HTAi 2022 Annual Meeting Poster Presentation Abstract Book

Poster Abstracts Lifecycle Approach: Coming Together to Make it Happen

Poster Presentation Number: PP02 Abstract Title: Is Glycated Hemoglobin A Valid Surrogate Endpoint To Evaluate The Effectiveness Of Drugs In Diabetes Mellitus Studies? Author Names: Paola Andrea Rivera ([email protected]), Fabián Fiestas Introduction In the field of drug development and effectiveness evaluation, the use of surrogate endpoints is acceptable if they reliably predict a positive effect on clinical outcomes such as mortality or morbidity. Hemoglobin A1c (HbA1c) is a widely used surrogate endpoint in phase 3 and 4 clinical trials evaluating drugs in patients with diabetes mellitus (DM). The objective of this study was to investigate whether HbA1c is a valid surrogate endpoint for evaluating the effectiveness of antihyperglycemic drugs in DM trials. Methods We conducted a systematic review of randomized placebo-controlled trials evaluating the effect of a treatment on levels of HbA1c and clinical outcomes in patients with DM. The association between the effects of treatment on HbA1c levels and clinical outcomes was then investigated using regression analysis at the trial level. The correlation coefficients (R) were interpreted using the cut-off points suggested by the German Institute for Quality and Efficiency in Health Care (IQWiG). HbA1c was considered a valid surrogate endpoint if it demonstrated a strong association with clinical outcomes (i.e., the lower limit of the 95% confidence interval [CI] of R≥ 0.85). Results Nineteen phase 3 or 4 randomized controlled trials (RCTs) were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate endpoint for any clinical outcome: mortality (R 0.34, 95% CI: -0.14, 0.69); myocardial infarction (R 0.20, 95% CI: -0.30, 0.61); heart failure (R 0.08, 95% CI: -0.40, 0.53); kidney injury (R -0.04, 95% CI: -0.52, 0.47); and stroke (R 0.81, 95% CI: 0.54, 0.93). Conclusions The evidence from multiple placebo-controlled RCTs of antihyperglycemic drugs in patients with type 2 DM suggests that a reduction in levels of HbA1c does not meet the IQWiG criteria for a valid surrogate endpoint. Consequently, the risk-benefit ratio of antihyperglycemic drugs in terms of patient relevant clinical outcomes, regardless of their hypoglycemic effect, should be the focus of therapeutic, regulatory, and reimbursement decisions.

Poster Presentation Number: PP03 Abstract Title: Early Assessment Of Video Consultations In Rehabilitation After Hand Injury Author Names: Linn Nathalie Støme ([email protected]), Tone Vaksvik, Christian Ringnes Wilhelmsen, Kari Jorunn Kværner Introduction With the aim of reducing patient travel and related costs, physiotherapists and occupational therapists at the Oslo University Hospital began offering video consultations to patients with hand and arm injuries in March 2020. A feasibility study was initiated to describe the first year of using video consultations in the rehabilitation of upper extremity injuries in children and adults, and to assess the acceptability of the service from the perspective of hand therapists. The secondary objective of the study was to investigate the economic effects of using video consultation for this patient group. Methods The therapists documented the individual consultations in an Excel spreadsheet. Utility and acceptability were analyzed based on the content of each video consultation. The therapists also registered the patient's municipality in order to calculate costs related to travel, accommodation, and other costs related to in-person consultation. Utility was analyzed using an early economic model based on scenario analysis to compare the costs of video consultations with in-person consultations. Results Based on the content analysis from 89 consultations, video consultations were deemed acceptable by the therapists. The total travel distance from patients’ homes to the hospital was 20,190 km, as hand rehabilitation is a national service. The video consultations that replaced the consultations at the hospital were potentially more time efficient, reduced patients’ travel time and absence from home and work, and saved costs for the Oslo University Hospital and society. Conclusions Based on early decision support provided by this study, adaptions were made to the delivery of video consultations to improve the cost effectiveness of the service. The findings from this study provided an indication of the potential value of the new service, which may be used for benchmarking purposes to ensure that it meets the needs of users, the health service, and society.

Poster Presentation Number: PP04 Abstract Title: Supporting The Social Integration Of Persons With Brain Injury Using Psychoactive Substances: A Health Technology And Intervention Assessment. Author Names: Christine Maltais ([email protected]), Akram Djouini, Frédéric Messier, Karine Bélanger, Nadia Lespérance, Élaine Deguise Introduction People with a traumatic brain injury and who present with an unsafe or problematic substance use of psychoactive substances (PAS) face specific challenges in social integration resulting from the negative impacts of substance use on the benefits of rehabilitation services and treatments. Methods A systematic review of grey and scientific literature was conducted. The selection and coding of the included interventions (according to their characteristics), as well as descriptive analyses, resulted in findings which describe the interventions under study. Grades of evidence strength were attributed to the findings based on a range of factors including the methodological characteristics of the studies. Findings resulting from the systematic review were contextualized with information collected from administrative databases, clinical program documentation, and experiential data obtained from rehabilitation professionals. Recommendations were elaborated based on the aggregated data sources and informal deliberations by a committee involving researchers and clinicians. Results Out of 5014 selected references, 14 studies examining 13 interventions which targeted social integration of the management of PAS were included. Interventions with the strongest evidence base are user-centered (i.e., support individual choices and personal autonomy), individualized (i.e., considered individual needs and characteristics), and educational (i.e., support the acquisition of strategies and abilities). The evidence base was considered “emerging” for interventions which are systemic in nature (i.e., relate to familial, social, cultural, educational or professional environments), interdisciplinary (i.e., involve clinicians with distinct training, competences and expertise), and ecological (i.e., which involve interventions in the client’s living settings). While additional research is necessary to better support their efficacy, these interventions exhibited promising effects on various outcomes. Conclusions The analysis and synthesis of three streams of information resulted in five clinical practice recommendations relating to integration to school and productive activities, psychological adaptation, integration in living settings and independence, social life and sense of belonging, and finally, use of PAS. Recommendations should help support clinicians in rehabilitation settings.

Poster Presentation Number: PP05 Abstract Title: Effect Modifiers In Indirect Treatment Comparisons: Guidance Is Needed To Ensure An Unbiased Identification In Decision-Making Author Names: Andreas Freitag ([email protected]), Laura Gurskyte, Maria Rizzo, Grammati Sarri Introduction Unadjusted effect modifiers (EM) in indirect treatment comparisons (ITC) can produce biased and uncertain results in health technology assessments (HTA). Even though research on advanced ITC methods to adjust for EMs has attracted much attention, less emphasis has been placed on how these EMs are identified and assessed in the first place. This is surprising given the evidence-based approach underpinning all analyses supporting HTAs. To address this gap, our aim was to identify what HTA guidance exists on the selection process for EMs, and how the selection of EMs has been justified in the context of published ITCs. Methods A pragmatic review of HTA guidance documents was conducted in 2021 to describe current requirements for the selection of EMs for ITCs. A supplementary Embase and Medline search was conducted to identify primary research on ITCs published between 2015-2021 presenting information on how EMs were selected to inform these analyses. Results Our review found that guidance on this topic focusses on developing and testing different methodologies to adjust for EMs. No detailed guidance was identified in any of the reviewed HTAs, although the National Institute for Health and Care Excellence (NICE) briefly mentioned that companies should identify EMs through a topical review or expert discussions. Similar findings were also revealed through the database search; few published ITCs included information on the EM selection process which was either based on evidence highlighted in the literature or findings from prior trial subgroup analyses. No reference to a systematic identification of EMs was found. Conclusions To fill the guidance gap identified in our review an extension of current ITC guidelines (including those from HTA bodies) is needed, including (i) indication on how EMs should be identified through systematic reviews, (ii) a quantitative assessment of the EM distribution and (iii) formal expert elicitation prior to the selection of ITC methods. Without these additional steps, ITC results may be biased, potentially negatively impacting decision- making and ultimately patient care.

Poster Presentation Number: PP06 Abstract Title: Clinical Effectiveness Of Fluticasone Furoate Nasal Spray For Perennial Allergic Rhinitis In Children: A Systematic Review And Meta-Analysis Author Names: Paola Andrea Rivera ([email protected]) Introduction Although previous studies suggest that fluticasone furoate nasal spray (FFNS) is superior to placebo in reducing symptoms in adolescents and adults with allergic rhinitis (AR), there is still uncertainty about its clinical effectiveness in the pediatric population. The aim of this study was to assess the clinical effectiveness of FFNS, compared with placebo, in reducing nasal symptoms in children with perennial AR. Methods A systematic review was conducted of studies identified from the MEDLINE and Embase databases that were published up to January 2021. The population of interest was patients aged 2 to 12 years with perennial AR. Included studies were limited to randomized controlled trials (RCTs) comparing FFNS (110 µg once daily) with placebo. The outcomes of interest included the reflective Total Nasal Symptom Score (rTNSS) and safety. Meta- analyses were performed using RevMan 5.4. The Cohen’s guideline was used to assess the minimum clinically important difference for rTNSS; that is, if the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceed -0.5, the treatment effect was considered clinically significant. Results Three RCTs (959 pediatric patients) were included. One study evaluated the short-term use of FFNS, one evaluated the long-term use of FFNS, and the third evaluated both the short- and long-term use of FFNS. FFNS produced a statistically significant reduction in rTNSS (SMD -0.35, 95% CI -0.63, -0.08; p<0.001) relative to placebo in the long-term treatment studies, but not in the short-term studies. However, since the mean reduction did not reach the minimum clinically important difference (SMD -0.5), these results were not considered clinically relevant. The safety outcomes for FFNS were similar to placebo. Conclusions The currently available evidence suggests that FFNS does not produce a meaningful clinical effect on nasal symptoms in children with perennial AR, compared with placebo. In the past decade, however, some guidelines have unequivocally endorsed this treatment.

Poster Presentation Number: PP07 Abstract Title: Improving The Use Of Real-World Evidence In The Development Of NICE Guidance Author Names: Seamus Kent ([email protected]), Stephen Duffield, Shaun Rowark, Lynne Kincaid, Vandana Gupta, Manuj Sharma, Pall Jonsson Introduction The National Institute for Health and Care Excellence (NICE) is determined to make better use of health and social care data in the development of its guidance. Real-world data (RWD) has the potential to significantly improve our understanding of the value of new and existing health and social care interventions. RWD is already widely used to characterise populations, interventions, and outcomes and to populate economic models, but its use in estimating the effects of interventions remains limited, especially for medicines. Key barriers to its greater use in this context include limited transparency around studies, sometimes a lack of confidence in their integrity, and methodological concerns around how studies have addressed major sources of potential bias. Methods This abstract focuses on the real-world evidence (RWE) framework developed by NICE to support its ambitions. The framework was developed in an iterative way based on: reviews of best practice approaches to the conduct and assessment of real-world evidence studies; case studies; and workshops with key external stakeholders. The initial version of this living framework focuses on de novo RWE studies using individual patient data. Results The RWE framework consists of an overarching research governance framework which describes expectations around the planning, conduct, and reporting of RWE studies across uses of real-world data. Uses are categorised by risk according to their importance to decision-making, the impact of decisions on patient and system outcomes, and their complexity as proxied by risk of bias. Studies of the effects of interventions on patient health and system outcomes are considered the highest risk. The research governance framework is supported by a tool to aid assessment of data suitability for its intended application, and detailed guidance on the conduct and reporting of comparative effect studies using RWD, following the target trial approach. Conclusions The RWE Framework underpins NICE’s ambitions to make better use of RWD in its guidance and is intended to improve the quality and utility of RWE studies submitted to NICE enabling more consistent and appropriate evaluation.

Poster Presentation Number: PP08 Abstract Title: Evaluation Of Nutritional Status In Diabetic And Non-Diabetic Chronic Kidney Disease Patients Using A Web Tool Author Names: Ishfaq Rashid, Pramil Tiwari ([email protected]), Sanjay D’Cruz, Shivani Jaswal Introduction Poor nutritional status, a complex consequence of numerous interrelated factors, is poorly characterized in patients with chronic kidney disease (CKD) before they commence dialysis. This study aimed to characterize the risk factors and prevalence of malnutrition among patients with CKD, with or without diabetes mellitus, before they underwent dialysis at a tertiary care public teaching hospital. Methods This longitudinal observational study utilized a Pt-Global web tool© to assess the nutritional status of patients based on their Subjective Global Assessment score as follows: a score of two to three indicates that patient and family education is required; scores of four to eight mean that intervention is required as indicated by symptoms; and a score of nine or more indicates a critical need for intervention. Glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration equation was used as the measure of kidney function. Multinomial regression analyses were used to ascertain the predictors of poor nutritional status. Results A total of 450 patients (265 men and 185 women) who had CKD, with or without diabetes, and were not on dialysis were recruited during the period of study. The average age of the patients was 53.9 years (standard deviation 14.2). ‘Severe’ malnutrition was present in 152 (33.8%) patients, while 140 (31.1%) were ‘mildly or moderately’ malnourished, and 158 (35.1%) were ‘well-nourished’. Patients with CKD and diabetes were more severely malnourished: 68 were rated as mild or moderate (15.1%) and 91 were rated as severe (20.2%). The prevalence of malnutrition increased with the decline of residual renal function. Fatigue, loss of appetite, pain anywhere in the body, constipation, dry mouth, feeling full quickly, and physical and functional inactivity were the most common risk factors for poor nutritional status. Conclusions This study presents real-world evidence of poor nutritional status in patients with CKD and confirms that it is more common in individuals who are diabetic and have poor kidney function and hypoalbuminemia. Emphasis on nutrition in patients with CKD is important for improving their health.

Poster Presentation Number: PP09 Abstract Title: Use Of Real-World Evidence For Managing Health Technologies Throughout The Life Cycle Of Transcatheter Aortic Valve Interventions Author Names: Danielle de Verteuil ([email protected]), Leila Azzi, Laurie Lambert, Lucy Boothroyd, Marie-France Duranceau, Élisabeth Pagé, Catherine Truchon Introduction A Cardiology Evaluation Unit was established in 2004 within Québec’s Institut national d’excellence en santé et en services sociaux (INESSS) with a novel mandate to collect real-world evidence (RWE) to complement literature-based health technology assessment. In 2010 following publication of the seminal PARTNER trial, INESSS was mandated by the health ministry to review the evidence on transcatheter aortic valve intervention (TAVI) for patients with aortic stenosis. Herein we show how RWE was used to evaluate health system performance throughout the technology’s life cycle and inform organizational and clinical decisions. Methods Various products were diffused by INESSS over the years: a guidance (2012), an updated literature review (2017) and provincial standards (2017), in parallel with RWE reports covering TAVI use from 2013-2015, from 2013- 2018, and a 2021 RWE report combined with administrative data covering transcatheter and surgical treatment of aortic stenosis from 2013-2019. Results Based on the guidance’s review of evidence, TAVI was initially recommended for patients considered at too high risk for the surgical approach, under the condition of continued evidence generation to address uncertainty. The subsequent literature review update highlighted that the indication for TAVI had been extended to patients at moderate surgical risk. INESSS produced standards in collaboration with clinical experts to optimize and harmonize the use of TAVI in designated centers. Evaluation of structures, processes and outcomes by INESSS continued until 2019, showing a continuous increase in the use of TAVI, improved short-term survival, and careful patient selection via a multidisciplinary process. RWE also highlighted the impact of TAVI on the overall organization of care for patients with aortic stenosis, as selection criteria further expanded to patients at lower surgical risk, raising important issues regarding patient selection processes, wait times, and longer-term outcomes. Conclusions TAVI clinical practice is constantly evolving and leads to changes in the management of aortic stenosis. RWE provided essential organizational and clinical input to inform clinical guidance and decision-making by Québec policy-makers, clinicians and patients.

Poster Presentation Number: PP10 Abstract Title: Impact Of COVID-19 On The Management Of Breast Cancer In Italy: The Perspectives Of Patients And Coordinators Author Names: Eugenio Di Brino ([email protected]), Roberta Laurita, Americo Cicchetti Introduction Breast Units (BU) represent an opportunity to adequately manage and improve quality of care for patients with breast cancer. The presence of specific national guidelines should promote safe and good quality, integrated care. In fact, the presence of a multidisciplinary team of specialists whose workflows follow specific guidelines, set to the highest European standards, should ensure that patients in Breast Units receive appropriate care at diagnosis and throughout the course of the disease. Methods Two surveys were developed and administered to Breast Unit coordinators and patients throughout Italy. The surveys investigated the provision of healthcare services and the implementation of a new organizational model over two time periods: the first wave of the coronavirus disease 2019 (COVID-19) pandemic from March 2020 to August 2020 and the second wave from September 2020 to December 2020. The surveys aimed to assess the continuity of care during the pandemic from the clinician and patient perspective. Results Patients observed a reduction in the postponement of care between the first wave of COVID-19 and the second wave. Some services were delayed, particularly in the second wave where a large number of services were not rescheduled. Management of the COVID-19 pandemic resulted in many healthcare professionals being reallocated to other duties and hospital departments. The effect of this was particularly relevant for both patients and clinicians, with few healthcare professionals having the capacity to focus on conditions other than COVID-19. In the first wave of the pandemic 42 percent of professionals were redeployed, compared with 27 percent in the second wave. Conclusions This study demonstrates how COVID-19 affected the care of patients with breast cancer in Italy. Patients and coordinators from Breast Units across the country highlighted many important aspects that should be considered when assessing the effects of the COVID-19 pandemic on the entire healthcare system in order to be better prepared for future pandemics

Poster Presentation Number: PP11 Abstract Title: Impact Of Qualitative Research In The Spanish Network Of Health Technology Assessment Author Names: Ana Toledo-Chávarri ([email protected]), Yolanda Triñanes, Vanesa Ramos-García, Lilisbeth Perestelo-Pérez, Eva Reviriego Introduction Qualitative research is being increasingly integrated in heath technology assessments (HTA) within the Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS). Qualitative research methodological guidelines are given in RedETS HTA guidelines and the Patient Involvement Strategy. A specific methodological guideline to systematically review qualitative studies was published in 2007 and is pending its update. The impact of their implementation is unknown. The aim of this work is to analyze the techniques, impact and reporting of qualitative research (primary and secondary) in HTAs. Methods A manual search of the HTAs published in the last 5 years in RedETS was conducted to locate assessments that include qualitative research. To ensure a complete identification, RedETS agencies and units were consulted to provide information about the assessments that have used qualitative techniques in their development over the past 5 years. A content analysis of the selected assessments was conducted to analyze the techniques, impact and reporting of qualitative research in HTA. Results In the past five years, focus groups, semi-structured interviews, evidence synthesis of observational studies including qualitative studies have been used and integrated in HTA in RedETS. Most of them have been linked to patient involvement facilitation or the inclusion of patient perspectives in HTA. Qualitative research has been used to analyze patient’s experiences and values, to elicit and select important outcome measures for patients, to research for barriers-facilitators for technology implementation and to inform evidence to decision frameworks. Conclusions Qualitative primary and secondary research is being used in HTA in Spain. It is mainly linked to patient involvement strategies both to elicit patient perspectives directly or to collect patient-based evidence. The impact of qualitative research in HTA is broad and diverse, extending from the scope of the assessments to the drafting of the recommendations.

Poster Presentation Number: PP12 Abstract Title: Challenges In Assessing The Efficacy Of Non-Pharmacological Measures In The Context Of The COVID-19 Pandemic Author Names: Lorena Aguilera-Cobos ([email protected]), Rebeca Isabel-Gómez, Juan Antonio Blasco- Amaro Introduction The outbreak of the COVID-19 global pandemic in 2020 has been a major challenge for the world's population and governments. The lack of vaccines, the saturation of health systems, and its rapid spread forced governments to take non-pharmacological interventions (NPI) that had a high impact on the population. Assessing the efficacy of these measures is a challenge for health technology assessment bodies. Methods The main NPIs for which assessment was required were: mobility restrictions, social distancing, cancellation of events or reduction of seating capacity, closure or reduction of seating capacity in non-essential businesses, closure or limitation of seating capacity in educational establishments, and promotion of teleworking in potential jobs. The implementation of these measures at a global level provides a large population for the study of the impact of these measures. However, the challenges for their evaluation are numerous: • The joint implementation of these measures makes it difficult to evaluate them in an isolated manner. • The heterogeneity between countries and regions of the pandemic situation at the time when these measures are initiated and terminated. • The different accuracy in the application of the measures. • Heterogeneity in the quality and accessibility of public health services for citizens. Results Outcome variables to assess the effectiveness of these measures should include parameters related to: • Incidence variables: the number of new or accumulated cases in a given time range, the variation in the number of cases in a given time range and the proportion of positive tests. • Transmission variables: the basic reproductive number (R0) and the effective reproductive number (Rt). • Severity and mortality variables: the number or variation of hospitalizations, the number or variation of intensive care unit (ICU) hospitalizations and the number or variation of deaths. Conclusions The large number of available data, the heterogeneity of the measures, the differences between populations, the numerous outcome variables and the possible inclusion of mathematical modelling studies, are a methodological challenge for the HTA bodies.

Poster Presentation Number: PP13 Abstract Title: Development Of Recommendations And Proposal For A Value-Based Managed Entry Agreement For Italian Setting Author Names: Americo Cicchetti, Entela Xoxi, Filippo Rumi ([email protected]) Introduction The continuous and pressing challenge that the drug regulatory authorities in Italy and in Europe are facing is that of guaranteeing patients' quick access to new drugs, ensuring the economic sustainability of the system at the same time. In recent years, flexible and diversified approaches have been developed known as Managed Entry Agreements (MEA). Methods We performed an analysis of the Italian legislative and regulatory aspects in reference to a new Value-based Managed Entry Agreement (VBMEA) pathway. Thus, we tried to investigate the rationale for a new pathway analyzing three main dimensions related to the new medical product (MP): value; time to entry access; and, data quality and registry design. Moreover, we shared the discussion of the proposal with an international experts’ panel. Results The proposal for a new pathway of VBMEA from a procedural point of view shows the novelty related to the possibility to organize joint CTS (Technical Scientific Committee) and CPR (Price and Reimbursement Committee) assessment. A 24-month contract with an ex-factory price (PP) equal to X EUR per dose and a transfer price to the National Public Health System (NPHS), following application of a confidential discount for public structures (- X%), of X EUR per dose. After 24-months, an analysis of VBMEA is carried out. The price of the MP is therefore established based on AIFA registries and VBMEA results. The cost value incurred by the NPHS, intended as the difference between the price in market (entry) access phase and the price negotiated (PVB) in the light of the VBMEA results, shall be returned by the pharmaceutical company in the form of a payback. Conclusions Currently, MEAs represent one of the main topics of discussion between the European National Payers Authorities. There is very little information on product performance that results from MEAs. This research project could provide advice to policy makers to decrease negotiation time by ensuring earlier access to innovation for patients.

Poster Presentation Number: PP14 Abstract Title: Value-Based Pricing For Advanced Therapy Medicinal Products: Emerging Affordability Solutions Author Names Elisabete Gonçalves ([email protected]) Introduction The emergence of advanced therapy medicinal products (ATMPs), a disruptive class of health technologies, is generating important challenges in terms of value assessment, and their high prices introduce critical access and affordability concerns. Methods The aim of this oral presentation is to expose the challenges of traditional value assessment and pricing and reimbursement methods in the evaluation of ATMPs, and to characterize the current and prospective financing solutions that may ensure patient access to and affordability for these health technologies. Results Standard health technology assessment (HTA) is not designed for assessing ATMPs and may delay access to these therapies; thus, a broader concept of value is required. As a result, value-based pricing methodologies have been gaining prominence as a way to cope with the specific challenges of ATMPs. The pricing and reimbursement framework should ensure a balance between encouraging innovation and maximizing value for money for payers through the attribution of a fair price to new health technologies. The provision of early scientific advice to developers by regulatory and HTA bodies is key, as it will help diminish the perspective gap between developers, regulators, and payers. Conclusions The high efficacy and high price dynamic of many ATMPs necessitates novel financing models, both in the European Union and in the USA. Managed entry agreements, where financing is conditional upon the submission of additional evidence, linked with leased payments may offer effective strategies to address the uncertainties caused by the evidence gap associated with ATMPs, ensuring affordable and sustained access to these therapies.

Poster Presentation Number: PP15 Abstract Title: The National Pricing And Reimbursement Process In China, A 2021 Update Author Names: Xirong Song ([email protected]), Shahela Kodabuckus, Preeti Patel Introduction The Chinese National Reimbursement Drug List (NRDL) was established in the early 2000’s and includes the drugs both fully and partially covered by National Basic Medicine Insurance. As China’s health system has been reformed over the past decade, it is important for manufacturers to understand the ever-changing reimbursement process and its implications on newly launched drugs. This study provides an updated overview of the process based on research conducted in 2021. Methods Targeted secondary research was undertaken to evaluate the pricing and reimbursement landscape in China. Primary research was conducted to assess the perspectives of three payers and one policy expert. Results National listing remains the most viable and exclusive pathway to get a product reimbursed by public health insurance in China. Since 2017, the NRDL has been updated annually, and revisions are managed by the National Healthcare Security Administration (NHSA). Insights from 2021 suggests that the process of listing a new product on the NRDL lasts five months (July to November). Manufacturers should ensure that submissions are made when the annual NRDL process formally begins, and clinical and health economic evidence is compulsory. If a successful opinion is made by the assessment board, the manufacturer will be invited to negotiate a price with the NHSA. Data from the NHSA indicated that a total of 704 applications were made in 2020. In addition, 138 exclusive drugs were eligible for price negotiation, of which 96 drugs were successful and added to the NRDL. Findings also suggested that the average discount rate increased from 44.0 percent in 2017 to 50.6 percent in 2020. Conclusions The national reimbursement process in China has become more transparent overtime. Even so, NRDL listing remains a challenge, with decisions driven by clinical and pharmacoeconomic evidence, and price. Significant price cuts should be considered and anticipated to ensure successful negotiation outcomes.

Poster Presentation Number: PP16 Abstract Title: Machine Learning In The Treatment Of Spinal Deformities: Early Life-cycle Economic Analysis In Australia Author Names: Rashmi Joglekar ([email protected]), Aaron Shikule Introduction Patients with spinal deformity require implanted spinal rods to be specifically shaped to their anatomy. Spinal rods which are manually shaped in the operating theatre are prone to fracture and malpositioning. This emphasizes the need for preoperative planning, intraoperative imaging, and accurate shaping of the implant. The application of machine learning (ML) has enabled precision in shaping patient-specific rods, with the potential to reduce adverse events. Our objective is to assess the economic value of this technology, early in its lifecycle, in the context of Health Technology Assessment (HTA) in Australia. Methods A budget impact analysis was performed to quantify the economic value of patient-specific spinal rods from an Australian payor perspective. Clinical outcomes were sourced from literature review, and cost inputs were obtained from Medicare, Private Health Data Bureau and Hospital Casemix Protocol Data databases. Results Preliminary analysis indicates that a reduction in the rate of revision surgery due to decreased instrument failure results in cost-savings to the healthcare system, despite a higher outlay for the patient-specific rods. Adolescents who may have remained sagittally malaligned after the implantation of manually bent rods are expected to derive the greatest benefit from this ML application. The key uncertainty in this analysis is the limited real-world data of this emerging technology. ML is an iterative process of continuous improvement, identifying correlations within the data collected. As additional surgical data are integrated into predictive models, we anticipate ML technology will enhance decision-making support in surgical strategy and enable better implant precision, resulting in further decreased operating time, reduced mechanical complications, and increased healthcare savings. Conclusions ML technology is enabling precision in patient-specific implants, which is expected to drive healthcare cost- savings due to a reduction in instrument failure. Fewer replacement surgeries are an important patient-relevant outcome, especially for adolescents with spinal deformity. This preliminary analysis demonstrates the economic value of ML enabled patient-specific rods to Australian payors, early in its lifecycle.

Poster Presentation Number: PP17 Abstract Title: Is the PriTec Tool Useful In The Identification Of Disruptive Healthcare Technologies? Author Names: Janet Puñal-Riobóo ([email protected]), Maria del Carmen Maceira-Rozas, Maria José Faraldo-Vallés, Leonor Varela-Lema Introduction A disruptive technology has been defined as an innovation that completely changes the way things are done. Early identification of potential disruptive health technologies has become a key point in the agenda of decision makers and health technology assessment (HTA) bodies. The PriTec tool is an automatically executable web application that was developed in 2009 by the Galician HTA Agency to facilitate decision-making regarding the selection of technologies for post-launch observation. The tool has been updated to allow scoring and ranking of technologies before their introduction into the healthcare portfolio. The aim of this work was to propose a framework for assessing the usefulness of the PriTec tool in relation to identifying possible disruptive innovations. Methods To evaluate the applicability of the PriTec tool for distinguishing disruptive from non-disruptive innovations, we selected a few examples from prior acknowledged disruptive and non-disruptive innovations. These technologies were scored against the predefined criteria and the results were compared and analyzed globally and by type of domain. The PriTec tool assesses six domains of technologies: clinical condition, comparative effectiveness and safety, economic impact, implementation consequences, and dissemination speed. Results Disruptive technologies (e.g. transcatheter aortic valve implantation or point-of-care tests) had higher weighted global scores than non-disruptive technologies. In the domain analysis, the scores for implementation consequences were higher for disruptive than for non-disruptive technologies. Both types of technologies had similar scores in the other domains. Conclusions The PriTec tool seems to be useful for identifying potential disruptive technologies through its implementation domain. Further validation strategies are required to confirm the tool’s applicability and to improve its accuracy in the field of health disruption. The tool could be used by governments, horizon scanning organizations, and HTA organizations to promote the evidence-based detection of disruptive technologies in clinical practice. However, it is advisable that the tool be further tested and validated in other contexts.

Poster Presentation Number: PP18 Abstract Title: Horizon Scanning For Clinical Biosimilar Medicines: Informing The Lifecycle Of Health Technology Assessment And Market Access Author Names: Amy Hussain ([email protected]), Ross Fairbairn, Dapo Ogunbayo Introduction The National Institute for Health and Care Research (NIHR) Innovation Observatory (IO) national horizon scanning research centre, has a remit to notify its stakeholders, including the National Institute for Health and Care Excellence (NICE), about innovative interventions; including biosimilar medicines in the pipeline. Biosimilar medicines bypass many developmental steps, making them substantially cheaper to manufacture for providers, which increases market availability and improves treatment access for patients. Methods Since 2017, the NIHR IO has monitored biosimilars in clinical development that align to the NICE health technology assessment remit. The data set explored was exported from our internal medicines innovation database - MInD. Data sets were created that included information on the characteristics of biosimilars and their associated clinical trials. Analyses and visualization creation were carried out using Microsoft Excel and Microsoft Power BI. Results A total of 100 unique biosimilar medicines in 136 clinical trials were included in the MInD since April 2017. Of these, 44 percent of biosimilars are currently EMA-approved (Nov 2021). Adalimumab was the reference medicine with the most unique biosimilars identified (12%). Seventy-two percent of the biosimilars in MInD were indicated for non-oncology conditions, twenty percent for oncology condition and eight percent for both. There were 46 biosimilars unapproved, which were in active development. Of these biosimilars 17.4 percent are indicated for an oncology condition, 78.3 percent for non-oncology conditions, and 4.3 percent for biosimilars for both. Aflibercept was the reference product with the most (eight) biosimilars in active development. There were 56 individual clinical trials in the MInD that list a biosimilar in development. For 26 trials, the primary completion date (PCD) was prior to 2021, whilst 28 trials listed a PCD post-2021, and 2 PCD’s were unavailable Conclusions Our analysis identified high levels of active clinical development for biosimilars. The majority of biosimilars being developed are indicated for non-oncology conditions, with many in trials due to readout in the near future. Early identification, monitoring and reporting of biosimilars allows for expedited patient access and benefits, including cost-savings for health services. This study is funded by the National Institute for Health Research (NIHR) [(HSRIC-2016-10009)/Innovation Observatory].

Poster Presentation Number: PP19 Abstract Title: Reimbursable Health Apps (DiGA) In Germany: Which Factors Impact The BfArM’s Assessment And Directory Listing? – Updated Research Author Names: Janika Drews ([email protected]), Doreen Bonduelle, Dr Johanna Schuller Introduction Since May 2020, reimbursement can be requested for Digital healthcare applications (DIGAs) in Germany. The prerequisite for reimbursement is a listing in the Federal Institute for Drugs and Medical Devices (BfArM) DiGA- directory, granted after successful completion of an assessment process. In June 2021, IQVIA first evaluated the BfArM’s decision-making and identified criteria that may positively impact a directory listing. In November 2021, the research was updated to consider the latest developments. Methods Published information for each app in the DiGA-directory was qualitatively compared according to pre-specified criteria by two independent reviewers. With no data available for denied apps, only DiGAs with permanent or preliminary listings were compared. Results By 26 November 2021, twenty-four apps had received a positive assessment. Permanently listed apps (n=6) focused on health status improvements and/or patients’ health competency. None claimed to improve patients’ quality of life. Results from at least one randomized controlled trial (RCT) showed efficacy with medium or strong significant effect sizes (Cohen’s d > 0.4) versus standard of care (SOC). For preliminarily listed DiGAs (n=18), final results of positive care effects were not yet provided, but applications included study designs for RCTs including definitions of primary endpoints. The BfArM accepted the trial designs to be suitable to measure an app’s positive effects on health care within twelve months after listing. Since the last analysis, no preliminarily listed apps have been granted permanent DiGA-status. Evaluation periods were extended by up to five months for three apps. With none of the trials for preliminary apps being completed, possibilities for assessment remain limited. Claims for either medical benefit and/or patient-relevant structural/procedural improvements do not seem to impact the type of listing. Conclusions Updated research confirmed previous findings. For a DiGA-directory listing DiGA, the (planned) provision of RCT data seems to be gold standard. Medium to strong effects on the improvement of health status compared to SOC appear to be important for a permanent listing. Evaluation periods of five preliminarily listed apps are expected to be completed in December 2021, allowing for further analyses in the future.

Poster Presentation Number: PP20 Abstract Title: Effectiveness And Safety Of Autogenic Training As A Treatment For Medical Conditions Author Names: Yolanda Alvarez-Perez ([email protected]), Amado Rivero-Santanta, Lilisbeth Perestelo-Perez, Andrea Duarte-Diaz, Vanesa Ramos-García, Alezandra Torres-Castaño, Ana Toledo-Chávarri, Nerea González-González, Leticia Rodríguez-Rodríguez, Carlos González-Rodríguez, Pedro Serrano-Aguilar Introduction Autogenic training consists of reaching a state of deep relaxation through mental representations of physical sensations in different parts of the body. It is a promising technique for improving the psychological well-being of people with chronic diseases, but there are no clinical practice guidelines recommending the use of autogenic training in this population. The aim of this work was to identify, critically evaluate, and synthesize the available evidence on the safety and effectiveness of autogenic training in the prevention and treatment of medical conditions. Methods We conducted a systematic search for systematic reviews and randomized controlled trials (RCTs) in MEDLINE, Embase, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials. The selection and assessment of risk of bias of the included studies was carried out independently by two reviewers. Results A total of 2,420 references were identified after eliminating duplicates. Of these, 141 were selected for reading the full text, and 13 systematic reviews and 18 RCTs were included. Compared with no intervention or delayed treatment, autogenic training significantly reduced levels of anxiety and depression as well as some physical symptoms (e.g., headaches and atopic dermatitis). Conclusions Autogenic training could be useful for improving the psychological well-being and physical symptoms of patients with chronic health conditions and as an additional element in multicomponent intervention programs. However, these conclusions are not definitive due to the low number of studies available for each health condition and their high or unclear risk of bias.

Poster Presentation Number: PP21 Abstract Title: Efficacy And Safety Of Aromatherapy: An Overview Of Systematic Reviews Author Names: Andrea Duarte-Díaz ([email protected]), Amado Rivero-Santana, Lilisbeth Perestelo- Pérez, Yolanda Álvarez-Pérez, Vanesa Ramos-García, Alezandra Torres-Castaño, Analía Abt-Sacks, Ana Toledo- Chávarri, María Padilla-Ruiz, Leticia Rodríguez-Rodríguez, Carlos González-Rodríguez, Pedro Serrano-Aguilar Introduction Aromatherapy is the field of herbal medicine that uses essential oils distilled from flowers, roots, and herbs and other plant compounds to promote physical and psychological well-being. Essential oils are absorbed into the body in different ways, with the inhaled and topical routes being the most widely used. The aim of this review was to critically evaluate and synthesize the available scientific evidence on the efficacy and safety of aromatherapy for the management of any therapeutic indication. This report was requested by the Spanish Ministries of Health and Science and Innovation. Methods An overview of systematic reviews (SRs) was performed. The MEDLINE, Embase, CINAHL, and PsycINFO databases were searched for literature published from January 2006 to August 2021. SRs reporting the efficacy and safety of aromatherapy were included. We applied no restrictions in terms of administration route or essential oil used. Two reviewers independently performed screening and selection, data extraction, and quality assessment. Results We included 74 SRs covering a wide variety of populations and settings. The most reported outcome was anxiety, followed by pain, and the most commonly used essential oil was lavender. Fifteen SRs reported mild adverse events with aromatherapy. Only 11 SRs assessed the certainty of evidence using the GRADE approach. Aromatherapy reduced heart rate and likely reduces anxiety and breathing rate in patients with cardiovascular diseases. Aromatherapy probably also reduces pain in women with primary dysmenorrhea. Additionally, it may reduce blood pressure, acute pain, subjective stress, and the need for antiemetic drugs after surgical procedures. However, the evidence was very uncertain regarding the effect of essential oils on anxiety, pain, and quality of life in patients with cancer, anxiety and pain after a caesarean section, and dental anxiety. Conclusions Aromatherapy may be useful for managing psychological and physical symptoms in different settings. However, the conclusions of this review are not definitive because of the moderate to high risk of bias in many of the primary studies included in the SRs.

Poster Presentation Number: PP22 Abstract Title: A Lifecycle Approach To The Use Of Real-World Evidence In HTA Submissions And Resubmissions: A Decade’s Experience Author Names: Dima Samaha ([email protected]), Eliana Tavares, Anke van Engen, Paula Szawara Introduction Health technology assessment (HTA) bodies worldwide recognize the importance of real-world evidence (RWE) in addressing uncertainties around the effectiveness of new drugs at the time of launch and as part of resubmissions. We assessed the use and acceptability of RWE by analyzing HTA recommendations. Methods We analyzed 24,841 HTA reports, including original submissions, resubmissions, extensions of original indications, and renewals, published from January 2011 to October 2021 from more than 100 HTA agencies across 37 countries. Results Our analysis showed that 3,820 (15%) reports mentioned RWE. Between 2011 and 2021 there was an eight-fold increase in the use of RWE, from 4 percent in 2011 to 34 percent in 2021. RWE was most commonly included in HTAs in oncology (26%) and endocrine and metabolic diseases (13%). The main areas supported were effectiveness (40%), safety (38%), and epidemiology (35%). RWE supplemented evidence on survival and quality of life as well as resource utilization, proxy comparators, and utility. Based on an analysis of the 1,474 reports that mentioned RWE, effectiveness was mainly supported by cohort (22%) and observational studies (13%), safety was mainly derived from pharmacovigilance data (9%), and epidemiology data were collected from registries (23%). The top five HTA bodies mentioning RWE in their reports were from France, Germany, Poland, and the United Kingdom (n=2). RWE was most accepted when it supported safety and epidemiological considerations, and to a lesser extent when it was used for effectiveness aspects or understanding management pathways. Conclusions The inclusion and acceptability of RWE in HTA recommendations varies between HTAs according to their data requirements and assessment methods. While it is not always specified how RWE was considered, there is a clear tendency for its increased use and acceptability, albeit not in all areas. Greater use of and transparency around RWE are likely to continue as multiple RWE initiatives emerge globally.

Poster Presentation Number: PP23 Abstract Title: Lost In Translation? The Differences In The Use Of Real-World Evidence Across Key Markets. Author Names: Christina-Jane Crossman-Barnes, Weiwei Xu ([email protected]), Ishneet Kaur Introduction Health Technology Assessment (HTA) agencies have recognized the importance of real-world evidence (RWE) to inform access decision-making and different HTA agencies establish distinct requirements for their local jurisdictions. The objective of this study is to understand the differences of RWE included in HTA reports and HTA agencies’ perception of RWE. Methods HTA reports from agencies in France, Germany, Spain, Italy, United Kingdom (UK), Canada, Australia and South Korea from January 2011 to November 2021, including original submissions, resubmissions, extensions of original indications and renewals were analyzed. Results Across the eight countries, RWE has been used in nineteen percent of all HTA reports (N=2,960/15,561), with an exponential increase observed between 2019 and 2021. RWE on clinical effectiveness was mostly used in HTA submissions in the UK (twenty-two percent), with twenty-six percent perceived with full acceptance. In contrast, RWE on safety and epidemiology was reported widely in HTA reports in France and Germany (83% and 87%), respectively. Ninety-three percent of RWE received full acceptance in France, followed by forty-four percent in Germany. A mixed picture of the types of RWE included in HTA reports was observed in the other countries, with high variance of acceptance (between 5 to 37%). Conclusions France, Germany, and the UK are the top three countries with a large proportion of HTA reports where RWE was mentioned. The type of RWE used is related to a large extent to the local evidence requirements. For example, RWE around epidemiology was included widely in Germany due to the needs of providing local data for budget impact analyses required by the Federal Joint Committee (G-BA); RWE on tolerability as reported in periodic safety update reports (PSURs) needs to be included in French HTA submissions. RWE on clinical effectiveness has been evaluated the most by the UK HTA bodies.

Poster Presentation Number: PP24 Abstract Title: Organizing Outpatient Parenteral Antibiotic Therapy: Lessons from Denmark Author Names: Claus Loevschall ([email protected]), Anne Marie Thomsen, Bettina Risoer, Lotte Groth, Stina Lou, Camilla Palmhoej Introduction Outpatient Parenteral Antibiotic Therapy (OPAT) is a complex medical treatment used to treat patients with severe infections. OPAT is provisioned outside hospitals. There is wide variation in the use and organization of OPAT in Denmark. OPAT is increasingly used in Danish regions and municipalities, however, there is limited knowledge on the clinical, economic and organizational consequences of this technology. The purpose of the project was to establish an evidence base for decision-making prior to any further prioritization of OPAT as an alternative to intravenous antibiotic treatment in the hospital (IPAT). The HTA was produced at the request of the Health Directors in the Danish Regions to examine the consequences of using OPAT compared with IPAT. Methods The results were based on a systematic literature review and qualitative interviews with leaders (n=5), administrative employees (n=5) and health professionals (n=13) involved in the delivery of OPAT. Furthermore, a micro-costing analysis based on interviews with clinical experts was conducted. Results The use of OPAT led to similar or better clinical results when compared with the use of IPAT. Current evidence supports OPAT as a safe model for intravenous antibiotic treatment. The organisation of OPAT varied in Denmark as well as internationally. The selection of suitable patients for the different OPAT models was crucial for a successful treatment. Insight into patients' understanding of the pros and cons of the technology indicated that most patients preferred treatment at home. In a Danish context the microeconomic analysis showed that different OPAT models generally led to a reduction in costs compared with IPAT. Conclusions The project contributes to practice and political decision making by identifying challenges and opportunities associated with OPAT. There is no one-size-fits-all solution. The choice of OPAT model must be based on careful clinical considerations. Coordination and communication across municipalities and hospitals is challenging. Reducing organizational complexity is necessary to achieve a more standardized practice.

Poster Presentation Number: PP25 Abstract Title: Brazilian Collaborative Network For COVID-19 Modeling: Successful Experience Of Using Real-Time Science To Support Evidence-Based Decision-Making Author Names: Ângela Maria Bagattini ([email protected]), Michelle Rosa, Lorena Mendes Simon, Gabriel Berg de Almeida, Leonardo Souto Ferreira, Marcelo Eduardo Borges, Roberto André Kraenkel, Renato Mendes Coutinho, José Alexandre Felizola Diniz Filho, Suzi Alves Camey, Ricardo de Souza Kuchenbecker, Cristiana Maria Toscano Introduction Modeling is important for guiding policy during epidemics. The objective of this work was to describe the experience of structuring a multidisciplinary collaborative network in Brazil for modeling coronavirus disease 2019 (COVID-19) to support decision-making throughout the pandemic. Methods Responding to a national call in June 2020 for proposals on COVID-19 mitigation projects, we established a team of investigators from public universities located in various regions throughout Brazil. The team’s main objective was to model severe acute respiratory syndrome coronavirus 2 transmission dynamics in various demographic and epidemiologic settings in Brazil using different types of models and mitigation interventions. The modeling results aimed to provide information to support policy making. This descriptive study outlines the processes, products, challenges, and lessons learned from this innovative experience. Results The network included 18 researchers (epidemiologists, infectious diseases experts, statisticians, and modelers) from various backgrounds, including ecology, geography, physics, and mathematics. The criteria for joining the network were having a communication channel with public health decision-makers and being involved in generating evidence for public policy. During a 24-month period, the following sub-projects were established: (i) development of a susceptible-exposed-infected-recovered-like, individual-based meta-population and Markov chain model; (ii) projection of COVID-19 transmission and impact over time with respect to cases, hospitalizations, and deaths; (iii) assessment of the impact of non-pharmacological interventions for COVID-19; (iv) evaluation of the impact of reopening schools; and (v) determining optimal strategies for COVID-19 vaccination. In addition, we mapped existing COVID-19 modeling groups nationwide and conducted a systematic review of relevant published research literature from Brazil. Conclusions Infectious disease modeling for guiding public health policy requires interaction between epidemiologists, public health specialists, and modelers. Communicating modeling results in a non-academic format is an additional challenge, so close interaction with policy makers is essential to ensure that the information is useful. Establishing a network of modeling groups will be useful for future disease outbreaks.

Poster Presentation Number: PP26 Abstract Title: Cost Utility Of Vaccination Against COVID-19 In Brazil Author Names: Ricardo Fernandes, Marisa Santos, Carlos Alberto Magliano ([email protected]), Bernardo Thura, Luana Macedo, Matheus Padila, Ana Claudia França, Andressa Braga Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a single-strand ribonucleic acid virus that was first identified in January 2020 in patients with viral pneumonia in Wuhan, China. The virus has since spread rapidly around the world, leading the World Health Organization to declare it a pandemic on 11 March 2020. In Brazil there have been 21.8 million cases of SARS- CoV-2 infection and 608,500 deaths. The objective of this study was to evaluate the cost utility of the Oxford, CoronaVac, and Janssen vaccines from the perspective of the Brazilian public health system. Methods Three microsimulation models were constructed using individual data. The simulations contained seven transition states related to the natural history of COVID-19. The model with a daily cycle had a time horizon of one year and used data from 289 days of the pandemic. The analysis considered direct medical costs from the Brazilian health system perspective. Outpatient, hospital, and mortality databases were used for the model inputs and patient data were stratified by age. Effective vaccines reduced the likelihood of patients becoming ill. Information on the quality of life of patients receiving treatment in the outpatient or hospital setting and disease sequelae were extracted from the published literature. The main outcome of the analysis was quality-adjusted life-years (QALYs). Results The vaccines had incremental cost-utility ratios ranging from USD 4,121 (Oxford) to USD 3,160 per QALY (CoronaVac). The older the population, the lower the incremental cost-utility ratio. Given a willingness-to-pay threshold of BRL 3,129 per QALY, all the vaccines were considered cost effective in the probabilistic sensitivity analysis. The incremental cost-effectiveness ratio stratified by age ranged from USD 6,327 per QALY in patients older than 75 years (Janssen) to USD 20,993 per QALY in patients younger than 59 years (CoronaVac). Conclusions The results of this analysis, stratified by patient age, can help in the preparation of a vaccination prioritization plan.

Poster Presentation Number: PP27 Abstract Title: Reusing And Adapting Health Technology Assessments (HTAs): An Example From The COVID-19 Time Author Names: Maria-Jose Faraldo-Valles ([email protected]), Alba Regueira-Castro, Yolanda Triñanes Introduction Health technology assessment (HTA) reports are complex technical documents that address multiple aspects of the incorporation of a technology into the health care system applying complicated methodologies coming from different disciplines. The purpose of HTA is to support decision-makers and these should have an adequate level of training to fully understand these assessments. However, most HTA education programs and courses are intended for HTA doers and there is a lack of practical guidance training aimed at preparing health managers or policy makers in HTA. The objective is to describe an HTA training program developed for decision-makers of the three levels (health care administration, hospital management and clinical practice). Methods Rolling Collaborative Review (RCR) 01 of convalescent plasma was identified and selected because it complied with our Population Intervention Comparator Outcome Design Question. The EUnetHTA HTA adaptation Toolkit was used to check the relevance (about research question); reliability (quality of the report) and transferability (application of information to the target setting). Additional considerations regarding the local context were examined. A panel of four professionals and one patient was formed to rate the importance of the outcomes and to carry out the external review Results According to the toolkit, information on RCR01 Convalescent Plasma could be adopted for the safety and effectiveness domains. The technical characteristics and current use domains were adapted and extended. It was considered of interest to include the domains of organization and ethics. The organizational aspects were answered through the information retrieved in a search for systematic reviews and guides, and with the collaboration of experts. The ethics domain was answered through a specific literature search on ethical issues related to COVID-19 and transfusions. Conclusions The use of the EUnetHTA Toolkit has been helpful in supporting the adaptation process. The adoption of the effectiveness and safety domains from already developed HTA assessments is an efficient way to provide useful information for the decision-making process. However, contextual elements should be included in the adaptation process to ensure a complete framework for the decision.

Poster Presentation Number: PP28 Abstract Title: Is My Medicine Suitable For An Outcomes Based Agreement? The Feasibility Conundrum Author Names: Graciela Sainz de la Fuente ([email protected]), Kate Halsby, Jessica R. Burton Introduction Outcomes Based Agreements (OBAs) are financial arrangements that offer the opportunity to align payment to health outcomes in the real-world, and share the financial risk by providing long-term solutions that grant access to medicines, with reimbursement only when performance is achieved. OBAs are most likely to be useful when there is high uncertainty in the clinical data, but they are difficult to design and implement, and other financial options are usually preferred by payers. As a result, OBAs have been more the exception than the norm, and there is not a clear pattern that indicates if an OBA is likely to succeed in practice. Methods Through a retrospective OBA exercise with NHS Wales (Project IDEATE: Innovation in Data to Evolve Agreements That Enhance patient health outcomes), we have explored the circumstances under which an OBA might be most appealing to payers, and assessed implementation challenges and solutions, to propose a framework to evaluate the feasibility of a medicine for an OBA. Results Along with mitigating some of the clinical uncertainties associated with a lack of mature data at the time of launch, an OBA must also consider other factors: the commercial viability of the agreement, the associated administrative burden, and its cost of implementation. Also, the Health System commitment to a Value-Based Healthcare agenda and, most importantly, its willingness to offer long-term sustainable solutions to optimise treatment, are key to support this approach. Practical considerations include: how the relevant outcomes are going to be selected and tracked in the real- world, how the whole model is going to fit within the current procurement and finance infrastructures, and how industry works in collaboration with the Health System. Conclusions Insights from Project IDEATE will be used to explore how our OBA feasibility framework might be applied in the future.

Poster Presentation Number: PP32 Abstract Title: Assessment Of Preferences For Treatment: A Discrete Choice Experiment Among Italian Patients With Prostate Cancer Author Names: Eugenio Di Brino ([email protected]), Rossella Di Bidino, Michele Basile, Filippo Rumi, Patrizia Beccaglia, Damir Vetrini, Americo Cicchetti Introduction The integrated patient-centered, evidence-based approach to care recognizes the role of patient preferences. A discrete choice experiment (DCE) was developed with the aim of identifying the preferences of men with prostate cancer in Italy regarding the different risk-benefit factors of various treatment options. Methods The DCE was developed with the support of prostate cancer patients and oncologists and was based on a targeted scoping review. The final DCE included 26 choice sets divided into two blocks. The first block focused on all prostate cancer patients (both metastatic and non-metastatic), while the second block aimed to assess preferences for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Patients were asked to choose from ten attributes in the first block and six in the second block. The aim was to identify attributes and levels with a statistically significant impact on patient preferences. Preference estimates were calculated using a conditional logit regression model and the results were stratified by cancer stage (metastatic or non-metastatic) in the first block. Results A total of 202 patients (mean age 72 years) completed the DCE. In the first block, the most important attribute was quality of life (QoL), particularly for patients with metastatic cancer. The other three attributes found to be significant, in order of relevance to patients, were the risks of experiencing cognitive impairment, hematologic complications, and fatigue. For patients with mHSPC, QoL was the strongest determinant of preference. The risk of experiencing fatigue was also a relevant attribute, followed by skin irritation. Conclusions This study shows that the effect of treatment on QoL was the most important attribute for patients diagnosed with prostate cancer. Specific risk factors play a different role in the choice of treatment depending on cancer type, with the risk of experiencing fatigue being valued by all groups. Identifying and understanding patients’ preferences related to treatments for prostate cancer will help physicians identify the best treatment strategy.

Poster Presentation Number: PP33 Abstract Title: Molecular Markers For The Detection Of Clinically Significant Prostate Cancer Author Names: Tasmania del Pino-Sedeño ([email protected]), Lidia García-Pérez, Diego Infante- Ventura, Aránzazu Hernández-Yumar, Leticia Rodríguez-Rodríguez, Aythami de Armas-Castellano, Pedro Serrano- Aguilar, María del Mar Trujillo-Martín Introduction It is estimated that approximately 1.1 million cases of prostate cancer (PCa) are diagnosed in the world every year. In general, PCa is a slow-onset cancer and less than 10 percent of cases are detected in the metastatic phase. In order to identify patients at risk of suffering from clinically significant prostate cancer (csPCa), as well as to avoid unnecessary biopsies, overdiagnosis and overtreatment, a variety of molecular biomarker detection tests have been developed. Methods We undertook a systematic review with meta-analyses on the effectiveness of diagnostic tests based on biomarkers in blood or urine samples for the identification of men at risk of csPCa. A cost-effectiveness analysis was conducted using a decision tree model for the short term and a Markov model for the long term, both from the social and the National Health System perspectives. The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis. Results Sixty-five studies were included with a total of 34,287 participants. The diagnostic tests analyzed were: PHI, Progensa® PCA3, SelectMDx, MyProstateScore, 4Kscore®, TMPRSS2: ERG, Stockholm3, ExoDx Prostate IntelliScore and Proclarix®. All studies included biopsy as comparator. The sensitivity and specificity of diagnostic tests depended on the test itself and the threshold chosen, and ranged from 42 percent to 99 percent and from 13 percent to 87 percent, respectively. In the cost-effectiveness analysis, the alternative that includes the biomarker, specifically the SelectMDx, led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio (ICER) of 6,640.21 EUR per QALY. The sensitivity analyses confirmed that the results were robust. Conclusions Biomarker testing to select men at risk of csPCa who should undergo prostate biopsy can be a cost-effective strategy depending on its cost per determination and its sensitivity/specificity. The analyses carried out indicate that the SelectMDx biomarker is cost-effective at a cost of EUR 375 per determination.

Poster Presentation Number: PP34 Abstract Title: Next Generation Sequencing For Informing Lung Cancer Therapy In Europe – Hospital Impact With A Lifecycle Perspective Author Names: Rhodri Saunders ([email protected]), Amanda Hansson Hedblom, Luca Quagliata, Jose Luis Costa, Robert Dumanois Introduction Next-generation sequencing (NGS) can be run in-house or outsourced to an independent laboratory. It has enabled wider use of deoxyribonucleic acid/ribonucleic acid (DNA + RNA) sequencing in clinical practice. Within oncology, NGS has paved the way for more effective treatment, including personalized medicine. There are, however, large variations in access and reimbursement across Europe. The aim is to understand the European NGS landscape and barriers to access. Methods Structured telephone interviews covered topics on NGS perception, guidelines, use-cases, benefits, costs, and future expectations. Twelve experts per country (France, Germany, Italy, Spain): two payers, five oncologists, and five pathologists were interviewed between June and August 2021. Responses were translated into English for qualitative analysis. Results NGS was considered most useful when there were approved, targeted treatments. Although often noted that there was a lack of published evidence to support a beneficial link, respondents perceived that NGS has the potential to improve patient quality of life (QoL) and reduce resource use through avoiding suboptimal treatment. All of the payer respondents expected the role of NGS to increase, though it may be held back by lack of reimbursement. Respondents favored in-house NGS over outsourcing in terms of clinical benefit: “Advantages of in-house NGS are turnaround time, results and lean processes” ... “you build the expertise in-house. If you have urgent samples, it’s easy to prioritize them”. Reasons for not having in-house NGS included “costs, lack of personnel. Basically, organizational and financial issues.” In-house NGS was perceived to be associated with high setup-costs (acquisition, setup, training), but lower running costs (per-test costs). There was a view that in-house solutions are mainly suitable in larger centers undertaking many tests. Conclusions NGS can save costs and provide QoL benefit through enabling optimized, personalized therapy, but published evidence establishing the outcomes link is lacking. From the hospital perspective, investing in NGS requires understanding the cost of NGS over its entire lifecycle, likely entailing a health-technology assessment including health-economic analysis.

Poster Presentation Number: PP35 Abstract Title: Defecography (Evacuation Proctography) For The Evaluation Of Pelvic Floor Disorders: A Literature Review Author Names: Ruslan Akhmedullin, Andrey Avdeyev ([email protected]), Valeriy Benberin, Nasrulla Shanazarov, Gulzada Bariyeva, Makhabbat Okesh, Makpal Akhmetova, Tansolpan Aimanova Introduction Pelvic floor diseases (PFD) often affect the adult population, with approximately 50 percent of women aged 50 years and older suffering from PFD. The condition has complex symptoms that may lead to stress and a negative impact on the quality of life. The USA spends about USD 1 billion annually on inpatient costs as a result of more than 700,000 emergency department visits and 50,000 hospitalizations associated with PFD. Defecography is currently the most commonly used method of diagnostic imaging used to evaluate PFD. This technology is not available in the Republic of Kazakhstan, despite its high diagnostic value. Methods In order to assess the clinical effectiveness of defecography, we have conducted a literature search in the MEDLINE database. We selected articles with pairwise comparisons of defecography with other tests: anorectal manometry; balloon expulsion test; electromyography; magnetic resonance imaging (MRI); and, ultrasound. Results The findings are primarily based on two meta-analysis (91 studies representing 10,768 cases). The results have been evaluated according to the detection frequency and omission of the following signs: cystocele, middle compartment descent, rectocele, intussusception, rectal prolapse, enterocele, and perineal descent. The literature review did not reveal significant difference in diagnostic value between MR defecography and defecography based on X-ray. However, the imaging endpoints (detection rate of structural and functional abnormalities) for defecography based on X-ray were significantly better than plain radiography. Conclusions The defecography is currently considered the gold standard and the most commonly used tool of diagnosis. The implementation does not require an expensive equipment purchase (MR defecography) and is reproducible on conventional X-ray equipment if the necessary inventory is available.

Poster Presentation Number: PP36 Abstract Title: Joint Replacement Under Computer Navigation And Robotic Systems Author Names: Ruslan Akhmedullin, Andrey Avdeyev ([email protected]), Valeriy Benberin, Nasrulla Shanazarov, Gulzada Bariyeva, Makhabbat Okesh, Makpal Akhmetova, Tansolpan Aimanova Introduction Osteoarthritis (OA) is a heterogeneous group of diseases of various etiologies based on the defeat of all components of the joint. OA is one of the main causes of disability in older people. To date, joint replacement is the most clinical and cost-effective method of the terminal stage treatment. The short and long-term success of total joint replacement is closely related to the accuracy of the prosthesis implantation. Published studies show that the accuracy of prosthesis implantation can be intraoperatively controlled by computed navigation and robotic systems better than by traditional methods. Methods In order to assess the clinical effectiveness of the technologies, we have conducted a literature search in the MEDLINE database. We included studies that reported a comparison of outcomes between conventional methods, computer navigation and robot-assisted surgery. Results The results of this literature review are based on six systematic reviews with meta‑analyses (101 studies representing 482,367 cases) and one national joint replacement registry. The outcomes compared included Knee Society Score (KSS)-function, alignment correction, mechanical axis (varus and vagus deviance >3°), prosthesis positioning, soft tissues balancing and functional outcomes. Thus, the cumulative success rate in the computed navigation and robotic systems group was reported to be 86.7 percent, which is crucial considering its lowered rate of revision (3%), correct mechanical axis (≤3%) and functional status. Conclusions The literature review demonstrates a high potential of the computed navigation and robotics systems in the intraoperative monitoring of important surgical parameters for achieving the best intervention outcomes. All the clinical endpoints were significantly better by comparison with conventional method.

Poster Presentation Number: PP37 Abstract Title: A Systematic Review of Machine Learning and Statistical Models For Predicting Coronary Heart Disease In Diabetic Patients Author Names: Li Jiu ([email protected]), Rick Vreman, Junfeng Wang, Aukje Mantel-Teeuwisse, Wim Goettsch Introduction Risk prediction models, using either machine learning or statistical algorithms, can act as inputs of a cost- effectiveness model when predicting costs and effectiveness of an intervention. This systematic review has two objectives: to evaluate methodological quality of the published models to predict diabetic coronary heart disease (CHD) risk; to evaluate whether the models were sufficiently reported to judge their applicability to the cost- effectiveness modelling. Methods A targeted review of journal articles published in English, Dutch, Chinese, or Spanish was undertaken in PubMed, Embase, Scopus, Web of Science, and IEEE Explore from 1 January, 2016 to 31 May, 2021. To assess the methodological quality and reporting of the models, we used PROBAST (Prediction model Risk Of Bias Assessment Tool), CHARMS (a Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies), and a checklist (Betts 2019) summarizing the application of cardiovascular risk prediction models to health technology assessment. Results Our search retrieved 6,579 hits, of which 18 models were eligible for inclusion. Among them, four studies developed machine learning models (2 recurrent neural networks, 1 random forest models, and 1 multi-task learning model) while 14 studies developed statistical models (8 Cox models, 5 logistic models, and 1 microsimulation model). More than 70 percent of models were of high methodological quality in aspects of participants (89%), predictors (72%), and outcomes (72%), while only five models (28%) in aspects of statistical analysis. For the reporting, only two models provided sufficient evidence in all aspects (i.e., participants, predictors, and outcomes) for judging their applicability to the cost-effectiveness modelling. Most models were reported sufficiently regarding participants (78%) and outcomes (72%), but only three models regarding predictors (17%). Conclusions To apply the CHD risk prediction models to cost-effectiveness modelling, concerns remain regarding the potential risk of bias due to inappropriate use of analysis methods, and regarding insufficient reporting on how to measure and assess the predictors.

Poster Presentation Number: PP39 Abstract Title: Evidence Generation For Reimbursement Of Digital Health Applications (DiGAs) In Germany Author Names: Naomi Fujita-Rohwerder ([email protected]), Stefan Sauerland Introduction In 2019, the German government established a new evaluation procedure for digital health applications (DiGAs) to facilitate their reimbursement by statutory health insurance. The procedure involves the assessment of a DiGA's \"positive healthcare effect\", which is defined as a medical benefit and/or \"a patient-relevant improvement of structure and processes\". If the available clinical evidence is insufficient to prove the manufacturer's claim on the positive healthcare effect, but the claim seems plausible, the DiGA is provisionally reimbursed, and further clinical evidence within twelve months must be generated. DiGAs eligible for provisional or permanent reimbursement are publicly listed in the DiGA directory. In contrast to the usual pathways for reimbursement of healthcare technologies which involve IQWiG as the national HTA agency and the G-BA (Federal Joint Committee) as the decision-making body, the DiGA procedure is currently carried out by the national competent authority (BfArM) and thus outside the joint self-government. Furthermore, legal evidence requirements for DiGAs are comparatively low. Methods This work analyzed the suitability of clinical studies that intended to prove a DiGA’s medical benefit. For this purpose, the key elements for clinical studies published in the DiGA directory and clinical trial registries were extracted and compared with the usual evidence requirements in the reimbursement context. Results As of October 2020, 20 DiGAs have successfully undergone the application procedure. Fourteen DiGAs (70%) were provisionally accepted. A randomized controlled study (RCT) design was chosen for all clinical studies to be conducted for further evidence generation. However, in four cases (28%), it is questionable whether the clinical study is suitable to demonstrate a medical benefit mainly due to the choice or operationalization of the primary endpoint (n=2), the timing of the endpoint survey (n=2) and/or the choice of the control intervention (n=1). Conclusions Even though all currently ongoing or planned clinical studies with DiGAs are RCTs, not all of them are adequate to demonstrate a medical benefit according to the usual evidence requirements.

Poster Presentation Number: PP40 Abstract Title: Health Apps To Manage Depression: Can We Separate The Grain From The Chaff? EvalDepApps Project Author Names: Carme Carrion ([email protected]), Ariadna Sales-Masnou, Sophie Eis, Noemí Robles, Elisa Puigdomènech, Andrea Duarte-Díaz, Josep Vidal-Alaball, Lilisbeth Perestelo, Meritxell Davins, Oriol Solà-Morales Introduction The use of mobile applications in the treatment of health issues is more frequently becoming common practice. Apps are fast, versatile, and manageable tools that allow the empowerment of patients and professionals, and can reduce the possible stigmatization suffered by some patients, mainly in mental health. There are more than 325,000 health apps on the market, but their impact remains unclear. There are several initiatives to define how health applications should be assessed, however, all of them address only partial aspects of the evaluation. The theoretical frameworks existing to date highlight the need to develop new tools and methodologies to assess mobile applications whose objective is the management of specific pathologies. Methods The primary goal of the EvalDepApps project is to develop and pilot an assessment tool for mobile applications whose main objectives are the treatment, monitoring or social support of people suffering from depression. The project is inspired by the results and lessons learnt from a previous project, EVALAPPS, whose central aim was to develop a tool to assess health apps targeted toward the management of overweight and obesity. The first steps of the EvalDepApps project are:(i) to explore and characterize the current landscape of mobile applications available in the market to treat depression through a systematic appraisal, and (ii) to review the existing evidence about the effectiveness and safety of these applications through systematic research of the existing evidence. Results Preliminary results show that all the depression management studies were by design based on cognitive- behavioral therapy (CBT) interventions (n=17) and the main management tools included in the services (web or apps) are psychoeducation and coaching (14), together with self-monitoring and feedback messaging (13). Conclusions Moreover, although health apps seem to be an interesting strategy to treat depression, there are very few apps available on the markets (30) and the supporting evidence is very limited. This result uncovers a need for further systematic and clinically oriented validation and testing of such apps.

Poster Presentation Number: PP41 Abstract Title: COVID-19 Modeling To Support Decision Making In Brazil: A Scoping Review Author Names: Michelle Rosa ([email protected]), Angela Maria Bagattini, Lorena Mendes Simon, Gabriel Berg de Almeida, Isabella Inês Rodrigues da Rosa, Cristiana Maria Toscano Introduction In the context of the COVID-19 pandemic, which required urgent responses from health systems, and ongoing decision making in a context of limited and evolving evidence, modeling played a significant role in supporting public policy making. Nonetheless, particularly in low and middle-income countries, modeling groups are scarce, and usually not routinely involved in supporting public health policy making. We aimed to appraise COVID-19 modeling work in Brazil during the pandemic. Methods We performed a scoping review following PRISMA guidelines to identify groups conducting COVID-19 modeling to support health decision-making in Brazil. Search strategies were applied to MEDLINE, LILACS, Embase, ArXiv, and also included National data repositories and gray literature. We excluded reports of models without modeling results. Titles, abstracts, data repository descriptions and full-text articles identified were read and selected by two reviewers. Data extracted included modeling questions, model characteristics (structure, type, and programming), epidemiologic data sources, main outcomes reported, and parameters. To further identify modeling groups that might have not yet published results, snowball sampling was performed, and a short survey was sent electronically. Investigators and policymakers were invited to an online interview, to obtain further information on how they interacted, communicated, and used modeling results. Results We retrieved 1,061 references. After removing duplicates (127), 1,016 abstracts and titles were screened. From an initial selection of 142 abstracts, 133 research groups were identified, of which 67 didn’t meet the eligibility criteria. Of these, 66 groups were invited for an interview, of which 24 were available, including 18 modeling groups from academic institutions, and four groups from State Health departments. Most models assessed the impact of mitigation measures in cases/hospitalization/deaths and healthcare service demand. Interaction and communication with decision-makers were not well established in most groups. Conclusions Despite a large number of modeling groups in Brazil, we observed a significant gap in modeling demand and communicating its results to support the decision-making process during the COVID-19 pandemic.

Poster Presentation Number: PP42 Abstract Title: Impact Of The COVID-19 Pandemic On Scottish Medicine Consortium Submission Characteristics, Acceptance Rates, And Time To Advice Author Names: Iain Leslie ([email protected]), Guy Berg Introduction Scottish Medicine Consortium (SMC) meetings were suspended in March 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic. This led to a high number of submissions awaiting appraisal, prompting interim process changes to ensure minimal disadvantages to patient access. We expanded the eligibility criteria for the shorter (abbreviated) submissions process and expedited advice for submissions the New Drugs Committee (NDC) intended to accept. This study aimed to evaluate the impact of the COVID-19 pandemic and these interim process changes on the characteristics of submissions received, acceptance rates, and time to advice publication. Methods Data for all submissions received between January 2015 and November 2021 (n=720) were extracted from an organizational database. Characteristics of and acceptance rates for submissions received before and after the start of the pandemic were compared using chi-squared and one-proportion Z-tests, respectively. Additional analyses explored the number of submissions received per month and the time from receipt of submission to NDC and SMC decision. Results The numbers of full and abbreviated submissions increased from March 2020 (6% in each case), with a corresponding decrease in the number of medicine-indication pairs (e.g., pembrolizumab for breast cancer) for which companies did not submit (8%; p=0.01). An increase in the SMC acceptance rate was also observed (62 to 72%; p=0.03). Fewer submissions were received in 2020 (n=65), compared with the pre-pandemic average (mean=79.6), whereas the total in 2021 to date was higher than average (n=92). Time series analysis suggested an increasing trend in monthly submissions (from approximately 6 to 9), which is the likely reason for the increase in average time to decision (146 versus 170 days). Conclusions Process changes in response to the pandemic have been effective in expediting advice for submissions with sufficiently robust evidence. This demonstrates agility and efficiencies for submitting companies and patient groups, with no perceived impact on process rigor. The average number of submissions has increased since March 2020, and further work is warranted to understand the influence of process improvements on reducing time to advice.

Poster Presentation Number: PP43 Abstract Title: Impact Of The COVID-19 Pandemic In The Brazilian National Committee for Health Technology Incorporation (Conitec) Recommendation Process Author Names: Marilia Cardoso ([email protected]), Lehana Thabane, Juliana Rugolo, Daniel Curado, Luis Gustavo Modelli, Silvana Lima, Silke Weber Introduction Health Technology Assessment (HTA) Process assists decision-making in health policies. The COVID-19 pandemic caused a high demand on protocol or guideline updates and incorporation of new drugs or therapies, overwhelming local agencies. A recent study reported that major HTA bodies in England, Scotland, Germany, and Canada reduced their number of drug recommendations in 2020, due to reprioritization of resources and COVID- related challenges. The present study aimed to evaluate the impact of the COVID-19 pandemic at the Brazilian National Committee for Health Technology Incorporation (Conitec) recommendation process. Methods This descriptive study evaluated all official recommendation reports available on the Government website in 2020 and 2021, extracting the data of disease category, technology type, the aim of the report, Public Involvement, and final result for the recommendation. The results were presented in tabular and graphical form using the machine learning, through the software R studio and excel. Results A total of 168 documents were evaluated, including guidelines and recommendation reports, with no reduction in the number of evaluations considering 2019. In 2020, there was a more significant evaluation of guidelines, and in 2021, a report on the non-incorporation of technologies. There were four specific documents about COVID 19, including vaccines and hospital care guidelines. The most incorporated and non-incorporated technologies were medication, targeting rare and highly prevalent diseases in balance. The Brazilian government was the main proposer. These results are part of the study “A Survey about the core methods of the recommendation reports for Brazilian Ministry of Health carried out by Brazilian Health Technology Assessment Centers”, which will characterize and analyze the core methods of the recommendation reports conducted by the Brazilian HTA Centers. Conclusions The pandemic had a low impact on demands in the routine of the Conitec. Establish indicators and technological norms applicable to health services, contribute to the identification of possible new practices, methods or criteria.

Poster Presentation Number: PP45 Abstract Title: The Cost-Of-Illness Of Diabetic Macular Edema In Italy Author Names: Michele Basile ([email protected]), Giovanna Elisa Calabrò, Francesco Bandello, Monica Varano, Giuseppe Castronovo, Filippo Amore, Tiziano Melchiorre, Americo Cicchetti Introduction Diabetic Macular Edema (DME) is an important complication of Diabetic Retinopathy (DR). Intravitreal steroids in slow-release systems represent a safe and effective therapeutic option for the management of DME, capable of improving patients' quality of life by reducing the number of injections thus increasing the therapeutic adherence and the effectiveness of the treatment. This study aims to determine the economic impact of DME and the consequences, in terms of both expenditure and organizational impact, associated with a greater use of the intravitreal dexamethasone implant. Methods The analysis entailed the comparison between two scenarios: a first scenario based on the current use of therapeutic alternatives available in the Italian healthcare setting (as is) and an alternative scenario based on the assumption of an increased use of intravitreal dexamethasone implant (to be). The results of the analysis are expressed in terms of resource absorption associated with the two scenarios as well as in terms of the cost differential given by their comparison. Results Despite an increase in expenditure in terms of acquisition costs of pharmacological alternatives (EUR 898,362) and interventions provided (EUR 22,093,160), the greater use of prolonged-release dexamethasone allows for significant savings in terms of healthcare professionals' time, follow-up and productivity losses incurred by patient/caregiver. These reductions in healthcare costs resulted in a saving of EUR 1,987,678 over a 5-year period. Such a reduction would allow, considering a total annual management cost of EUR 6,115 for the intravitreal dexamethasone, to treat 325 more patients at the same cost of the as is scenario based on the current rate of use of dexamethasone. Conclusions In a context characterized by the need to increase the allocative efficiency of economic resources, the recourse to therapeutic alternatives, such as prolonged release dexamethasone, allowing the reduction of costs for the management of a given pathology is crucial to generate more value for patients and the entire society.

Poster Presentation Number: PP46 Abstract Title: INEAS Guidelines For Pharmacoeconomic Evaluation: Focus On Health-Related Quality of Life Recommendations Author Names: Jaafar Chemli, Nabil Harzallah ([email protected]), Hela Grati, Marie Christine Jebali, Mouna Jameleddine, Chokri Hamouda Introduction In many low- and middle-income countries scarcity of local data on health outcomes and health-related quality of life (HRQoL) is a hindrance to conducting cost-effectiveness analyses. The Tunisian National Authority for Accreditation and Assessment in Healthcare (INEAS) developed a set of methodological guidelines to support pharmaceutical companies in the submission of health technology assessment (HTA) dossiers. The guidelines include INEAS’ methodological choices for pharmacoeconomic analysis, which take into consideration the specificities and constraints of the Tunisian context. We aimed to present the principal recommendations of the Tunisian guidelines for pharmacoeconomic studies, with a focus on patient-reported outcome and HRQoL measurement. Methods The INEAS pharmacoeconomic analysis guidelines were reviewed and the recommendations regarding outcome measurement and HRQoL were retrieved and reported. Results To populate the economic model, INEAS recommends using the best available evidence. Health outcomes should be measured in terms of life-years gained and quality-adjusted life-years (QALYs); disability-adjusted life-years can be used but are not the preferred method. To estimate QALYs, INEAS favors the indirect measure of patient preferences with a validated measurement instrument. Alternatively, other measures of utility may be used, including those identified through a systematic review of the scientific literature and the publications of other HTA agencies. Justification and details of the source of the data must be provided. The utility values selected should be recent and representative of the Tunisian population, as far as possible. The guidelines refer to a set of generic preference-based HRQoL instruments, including the EuroQol five-dimensions (EQ5D), the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3), and the Short-Form Six-Dimension (SF-6D), but do not provide any explicit recommendations on their use. Conclusions The INEAS pharmacoeconomic analysis guidelines adhere to international best practices but provide more flexibility for overcoming the lack of local data. The INEAS economic guidelines constitutes a further milestone in the process of implementing HTA in Tunisia and in the Middle Eastern and African regions

Poster Presentation Number: PP47 Abstract Title: Modelling Non-small Cell Lung Cancer Treatment: Predicted and Observed Impact Of Immunotherapy In The Netherlands Author Names: Zakile A Mfumbilwa ([email protected]), Janneke A Wilschut, Mr Martijn J.H.G Simons, Bram Ramaekers, Manuela Joore, Valesca Retel, Christine M Cramer-van der Welle, Franz M.N.H Schramel, Ewoudt M.W van de Garde, Veerle M.H Coupé Introduction Patients treated with immunotherapy are divided into two subgroups: (i) long-term survivors (LTS) and (ii) moderate survivors. Nevertheless, clinical trials (RCTs) report only average treatment effects such as hazard rate (HRs). Health economic-models often only input average treatment effects, even though it has been shown that accounting for the LTS subgroup is crucial for accurate projection of long-term survival under immunotherapy. We investigated the incorporation of a statistical mixture cure model (MCM) in a health-economic model for lung cancer as a way to account for LTS while incorporating reported average RCT-based treatment effects. Methods We developed a microsimulation model describing disease progression under three treatment lines in advanced lung cancer using Dutch real-world data of chemotherapies treated patients. Here we focus on first-line treatment, for which we used gompertz distribution to simulate time-to-progression. To simulate the impact of immunotherapy, we adjusted base-model assuming MCM for first-line treatment, where the LTS subgroup was not at risk to progress, but instead die from background mortality. The subgroup of moderate survivors on the other hand are at risk to progress with adjusted progression-free HR (PF-HR). We simulated the model with size of LTS (prop_LTS) ranging from 14-34 percent (keynote-001 five-year overall survival [OS], 95% confidence interval) while fixing average RCT PF-HR at 0.5. Model predictions under the different prop_LTS were compared to real-world Dutch OS as well as the long-term RCT five-year OS. Results With respect to observed short-term survival outcomes, model predictions were insensitive to assumptions regarding the size of the LTS subgroup. However, to match the five-year RCT OS rate reported (32%), the prop_LTS had to be equal to 34 percent. Under this latter setting for the prop_LTS, the progression HR in the subgroup of moderate survivors was calibrated to be 1.1. Conclusions The use of a mixture cure model improves long-term model-based projections with the implicit assumption that moderate survivors have little or no treatment benefit.

Poster Presentation Number: PP48 Abstract Title: A Micro-Costing Study For Circulating Tumor DNA testing In Oncology Author Names: Astrid Kramer ([email protected]), Ed Schuuring, Daan Vessies, Paul van der Leest, Maartje Geerlings, Pim Rozendal, Mirthe Lanfermeijer, Theodora Linders, Léon van Kempen, Remond Fijneman, Marjolijn Ligtenberg, Gerrit Meijer, Daan van den Broek, Valesca Retèl, Veerle Coupé Introduction Circulating tumor DNA (ctDNA) is a promising new biomarker with multiple potential applications in cancer care. As part of the “ctDNA on the way to implementation in the Netherlands (COIN)” project, an early, comprehensive Health Technology Assessment (HTA) is ongoing. Information about the costs of ctDNA testing is essential for implementation. Estimating the total cost associated with ctDNA-testing is challenging due to variation in the workflow, wide range in purchase and operational costs of the platforms, and the highly dynamic field. As a first step in the HTA, the aim of this study was to develop a flexible micro-costing framework and open-access model for consistent cost calculation of ctDNA-testing. Methods First, the complete diagnostic workflow of ctDNA-testing was mapped based on expert discussions. This step- wise workflow was used as the foundation of the framework. Second, the activity-based costing method was used and included costs for personnel, materials, equipment, overhead, housing, and test failures. Third, the framework was validated by experts and by applying the cost calculation model to six case studies. Results The diagnostic workflow was mapped from blood sample collection to reporting the diagnostic findings. The framework was developed from a Dutch perspective and takes into account the testing volume. The total cost per sample for the case studies with different workflows and testing volumes ranged from EUR 168 to EUR 7,638. Conclusions The developed micro-costing framework can be used to calculate the costs for ctDNA-testing for different workflows. The results from the case studies show the wide range of costs for ctDNA-testing and that the costs are determined by the choice of platform, setting, and testing volume. The open access model allows users to adapt and specify parameters in the diagnostic workflow matching their setting and can be used to support investment decisions and future cost-effectiveness studies.

Poster Presentation Number: PP49 Abstract Title: Financing The Line Of Care In The First Biochemical Relapse Of Prostate Cancer After [68Ga] PSMA PET- CT Author Names: Marcia Maria Diniz Pontes Paiva, Lorena Pozzo ([email protected]) Introduction It is estimated that prostate cancer will reach 66 thousand by the triennium 2020-2022 according to the National Cancer Institute (INCA). After initial diagnosis and staging the patient may undergo radical prostatectomy and/or curative radiotherapy. In patients with biochemical relapse (PSA >0.2 ng/ml) initially treated with radical prostatectomy, salvage external radiotherapy is indicated. The [68Ga] Prostate Specific Membrane Antigen Positron Emission Tomography-Computed Tomography (PSMA PET-CT) scan is mainly used for localization of prostate cancer in the setting of first biochemical recurrence and can significantly influence the clinical management of the patient. Methods The overall objective of this work is to perform a treatment cost analysis for patients in first biochemical recurrence of prostate cancer after curative radical prostatectomy and after performing [68Ga] PSMA PET-CT from the perspective of the Brazilian Health System (SUS). A decision tree was constructed through consultation with experts to outline the patient's entire treatment. Values per modelled therapeutic procedure were surveyed in two different scenarios, with and without [⁶⁸Ga] PSMA PET-CT. The average treatment in scenario 1 was stereotaxic radiation therapy (SBRT), and rescue radiotherapy and androgen deprivation therapy (ADT). In scenario 2, it was salvage radiotherapy and ADT. The reimbursement table was prepared from data collected by SUS system. Variations were analysed using a sensitivity study. Total average values included: individual procedure, according to medical management (up to 3 years) and population percentage with and without [⁶⁸Ga] PSMA PET-CT. Results Values were calculated in Brazilian currency (BRL) for each procedure. The total amount calculated for scenario 1 was BRL 264,965,465.00 (USD 55,642,747.65) and for scenario 2 was BRL 123,585,612.72 (USD 26,162,978.67). Conclusions The reimbursement of line of care adopted after [68Ga] PSMA PET-CT is an important information to expand access to the Brazilian population. It shows an increased cost with [68Ga] PSMA PET-CT adoption. A prospective study should be considered with high follow up.

Poster Presentation Number: PP51 Abstract Title: Strengths And Limitations Of Migraine Management Guidelines In The USA and Europe: A Targeted Literature Review Author Names: Richard Perry ([email protected]), Kayla Mills, Janet H. Ford, Zach McCosh Introduction Migraine, the second leading cause of disability worldwide, remains underdiagnosed and undertreated. Considering the high burden of migraine, we analyzed the strengths and limitations of existing migraine management guidelines. Methods A targeted literature review was conducted using MEDLINE on 24 March 2021 to identify current migraine management guidelines (including policies and position statements) published in the English language from France, Germany, Italy, Spain, the United Kingdom, and the USA. This was supplemented by a gray literature search. Disease state or pharmacological management guidelines for adults with migraine comprising any of the following perspectives were included: health economics; payer; health technology assessment; treatment access; and impact of guideline implementation on economic or disease burden. Guidelines were analyzed using the Centers for Disease Control and Prevention (CDC) policy analytical framework, which comprises three domains: problem identification, policy analysis, and strategy or policy development, with ranking criteria for each. Results Of 39 selected guidelines, 25 adequately identified problems related to migraine, 35 sufficiently reviewed the literature on migraine treatment, three failed to cite literature, and one lacked sufficient content. Twenty-three guidelines targeted healthcare professionals. Almost all guidelines lacked a stepwise migraine treatment approach; only the American Academy of Family Physicians guideline offered first- and second-line treatment options. Four guidelines mentioned current political forces, and coverage of economic or budgetary impact aspects was limited. Numerous guidelines described the substantial economic burden of migraine and were categorized as ‘high’ for benefits. Public health impact was categorized as ‘high’ for 28 guidelines and budgetary impact was rated as ‘more favorable’ for 27 guidelines. Thirteen guidelines defined a strategy for the intended purpose. Only the United States Department of Health and Human Services pain management guideline met all of the CDC criteria. Conclusions Future policies on migraine management may benefit from the inclusion of information on economic data, political feasibility, and public health impact. Furthermore, migraine management guidelines could potentially be improved by considering a comprehensive treatment approach and guideline implementation, as well as addressing knowledge gaps in disease state, public health, and economic aspects.

Poster Presentation Number: PP52 Abstract Title: Transcranial Magnetic Stimulation For The Treatment Of Cocaine Addiction: A Systematic Review Author Names: Alezandra Torres-castaño ([email protected]), Amado Rivero-Santana, Lilisbeth Perestelo-Pérez, Andrea Duarte-Díaz, Ana Toledo-Chávarri, Vanesa Ramos-García, Yolanda Álvarez-Pérez, Javier Cudeiro-Mazaira, Ivan Padrón-González, Pedro Serrano-Pérez Introduction Long-term cocaine use is associated with a wide range of cognitive deficits and neuropsychiatric pathologies. Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapeutic strategy that stimulates the prefrontal cortex and may improve cognitive inhibitory control and decision-making. This systematic review aimed to evaluate and synthesize evidence on the safety, effectiveness, and cost effectiveness of rTMS for the treatment of cocaine addiction. Methods A systematic review of the literature was carried out. The following electronic databases were searched to identify relevant studies published from inception to October 2020: MEDLINE, Embase, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials, and Web of Science. Randomized controlled trials (RCTs), non- randomized controlled trials (nRCTs), case series studies, and full economic evaluations were included. Results A total of 12 relevant studies were identified, which included five RCTs, one nRCTs, and six case series studies. None of the studies reported data on cost effectiveness. The results indicated that rTMS reduces cocaine cravings and the number of doses consumed. No serious adverse effects were observed. Conclusions The ability to modulate the craving for cocaine in a specific way with non-invasive brain stimulation techniques, such as rTMS, could be a new adjunct to the behavioral treatment of addiction, especially for cocaine use where there is currently no approved pharmacological treatment. Despite the low quality of the included studies, preliminary results indicate that rTMS may reduce cocaine use and cravings. In any case, since this effect is considered moderate, future studies with larger sample sizes and longer follow up are required.

Poster Presentation Number: PP53 Abstract Title: Applying The VALIDATE Approach To Frame The Assessment Of Integrated Care Management In Aortic Valve Stenosis Author Names: Victòria Valls-Comamala, Carla Fernandez-Barceló ([email protected]), Marc Trilla, Barbara Vidal, Marta Sitges, Laura Sampietro-Colom Introduction The assessment of current technologies needs a more holistic approach to obtain accurate recommendations for decision-making. The VALues In Doing Assessments of health TEchnologies (VALIDATE) methodology considers that facts and values from all stakeholders need to be included in the scoping of an assessment to gather the comprehensive information needed for unbiased decision-making. This report aimed to explore how to properly assess the integrated care of patients with aortic valve stenosis (AVS) using the VALIDATE approach. Methods A literature review was conducted, and 11 semi-structured interviews were performed with various hospital- based healthcare professionals (cardiac surgeon, clinical cardiologist, interventional cardiologist, anesthetist, process coordinator nurse, and others) and patients. Content analysis was used for data analysis and integration. Results The literature review showed that the cardiology and cardiac surgery perspectives were dominant in 90 percent of the articles and present in the remaining ten percent. The perspectives of other specialties (anesthesiology, primary care, and psychology) were included in three percent of the articles and patient perspectives were included in nine percent. Interviewing and considering the perspectives of the different stakeholders involved in the care pathway identified the following indicators that should be included in the assessment care for patients with AVS: difficulties associated with late diagnosis of AVS; the need to incorporate a multidisciplinary approach in patient risk assessment; the importance of geriatric evaluations; considering patient (and family and caregiver) preferences for type of treatment; the importance of following up pharmaceutical treatment and palliative care; use of telemonitoring; and digital exclusion of patients with respect to the use of apps for prehabilitation and rehabilitation. Conclusions The stakeholders interviewed were involved in different steps of the care pathway and had differing needs, some of which were not found in the literature. The indicators suggested for inclusion in the assessment differed according to type of stakeholder and their involvement in the care pathway. Therefore, this case study exemplifies the VALIDATE method and endorses the need for multistakeholder involvement in eliciting values when scoping the assessment of a complex technology.

Poster Presentation Number: PP56 Abstract Title: The Use of Computed Tomography for Detecting COVID-19 Pneumonia: Rapid Evidence Review Author Names: Samson Mideksa ([email protected]), Sabit Ababor, Yosef Gebreyohannes, Firmaye Bogale, Dagmawit Solomon, Tsegaye Getachew, Desalegn Ararso, Ermias Wolde, Zelalem Kebede and Getachew Tollera Introduction The reverse transcription polymerase chain reaction (RT-PCR) test is the gold standard for detecting coronavirus disease 2019 (COVID-19), but recent studies have reported false negative results for RT-PCR. Consequently, several countries are looking at chest computed tomography (CT) for the diagnostic workup of patients with suspected or probable COVID-19 to inform clinical management. Therefore, this rapid review provides the best available evidence on the use of chest CT for detecting COVID-19 pneumonia. Methods Literature searches were conducted in the PubMed, Cochrane Library, JBI Library, Epistemonikos, and Evidence Aid databases for relevant papers published from 1 December 2019 to 12 June 2020. The search strategy was based on the identified population, concept, and context with respect to the objective of the review. The methodological quality of the seven systematic reviews identified was appraised using the AMSTAR checklist. Results The use of CT as a first-line screening tool for COVID-19 is not beneficial. Nevertheless, for patients with suspected COVID-19 pneumonia who had a false-negative RT-PCR results, cross-checking with CT and a repeated RT-PCR test is essential to avoid misdiagnosis. Chest CT offered high sensitivity for detecting COVID-19 pneumonia among symptomatic individuals, especially in those with severe disease. It was also useful for evaluating the potential complications, disease severity, and progression of COVID-19 pneumonia. The features of CT images differed at the early, intermediate, and late stages of COVID-19 pneumonia, but the most common imaging findings were patchy and ground glass opacities. It was also found that diagnosing COVID-19 in children using CT is challenging. Conclusions Even though chest CT is not useful for primary screening of COVID-19, it is useful for detecting later stage disease and for evaluating patients with COVID-19 pneumonia. For patients with suspected COVID-19 pneumonia and a false negative RT-PCR result, cross-checking with a chest CT and a repeat RT-PCR test is essential to avoid misdiagnosis.

Poster Presentation Number: PP57 Abstract Title: Collaborating In Times Of COVID: The Launch Of The National Wales COVID-19 Evidence Centre Author Names: Lauren Elston ([email protected]), Thomas Winfield, Jenni Washington, David Jarrom, Susan Myles, Ruth Lewis, Alison Cooper, Micaela Gal, Adrian Edwards Introduction The COVID-19 pandemic has had a dramatic impact on the health and social care landscape, both in terms of service provision and citizen need. Responsive, evidence-based research is essential to develop and implement appropriate policies and practices that manage both the pandemic itself, and the impact COVID-19 has on other health and social care issues. To address this, the Wales COVID-19 Evidence Centre (WCEC) was launched in 2021 with the aim of providing the best available, up-to-date, and relevant evidence to inform health and care decision making across Wales. Methods Funded by the Welsh Government, the WCEC comprises of a core team and several collaborating partner organizations, including Health Technology Wales, Wales Centre for Evidence-Based Care, Specialist Unit for Review Evidence Centre, SAIL Databank, Public Health Wales, Bangor Institute for Health & Medical Research in conjunction with Health and Care Economics Cymru, and the Public Health Wales Observatory. Over the last year, WCEC has developed its rapid review processes and methodology informed by best international practice and aims to provide around 50 reviews each year. WCEC works alongside various stakeholder groups from health and social care across Wales, and they form an integral part of the review process, from scoping to knowledge mobilization. Results To date, the WCEC has produced reviews on a diverse range of COVID-19 topics, including transmission, vaccination uptake (barriers, facilitators and interventions), mental health and wellbeing, as well as face coverings and other preventative interventions. The topics have also covered a wide range of populations, from general public, to healthcare workers, to children. These reviews have been used to inform policy and decision- making, including the Welsh Government’s Chief Medical Officer 21-day COVID-19 reviews. Conclusions The WCEC has brought together multiple specialist centers with a diverse range of skills to produce timely reviews of the most up-to-date research to support decision makers across health and social care. These reviews have informed policy and decision-making across Wales.

Poster Presentation Number: PP58 Abstract Title: SARS-CoV-2: A Rapid Review Of The Transmission Risk From Vaccinated Populations Author Names: Sasha Barrate ([email protected]), Lauren Elston, Katie McDermott, Jenni Washington, Elise Hasler, David Jarrom, Charlotte Bowles, Jessica Williams Tom Winfield, Susan Myles Introduction Since the vaccine roll out, research has focused on vaccine safety and efficacy, with large clinical trials confirming that vaccines are generally effective against symptomatic COVID-19 infection. However, breakthrough infections can still occur, and the effectiveness of vaccines against transmission from infected vaccinated people to susceptible contacts is unclear. Health Technology Wales (HTW) collaborated with the Wales COVID-19 Evidence Centre to identify and examine evidence on the transmission risk of SARS-CoV-2 from vaccinated people to unvaccinated or vaccinated people. Methods We conducted a systematic literature search for evidence on vaccinated people exposed to SARS-CoV-2 in any setting. Outcome measures included transmission rate, cycle threshold (Ct) values and viral load. We identified a rapid review by the University of Calgary that was the main source of our outcome data. Nine studies published following the rapid review were also identified and included. Results In total, 35 studies were included in this review: one randomized controlled trial (RCT), one post-hoc analysis of an RCT, 13 prospective cohort studies, 16 retrospective cohort studies and four case control studies. All studies reported a reduction in transmission of the B.1.1.7 (Alpha) variant from partial and fully vaccinated individuals. More recent evidence is uncertain on the effects of vaccination on transmission of the B.1.617.2 (Delta) variant. Overall, vaccine effectiveness in reducing transmission appears to increase with full vaccination, compared with partial vaccination. Most of the direct evidence is limited to transmission in household settings therefore, there is a gap in the evidence on risk of transmission in other settings. One UK study found protection against onward transmission waned within 3 months post second vaccination. Conclusions Early findings that focused on the alpha variant, showed a reduction in transmission from vaccinated people. There is limited evidence on the effectiveness of vaccination on transmission of the Delta variant, therefore alternative preventative measures to reduce transmission may still be required.