operationalized in some regional care settings (e.g., adult social care). However, it remains largely aspirational due to operational considerations and challenges. Outcomes-based commissioning shares a common goal with economic evaluation alongside health technology appraisal (HTA): to achieve value for money for outcomes from a finite budget. Methods. We explored the considerations, implications, and challenges regarding the practical role of relevant outcomes in economic evaluation, relative to care commissioning, using England as a case study. Our exploration bridges a gap between economic evaluation evidence and practical resource allocation decision-making, focusing on conceptual (e.g., what are ‘relevant’ outcomes), practical considerations (e.g., quantifying and using relevant endpoints or surrogate outcomes alongside costs), and pertinent issues when linking these to commissioning based payment mechanisms. Results. Firstly, there is a disconnect between existing economic evaluation approaches and commissioning processes. For example, using a single quality-adjusted life-year (QALY) maximum and limited consideration of affordability relative to cost effectiveness. Secondly, service-focused outcomes (e.g., seeing a specialist team) rather than person-focused outcomes (e.g., QALYs) are often desirable from a practical commissioning and service provider perspective as they make it easier to measure key performance indicators. Thirdly, both person- and service-focused payment structures could lead to market inefficiencies when activity is focused on only people for whom a prespecified outcome can be achieved or service delivered; these approaches require additional efficiency-equity tradeoff considerations (e.g., using distributional cost-effectiveness analyses). Conclusions. We highlight payment structures as a major and complex consideration for commissioning, for which economic evaluation provides little to no consideration. Service-related outcomes and payments can be used as surrogate outcomes within economic modeling frameworks, while monitoring and evaluation can still be based on economic outcomes (e.g., QALYs and aggregated costs). Accounting for and explaining direct links

from payment structures to economic outcomes is a major step to bridging a gap between economic evaluation evidence and practical resource allocation.

Oral Presentation Number: OP45 Abstract Title: HTA And Gender Medicine: Time To Take Action! Author Names Rosalia Ragusa ([email protected]), Vincenzo Guardabasso, Maria Alessandra Bellia, Filippo Piana, Rosalba Quattrocchi Introduction. Gender medicine responds to the need for a reassessment of the medical-scientific approach in a gender perspective, to increase knowledge of the different aspects underlying gender differences and the appropriateness/ effectiveness of health interventions. Methods. A policy review of documents prepared by the Italian Ministry of Health on gender medicine was carried out, to investigate the possible areas of intervention of health technology assessment in the development of this interdisciplinary dimension. The areas of highest priority for action have been identified. Results. In Italy, the Ministry of Health, with the support of the National Institute of Health, issued a Plan for Application and Dissemination of Gender Medicine in June 2019. Our review shows that for the development of research on the mechanisms of pathogenesis the Italian Plan gives indications on the identification of diagnostic markers, prognostic and predictive response in a gender perspective, but there are no formalized rules that constitute a constraint or an obligation to do so. In Horizon Europe calls, for example, \"Pragmatic trials on minimally invasive diagnostics\" (HORIZON-MISS-2023-CANCER-01-03) on the other hand, it is required that gender and gender issues should be taken into account in all projects and all data should be disaggregated by gender, socio-economic status and ethnicity. Separating subjects into two groups in the analysis leads to greater complexity. This is even more true when considering the different types of gender. The total number of subjects to be included must likely increase to maintain statistical power in evaluating effects in subgroups. This increase leads to an increase in time and cost, if one needs to provide separate data by sex and even more so by gender. Different statistical tests to be used, according to the type of variables of the primary endpoint, should be considered in the study protocols. Conclusions. It seems appropriate to suggest reviewing upcoming health technology assessments with an eye to gender medicine. Gender medicine should become a strategic goal of prevention in public health and will strengthen the concept of the patient centrality until the personalization of therapies is achieved.

Oral Presentation Number: OP46 Abstract Title: The Decision Uncertainty Toolkit: Risk Measures And Visual Outputs To Support Health Technology Decision-making During Public Health Crises Author Names Erin Kirwin ([email protected]), Chris McCabe, Jeff Round Introduction. During public health crises such as the COVID-19 pandemic, decision-makers have relied on infectious disease models to predict and estimate the impact of various health technologies. The difficulties associated with capturing and representing uncertainty using infectious disease models leads to a high risk of making decisions that are misaligned to policy objectives. Even when uncertainty is adequately captured in the analysis, the tools for communicating the risks and harms of making wrong decisions have proved inadequate, which can lead to the suboptimal adoption of critical health technologies including vaccines and antivirals. We aim to adapt and extend health economic methods for the characterization, estimation, and communication of uncertainty to infectious disease modeling. Methods. Economic and infectious disease models share many features, including the comparison of policy alternatives on outcomes important to decision-makers (such as hospital census, total infections), but each takes a different approach to analysis of uncertainty. We extend best practices from health economics to infectious disease modeling and develop a suite of tools and visualization techniques which represent parameter uncertainty and the risk these unknowns present to decision-makers. Results. In consultation with decision-makers and infectious disease modeling experts we developed the ‘Decision Uncertainty Toolkit’ of model outputs and visuals. Visual tools for uncertainty are developed to: (i) accurately capture uncertainty in key infectious disease model outputs, and (ii) support intuitive and direct interpretation by infectious disease modelers and decision-makers. We also developed quantitative measures for the downside risk of policy alternatives, specified to capture both the probability and magnitude of losses relative to policy targets for a range of infectious disease model outputs. Together, these outputs can support decision-making by quantifying outcome uncertainty and the risks associated with policy alternatives. Conclusions. We developed the toolkit visuals and risk measures alongside infectious disease modelers and decision makers. The toolkit is designed to improve decision-maker understanding of decision risk in order to improve outcomes during future public health crises.

Oral Presentation Number: OP47 Abstract Title: The Risk-Based Price: Incorporating Uncertainty And Risk Attitudes In Health Technology Pricing Author Names Erin Kirwin ([email protected]), Mike Paulden, Chris McCabe, Jeff Round, Matt Sutton, Rachel Meacock Introduction. Decision makers often use value-based decision rules to determine whether technologies offer good value for money and should therefore be adopted, comparing cost-effectiveness analysis results with a threshold value. This assumes that decision makers are indifferent to interventions with the same expected value but different levels of underlying uncertainty. Such indifference is unlikely to hold in practice. We propose a risk-based price and accompanying decision rules to address this limitation. Methods. We characterized risk using the per-patient expected value of perfect independent information (EVPII), a modification of a standard output from value of information analysis. The EVPII estimates the expected value of net benefit losses caused by uncertainty related to a technology, independent of the uncertainty related to alternative treatments. ‘Payer risk tolerance’ is then defined as the maximum per-patient risk of making wrong decisions that payers are willing to accept, expressed in monetary terms. The risk-based price is the price at which the EVPII is equal to the payer risk tolerance. Results. The risk-based pricing decision rules are as follows: (i) a technology is acceptable for adoption at the submitted price if the incremental net benefit of the technology is greater than or equal to zero and the EVPII is less than or equal to the payer risk tolerance; and (ii) the optimal technology has the greatest expected net benefit at the lowest of the sponsor submitted, value-based, or risk-based price at a given cost-effectiveness threshold value. Conclusions. The risk-based price incorporates uncertainty and risk attitudes into decision-making. We demonstrate that both risk-averse and risk-neutral payers prefer the outcomes of risk-based pricing. Risk-based decision rules incentivize sponsors to develop evidence. Implementation of the risk-based price improves outcomes for patients by increasing health system net benefits under constrained resources, with better alignment to decision maker risk attitudes.

Oral Presentation Number: OP48 Abstract Title: Is It Time for (Disease-Specific) Reference Models? Author Names Hossein Afzali ([email protected]), Jonathan Karnon Introduction. In countries such as Australia and the UK, economic evidence, predominantly generated by decision analytic models, is one of the key inputs into the health technology assessment (HTA) process to inform the government decisions regarding public funding and pricing of new health technologies. This highlights the need for developing and using high-quality models. However, important concerns have emerged about the model development process in HTA submissions with significant impacts on the accuracy and comparability of model-based evaluations. Also, uncertainty in the model development process can result in several resubmissions leading to significant delay in patient access to a new health technology. Recent empirical evidence indicate that alternative models (with alternative structural choices and model inputs) are used to evaluate a range of health technologies proposed for the management of a specific disease, with a significant impact on estimates of cost effectiveness. These impacts can be minimized if valid (benchmark) models for a specific disease are developed from the outset and used to inform public funding decisions. This project aims to introduce ‘disease-specific reference models’ within national HTA processes. Methods. This project proposes to use ‘good practice for modelling’ to standardize the model development process and develop reference models. The process includes five main steps: Model conceptualization, choice of modelling technique, construction, validation, and uncertainty analysis. Results. Using the proposed process, the outcome will be the development and use of reference models for a number of conditions (e.g., depression) within national HTA processes to inform public funding decisions. Reference models fully represent both the current knowledge and uncertainty about a specific disease and can be used to evaluate multiple HTA submissions proposing alternative health technologies for the disease. Conclusions. The use of reference models will improve the validity of economic evidence used to inform funding decisions. It will also expedite patient access to effective health technologies by minimizing uncertainty in models in HTA submissions and hence reducing the number of re-submissions to funding bodies.

Oral Presentation Number: OP51 Abstract Title: Use Of Real-World Data In Cost-effectiveness Analysis Of Sequential Biologic Treatment For Rheumatoid Arthritis Author Names Janharpreet Singh ([email protected]), Matt Stevenson, Kimme Hyrich, Clare Gillies, Keith Abrams, Sylwia Bujkiewicz Introduction. In health technology assessment (HTA), economic evaluations assessing biologic drugs for rheumatoid arthritis (RA) involve modeling patients’ responses to multiple treatments given sequentially over a lifetime horizon. When data from randomized controlled trials (RCTs) are scarce, data from non-randomized studies (e.g., single-arm trials [SATs] and disease registries) can be used to supplement the evidence base. This research aimed to demonstrate meta-analytic methods for combining effectiveness data from randomized and non- randomized studies and their corresponding impact on cost-effectiveness estimates. Methods. Data comparing patients receiving second-line rituximab with continued background non-biologic treatment were extracted from one RCT and six SATs identified in an HTA assessing second-line rituximab for RA, and from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis, by applying a target trial emulation approach. A binomial meta-analysis model was used to estimate the probabilities of achieving the European League against Rheumatism (EULAR) response criteria by pooling data from the RCT, SATs, and the registry. The probabilities were entered into a decision model from a previous HTA to derive incremental cost- effectiveness ratio (ICER) estimates for treatment strategies with and without biologic drugs. Results. Compared with the original analysis, the estimated probability of at least a moderate EULAR response on rituximab from combined sources was substantially lower. For example, the probability obtained from an RCT was 0.68 (95% credible interval [CrI]: 0.345, 0.907), but only 0.29 (95% [CrI]: 0.242, 0.333) when using RCT plus registry data and 0.29 (95% CrI: 0.244, 0.336) for combined RCT, registry, and SAT data. In the cost- effectiveness analysis, the median ICERs were higher when including real-world data. Conclusions. Synthesis of all relevant data, including RWD, provides additional information regarding the variability in cost- effectiveness estimates and can be considered in sensitivity analyses for HTA decision-making.

Oral Presentation Number: OP52 Abstract Title: Treating Osteoporosis In Postmenopausal Women With Denosumab (Prolia®): A Systematic Review And Network Meta-Analysis Author Names Magdalena Ruth Moshi ([email protected]), Konstance Nicolopoulos, Danielle Stringer, Ning Ma, Mathias Jenal, Thomas Vreugdenburg Introduction. It is estimated that osteoporosis affects over 200 million people globally. Postmenopausal women (PMW) have an increased risk of developing osteoporosis due to low estrogen levels. This study assessed the safety and effectiveness of denosumab (Prolia®) relative to placebo, selective estrogen receptor modulators (SERMs) (bazedoxifene and raloxifene), and bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) for the treatment of osteoporosis in PMW. Methods. Systematic searches were conducted in three biomedical databases (PubMed, the Cochrane Library, and Embase) to identify randomized controlled trials (RCTs) of PMW with osteoporosis allocated to denosumab, placebo, bisphosphonates, or SERMs. The Cochrane Risk of Bias 2.0 tool was used to critically appraise included RCTs. Pairwise and Bayesian network meta-analyses were performed on the following predetermined outcomes: fractures (vertebral and nonvertebral); adverse events (AEs); mortality; serious AEs (SAEs); withdrawals due to AEs; bone mineral density (BMD); and AEs caused by denosumab discontinuation. Results. The analyses included 12 RCTs (22 publications, 25,879 participants). Denosumab, ibandronate, alendronate, zoledronate, and risedronate produced a statistically significant improvement in total hip (TH) and lumbar- spine (LS) BMD, compared with placebo. Similarly, ibandronate, risedronate, and alendronate showed a statistically significant improvement in femoral neck (FN) BMD. Risedronate produced a statistically significant decrease in nonvertebral fractures (risk ratio 0.20, 95% confidence interval: 0.00, 0.97) relative to placebo. However, there were no significant differences between any of the interventions for rates of vertebral fractures, AEs, SAEs, withdrawals due to AEs, or mortality, compared with placebo. None of the included trials reported evidence on AEs caused by denosumab discontinuation. Conclusions. Denosumab was associated with significant improvements in both LS and TH BMD relative to placebo. Similarly, compared with placebo, denosumab was not associated with significant changes in nonvertebral or vertebral fractures. Denosumab was not associated with significant changes in safety outcomes relative to placebo. Given that some of the analyses suffered from statistical imprecision, these findings should be interpreted with caution. Regarding policy, continued funding of denosumab needs to be reviewed.

Oral Presentation Number: OP53 Abstract Title: Return on Investment of Fracture Liaison Services: A Systematic Review Author Names Lizheng Xu ([email protected]), Ting Zhao, Mingsheng Chen, Stephen Jan, Steven Frost, Lin Perry, Lei Si Introduction. Fracture liaison services (FLS) are clinically effective and cost effective in preventing subsequent fractures in patients with an existing osteoporotic fracture, but the economic benefits of FLS using simple outcome measures, such as return on investment (ROI), have not been systematically reviewed. This study aimed to review the ROI of FLS. Methods. Databases, including MEDLINE, Embase, PubMed, and Cochrane Central, were searched for studies on the cost effectiveness of FLS. Studies published between January 2000 and September 2022 were included. Study selection and data extraction were conducted independently by two reviewers. The economic return of FLS was calculated using the quality-adjusted life-years (QALYs) reported in the included studies and country- specific willingness-to-pay thresholds for an additional QALY. ROI was calculated as the difference in economic benefits and costs of FLS divided by their cost. Subgroup analysis was conducted across study characteristics to identify factors associated with ROI. Results. A total of 24 studies from Australia, Canada, Japan, Spain, the UK, and the USA were included in the review. The mean ROI of all FLS was 18.4 for every dollar invested. FLS with a high ROI had the following characteristics: a remote component, such as phone calls or emails (ROI 17.4); targeting of patients older than 70 years (ROI 33); and originating in Japan (ROI 56). FLS that contained drug treatments achieved the highest ROI of 23.1 and was higher than FLS without a specific focus on medications. FLS led by primary care providers or program coordinators had higher ROI than those involving nurses or specialists. Conclusions. At more than 18 times the implementation cost, the monetary return of FLS represents an excellent investment. The characteristics identified enable simultaneous maximization of returns alongside tailoring to local settings. Together with the recognized health gains attributable to FLS, the findings present a strong business case for the roll out and upgrade of these services internationally.

Oral Presentation Number: OP54 Abstract Title: Experiences With Out-Of-Hospital Drug Treatment For Systemic Lupus Erythematosus: A Thematic Synthesis Author Names Clarice Portugal ([email protected]), Adriana Sacramento, Andrea Brigida de Souza, Andrija Almeida, Luiza Losco, Mariana Fonseca, Melina Barros, Vania Canuto Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects quality of life and sometimes requires the use of multiple drugs. Therefore, it is relevant to address the experiences of patients, family members, and caregivers in relation to out-of-hospital SLE drug treatment. This paper presents the results of a pilot project of a Qualitative Evidence Synthesis (QES) conducted by the National Committee for Health Technology Incorporation (Conitec) in the Brazilian public health system. Methods. For this thematic synthesis, a structured search was conducted in the MEDLINE, CINAHL, and LILACS databases. Seventeen articles were included, and their quality was evaluated using the Critical Appraisal Skills Program criteria. Article content, which was extracted into a spreadsheet adapted from JBI SUMARI, underwent thematic content analysis. Confidence in the findings was evaluated using the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool. Results. Fifteen findings related to three central themes: self-image and appearance; SLE as a chronic disease (disease oscillation, recurrence of symptoms, fear of organ damage, expectation of cure or modification of the disease course, and frequency of medical appointments); and experience with drug therapy (belief in the need for drugs, skepticism, chronicity of treatment, financial difficulty, adverse effects as obstacles to adherence and a source of suffering, efficacy/effectiveness, large quantity and frequency of drugs, and multiple therapeutic attempts). Conclusions. The findings suggest that patients, family members, and caregivers have an ambivalent relationship with drug treatment. Even though they believe in the effectiveness of the drugs, they also distrust the need to keep using them, especially when SLE is controlled. The improvement of cosmetic manifestations and adverse effects also seem to be important outcomes. Furthermore, the high occurrence of adverse effects and the daily use of many drugs can make treatment adherence harder. In any case, there is an expectation of cure or more significant impact on the course of the disease through pharmacotherapy.

Oral Presentation Number: OP55 Abstract Title: Did It Matter? Developing A Common Framework For Characterizing Impact Of Patient Involvement In Health Technology Assessment Author Names Veronica Lopez Gousset ([email protected]), Aline Silveira Silva, Anke-Peggy Holtorf, Ana Toledo-Chávarri, Ann Single Introduction. While the impact of health technology assessments (HTAs) is often not evaluated, some HTA bodies measure the impact of patient involvement in their processes. Evaluating how patient involvement is perceived by all stakeholders may help to improve practices and avoid activities that unduly burden patient and HTA communities. Frameworks and tools have been designed to analyze the impact of patient engagement along the healthcare development lifecycle. Reporting on the impact of patient involvement in HTA-specific activities, however, continues to be infrequent, unstandardized, and not comprehensive. Having a common framework to characterize and report on the impact of patient involvement may enable this practice to be optimized and harmonized across HTA contexts. Methods. The Patient and Citizen Involvement Interest Group (PCIG) within Health Technology Assessment International set out to contextualize this impact and support reporting. A questionnaire was developed, piloted, and rolled out to collect multistakeholder personal perceptions of the impact of patient involvement in individual HTAs. Questions included: “What difference did you feel patient involvement made in the HTA activity?” and “What would have been missed without patient involvement?”. From January 2019 to September 2021, 24 responses (including one joint submission) were collected through the PCIG’s network from HTA bodies (11), patient representatives (12), and industry representatives (2) from North America (5), South America (3), Europe (13), and Australia (3). Results. Common themes were extracted from these experiences to characterize the impact of patient participation in HTA processes. Based on these commonalities, a harmonized framework consisting of three “domains” is proposed: impact on the decision-making process; impact on patient stakeholders; and impact on the HTA body. The framework includes a set of items under each domain to support reporting. Conclusions. By having common language and measures, the HTA community can harmonize processes across jurisdictions to evaluate and communicate the value of patient involvement in HTA. Improving consistent reporting may facilitate more efficient process improvement for meaningful integration of patient stakeholders into HTA decision-making.

Oral Presentation Number: OP56 Abstract Title: ‘Conversations For Change’ – Identifying Meaningful Ways To Improve Consumer Participation In Health Technology Assessment Processes Author Names Jo Watson, Sally Wortley ([email protected]), Liz Marshall, Anne McKenzie Introduction. Over the past year the Australian Department of Health and Aged Care Office of Health Technology Assessment (HTA) conducted a community consultation series titled ‘Conversations for Change’. The consultation asked what, when, and how consumer views and experiences may best be included in HTA processes. Considerations from regulatory approval to post-market surveillance were included, with a focus on developing proposals for implementation within the health technology subsidization decision phase. Methods. The project targeted individual patients and carers and representatives of consumer groups who have an interest in, or prior experience with, HTA processes. Healthcare professionals, industry, and independent consumer consultants were also targeted for added perspectives. The consultation collected qualitative participant input through three activities: (i) an online survey accessed via the Office of HTA’s Consultation Hub website; (ii) a workshop conducted at the HTA Consumer Symposium (October 2022); and (iii) subsequent community conversations with stakeholder groups to consider and prioritize the preceding responses. Data from activities (i) and (ii) were analyzed and collated into themes of related suggestions for change on which the subsequent community conversations were based. Outcomes from the latter were developed into prioritized actions to inform planning and provide input into other consultation activities being conducted in the HTA environment. Results. Initial themes identified from activities (i) and (ii) were: providing additional support and capacity building; developing partnerships; improving communication and transparency; and more active participation, particularly in the phases prior to considering the subsidization of a health technology. Outcomes from subsequent review of these themes will be presented as prioritized proposals for implementation. Conclusions. Consumers, like other stakeholders in HTA processes, want an efficient system where participation and dialog are encouraged throughout a technology’s lifecycle. What this looks like will vary depending on the health system, but in Australia consumers have identified opportunities to improve how the views and experience of patients are included. Continuing to involve consumers in shaping the system is essential.

Oral Presentation Number: OP57 Abstract Title: Consumer Engagement In Health Technology Assessment: An Australian Journey To Date Author Names Jo Watson ([email protected]), Sally Wortley Introduction. Australian health technology assessment (HTA) committees and processes at the national level have needed to consider an increasing focus on patient involvement and interactions within their scope. As various approaches have been explored, the visibility and impacts of patient involvement and consumer representation has evolved markedly over the most recent five years. Methods. Program activities were developed from review of contemporary HTA models of practice across various HTA sectors internationally alongside input from individual patients and patient groups. Practical application of program pilots was influenced by specific requirements of the Office of HTA, the coordination of HTA Committee procedures and timelines, and involvement of HTA Committee consumer members. Results. The development of capacity building programs for HTA consumer committee members, the growth of external activity and communications targeting patient groups and networks, and the establishment of an expert position to develop the HTA Consumer Evidence and Engagement Unit within the Department’s Office of HTA, are all examples of the work delivered in this period to better integrate patient evidence and inputs into HTA processes and decision-making. Activities over the next period will seek to establish formal frameworks for meaningful involvement that can demonstrate these contributions to evaluations and decision-making. Conclusions. Various examples of patient involvement and participation in processes have evolved over time. The scope and impacts of these experiences have illustrated important participatory demands and resourcing needs, as well potential benefits for deliberations. The Australian Government and Departmental frameworks for HTA currently seek to enhance the development of patient evidence inputs and participation. These developments will be informed by the Australian context and comprehensive consultation with Australian patient groups and their networks. Strategies for improvements are anticipated to be relevant across all HTA processes and Committees within HTA areas.

Oral Presentation Number: OP58 Abstract Title: Challenges In Maintaining Up To Date Health Technology Assessments in Rare Diseases: Lessons From Fabry Disease In Australia Author Names Kathleen Nicholls, Charles Denaro, Michel Tchan, Carolyn Ellaway, Drago Bratkovic, Hazel Palmer ([email protected]), Sheridan Campbell, Megan Fookes, Mark Thomas Introduction. Fabry disease is a rare, inherited X-linked lysosomal storage disease characterized by a wide spectrum of heterogeneously progressive clinical phenotypes, and which results in progressive kidney disease, cardiomyopathy, cerebrovascular disease, and reduced life expectancy. Disease-specific therapy aims to improve symptoms, stabilize current disease and delay progression. In Australia treatment access requires that patients meet pre-specified criteria, which have been in place for more than 15 years. Patient questions prompted the patient organization, Fabry Australia, to investigate why these criteria had remained unchanged despite significant progress in the understanding and management of Fabry disease. Methods. A panel comprising two members of Fabry Australia and its Medical Advisory Committee conducted a review of the literature. The aim of this was to inform the clinical quality of the Australian treatment access criteria with reference to international guidelines and contemporary data. The findings from the literature were applied to develop consensus recommendations for classification and Fabry-specific treatment initiation criteria in diagnosed patients. Results. Evidence supports earlier treatment with reduced barriers to access in some circumstances. Australian access criteria are misaligned with this. They do not distinguish between classical and non-classical Fabry phenotypes, neglect the impact of quality of life and gastrointestinal symptoms, and impose symptom-severity related criteria, which may lead to unnecessary treatment initiation delay. An updated framework is presented. It differentiates phenotypes, facilitates more timely access to Fabry-specific treatment for classical males, and supports relevant organ involvement criteria in classical females and patients with non-classical disease. Conclusions. A well-performing health technology assessment system facilitates patient access to cost-effective treatments that improve health outcomes. Timely treatment initiation is important to avoid irreversible organ damage in Fabry patients. Patients’ questions about out-dated access criteria has prompted research and uncovered barriers that are no longer clinically valid. The perspectives of the patient as a stakeholder in their disease management should not be overlooked when assessing the value of health technologies in the rare disease setting.

Oral Presentation Number: OP59 Abstract Title: Do Digital Health Terms Provide Sufficient Information To Allow For Health Technology Assessment? Author Names Zsombor Zrubka, Champion Annette, Rossella Di Bidino ([email protected]), Anke-Peggy Holtorf, Jagadeswara R Earla, Artem Boltyenkov, Masami Tabata-Kelly, Carl Victor Asche, Anita Burrell Introduction. Umbrella digital health term (DHT) (digital health, eHealth, mHealth, telehealth, and telemedicine) definitions contain insufficient information about patient value for health economics and outcomes research and health technology assessment (HTA) purposes. Qualitative content analysis of secondary DHT (e.g., telesurgery and teleradiology) definitions was performed by the ISPOR Digital Health Special Interest Group to determine if they were more useful for health economics and outcomes research purposes. Methods. Secondary DHT definitions were extracted from a previous scoping review and consolidated by reviewer pairs using uniform rules. Definitions were analyzed for explicit (directly stated) or implicit (inferred) information on 24 categories: Patient, Intervention, Comparator, Outcome, Timing, Setting (PICOTS); the Shannon-Weaver communication model (SWE) (sender, message, encoder, channel, decoder, and receiver, extended with mode of information exchange); the quality domains of Agency for Healthcare Research and Quality (AHRQ) (safe, effective, patient-centered, timely, efficient, and equitable); information related to applied technology or geographic scope; and the World Health Organization (WHO) classification of digital health interventions v1.0 (digital health interventions category, health system challenges, and system categories). Results. Across 107 unique definitions of 73 secondary DHTs, the number of explicitly or implicitly addressed categories across the frameworks ranged from zero to 15, with references to elements of PICOTS (79.4%), SWE (90.7%), AHRQ (30.8%), applied technology (52.3%), geographic scope (0%), and WHO frameworks (86.9%). PICOTS information was found for Patients in 35 percent of definitions, Intervention in 59 percent, Comparator in 20 percent, and Outcomes in 18 percent. Conclusions. Secondary DHT definitions do not adequately specify PICOTS or other characteristics of interest for HTA. An online Delphi survey has been launched among a wider group of ISPOR members to identify the minimum information set to define patient facing DHTs for evidence summaries and value assessments. The results of this research should be shared for discussion with other digital health stakeholder groups.

Oral Presentation Number: OP60 Abstract Title: Community Funding Prioritization Of Drug Treatments: A Discrete Choice Experiment Author Names Simon Fifer ([email protected]), Bronwyn West, Samson Kong Introduction. Allocating government resources for drug treatments continues to be a challenge in health care, particularly given the increasing number of high-cost personalized drug treatments, finite resources, and aging population. Since taxpayers fund government health budgets, it is important to understand how they think funding should be distributed, considering attributes such as cost of drug treatments, risk of dying, commonality of medical conditions, and quality of life changes with drug treatments. The aim of this study was to understand what attributes of a medical condition and treatment determine a community’s willingness to fund new drug treatments. Two decision-making contexts were explored: the allocation of funds from a health budget and a willingness-to-pay (WTP) perspective. Methods. A representative sample of 500 Australian adults completed an online survey. The survey comprised two discrete choice experiments (DCEs) with different framing: an allocation of government funds and a WTP for drug treatments. The government allocation DCE allowed a choice between two hypothetical alternatives, each describing the medical condition and the drug treatment, while the WTP for funding showed one hypothetical alternative with an option to not fund the drug treatment. Seven DCE attributes, informed by a literature review, were displayed in each choice set relating to the medical condition (risk of dying, prevalence, and ages affected) and to the drug treatment (change in quality of life, additional life-years, availability of other drug treatments, and cost to the government and the taxpayer). Results. The resulting DCE model will establish the funding prioritization choices made by the general community. We expect changes in quality of life and risk of dying to be very important attributes. Of key interest for this study is how the difference in the decision-making context impacts preferences. We expect taxpayers to employ a stricter rule set in funding decisions when paying out of pocket (WTP exercise). Conclusions. The findings from this research have implications for decision makers when aligning funding decisions with community preferences and values.

Oral Presentation Number: OP61 Abstract Title: Value Of Disinvestment: The Journey From Possibility To Reality Author Names: Ku Nurhasni Ku Abd Rahim ([email protected]), Hanin Farhana Kamaruzaman, Mohamed Hirman Abdullah, Izzuna Mudla Mohamed Ghazali Introduction. In recent years, most countries have struggled to meet the annual demand for increases in healthcare resources. This scenario poses a significant challenge for those who pay for or manage healthcare services, namely the clinicians and hospital managers Thus, value-based implementation for resource allocation may include disinvestment initiatives to maximize benefits to patients and the population. The purpose of this study was to explore the feasibility of incorporating a systematic and explicit value assessment in hospital- based decision-making for the prioritization of resource allocation. Methods. An evidence-informed stakeholder engagement workshop was held with approximately 50 hospital directors and utilized a scenario analysis of making decisions for hospital procurement. The key question discussed was what should be considered when making decisions about resource allocation and disinvestment in health services at the hospital level. The participants were divided into five groups with a mix of multilevel institutional categories. Each group was given a similar resource allocation scenario, a wish list, and a shift list. The participants were involved in a facilitated discussion on the process, criteria for prioritization, and the justification of their final selections. Subsequently, a deliberative discussion was held at the end of the workshop to explore the feasibility of this prioritization method. Results. Prioritization criteria that were identified and unanimously agreed upon included effectiveness, safety, burden of disease, suitability of services, human resources and facilities, and economic considerations. The deliberative discussion also highlighted the impact of the disinvestment of services, managing the expectation of patients and clinicians, and monitoring and audit mechanisms. Conclusions. The value of disinvestment should not compromise access to services and quality of care. There is a huge potential for implementing a systematic and explicit value assessment in hospital-based decision-making for prioritization of resource allocation. Further refinement of the process and mitigation of challenges will enable its use.

Oral Presentation Number: OP62 Abstract Title: Development Of The Oral Health Risk Adjustment Model To Predict The Outpatient Dental Expenditure In Children With Autism Author Names: Mei-chi Lai ([email protected]), Ruei-Yi Chang, Li-Ying (Grace) Huang, Shu-Mei Hsu, Ying-Li Chen, Perng-Haur Wang Introduction. National health insurance (NHI) Taiwan has provided additional markups on dental service fees for people with specific disabilities, and the expenditure has increased significantly from TWD473 million (USD15 million) in 2016 to TWD722 million (USD24 million) in 2022. The purpose of this study was to determine oral health risk and to develop a risk assessment model for capitation outpatient dental payments in children with Autism. Methods. Based on the literature and expert opinion, we developed a level of oral health risk model from the claim records of 2019. The model uses oral outpatient claim data to analyze: (i) the degree of caries disease; (ii) the level of dental fear or cooperation; and (iii) the level of tooth structure. Each factor was given a score from zero to four and a total score was calculated. Low-, medium-, and high-risk groups were formed based on the total points. The oral health risk capitation models are estimated by ordinary least squares using an individual’s annual outpatient dental expenditure in 2019 as the dependent variable. For subgroups based on age group and level of disability, expenditures predicted by the models are compared with actual outpatient dental expenditures. Predictive R-squared and predictive ratios were used to evaluate the model’s predictability. Results. The demographic variables, level of oral health risk, preventive dental care, and the type of dental health care predicted 30 percent of subsequent outpatient dental expenditure in children with autism. For subgroups (age group and disability level) of high-risk patients, the model substantially overpredicted the expenditure, whereas underprediction occurred in the low-risk group. Conclusions. The risk-adjusted model based on principal oral health was more accurate in predicting an individual’s future expenditure than the relevant study in Taiwan. The finding provides insight into the important risk factor in the outpatient dental expenditure of children with autism and the fund planning of dental services for people with specific disabilities.

Oral Presentation Number: OP63 Abstract Title: Incorporating Machine Learning Methods In Health Economic Evaluations: A Case Study On Depression Prevention Author Name: Joran Lokkerbol ([email protected])[email protected]) Introduction. New methodologies such as machine learning are becoming widely available and are increasingly used. However, more guidance on their role in the context of economic evaluations would be beneficial. Methods. We developed a machine learning model to predict recurrent depressive episodes and incorporated the model outcomes in a health economic model to assess the cost effectiveness of offering targeted prevention of recurrent depression. We considered the impact on cost effectiveness (defined as cost per quality-adjusted life-year) for machine learning models with different thresholds for classifying a patient as being at risk, resulting in different precision-recall pairs. Results. Targeted prevention of recurrent depression could enhance the cost effectiveness of depression treatment by preventing a small number of recurrent depressive episodes in patients where the estimated risk of recurrence is relatively high. More depressive episodes could be prevented with the trade-off of less cost effectiveness for the healthcare system. Conclusions. Health economic modeling approaches can be augmented with machine learning methods, which broadens the areas in which evidence can be generated for policy makers to base their budget allocation. The precision of such predictive machine learning models must be high enough to be able to improve a care-as-usual healthcare system. Machine learning models generally let you set the level of precision acquired, at the cost of a possibly low recall, thereby limiting the impact on the healthcare system as a whole. More and better data for training these machine learning models will allow developed models to better distinguish patients who will and won’t develop a recurrent depressive episode, and for higher recall given a desired precision threshold. This will translate into a more substantial improvement in the treatment of depressive disorders in the healthcare system.