HTAi 2022 Annual Meeting Oral Presentation Abstract Book

Oral Abstracts Lifecycle Approach: Coming Together to Make it Happen

Oral Presentation Number: OP01 Abstract Title: Convergent Validity Between Discrete Choice Experiment And Other Stated Preference Methods: A Multistudy Comparison Author Names: Jorien Veldwijk ([email protected]), Tommi Tervonen, Esther de Bekker-Grob, Brett Hauber, Catharina G.M. Groothuis-Oudshoorn Introduction To assess convergent validity of stated preference methods in studies where they were used to elicit patient preferences for informing medical product decisions. Methods In four studies, two stated preference methods were used to elicit preferences of patients with neuromuscular diseases (NMD; n = 140, Discrete Choice Experiment [DCE] and Best-Worst Scaling [BWS] case 2), diabetes (n = 495, DCE and swing weighting [SW]), myocardial infarction (MI; n = 335, DCE and BWS case 1), and rheumatoid arthritis (RA; n = 982, DCE and probabilistic threshold technique [PTT]). In each study, results of the two methods were compared using a normalized preference measure for which confidence intervals (CIs) were estimated using nonparametric bootstrapping of 500 samples. Normalized preference measures comprised of mean relative attribute importance weights (NMD and diabetes studies), attribute uptake probability (MI study), or maximum acceptable risk (RA study). Results In all four studies, attribute ranking showed similar patterns between DCE and other methods for the most important attributes. The same attribute had highest importance in three out of four studies. Significant differences were found in ranges of normalized preference measures of each study between DCE and the other methods: 4.1–43.4 versus 8.9–24.7 for DCE and BWS case 2 in NMD; 3.8–49.7 versus 11.9–16.8 for DCE and SW in diabetes; 2.0–85.5 versus 0.2–69.0 for DCE and BWS case 1 in MI; -3.5–49.2 versus 1.1–18.1 for DCE and PTT in RA. Conclusions Preferences differed significantly between DCE and other preference methods implying limited convergent validity. The substantially larger ranges in normalized outcome measures in DCE compared to other methods, are likely due to differences in mechanics and bias related to the methods. Since none of the methods is considered the golden standard for measuring stated preferences as true preferences are unknown, further studies are necessary to compare stated preference methods, determine internal validity and data quality, and potentially measure external validity.

Oral Presenta�on Number: OP02 Abstract Title: The Use Of Discrete Choice Experiments For Measuring Patient Preferences In Health Technology Assessment Author Names: Michael Strauss ([email protected]), Gavin George, Yael Hirsch-Moverman, Joanne Mantell, Miriam Rabkin, Elizabeth Kelvin Introduction Understanding patient preferences and the demand for healthcare interventions and technology is critical for health technology assessment (HTA). New health technologies have potential for savings and increased efficiency but even the most cost-effective and efficacious interventions can fail if patient preferences are not properly accounted for. Patient preferences in HTA are primarily limited to representation in appraisal committees; however, more robust methods are available and should be incorporated into the assessment of interventions. Methods Using data from three discrete choice experiments (DCEs), we reflect on the importance of patient preferences in the design of healthcare interventions. We draw insights from three studies which investigated preferences relating to HIV self-testing amongst long distance truck drivers in Kenya; differentiated antiretroviral therapy services amongst stable HIV patients in Zimbabwe; and tuberculosis preventive therapy for children in Eswatini. Results We highlight three key findings. First, understanding patient preferences is crucial when designing services, and providers sometimes underestimate behavioural barriers and overestimate the extent to which people are motivated simply by health benefits. Optimism is often driven by evidence showing high acceptability, but when preference structures are incorporated in intervention design, there are important insights into how patients plan to utilise services. Second, trade-offs matter in determining which characteristics are perceived to be most important to patients – a key strength of the DCE methodology. Understanding of these trade-offs can help prioritise which characteristics of interventions to target. Finally, disentangling the effect of different characteristics of service delivery models on preferences is important for rethinking how interventions are delivered. If services are designed to better align with preferences, implementers can ensure new interventions have the desired effect on health and economic outcomes. Conclusions These findings highlight the value of behavioural economic approaches for investigating preferences for health interventions and providing insights into the demand for services, which must feed into the HTA analyses. Incorporating DCEs into HTA is inexpensive and provides robust data for improving HTA.

Oral Presentation Number: OP03 Abstract Title: Patient Characteristics Affect Their Treatment Choice: A Discrete Choice Experiment With Breast Cancer Patients In Six European Countries Author Names: Eugena Stamuli ([email protected]) Sorcha Corry, Petter Foss Introduction The evolution of breast cancer treatments over the last decade has resulted in tailored therapies for the different types and stages of breast cancer. Each treatment has a profile of benefits and adverse effects which are taken into consideration when planning a treatment pathway. The objective of this study is to examine whether patients’ preferences are in line with what is considered important from policy-makers viewpoint. Methods An online discrete choice experiment (DCE) was conducted in six European countries (France, Germany, Ireland, Poland, Spain, UK) with breast cancer (BC) patients. The DCE comprised of six attributes: overall survival (OS), hyperglycaemia, rash, pain, functional well-being (FWB) and out-of-pocket payment (OOP). 16 choice sets with two hypothetical treatments and a “no treatment” option were presented. Sociodemographic and disease related data were collected. Heteroscedastic conditional and mixed logistic models accounted for scale and preference heterogeneity between countries and patients respectively. Latent class analysis categorized patients in classes. Marginal rates of substitution (MRS) were estimated for OOP versus the rest of attributes to establish the ranking of preferences for each attribute. Results Two hundred and forty-seven patients with advanced or metastatic BC and 314 with early-stage BC responded. Forty-nine percent of patients were less than 44 years old and 65 percent had completed university education. The MRS of the analysis demonstrated that “severe pain” is the highest dis-preferred attribute level, followed by “severe impairment in FWB” and OS. Four classes of patients as “decision-makers” were identified. Additionally, there is sensitivity in preferences for both levels of pain and FWB depending on the stage of the disease. Conclusions This study suggests that there is heterogeneity in treatment preferences of breast cancer patients depending on their sociodemographic and disease related characteristics. In combination with clinical guidelines, patient preferences can support the selection and tailoring of treatment options.

Oral Presenta�on Number: OP04 Abstract Title: Methodological Challenges Of Assessing An Evolving Technology: The Cochlear Implant For Deaf People Author Names: Hugo Nijmeijer ([email protected]), Hans Groenewoud, Emmanuel Mylanus, André Goedegebure, Wendy Huinck, Gert Jan van der Wilt Introduction When Cochlear implants (CI) were first introduced, only postlingually, profoundly hearing impaired individuals were implanted unilaterally. As experience grew, eligibility was followed by prelingual deaf children, and a second contralateral CI was being considered. Due to surgical and technological improvements, eligibility criteria for CI are now shifting, encompassing patients with more residual hearing. We aimed to explore, ex ante, whether such shift is warranted. Methods A dynamic, population-based Markov modeling study was conducted. Model parameters were based on available evidence, expert opinion, and calibration. The model mimics Dutch demographic development in three age categories over a period of 20 years. Impact of changing eligibility was explored in terms of number of CI recipients, costs, quality of life and cost-effectiveness from a societal perspective. Results If those with severe hearing loss would qualify and opt for CI similar to those with profound hearing loss, this would lead to a fourfold increase of CI recipients (from 8,815 to 35,630) over a 20 year period, resulting in an increase in costs (EUR 550 million) and QALYs (54,000), with an Incremental Cost Utility Ratio of EUR 10,771/QALY (2.5–97.5 percentiles: 1,252–23,171). Conclusions Results suggest that expected health gains could be such, that the investment may be considered cost- effective against the backdrop of currently prevailing criteria. However, for this, a substantial increase in operating capacity, follow-up care and rehabilitation are required. Further inquiries are needed to investigate whether such increased capacity can be achieved, to ensure equitable access to those services.

Oral Presentation Number: OP05 Abstract Title: The Role Of Conditional Reimbursement In The Lifecycle Approach Author Names: Hedi Schelleman ([email protected]), Simone van Montfort, Lenneke Sicking, Daniëlle Haasnoot-Volker Introduction In 2012, the Netherlands introduced a conditional reimbursement (CR) program to give patients earlier access to promising treatments (i.e., drugs and medical devices). After completion of the CR-study the results are used to (re)assess whether the treatment fulfills the criteria for reimbursement. Methods Promising treatments were identified via a bottom-up (physicians/researchers initiated) or top-down process (after the Dutch National Health Care Institute (Zorginstituut Netherland; ZIN) concluded that the intervention did not fulfill the criteria for reimbursement but the initial results seemed promising). A CR- grant was only approved if a committee determined the treatment had an added (health, social, ethical or organizational) benefit compared to Standard of Care (SoC) and the grant proposal was of good quality and fit for purpose. After approval from the Dutch Ministry of Health, all Dutch insurance companies were obliged to reimburse the treatment for patients participating in the CR-study. Researchers could also apply for a research grant (maximum EUR 400,000) from the Netherlands Organization for Health Research and Development (ZonMw), if there was no ‘wealthy’ manufacturer. Results Currently, there are 23 (ongoing and completed) CR-studies. All of them are closely monitored by ZIN, ZonMw, and stakeholders. The results of all completed CR-studies (n = 11) have been used in a (re)assessment. ZIN concluded that five treatments were not effective compared to SoC. Six interventions were effective and cost-effective compared to SoC and are now reimbursed. In most cases (>80%) the physician and patient groups agreed with the conclusion about reimbursement. In some cases there were additional requirements to maintain the clinical effectiveness and cost-effectiveness in clinical practice (such as training of new physicians). Conclusions Data from CR-studies are important for reassessments. Factors with a posi�ve influence are: a maximum dura�on for a CR-study, close monitoring, possibility to adapt the study design (only with approval from ZIN and ZonMw), and ac�ve involvement of stakeholders (physician and pa�ent groups). A nega�ve influence was: the legal requirements to ensure only reimbursement for pa�ents par�cipa�ng in a CR-study.

Oral Presentation Number: OP06 Abstract Title: Percutaneous Transforaminal Endoscopic Discectomy: From Insufficient Evidence To Reimbursement Author Names: Hedi Schelleman ([email protected]), Ingrid de Groot, Daniëlle Haasnoot-Volker, Petra Jellema Introduction The standard surgical technique for lumbosacral radicular syndrome in the Netherlands is open microdiscectomy (OM). An alternative technique, preferred by some Dutch physicians, is percutaneous transforaminal endoscopic discectomy (PTED). However, in 2006 the Dutch National Health Care Institute (Zorginstituut Netherland [ZIN]) concluded that the available evidence was insufficient, and a high quality randomized controlled trial (RCT) was needed to assess the cost-effectiveness of PTED compared to OM. The relevant physician group agreed with this conclusion, but they were unable to perform this RCT due to lack of funding and high treatment costs. Methods In 2012, the Netherlands introduced a conditional reimbursement (CR) program to give patients earlier access to promising treatments. Researchers, in collaboration with physicians and patients, submitted a grant proposal and in 2016 the Dutch Ministry of Health approved the CR of PTED. Due to this decision, insurance companies were obliged to reimburse PTED for patients participating in the PTED-study (NCT02602093). The Netherlands Organization for Health Research and Development (ZonMw) also provided a research grant to fund the PTED-study. In total, 682 adult patients with greater than 10 weeks of radiating pain, or greater than 6 weeks of excessive radiating pain and an indication for surgery were included. After 4 years and 5 months the PTED-study was completed. Results Outcomes of published studies and the unpublished PTED-study were used in the HTA reassessment. Results showed that PTED was noninferior to OM with regards to leg pain (Visual Analogue Scale: mean difference (MD) -0.73; 95% confidence interval [CI] -5.04, 3.59), functional status (Oswestry Disability Index: MD -2.07; 95% CI -3.61, -0.53), and rate of complications (relative risk 0.45; 95% CI 0.18, 1.12) after 6 months (GRADE level ‘moderate’). Furthermore PTED was, after the surgeons’ learning-curve, cost-effective. Conclusions This CR project was successful and PTED is now reimbursed as part of the Dutch healthcare package. However, in order to maintain high quality care in clinical practice, safeguards should be developed (including the appropriate training of surgeons). This example shows that CR programs are essential for promising treatments without ‘wealthy’ manufacturers. Additionally, all stakeholders are needed to make a CR-study successful.

Oral Presentation Number: OP07 Abstract Title: Dealing With Uncertainty In Early Health Technology Assessment: An Exploration Of Methods For Decision-Making Under Deep Uncertainty Author Names: Mirre Scholte ([email protected]), Vincent Marchau, Jan Kwakkel, Maroeska Rovers, Janneke Grutters Introduction In early stages, the consequences of innovations are often unknown or deeply uncertain. This complicates health economic modelling. The field of decision-making under deep uncertainty (DMDU) uses exploratory modelling (EM) to help decision-makers make sound decisions under conditions of deep uncertainty (i.e. when stakeholders do not know, or cannot agree on, the system model, the probability distributions to place over the inputs to these models, which consequences to consider, and their relative importance). The aim of this research was to evaluate the potential of EM for the early evaluation of health technologies. Methods EM and early health economic modelling (EHEM) were applied to an early evaluation of minimally invasive surgery (MIS) for acute intracerebral hemorrhage, and were compared to derive differences, merits, and drawbacks of EM. Results The approaches fundamentally differ in the way uncertainty is handled. Where in EHEM the focus is on the value of the technology, while accounting for the uncertainty, EM focuses on the uncertainty. EHEM aims to assess whether the innovative strategy is potentially cost-effective, often using assumptions. EM on the other hand focuses on finding robust strategies (i.e., strategies that give relatively good outcomes over a wide range of plausible futures). This was also reflected in our case study. For example, EHEM provided cost- effectiveness thresholds for MIS effectiveness, assuming fixed MIS costs. EM showed that a strategy with a population in which most patients had severe intracerebral hemorrhage was most robust, regardless of MIS effectiveness, complications, and costs. Conclusions EM seems most suited in the very early phases of innovation (i.e., when a problem is signaled). Here, it can explore the robustness of many potential strategies under uncertainty. When potential strategies are selected, EHEM seems useful to optimize these strategies. Yet, EM methods are complex and might only be fully effective when a policy window exists that facilitates flexible research and adoption strategies.

Oral Presenta�on Number: OP 08 Abstract Title: Early Access To New Direct-Acting Antiviral: A Journey On Introduction Of Ravidasvir For Hepatitis C Treatment In Malaysia Author Names: Nazatul Syima Idrus ([email protected]), Faridah Aryani Md Yusof, Rosliza Lajis Introduction Access to affordable direct-acting antiviral (DAA) remains limited in developing countries, often due to high treatment cost. This study aimed to elaborate the initiatives taken by the Ministry of Health Malaysia (MoHM) to provide early access to ravidasvir, a new DAA for hepatitis C treatment, in Malaysia. Methods MoHM collaborated with Drugs for Neglected Diseases initiative (DNDi) to develop ravidasvir, a new chemical entity of oral non-structural protein 5A (NS5A) inhibitor. MoHM co-sponsored and participated the DNDi-led Phase II/III study (STORM-C-1 trial) to assess the efficacy and safety of ravidasvir-sofosbuvir combination therapy. Agreement was signed between Pharmaniaga, Pharco Pharmaceuticals and DNDi to register and supply affordable hepatitis C treatment in Malaysia and South-East Asia. MoHM and Pharmaniaga mutually worked on the registration of ravidasvir in Malaysia. Series of pre-submission meetings took place, rolling submission was allowed and conditional registration pathway was used. As a separate initiative, MoHM partnered with the Foundation for Innovative New Diagnostics (FIND) to implement decentralization and test- and-treat strategies for screening of hepatitis C virus (HCV). Results First stage of the STORM-C-1 trial reported that the combination of ravidasvir-sofosbuvir was highly effective across all genotypes and safe. The Drug Control Authority (DCA) Malaysia has granted a conditional registration for ravidasvir hydrochloride 200mg tablet (Ravida®) in June 2021, making Malaysia as the first country in the world to approve ravidasvir. Registration process expedited and took place within 15 months. The supply of Ravida® in Malaysia is expected in near future. Meanwhile, MoHM also implemented nationwide HCV screening using rapid diagnostic test kit in private hospitals, community clinics, prisons and rehabilitation centers which previously was done only in hospitals for outreach to the targeted group. Conclusions Ravidasvir-sofosbuvir has potential as a tool to eliminate hepatitis C in Malaysia by 2030, the WHO’s global elimination targets. This alternative new drug development model was successful due to strong leadership, public-private partnership and collaborative strategies. This could also be exercised in other disease area.

Oral Presenta�on Number: OP10 Abstract Title: Outcomes Of Expanded Access To Transcatheter Aortic Valve Implantation In Ontario: A Model-Based Analysis Author Names: Rafael N Miranda ([email protected]), John Peel, David Naimark, Harindra Wijeysundera Introduction Transcatheter aortic valve implantation (TAVI) is a minimally invasive therapy for patients with severe aortic stenosis. In Ontario, increases in capacity have not matched the rapidly growing demand for TAVI. As a result, wait-times for TAVI in Ontario exceed guideline targets, and waitlist morbidity is consequently considerable. The objective of this study was to evaluate the clinical implications of expanded TAVI capacity. Methods We performed a decision analysis using an open, parallel, resource-constrained microsimulation from the Ontario Ministry of Health perspective. Simulated patients entered the model during a five-year period, and stayed in the model until death or end of time horizon. Referral numbers increased annually according to historical trends. The additional capacity required to meet wait-time benchmarks in five years was identified by a sensitivity analysis. Clinical outcomes were estimated for three strategies: (i) current practice with annual capacity increases; (ii) accelerated capacity increases achieving benchmarks after five years; and (iii) no increase in capacity. Outcomes included pre-procedural mortality and hospitalization, and the proportion of TAVIs performed urgently. Results Over the five years, we estimated that TAVI referrals would increase from 1,980/year to 3,268/year. To achieve wait-time benchmarks during this period, TAVI rates must be increased by approximately 6.3 percent annually, for a total of 12,220 procedures performed over the 5 years. Compared to current TAVI capacity increase, an accelerated increase in capacity achieving wait-time benchmarks led to a reduction of 29.36 percent in pre-procedural deaths, as well as 26.38 percent in pre-procedural hospitalizations and 30.31 percent in nonelective TAVIs. Conclusions Increases in TAVI capacity in Ontario must be accelerated to meet wait-time benchmarks in five years. Expansion of TAVI care in Ontario would be associated with considerable reductions in mortality and hospitalizations. Without intervention, both wait-times and adverse outcomes on the waitlist are expected to continue increasing. Prioritization strategies to mitigate the adverse effects of long wait-times must be used until wait-time targets are achieved.

Oral Presentation Number: OP11 Abstract Title: Differences And Similarities In Past Health Technology Assessments In Beneluxa Initiative Countries Author Names: Rick Vreman ([email protected]), Daan van Hoof, Roisin Adams, Marc van de Casteele, Anna Nachtnebel, Lonneke Timmers Introduction Conducting joint health technology assessments (HTA) is one of the main goals of the Beneluxa Initiative. To strengthen this collaboration, this study aimed to assess similarities and differences between past assessments of Beneluxa Initiative member countries (Austria, Belgium, Ireland and the Netherlands). Methods A retrospective comparative analysis was performed that investigated the similarities and differences in drug assessments in the period 2016 to 2020 in (i) the number and type of assessed indications; (ii) the conclusions within assessments performed by at least two member countries; and (iii) the main arguments leading to the conclusions through a qualitative analysis of selected cases, looking into the patient population, the intervention, comparator, outcome, timing, and included evidence. Results The scope of HTA differs between the countries, with Belgium and Ireland assessing most, the Netherlands focusing on drugs above a budget impact threshold and Austria on outpatient drugs. Furthermore, indications might slightly differ between countries. Therefore, only 44 (10%) of the 444 included drug- indication combinations were assessed through a full HTA by all four countries. Between any pair of countries, the overlap was higher, from 63 (Austria-the Netherlands) to 188 (Belgium-Ireland). Added benefit conclusions matched exactly in 62 to 76 percent of the indications, depending on the compared countries. In the remaining cases, often a difference of one added benefit level was observed (e.g., higher versus equal relative effect). Contradictory outcomes were very rare. Differences were observed with regards to whether a cost-effectiveness analysis was performed. When assessing the underlying arguments within the reports for nine cases with different outcomes, it became clear that organizations agree on almost all aspects, and that differences are mostly attributable to slight differences in weighing of some aspects and uncertainties. Conclusions Overall, which indica�ons are assessed differs, but for those indica�ons that are assessed by mul�ple member countries, considera�ons and assessment outcomes are similar.

Oral Presentation Number: OP12 Abstract Title: Post-Launch Evidence Generation Among Health Technology Assessment Bodies In Europe Author Names: Leonor Varela Lema ([email protected]), Janet Puñal-Riobóo, Chantal Guilhaume, Maggie Galbraith, Chantal Bélorgey, Maria José Faraldo Vallés, Amélie Meillassoux Amélie Introduction The need for timely access to innovative technologies has placed a special focus on the development of policies and practices that can guarantee the availability whilst ensuring the safety of these technologies after launch or licensure. The aim of this paper is to present and discuss Post-Launch Evidence Generation (PLEG) practices among health technology assessment (HTA) bodies at the European level to explore cross- border collaboration opportunities. Methods In December 2019, a survey composed of nine closed-ended questions with multiple choice answers about the PLEG practices in each country was sent to 25 partners of the European Network of Health Technology Assessment (EUnetHTA) Joint Action 3. In addition to the survey, the national practices were discussed during a face-to-face meeting with all partners of the dedicated work package. A quantitative analysis and a qualitative synthesis of the results was carried out. Results Twelve HTA bodies completed the survey. Of these, 11 reported procedures in place for official PLEG requests. In nine of the agencies, the requests are made at the time of the assessment/appraisal. Data collection and analysis mainly lies with companies for pharmaceuticals (60%) while it is more the responsibility of the HTA body for medical devices (75%). Only one agency reported owning the data and being able to exchange the data without asking permission. During the face-to face discussions, it was acknowledged that PLEG practices differ between countries depending on the topic concerned, but most rely on the usage of registries (mainly disease registries) for data collection. Most agencies estimated that a European collaboration could take place. Conclusions PLEG practices are in the remit of many European HTA bodies. Data sharing should be anticipated as only some own the data and can exchange them without asking permission. European collaboration on PLEG could commence once the evidence gaps have been defined or during the production of the HTA reports in the case of joint assessments.

Oral Presentation Number: OP 13 Abstract Title: EUnetHTA Relative Effectiveness Assessments Of Pharmaceutical And Other Technologies: Procedural Changes Implemented During Joint Action 3 Author Names: Sabine Ettinger ([email protected]), Anne Willemsen, Judit Erdos, Catharina Helmink, Krystyna Hviding, Sari Susanna Ormstad Introduction The European Network for Health Technology Assessment (EUnetHTA) Joint Action 3 (JA3) aimed to develop a sustainable European model for scientific and technical collaboration on HTA. It succeeded EUnetHTA JA2, which focused on strengthening practical applications of approaches and tools in the European HTA collaboration. Compared to JA2, several changes in procedures and processes were undertaken throughout JA3 in order to improve the different steps in joint HTA production. Methods Findings and identified challenges regarding the assessment production processes from JA2 were considered as a basis. In JA3, vast majority of structured and informal feedback was gathered from the assessment teams and project managers via feedback surveys and meetings. Only limited informal feedback from stakeholders (such as patients, health care professionals, and health technology developers) that were involved in EUnetHTA assessments was collected. To this end, experiences were documented and recommendations for a future production process were developed. Results During the course of JA3, the joint production resulted in 16 pharmaceutical assessments and 27 assessments of other technologies. The latter included medical devices, diagnostics, interventions, and screening. Due to the different context of pharmaceuticals and other technologies, some technology-specific changes needed to be made in their production process. However, the majority of implemented changes were made for both types of technologies to ensure maximum possible alignment in processes. The implemented changes affected several steps in the production process as well as the involvement of stakeholders in EUnetHTA assessments. The production and related project management of assessments was fine-tuned and resulted in clearer, standardised, and comprehensible processes that facilitated transparency and inclusiveness. Conclusions The procedural changes led to further standardisation and elaboration of assessment production processes in preparation for a future European HTA system under the EU HTA Regulation. However, some methodological challenges remained to be tackled further in the currently ongoing EUnetHTA 21 service contract.

Oral Presentation Number: OP14 Abstract Title: Involving People With A Lived Experience When Developing A Proposed Health Technology Assessment Of Pelvic Organ Prolapse Treatments Author Names: Eugenie Johnson ([email protected]), Fiona Pearson, Joanne Lally, Allison Farnworth Introduction Patient and public involvement (PPI) is an expectation when conducting a health technology assessment (HTA), but there is little guidance for those wishing to embed PPI when developing an HTA proposal. We wanted to ensure PPI was central in preparing a proposal for an HTA potentially of any intervention for pelvic organ prolapse (POP) in women. Methods We conducted an open process to recruit two PPI co-applicants who, after induction to the project, were jointly responsible for governance of PPI in partnership with the PPI Lead throughout project planning. We facilitated an online workshop with the PPI co-applicants and other women with a lived experience of POP to: develop our question and scope; decide interventions and outcomes for the evidence synthesis; discuss the care pathway for the economic evaluation component; and plan dissemination. The PPI co-applicants were encouraged to comment on the full proposal, while workshop attendees were invited to comment on the plain language summary. Our work adhered to United Kingdom (UK) Standards for Public Involvement. We obtained funding to facilitate PPI within the proposal and reimburse those with lived experience for their time. Results Involving the co-applicants and workshop participants strengthened the HTA proposal by: solidifying the rationale based on lived experience; adding interventions to our evidence synthesis not previously considered; and highlighting dissemination outlets that appealed to the public. Comments on the full proposal and plain language summary ensured the proposal was accessible. However, we were unable to discuss everything we originally planned even though researcher time spent on embedding PPI into the proposal was substantial. Conclusions Including PPI can be valuable for developing HTA proposals. However, research is required to explore the appropriate level of involvement at the HTA proposal stage, particularly given the large amount of researcher time and additional resource needed to incorporate meaningful PPI.

Oral Presentation Number: OP15 Abstract Title: Improving The Osteoporosis Care Trajectory By Collaboration Between Clinicians, Patients And Health Insurers Within the Appropriate Care Program Author Names: Iris Groeneveld ([email protected]), Janneke Witteveen, Saskia Boonzajer-Flaes, Pé Mullenders, Celine Leenen Introduction The cyclic appropriate care program of the National Health Care Institute aims at enhancing quality of care in the Netherlands. A full cycle consists of four phases: (i) screening each ICD-10 chapter and selecting a care trajectory, (ii) in-depth analysis of the care trajectory and formulating actions for improvement, (iii) implementation, and (iv) evaluation. Collaboration with and between relevant parties from the field is key to its success. We describe the 2nd and 3th phase of this cycle, aimed at osteoporosis. Methods First, nine clinicians, one nurse practitioner, two physiotherapists and one pharmacist representing scientific organisations, two patient representatives and one health insurer, defined research questions. Second, by in- depth analysis on declaration data of health care activities, and comparing the results to the guidelines, research questions were addressed. Last, results were discussed among all parties and actions for making wiser choices and improving the appropriateness of care were formulated. For each action, the parties defined who would take the lead and who would be involved. Results The analyses showed that only 26 percent of Dutch fracture patients 50 years of age and above underwent dexa-scanning, as opposed to more than 80 percent in the guideline. All parties underlined this percentage should be increased. Possible actions were defined: to describe the care trajectory in the update of the multidisciplinary guideline; to better inform fracture patients about the importance of dexa-scanning; and to make adjustments to the hospital electronic system in order to facilitate the ordering of dexa-scans. For these actions, medical specialists were in the lead. Other data-analyses showed that half of osteoporosis patients stopped using medication within two years. For the jointly defined actions aimed at raising medication adherence, such as better patient education, the general practitioner and pharmacist were in the lead. Currently, the National Health Care Institute facilitates implementation and monitors improvement. Conclusions Close collaboration with relevant parties led to well-considered actions on improvement of osteoporosis care.

Oral Presenta�on Number: OP16 Abstract Title: Learning From Engagement With Human Immunodeficiency Virus Community Organisations In The Health Technology Assessment Lifecycle Author Names: Laura Marsden ([email protected]), Heidi Livingstone, Mandy Tonkinson Introduction Involving patients and community organisations in the health technology assessment (HTA) lifecycle is a core principle at the National Institute for Health and Care Excellence (NICE) and helps build public confidence in the healthcare decision-making. From 2019 to2021 NICE assessed a HIV-1 medicine for the first time. This presented new opportunities and challenges for engaging with Human Immunodeficiency Virus (HIV) community organisations who hadn’t participated in a NICE HTA before. To understand their experience, we collected feedback on the impact and experience of community involvement throughout the assessment. Methods We used a mixed-method approach using a survey and qualitative feedback from the committee lay member, community experts, and the community organisations. An impact survey was sent to key committee members, the NICE technical team and Associate Director. It included Likert scale questions and open text boxes to capture both quantitative and qualitative data. Additionally, qualitative feedback was gathered throughout the assessment’s lifecycle from the NICE team and the community stakeholders. Results Results from the impact survey showed that the community input: had significant impact on the evaluation (100% (n=5)); helped interpret the other evidence and information (80% (n=4)); provided new evidence (60% (n=3)); and, was consistent with the other evidence (40% (n=2)). Examples of impact included highlighting the population heterogeneity, stigma, side effects and the effects of frequent clinic attendance. The key feedback from the qualitative data from the community organisations and experts in terms of their experience were: early support and support throughout from the NICE team; NICE’s flexibility in involving them; and, meaningful inclusion of their evidence in the committee slides. Conclusions Both the NICE committee and the community stakeholders recognised that the community input was valued and had an impact on the decision-making. To ensure meaningful community engagement, support and flexibility from NICE were required throughout the assessment. This level of engagement will be adopted in future for community organisations new to medicines HTAs at NICE.

Oral Presentation Number: OP17 Abstract Title: Robotic Versus Conventional Surgery: An Overview Of Systematic Reviews For Clinical Effectiveness With Quality Assessment Of Current Evidence Author Names: Tzujung Lai ([email protected]), Janet Bouttell, Kathleen Boyd Introduction Robot-assisted surgery (RAS) is being adopted rapidly internationally across a wide range of surgical procedures. Although a great deal of evidence of the clinical effectiveness of RAS has been generated, it is possible that the evidence base is not complete or persuasive in some areas where adoption is being considered. This review seeks to summarize systematic reviews (SRs) undertaken to date to illustrate the weight of evidence across specialties. We then take an in depth look at the quality of evidence across several indications where the adoption of RAS is currently underway. Methods A comprehensive literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of Systematic Reviews from January 2017 to April 2021 for SRs describing clinical effectiveness outcomes. The body of evidence was mapped across all specialties. For a selected number of indications currently under consideration in Scotland, results were comparatively summarized, and the quality of the reviews was evaluated with the AMSTAR-2 tool. Results A total of 451 SRs were found. Most were in urology (n = 130) where RAS is well established, followed by colorectal (n = 63), hepatology (n = 58), and gynecology (n = 41). From within these latter three specialties, we selected six indications in which RAS is currently being considered for adoption in Scotland for in depth review (colorectal cancer surgery, hysterectomy, gastrointestinal oncological resection, hepatic, pancreatic and biliary surgery). Evidence for the clinical effectiveness of RAS versus conventional laparoscopic surgery is mixed across indications and outcomes. In colorectal cancer surgery, for example, evidence was positive for conversion rate and neutral for length of hospital stays, blood loss and postoperative complication and negative for operative time. For hysterectomy, evidence was positive for the length of hospital stays and neutral for operative time, blood loss, conversion rate and postoperative complication. The quality of the included reviews was judged to be critically low. Conclusions The currently available evidence of clinical effec�veness is mixed across indica�ons and of low quality.

Oral Presenta�on Number: OP18 Abstract Title: Clinical Effectiveness And Safety Of Implantable Bulking Agents For Faecal Incontinence: A Systematic Review Author Names: Lucia Gassner ([email protected]), Claudia Wild, Melanie Walter Introduction The purpose of this systematic review is to evaluate whether implantable versus injectable bulking agents (second-line therapies) are equal/superior in terms of effectiveness (severity, quality of life [QoL], sustainability) and safety (adverse events) for faecal incontinence (FI). Methods A systematic review was conducted and five databases were searched (Medline via Ovid, Embase, Cochrane Library, University of York Centre for Reviews and Dissemination, and International Network of Agencies for Health Technology Assessment database). In-/exclusion criteria were predefined according to the PICOS scheme. The Institute of Health Economics risk of bias (RoB) tool assessed studies' internal validity. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the strength of evidence for safety outcomes was rated. A qualitative synthesis of the evidence was used to analyse the data. Results Six prospective uncontrolled trials (143 patients) were included. The evidence consists of six prospective single-arm, before-after studies fulfilling the inclusion criteria for assessing clinical effectiveness and safety for implantable bulking agents. FI severity (Cleveland Clinic FI Score) statistically significantly improved to three months (p<0.01) and six months (p<0.05) follow-up (five studies). Improvements in severity sustainability were reported after 12, 14 (p<0.01), and 36 (p<0.0001) months postoperatively. Improved disease-related QoL (FI QoL Score) was found (p<0.05) 12 months after surgery, and statistically significant improvements in QoL's sustainability after 12 months (one study). Procedure-related adverse events (n=3) occurred, where prostheses extruded during surgery, and anal discomfort/pain was felt (n=11). Device-related adverse events, i.e., prostheses’ dislodgement (n=31) and removed/extruded prostheses (n=3), occurred. Studies were judged with moderate/high RoB. The strength of evidence for safety was judged to be very low. Conclusions Implantable bulking agents might be an effective and safe minimally invasive option in FI treatment if conservative therapies fail. FI severity significantly improved, but not QoL, which needs to be explored in further studies. Due to the uncontrolled nature of the case series, comparative studies need to be awaited.

Oral Presenta�on Number: OP19 Abstract Title: Comparative Effectiveness Of Common Treatment Options For Benign Prostatic Hyperplasia: A Systematic Review And Network Meta-Analysis Author Names: Sirikan Rojanasarot ([email protected]), Kurt Neeser, Shuai Fu, Samir Bhattacharyya, Kevin McVary Introduction Treatment options for men with moderate-to-severe lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) include medical therapy, minimally invasive surgical therapies (MISTs), and invasive surgical procedures. While these treatments are recommended by American Urological Association Guidelines, they have different clinical profiles impacting both efficacy and durability outcomes. Using an indirect comparison approach, this study assessed the clinical effects of combination therapy (CT) using alpha-blockers and 5-alpha reductase inhibitors, two emerging MISTs (prostatic urethral lift [PUL] and water vapor thermal therapy [WVTT]), and two invasive surgical procedures (photoselective vaporization of the prostate [PVP] and transurethral resection of the prostate [TURP]). Methods A systematic search of Medline, Embase, Cochrane Library, and relevant health technology assessment (HTA) databases was conducted to identify randomized and non-randomized clinical trials of the five treatments published prior to December 2020. Trials were included if they reported changes in International Prostate Symptom Score (IPSS) and retreatment rates, without any country or language restrictions. A random-effects network meta‐analysis (NMA) with an aggregate regression model was performed to account for the baseline BPH severity and characteristic differences among men from the different trials. Results A total of 237 of 3,104 retrieved abstracts were included for full-text review. Of these, 16 randomized and four non-randomized clinical trials were included in the NMA. The random-effects NMA showed among medical and minimally invasive therapies, WVTT had the greatest one-year IPSS improvement (-∆11.7), followed by PUL (-∆10.4) and CT (-∆10.3). The one-year IPSS improvement for TURP and PVP was comparable (-∆14.1 vs. -∆13.8, respectively; p-value=0.675). The one-year retreatment rates were lowest for WVTT (3.0%), followed by CT (3.6%), TURP (6.3%), PVP (7.8%), and PUL (8.0%). Conclusions WVTT provided greater clinical and durability benefits compared to other less invasive treatment options for men with BPH. Given NMA is increasingly used in HTA processes, this study provided systematically synthesized evidence that could facilitate decision-makers in determining new technology coverage decisions globally.

Oral Presentation Number: OP20 Abstract Title: Is The Quality Of Evidence In Health Technology Assessment Deteriorating Over Time?: A Case Study On Cancer Drugs In Australia Author Names: Yuan Gao ([email protected]), Mah Laka, Tracy Merlin Introduction Recently, there have been concerns regarding a trend toward poorer quality evidence being accepted by regulatory institutions and the consequent impact on health technology assessment (HTA) decision-making. This study aimed to determine whether there has been a change in the quality of evidence provided on cancer drugs proposed for listing on the Pharmaceutical Benefits Scheme, using data solely extracted from public summary documents (PSD) published by the Australian government. Methods PSDs published from July 2005–2020 were reviewed. Metrics associated with quality of evidence were extracted, including the directness of comparison, study design, sample size, and risk of bias (RoB). Additional data were extracted to provide greater context to any observed trends in quality of evidence. Analyses were performed across different time periods. Associations between the quality of evidence and time periods were explored using logistic regression analysis. Results In total, 214 PSDs were included in the analysis. Only 13 percent of submissions provided a single arm study or observational study as the key evidence; however, 37 percent of submissions did not contain a direct (‘head-to-head’) comparison relevant to Pharmaceutical Benefits Advisory Committee (PBAC) decision- making. Among all submissions containing direct evidence, about half had findings of a moderate/high/unclear RoB. Among all submissions containing indirect comparisons, over half had transitivity issues. In submissions containing direct comparisons, there was an increase in the RoB over time even after adjusting for trial data maturity and the rareness of the drug indication (odds ratio [OR] 1.30; 95% confidence interval [CI] 0.99, 1.70). There were no clear time trends observed in sample size, directness, study design, or transitivity issues during any of the observed time periods. Conclusions In the last 7 years, a high propor�on of cancer drug submissions presented findings with a high RoB and transi�vity issues. As the evidence dossiers provided to the PBAC are o�en congruent with submissions made elsewhere, this poor evidence quality is of concern and can only lead to higher levels of decision-maker uncertainty.

Oral Presentation Number: OP21 Abstract Title: A Critical Review Of Existing Health Inequality And Health Inequity Frameworks In Evidence Synthesis Author Names: Patience Kunonga ([email protected]), Barbara Hanratty, Pete Bower, Dawn Craig Introduction In recent years, there has been a growing recognition that health equity and health inequalities should be a consideration in all aspects of research. Since the Commission on Social Determinants of Health by the World Health Organization was established in 2005, there has been a growing interest in tackling systemic differences in health outcomes, including expanding the scope to health research including evidence synthesis and health technology assessments (HTA). This analysis aims to identify health inequality and health inequity frameworks that exist to help structure and plan research methods in evidence synthesis. Methods A critical analysis of the existing frameworks used in evidence synthesis to address health inequality and/or inequity was undertaken. Comprehensive, systematic searching of seven social science electronic databases and grey literature was undertaken based on the Behavior/phenomenon of interest, Health context and Model/Theory (BeHEMoTh) model, from 1990 to May 2022 to identify all relevant studies. A narrative synthesis approach was used to critically appraise the existing frameworks. Results Sixty-two reviews published between 2008 and 2022 reporting on using a framework to stratify health opportunities and outcomes met the inclusion criteria. Frameworks identified included the PROGRESS (place of residence, race or ethnicity, occupation, gender, religion, educational level, socioeconomic status, and social capital), PROGRESS-Plus (plus age, disability and sexual orientation) and Preferred Reporting Items for Systematic Reviews and Mata Analysis (PRISMA) – Equity checklist. Conclusions Currently, there does not seem to be consensus in how evidence of inequality or inequity in evidence synthesis or HTA are reported. As research interests in health inequality and inequity con�nue to grow, there is a need to develop a framework that provides an in-depth understanding of how inequali�es in health and inequi�es in health should be considered within evidence synthesis and HTA. This will allow researchers to analyze not just the effects of interven�ons, but also how healthcare outcomes are impacted by inequali�es or inequi�es.

Oral Presenta�on Number: OP22 Abstract Title: Using Threshold Analysis To Guide Searches For Additional Sources Of Evidence Author Names: Sumayya Anwer ([email protected]), Sofia Dias, Mark Simmonds, Emily South, Ros Wade, Alison Eastwood Introduction Threshold analysis is a novel statistical approach which can be used to investigate which direct comparisons in a network meta-analysis (NMA) have estimated relative effects that may not be robust to changes in the evidence, either due to possible bias, sampling variation, or relevance. Methods In a health technology assessment of the clinical effectiveness of ablative and non-invasive therapies for patients with early hepatocellular carcinoma (HCC), we conducted a threshold analysis to identify treatment comparisons that would be sensitive to changes in the randomized controlled trial (RCT) evidence used in the NMAs, potentially leading to a change in the recommended treatment. The results of the threshold analysis were used to guide a targeted systematic review of high-quality, non-randomised, prospective comparative studies that could strengthen the evidence for those comparisons identified as sensitive to change. Results We conducted NMAs of RCT evidence for four outcomes: overall survival (16 RCTs), progression-free survival (6 RCTs), overall recurrence (7 RCTs), and local recurrence (10 RCTs). The results of the NMAs displayed a high level of uncertainty, attributable to the sparse nature of the network, characterised by interventions being mainly compared in small trials. A targeted systematic review was conducted on relevant interventions that were identified as being sensitive to changes in evidence by the threshold analysis. The studies identified in this review were incorporated into a second NMA to support the RCT evidence. Conclusions Threshold analysis has been typically used as a tool to assess how robust comparisons in an NMA are to additional sources of evidence, but it can also be used to guide the search for additional non-randomised evidence when the available RCT evidence is sparse.

Oral Presenta�on Number: OP24 Abstract Title: Impact Of Patient Input On Cancer Drug Funding Recommendations In Canada Author Names: Wiesława Dominika Wranik, ([email protected]), Anh Thu Vo, Min Hu Introduction Patient involvement in health technology assessment (HTA) has documented advantages, such as improved understanding of disease context, and increased legitimacy and transparency of the HTA process. In the absence of clear metrics, thresholds, or criteria, it is not clear how input regarding patient preferences influences HTA based recommendations of the pan Canadian Oncology Drug Review (pCODR). Methods This is a concurrent complementary mixed methods study. A quantitative model (logit) is used to estimate the impact of patient input and other HTA criteria on pCODR recommendations. A qualitative analysis of semi-structured interviews with Canadian HTA committee members is used to describe the mechanisms of action through which patient input influences recommendations. Results Patient input was considered important in providing context to the HTA discussion, but committee members were not able to explicate how any specific elements of patient submissions weighted into the committee's recommendation. There was an element of mistrust in the patient input data. The estimated impact of patient input on funding recommendations is not statistically significant, recommendations remain driven by evidence of clinical benefit. Conclusions The commitment to inclusion of patient perspectives in HTA in Canada is strong, and procedurally Canada is among the leaders in this regard. The tangible impact of patient input could be increased with an improved system for collection of most relevant data, and clear guidelines about how patient input should weigh into HTA recommendations.

Oral Presentation Number: OP26 Abstract Title: Policy Perspectives Of Health Technology Assessment In Ethiopia Author Names: Desalegn Ararso ([email protected]) Introduction Health technology assessment (HTA) is defined as a multidisciplinary field of policy research that provides evidence on the consequences of adopting and using health technologies. A ministry of health with jurisdiction over HTA should determine the influence of public law on all HTA-related activities and the rules that apply. Therefore, health decision-makers interested in HTA must learn to navigate the legal system, starting by situating it in the legal apparatus of the country. As a result, establishing a national HTA system requires designing a legal pathway towards HTA. However, a historic overview of HTA, in the context of policy documents of Ethiopia is not clearly reported. Therefore, this review is warranted to understand the historic overview of HTA in the context of health policy documents of Ethiopia. Methods A review of online policy documents was conducted in advanced Google Scholars and websites of the Ministry of Health (MoH) of Ethiopia. Some of the policy documents were also obtained through contacting experts at MoH. The review findings were organized into six categories. Results Regulatory documents have emphasized the approval of new health technologies before selecting health technologies. Health Policy of Ethiopia and the Directive on Medical Equipment also clearly stated the importance of institutionalizing HTA and establishing HTA organizations. Additionally, the National Medical Device Policy clearly indicated the importance of establishing an HTA advisory team at MoH. Similarly, the Health Sector Transformation Plan II (HSTP II) stressed the need to build a national capacity to conduct HTA. Even though policy statements on HTA appear scattered across different policy documents, they were not put into a national HTA system. Conclusions It is important to refer to policy statements outlined in different policy documents when establishing a national HTA system in Ethiopia. Also, attention should be given to the development of policy documents related to HTA guidelines, strategic documents in HTA, and policy documents that can link HTA results to policy-making.

Oral Presentation Number: OP27 Abstract Title: Health Technology Assessment Processes, Characteristics, And Key Differences In High, Middle, And Low-Income Countries Of Asia Pacific Region Author Names: Ashish Verma ([email protected]) Introduction The healthcare sector in the Asia Pacific (APAC) region is in a period of rapid growth and exciting innovation. This has led to an increase in the number of APAC countries adopting and implementing health technology assessment (HTA) to assess the clinical, ethical, economic, and societal aspect of healthcare technology. The aim of this study is to provide an updated snapshot of the status of HTA and key differences in selected countries of APAC region. Methods HTA robustness and gap requirements, including its structure, process, use in decision-making and resource allocation processes were assessed through a review of published and gray literature for each of the selected country. A qualitative analysis was carried out by using a set of 15 principles of an International Working Group for HTA Advancement to identify the robustness and key differences in HTA based decision-making process in scoping countries. Results The finding of this study reveals that maturity of HTA determined by country-specific factors, such as presence of independent HTA agency, healthcare funding and expenditure, etcetera, and varies across the high-, middle-, and low-income countries of APAC region. Based on the study’s results, HTA ecosystem of selected countries categorized into rising HTA followed by advancing and mature HTA categories. In addition to the differences in HTA structure, the influence of stakeholder engagement differs among HTA bodies. The variation in the time frame of HTA decisions was significant among countries, with a general lack of awareness and transparency among health policy decision-makers and resulted in longer time for assessment for rising HTA category compared to the advance and mature HTA categories. Conclusions The vision of a comprehensive and robust HTA system can be achieved by implemen�ng a transparent, independent, decision-making, and strongly integrated HTA process in the region. We recommend that efforts should be directed to promote a transparent and sustainable HTA, throughout the low- and middle- income countries of APAC region which eventually, lead to more effec�ve HTA ecosystem.

Oral Presentation Number: OP28 Abstract Title: Health Technology Assessment: A Situation Analysis Of Zimbabwe Author Names: Blessing Dzingirai ([email protected]), Celia Matyanga, Pinky Manyau, Maarten Jacubos Postma, Marinus van Hulst, Nyashadzaishe Mafirakureva Introduction With ever increasing burden of disease and limited resources, health technology assessment (HTA) is required for efficient resources allocation and priority setting in healthcare. The objective of this study was to establish the baseline HTA evidence generation and use in Zimbabwe. Methods In 2019, we convened a stakeholder workshop on HTA at the University of Zimbabwe. Presentations on HTA processes, current healthcare reimbursement model, priority setting in the Ministry of Health and selection of medicines into the treatment guidelines, were done by the experts. We adapted the Health Intervention and Technology Assessment Program questionnaire for situational analysis of HTA introduction at national level and administered it among the workshop participants. We report the baseline information on HTA situation, the need, demand and supply of HTA in Zimbabwe obtained from the presentations and responses from workshop participants. Results A total of 33 participants attended the workshop. Participants indicated that there is no formal HTA agency or process in Zimbabwe. The selection of medicines into treatment guideline is determined by disease burden, safety, efficacy and cost data, and it is done by a group of experts. The Association of Healthcare Funders of Zimbabwe (AFHOZ) reported that private healthcare funders use resource-based relative value scale system to determine tariffs and reimbursement levels. The regulator requires safety, efficacy and product quality data for the registration of medicines. Transparency in decision-making, registration of heath technology and formulation of essential medicines and treatment guidelines were reported as the major needs of HTA. The major users of HTA outputs were reported as medicines regulator, AFHOZ and Ministry of Health. Key suppliers of HTA evidence are academic and clinical research institutions and healthcare workers. Lack of training in health economics was cited as the major challenge to supply of HTA evidence. Conclusions There is a need to institute a formal, systematic and transparent processes of determining value of health technologies.

Oral Presentation Number: OP29 Abstract Title: Lifecycle Assessment Of Machine Learning-Derived Early Warning System. An Early Economic Evaluation Of An Intraoperative Hypotension Prediction Index Author Names: Davide Piaggio ([email protected]), Carlo Federici, Rossella Di Bidino, Umberto Bracale, Leandro Pecchia Introduction An iterative, life-cycle approach to the evaluation of healthcare technologies requires that clinical and economic evidence is collected since the initial stages of diffusion. Nevertheless, early cost-effectiveness models are challenging mainly due to the difficulties in estimating model parameters and faithfully characterizing parameter uncertainty. This is especially true with AI-based diagnostics, where attribution of effects on costs and patient-relevant outcomes is more challenging. Empirical applications of early-models are useful to identify the main challenges of iterative modelling and provide recommendations on best- practices. Here, we reported on a case study on a machine learning-derived hypotension predictive index (HPI), that predicts the onset of intraoperative hypotension and trigger corrective measures. Methods A hybrid decision-tree/Markov model was developed comparing an HPI-based intervention protocol to standard-of-care intervention protocol during gynecological procedures. A short-term component of the model was populated using data from individual patients collected at one hospital in Italy. An historical control group was also defined using propensity score matching. Long-term costs and consequences of HPI were modelled using secondary data. A probabilistic version of the headroom approach was used to determine the maximum achievable price of HPI based on available evidence. Value of Information analysis was also conducted to identify the parameters that contribute the most to the overall uncertainty, and to identify optimal future study designs. Extensive deterministic and probabilistic sensitivity analyses were conducted to characterize the uncertainty over the cost-effectiveness of HPI. Results The preliminary results of the analysis suggest that HPI has potential to improve patients’ outcomes and generate efficiency gains by reducing hypotension events and permanent complications, such as acute kidney injury. The link between reduction in hypotension and the rate of complications, or the long-term effects on healthcare costs and patients’ quality of life are the parameters that contribute the most to model uncertainty. Conclusions Early cost-effectiveness models are a valuable tool to inform further product development and evidence requirements, but characterization of uncertainty and transparency in modelling assumptions are key.

Oral Presenta�on Number: OP30 Abstract Title: Model for ASsessing The Value Of AI In Medical Imaging (MAS-AI) Author Names: Iben Fasterholdt ([email protected]), Tue Kjølhede, Mohammad Naghavi-Behzad, Thomas Schmidt, Quinnie Rautalammi, Kristian Kidholm, Malene Hildebrandt, Anne Gerdes, Astrid Barkler, Benjamin Rasmussen Introduction Artificial intelligence (AI) is seen as one of the major disrupting forces in the future healthcare system. However, assessment of the value of these new technologies is still unclear and no agreed international HTA- based guideline exists. Therefore, a Model for ASsessing the value of AI (MAS-AI) in medical imaging was developed by a multidisciplinary group of experts and patient representatives. Methods The MAS-AI guideline is based on four steps. First a literature review of existing guides, evaluations, and assessments of the value of AI in the field of medical imaging (5,890 studies were assessed with 86 studies included in the scoping review). Next, interviews with leading researchers in AI in Denmark. The third step was two workshops where decision-makers, patient organisations and researchers discussed crucial topics when evaluating AI. Between workshops, the multidisciplinary team revised the model according to comments from workshop-participants. Last step is a validation workshop in Canada. Results The MAS-AI guideline has three parts. There are two steps covering nine domains and then advises for the evaluation process. Step 1 contains a description of patients, how the AI-model was developed, and initial ethical and legal considerations. Finishing the four domains in Step 1 is a prerequisite for moving to step 2. In step 2, a multidisciplinary assessment of outcomes of the AI-application is done for the five remaining domains: safety, clinical aspects, economics, organisational aspects and patient aspects. The last part, is five advices to facilitate a good evaluation process. Conclusions We have developed an HTA based framework to support the prospective phase while introducing novel AI technologies into healthcare in medical imaging. MAS-AI can assist HTA organisations (and companies) in selecting the relevant domains and outcome measures in the assessment of AI applications. It is important to ensure uniform and valid decisions regarding the adoption of AI technology with a structured process and tool. MAS-AI can help support these decisions and provide greater transparency for all parties involved.

Oral Presenta�on Number: OP31 Abstract Title: Assessment Of AI Supported Health Technologies - How To Move Forward? Author Names: Signe Daugbjerg ([email protected]), Rossella Di Bidino, Americo Cicchetti Introduction Artificial intelligence (AI)-supported technologies are rapidly developing and have the potential to improve healthcare quality at reduced cost. However, few examples exist of successfully deployed AI-technologies in a real-world context that have been adequately assessed. Therefore, the objective of this research is to: (i) identify existing health technology assessment (HTA) methods developed or adapted to assess AI-supported health technologies, (ii) identify new assessment topics or domains relevant for AI-technology uptake, and (iii) take the first step in developing a framework applicable for new challenges that emerge with the introduction of AI. Methods A systematic literature review of studies describing methods or frameworks to assess AI-supported health technologies was performed on PubMed from January 2010 until February 2021. Furthermore, a web page search of international HTA agencies and international organizations such as the World Health Organization, Organziation for Economic and Co-ordination and Development, and the European Commission was performed to identify important aspects to consider when implementing and assessing AI technologies. Results No assessment frameworks for AI technologies were identified from the systematic literature review or web page searches of international HTA agencies. Reports from international organizations highlight limitations or inability of most AI technologies to ‘explain’ their decision-making process (black box issue), leading to lack of trust in the technology that affects its adoption. It is recommended to put more emphasis on assessing transparency and ‘explainability’ of the AI solution as well as aspects of safety, ethical, legal, and social issues related to implementation and the development/training phase of the AI technology. Conclusions The results from this study uncover key gaps in frameworks posed for performing a systematic and holistic assessment of AI in a real-world context of health care. However, valuable information on relevant assessment aspects for AI-supported technologies have been identified. The results will form the basis for the development of a framework to assist decision-makers in assessing AI- supported technologies in a holistic manner for a responsible deployment – the HTA AI Framework.

Oral Presentation Number: OP32 Abstract Title: A Multistep Multistakeholder Priority Setting Exercise For Fecal Incontinence Author Names: Nicole O'connor ([email protected]), Katie Thomson, Kim Dangova, Sean Gill, Sheila Wallace, Sara Jackson, Fiona Pearson Introduction Fecal incontinence (FI) is the involuntary loss of feces and can affect up to 17 percent of community dwelling individuals, rising to 40 percent of older people in residential care homes. There is limited up-to-date evidence which formally set research priorities addressing FI. This project aimed to identify research topics of highest importance to key FI stakeholders. Methods An evidence gap map was produced incorporating three streams of evidence coded against predefined topic domains. The evidence streams included: emerging evidence identified through horizon scanning; existing evidence identified through systematic searches of bibliographic databases; and key FI stakeholder insights collected through an international survey. Findings were presented as a visual map to facilitate knowledge exchange during an online workshop with a purposeful sample of multidisciplinary stakeholders. The identified gaps in research were explored to see whether they were deemed representative of unmet needs, and as such, areas of priority to key FI stakeholders. Ideation techniques and group discussions were used to refine and rank priority areas. Results Overall, there was a mismatch between the existing and emerging evidence, and the priorities of key FI stakeholders. New pharmaceutical and medical technology innovations were limited. Eight percent of early- stage trials identified were concerned with the use of repurposed drugs. Within the existing evidence base, individual bowel management strategies and treatments were examined, however, key FI stakeholders desired interventions to improve patient education and the psychological aspects of living with FI. The five priority topics identified in order of importance are as follows: psychological support; lifestyle interventions; long-term effects; education; and constipation. Conclusions The robust methodology used to identify priority topics were successful in identifying broad and wide- ranging areas of importance to key stakeholders. The evidence gap map was a useful visual tool to facilitate knowledge exchange and highlight where research efforts have been focused historically, identifying a mismatch between the existing evidence base and what stakeholders consider important.

Oral Presentation Number: OP33 Abstract Title: Expectations, Needs And Challenges Of Setting Up An International Collaboration On Horizon Scanning For Medical Devices Author Names: Renee Else Michels ([email protected]), Bert de Graaff, Payam Abrishami, Diana Maria Johanna Delnoij Introduction International collaboration on horizon scanning for medical devices is seen as desirable, because the development of medical devices is not limited to the national level, and horizon scanning for medical devices on a country-level can be challenging due to scarcity and diversity of information. The International Horizon Scanning Initiative Medical Devices Working Group (IHSI MDWG) was set up in June 2021. The objective of this study was to research the expectations and experiences of the participants of this initiative, in order to reflect on the possibilities and challenges of governing innovative medical technologies. Methods A questionnaire was sent out to 10 purposively selected representatives of the IHSI MDWG participating counties: Austria, Belgium, Canada, Denmark, Italy, Luxembourg, Netherlands, Norway, Portugal, and Sweden. The survey covered individual countries’ respective purposes for an international horizon scanning system as well as questions related to the desired scope and perceived challenges of such a system. The questionnaire was supplemented with online, semi-structured, in-depth interviews with the same representatives from each participating country. These interviews provided for diving deeper into the survey topics as well as discussing the relation between horizon scanning and health technology assessment, the relation to other international horizon scanning collaborations, and the relation between an international versus a national horizon scanning system. In addition, participant observations were conducted at the Dutch National Health Care Institute and during IHSI MDWG working group meetings. Results Preliminary results are discussed first with participants after which we will draw our final conclusions and recommendations for practice. Our analysis focuses on exploring participants’ expectations and experiences with international horizon scanning through triangulating the three sources of data in our analysis. Conclusions The study will report on the expectations, needs and challenges of setting up an international collaboration for horizon scanning of medical devices and reflect on the regulation and governance of innovative medical technologies across several countries in Europe and Canada.

Oral Presentation Number: OP34 Abstract Title: Horizon Scanning A Matter Of Collaboration. A Description Of The Processes Of I-HTS Member Organisations Author Names: Iñaki Gutierrez-Ibarluzea ([email protected]), Maximiliam Otte, Hans-Peter Dauben, Juan Antonio Blasco-Amaro, Izzuna-Mudla Mohamed Ghazali, Syaqirah Bt Akmal, Pollyanna Gomes, Grace Huang, Brendon Kearney Introduction Horizon Scanning (HS) has been part of the health technology assessment (HTA) world since the end of 20th century. In accordance with the life cycle concept of heath technologies, there have been different organisations that have devoted part of their portfolio to HS’s so called Early Awareness and Alert Systems. In 2017, a legal entity international Health Tech Scan (iHTS) was created on the basis of the previous existing network EuroScan. Our aim is to describe the current achievements of the network, the methods used by its members, and their achievements. Methods In 2010, EuroScan decided to analyze its members’ methods and processes to perform HS. We used a previously defined questionnaire to revisit the analysis of methods, processes, and impact of the founded legal entity i-HTS. We analysed the clients, stakeholders involved, impact on health systems and alliances, as well as the current achievements as a group. Results i-HTS is currently rooted mainly in Europe and Asia-Pacific with members in the Americas and with ambassador programmes in Africa. The individual members have continued their achievements with special focus on three main aspects: proactive approach to innovators, stakeholder involvement, and client orientation. In most cases, the members of i-HTS produce information that is used for decision-making purposes, some of which influences the national or regional benefit package. Methods did not differ but the level of involvement of stakeholders in the different phases of the process. Some members also include in their portfolio early advice to innovators. Conclusions Early Awareness and Alert Systems are key to inform health care systems around technologies that could impact the management of patients in different contexts. There is a need to better understand the needs of the clients and the importance of HS in order to improve their efficiency. iHTS is in the process of redesigning its methods toolkit with the participation of all its members.

Oral Presentation Number: OP35 Abstract Title: Suitability Of Preference Methods Across The Medical Product Lifecycle: A Multicriteria Decision Analysis Author Names: Jorien Veldwijk ([email protected]), Esther de Bekker-Grob, Juhaeri, Eline van Overbeeke, Stephanie Tcherny-Lessenot, Cathy Anne Pinto, Rachael L. DiSantostefano, Catharina G.M. Groothuis-Oudshoorn Introduction To understand the importance of the preference methods criteria to stakeholders at each decision point in the Medical Product Lifecycle (MPLC) and to determine the suitability of commonly applied preference methods (Discrete Choice Experiment [DCE], swing weighting [SW], probabilistic threshold technique [PTT], Best-Worst Scaling case 1 [BWS1], Best-Worst Scaling case 2 [BWS2]) for a given decision-point. Methods Nineteen preference methods criteria of an existing performance matrix were incorporated in an online survey of industry, regulatory, and health technology assessment (HTA) stakeholders. All methods criteria were given a relative weight based on the SW ranking and point allocation task in the survey. Based on this relative weight and the performance matrix values, an overall suitability score was calculated for each method per critical decision point along the MPLC. Several sensitivity analyses were conducted for which the performance matrix was adapted. Results In total 59 industry, 29 regulatory, and 5 HTA representatives completed the survey. In general, ‘estimating trade-offs between characteristics’, and ‘estimating weights for treatment characteristics’ were important preference method criteria throughout all MPLC decision points, while other preference method criteria were most important only for specific MPLC stages. Both BWS1 and BWS2 seem equally suitable across decision points, DCEs seem most suitable during clinical development and regulatory launch, and SW and PTT seem most suitable throughout industry decision points. Sensitivity analysis showed substantial impact of slight changes in the performance matrix. Conclusions With rapid changes in preference research, performance matrices of preference methods should continue to be re-evaluated as more and more evidence accumulates. While DCE is the most applied preference elicitation method, other methods should also be considered to address the needs of MPLC stakeholders. Development of evidence-based guidance documents for designing, conducting, and analyzing such methods could enhance their use.

Oral Presentation Number: OP36 Abstract Title: A Lifecycle Approach In Evaluating Medical Technologies: Insights From The National Institute For Health And Care Excellence Guidance Review Process Author Names: Ivan Maslyankov ([email protected]), Ying-Ying Wang, Dionne Bowie, Joanne Heaney, Anastasia Chalkidou Introduction Health Technology Reassessment (HTR) is emerging, as the focus of health technology assessment agencies shifts from traditional methods of technology adoption to managing technologies throughout their lifecycle. The National Institute for Health and Care Excellence (NICE) evaluates devices, digital and diagnostic technologies by producing medical technologies guidance, which could recommend for adoption, no adoption, or further research. The desire to move to a lifecycle approach in the evaluation of medical technologies is reflected in the guidance review process, which involves review of the technology every three years or upon notification of significant new evidence. The outcomes of the guidance review can be to amend, update, withdraw, or leave the guidance unchanged. Methods Information on all technologies which have undergone guidance review since the commencement of the process was collected, including the recommendation before and after review and the basis for this recommendation. The proportion of guidances which were not changed, amended, updated, and withdrawn was calculated and the trends, including the bases for recommendation change were analyzed. Results In total, 34 medical technology guidance reviews have been performed. During the process, 15 (44%) were amended to reflect minor changes in the economic or clinical evidence, which did not change the recommendation. Ten (29%) were not changed, while three (9%) were updated respectively. Three (9%) were withdrawn. Another three (9%) represent special cases, which entered guidance review, but were paused due to external reasons. Among the guidances that progressed to update, two out of three had a cost increase, whereas one was broadened to reflect evidence for a larger population. Conclusions HTR is an important mechanism to improve patient care and system efficiency. In NICE’s evaluation of medical technologies, changes in the recommendation stemmed from changes in the technology’s (or standard care’s) cost, the evidence for clinical effectiveness, or the safety profile.

Oral Presentation Number: OP37 Abstract Title: Lifecycle Evaluation Models And Frameworks Used To Assess Medical Devices: A Qualitative Evidence Synthesis Author Names: Kathleen Harkin ([email protected]), Jan Sorensen, Steve Thomas Introduction Due to the iterative nature of medical device innovation and development, a single once-off assessment does not provide all the answers that decision-makers need over the device’s lifetime. Consequently, a lifecycle approach is frequently recommended. However, there is no lifecycle model recognized internationally for conducting such evaluations, nor is there explicit agreement regarding what is meant by, or evaluated over, the lifecycle. The purpose of this review was to identify and explore the range of models/frameworks used for evaluating medical devices across their lifetime – to determine what people mean by ‘the lifecycle’, what is evaluated, how, and why. Methods A qualitative evidence synthesis of lifecycle models described in the literature from a wide variety of disciplines was performed. Literature searching and selection of models iterated with analysis. Similarities, differences, and patterns were identified, from which themes became apparent, and explanatory theories were developed. Results Fifty-three models are included in the synthesis. The dimensions of difference include, amongst others, the lifecycle scope, level of application, evaluation timepoints and methods, factors included in the models, and the focus of interest. These are each influenced by the purpose of the lifecycle evaluation, which depends on the perspective and the decision or activity the evaluation is intended to inform. Few models provide a lifecycle approach to evaluating safety or efficacy. Theories explaining the differences are postulated. Conclusions Lifecycle evaluation means different things to different actors, with varied reasons for evaluation and different variables included in the models. Thus, discussions between different actors on lifecycle evaluation may be inadvertently at cross-purposes. Without first defining what is meant by the lifecycle (including the stages or phases of activity it covers) and the variables included in an evaluation, care must be exercised when discussing a lifecycle evaluation approach – to ensure that the meaning (and intended objective) is not lost in translation. Indeed, promoting lifecycle evaluation may result in necessary evidence not being generated early enough, being deferred instead until later.

Oral Presenta�on Number: OP38 Abstract Title: Managed (Early) Access In England: The ‘Ins And Outs’ Author Names: Charlotte Bee ([email protected]), Claire Hawksworth, Leanne Wakefield, Brad Groves Introduction Managed access approaches have been used by The National Institute for Health and Care Excellence (NICE) in partnership with NHS England since 2015. The Cancer Drugs Fund is an exemplar of this approach which enables earlier patient access to promising new treatments while further real-world data is collected to address evidential uncertainties. Increasingly, this approach is being applied to rare diseases and other conditions to address unmet clinical need with extensive involvement from patient organisations and clinicians. Methods All Managed Access Agreements (MAAs) in development or published in England were reviewed to present data on the number of technologies (i) entering, (ii) in active monitoring, and (iii) exiting managed access, for both cancer and other disease areas. Results After six years since the first MAA (at December 2021), over 73,000 patients have benefited from earlier access to promising new treatments for cancer, genetic and rare diseases, including cystic fibrosis, spinal muscular atrophy and sickle cell disease via managed access. 58 technologies were commissioned via managed access: thirty technologies in active data collection, eleven technologies being re-evaluated, and seventeen technologies have exited managed access. Patient and clinical engagement have been essential to the successful real-world data collections delivered and underway. Conclusions Managed access is an approach for providing earlier patient access to promising new technologies that would not otherwise be recommended for use in England. The approach to managed access in England is maturing at the same time the volume of topics entering and exiting managed access in England is expected to grow throughout 2022 with the introduction of the Innovative Medicines Fund.

Oral Presenta�on Number: OP39 Abstract Title: The Real-Option Rate Of Return Approach To Inform The Pricing Of Medicines Author Names: Simon van der Schans ([email protected]), Marcel Schöttler, Maarten Postma, Cornelis Boersma Introduction Prices of medicines have increasingly come under payer and societal scrutiny in many countries around the world. As the price-setting process is quite untransparent, the concept of cost-based pricing has been brought forward as an alternative method to inform reimbursement decision-making. A Real-Option rate of Return (ROroR) approach, was recently proposed as a method for a multi-stakeholder driven collaborative investment model. This study showed that there are public-private medicine development opportunities that could lead to lower research and development (R&D) costs for products with a challenging business model. The aim of the current study is to assess the practical use of the ROroR approach and highlight its sensitivity regarding input parameters. Methods The ROroR approach incorporates medicine-specific parameters: R&D costs, the number of patients treated per year, the time horizon for recouping the investments set by the stakeholders, the production costs and a predefined profit margin. Three hypothetical case-studies were selected for the ROroR analysis comprising of an orphan, oncology, and a more regular medicine. Parameter input data was derived from the available literature. Cost-based prices were calculated based on applying the ROroR equation under a constant profit margin. Ultimately, the corresponding prices of the case-studies were analysed for their sensitivity using ten changes of the original value. Results The ROroR approach was most sensitive to the length of the time horizon and the number of patients treated per year. The largest sensitivity was found for the oncological drug, with an asymmetric price change ranging from -25 percent to +271 percent if varying the time horizon or number of patients. The profit margin, and total R&D costs have the least effect on the price: +/-4 percent and +/-45 percent, respectively. Conclusions This study shows that cost-based pricing is highly beneficial in uncovering pricing-underlying business or economic mechanisms and suggesting a transparent price. Further research is needed on implementing public-private development models and cost-based price determination using the core parameters.

Oral Presentation Number: OP41 Abstract Title: Facilitating Dialogue Of Real-World Evidence Use In Health Technology Assessment: Taxonomy Of Question/Data Source Pairings To Support A Registry Of Studies Author Names: Ron L Akehurst, Linda A Murphy ([email protected]), Jorge Mestre-Ferrandiz, Oriol Solà-Morales, Gérard de Pouvourville, David Cunningham, Sorcha Corry, Matthew Franklin, Ann-Marie Chapman Introduction This paper reports the results of the collaboration within the European initiative of new Reimbursement and aCCess Approaches (EUreccA) which is concerned with the use of real-world evidence (RWE) in health technology assessment (HTA) decision-making. The work grew from the observation of a large, very experienced group of HTA practitioners which found that the use of RWE varied depending on the type of question asked and the particulars of the data source(s) used. We set out to examine how RWE is used in HTA decision-making and to make proposals on its facilitation. Methods Literature reviews covering earlier reviews of RWE use, academic papers, and HTA agency websites were combined with case studies involving interviews with decision-makers in four countries (England, France, Italy, Sweden) to identify the circumstances of breakdown of RWE use and to build a categorization of the uses of RWE and associated difficulties. This evidence supported the creation of a taxonomy of pairings of data sources and the questions they were used to address. The face validity of the approach was tested at an advisory board of senior HTA practitioners. Results In total, 27 questions were identified and 10 types of data source, giving 270 pairings. These pairings were linked to relevant methods guidance and to examples of their use, itemizing HTA issues and decisions made. Reports are being prepared for publication, covering the detail of the methods of the literature searches; methods of the country case studies; a description of the taxonomy; and guidance on governance. Conclusions When using RWE in HTA decision-making, the detail of the par�cular data sources and ques�on addressed mater. Recently, both the Interna�onal Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Real-World Transparency Ini�a�ve have argued for a registry of the uses of RWE. The work described here offers a star�ng classifica�on of the material that should be held in such a registry, and which in itself could be developed by the stakeholders, both agencies and companies, that use it, furthering trust and confidence.

Oral Presentation Number: OP42 Abstract Title: Increasing Access To Real-World Data To Move From Health Technology Assessment To Health Technology Management Author Names: Shaun Rowark ([email protected]), Pall Jonsson, Seamus Kent Introduction When assessing existing or emerging technologies using a one-off health technology assessment (HTA) we do not take into consideration the effects on people who will receive the technology once approved. Developments in real-world data (RWD) can help to address this by moving to ongoing health technology management (HTM). Methods To move to HTM, we first need to develop HTM data requirements. We undertook user interviews with National Institute for Health and Care Excellence (NICE) HTA developers to develop a list of requirements. We surveyed the types of data that NICE currently has access to and performed a gap analysis to understand where further data is needed. We then worked with external systems partners to identify and review available data sources that could support HTM. Results From our user interviews we established eight HTM data requirements. Data needed to be linked, cover full care pathways, contain data from new collections, be shareable, have direct access, be of high quality, have comprehensive coverage, and be responsive to technological developments (such as artificial intelligence). The review of data sources revealed a fragmented landscape of health data in the United Kingdom (UK). We identified National Health Service Digital’s (NHSD) Trusted Research Environment as the main data source that could address HTM requirements. This addresses challenges with fragmented data by providing approved researchers with timely and secure access to a range of linked health and care data. We also identified that a large national data collection would not capture all technologies, such as orphan technologies for rare conditions. We therefore established a process for accessing data from smaller data collections such as disease specific registries. To address how we can use this data, we developed the NICE Real-World Evidence (RWE) Framework that provides clear guidance on the expectations for the planning, conduct, reporting, and appraisal of RWE studies. Conclusions We have established requirements for the type of data that will help to deliver HTM as well as developed a process for accessing several suitable data sources that meet these requirements.

Oral Presentation Number: OP43 Abstract Title: Conceptual And Methodological Factors Driving The Integration Of Real-World Evidence In Drugs And Technologies Reimbursement Appraisals Author Names: Geneviève Plamondon ([email protected]), Yannick Auclair, Marie-Ève Tremblay, Sara Beha, Isabelle Ganache Introduction Real-world evidence (RWE) can be of value to support comparative effectiveness of drugs and technologies by providing additional information about their use for a variety of patients in real contexts of care. However, the integration of RWE in appraisals can be challenging, and INESSS felt the need to reinforce and explicit the underlying methodological and theoretical foundations. Methods A comprehensive literature review was carried out, followed by collaborative development work by members of the methodological and assessment teams. Results The literature review led to a common understanding of RWE underlying principles and fed the subsequent phases of the project. Three factors were identified as driving the integration of RWE in reimbursement appraisals at INESSS. Specifically, (i) the design and conduct of the real-world studies are done in accordance with best practices, (ii) the results are presented transparently and include all relevant information to assess the quality of the study and the data, and (iii) the RWE submitted is appropriate and relevant for decision- making. This third component is further ascertained by considering the decisional context (what are the circumstances motivating the submission of RWE and how does it correlate or not with existing evidence?), the data (is the dataset fit for decision needs?) and the study methods (are study design and analytical methods robust enough?). Globally, INESSS considers the integration of RWE in appraisals and its weighting, in relation with the (more traditional) available evidence, to be a case-by-case exercise. Conclusions The characterization of the main factors driving the integration of RWE in reimbursement appraisals at INESSS serves as a basis for communicating the requirements for evaluation submissions by sponsors. It further reinforces INESSS capabilities in assessing innovations, which can imply an appraisal of value at various moments along the lifecycle and with a diversity of evidence types. Considering the rapidly evolving literature and international experience, this work is expected to evolve too, and will be updated as needed.

Oral Presentation Number: OP44 Abstract Title: Does The Health Economic Modelling Structure Matter? An External Validation Of Three Approaches Commonly Used In Obesity Modelling Author Names: Bjoern Schwander ([email protected]), Klaus Kaier, Mickaël Hiligsmann, Silvia Evers, Mark Nuijten Introduction Obesity, defined as a body mass index (BMI) greater than 30kg/m², is a multifactorial disease with severe health and economic consequences. As obesity associated events impact long-term survival, health economic (HE) modelling is commonly used. However, the current set of modelling approaches are very diverse and lack external model validation. The aim of our research was to compare the event simulation and the HE outcomes of different structural approaches. Methods We performed an external validation of three main structural modelling approaches for estimating obesity- associated events: (i) continuous BMI-related risks; (ii) general risk equations; and (iii) categorical BMI- related risks. The Swedish Obese Subjects (SOS) intervention study was used for validation. Outcomes compared were mortality, cardiovascular events (CVE), and type 2 diabetes (T2D), over time using the long- term data from the SOS study, looking at both the surgery arm and the control arm. Concordance between modelling results and the external validation study was measured by visual examination of the best fitting linear regression lines, R² coefficients, the root mean squared errors, and F-tests. Furthermore, we compared the HE modelling results, comparing surgery versus control, expressed as cost per quality-adjusted life-year (QALY) gained based on 1,000 Monte Carlo simulation samples. Results Mortality was overestimated by all approaches irrespective of the study arm. For CVE an overestimation by all structural approaches was observed for the control arm. The CVE surgery arm was overestimated by the categorical BMI approach and slightly underestimated by the others. For T2D an underestimation was observed for the continuous and the categorial BMI approaches, whereas there was an overestimation by the risk equation approach. Considering different confidence interval limits, the cost per QALY gained are comparable between all structural approaches. Conclusions None of the structural approaches provided perfect external event validation results although the risk equation approach showed the smallest deviations compared to the external validation study. The cost per QALY gained resulting from the three approaches were fairly comparable.

Oral Presenta�on Number: OP46 Abstract Title: Assessing The Quality Of Pharmacoeconomic Evaluations About Type 2 Diabetes Mellitus Drugs In National Reimbursement Drug List Author Names: Shi-Yi Bao, Liu Liu, Fuming Li, Yi Yang, Yan Wei, Hui Shao, Jian Ming, Juntao Yan, Yingyao Chen ([email protected]) Introduction With the disease spectrum changing in China, type 2 diabetes mellitus (T2DM) has become the main chronic disease which affects people’s health severely, bring patients serious economic burden of disease. For T2DM patients, reliable quality of evidence in decision-making are significant, improving the efficiency of the adjustment of the National Reimbursement Drug List (NRDL). Based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), we aimed to evaluate the quality of all published pharmacoeconomic evaluations on T2DM drugs in 2020 NRDL. Methods Because the 2020 NRDL came into effect on 1 March 2021, we searched all published pharmacoeconomic evaluations about T2DM drugs in 2020 NRDL before March 2021 in China National Knowledge Infrastructure (CNKI), Wan fang Data, China Science and Technology Journal Database (VIP), PubMed, and Web of Science. According to the criterion of inclusion and exclusion, all documents were screened and then relevant basic information of targeted documents was extracted. The quality was evaluated by calculating the final scores based on CHEERS. Two reviewers assessed each publication’s quality using the CHEERS instrument and summarized study quality. Results A total of 910 papers were searched, and 24 papers were included. These involved six T2DM drugs, specifically IDegAsp, exenatide, liraglutide, lixisenatide, dapagliflozin and empagliflozin. The average score was 18.31, the standard deviation was 3.67, and the average scoring rate was 77.41 percent. Among all items, \"characterizing heterogeneity\" scored 0.04, least satisfied with requirements. \"Setting and location\", \"choice of health outcomes\" and \"assumptions\" scored one, most satisfied with requirements. Among the average scores of all parts, “results” scored lowest at 0.55, and “methods” scored highest at 0.85. The Wilcoxon sum-rank tests showed that score rate which represented reporting quality of economic evaluation (EE) was significantly related to “journal type”, “EEs type”, “model choice” and “study perspective”. Conclusions The methodological quality of pharmacoeconomic evaluations about T2DM drugs in 2020 NRDL needs to be improved. Improving the quality of literature is the basic guarantee of scientific decision-making in national medical insurance negotiation.

Oral Presenta�on Number: OP48 Abstract Title: Interactions Between Regulatory, Health Technology Assessment And Companies: Multi- Stakeholder Survey On The Current Experiences And Future Landscape Evolvement Author Name: Tina Wang ([email protected]) Introduction The interactions between regulators, health technology assessment (HTA), and companies play a significant role in the process of getting medicine to patients. These have evolved at a product level as well as at a policy and cross-jurisdictional level; however, it is important these activities are adding value for stakeholders involved. A survey conducted in March 2021 assessed the current interactions from multi- stakeholders, and their perceptions on the added value these interactions bring to better decision-making. Methods Three separate questionnaires containing nine questions were developed to assess the perceptions from pharmaceutical companies, regulators, and HTA agencies. The three questionnaires contained analogous questions where appropriate. The company questionnaire was sent to senior management at 19 international pharmaceutical companies, the agency survey was sent to 32 agencies (17 regulatory agencies and 15 HTA agencies) in Australia, Canada, Europe, and Asia. Results Seven regulators, seven HTA agencies, and nine companies responded to the survey. All regulators and HTAs indicated they have interactions with their peer agencies, as well as between regulators and HTA. The top areas of interactions for regulators were formal work-sharing between regulators during review (86% response) and regulatory strengthening (86%), whilst for HTAs, interactions between HTA on methodology/framework (83%) and HTA capacity building (67%). Regulatory-HTA interactions were seen to have fewer practical benefits, which may suggest areas for improvement. Both companies and agencies believed an effective engagement model should support evidence generation; agencies also viewed an aligned process and improved decision-making as important. Respondents believed that an ideal ecosystem for interactions should facilitate separate remits for stakeholders, converged requirements, aligned process and increased transparency and trust. Conclusions This survey provided a snapshot of the current landscape interactions between stakeholders during the life cycle of new medicines, identified the areas where value is added and improvement are needed. Suggested building blocks to improve future interactions included early scientific advice, alignment of evidence requirements, and a collaborative approach among all stakeholders.

Oral Presenta�on Number: OP49 Abstract Title: A Systematic Review Of The Activities Of Early Advice, Early Dialogue, Scientific Advice By HTA Doers Author Names: Nora Ibargoyen-Roteta ([email protected]), Gaizka Benguria-Arrate, Lorea Galnares- Cordero, Claudia Guevara, Ilich Herbert De la Hoz Siegler, Kelly Rocio Chacon, Eduardo Low, Maximiliam Otte, Hans Peter Dauben, Iñaki Gutierrez-Ibarluzea Introduction There is a range of activities that health technology assessment (HTA) doers have started to improve the process of generation of required evidence for new technologies, and the alignment of regulatory and reimbursement processes that retard the access to patients to them. Different organisations call those processes early advice, early dialogue, or scientific advice to those activities. Methods We performed a systematic review of the activities named scientific advice (SA), early advice (EA) and early dialogue (ED). Major databases and HTA organisations were explored. The protocol and search strategy were published in PROSPERO. The selection of final articles and documents was done in pairs, and when discrepancies were found a third person resolved with the consensus of the others. A matrix was used to define the commonalities and differences of the described processes. Results We initially retrieved 949 documents, after the analysis of duplications and the full text reading of the selected ones, we finally selected 39 documents and described: the type of technologies, the process, the stakeholders, the duration, the costs, and the impact. Big HTA agencies such as the Canadian Agency for Drugs and Technologies in Health (CADTH) or the National Institute for Health and Care Excellence (NICE) included EA or SA among their portfolio of activities as well as networks (European Network for HTA (EUnetHTA) or smaller agencies such as HTA Wales or Basque Office for HTA (Osteba) among others. The type of activity, the process, duration, purpose and costs differ among HTA doers. Conclusions There is a need to define what we meant when we are talking about SA, ED, and EA. In fact, regulators used the same processes with different purposes. Our systematic review and the lessons learnt from the European-funded SAFENMEDTECH project will propose a detailed framework that can be useful to better understanding the needs of each of the involved parties and how to make the processes involved more efficient.

Oral Presenta�on Number: OP50 Abstract Title: Health Equity Considerations In HTA: A Case Example Of Prenatal Screening Author Names: Beth Shaw ([email protected]), Valerie King, Josiah Morse, Shannon Robalino, Curtis Harrod Introduction The Washington Health Technology Assessment (HTA) program has been guiding coverage decisions in the state since 2007. The Center for Evidence-based Policy works with the program to develop evidence-based HTA reports. In 2020, we presented an HTA on cell-free DNA prenatal screening for chromosomal aneuploidies. In the committee’s discussion, questions around access to screening tests and to prenatal care more generally were raised. We present a case study of how health equities were considered in the development of coverage criteria. Methods We conducted an HTA using standard systematic review methodologies. Outcomes focused on test accuracy and the impact of screening. We did not look for evidence on access to prenatal screening tests or people’s experience of prenatal screening. We reviewed the meeting transcript to identify issues of health equity and how they influenced the final decision. Results During the discussion of the evidence, the committee raised concerns around equitable access to cell-free DNA tests and prenatal screening, including: direct costs to the person; access to the full range of prenatal screening, including ultrasound; and, uptake of prenatal screening. Based on the findings from the evidence report, expert testimony, and public comment, the committee voted to cover cell-free DNA prenatal screening for chromosomal aneuploidies unconditionally. Conclusions Health equity is increasingly important in healthcare decision-making. Decision makers should consider how a decision may reduce health inequities and how it may inadvertently increase existing health inequities. Decision makers also need to understand the context within which the decision will be implemented. Consideration of health equity can be addressed in a number of ways, for example through systematic review of equity issues or patient experience or through the use of contextual knowledge from expert and public testimony. Regardless of the method, decision makers should remain transparent in how health equity considerations influenced their final determination.

Oral Presenta�on Number: OP 51 Abstract Title: Improving Childhood Cancer Management And Financing In Ghana: Results From Stakeholder Mapping and Analysis Author Names: Richmond Owusu ([email protected]), Lieke Fleur Heupink, Godwin Gulbi, Brian Asare,Justice Nonvignon, Lumbwe Chola Introduction Coverage of childhood cancer treatment under the Ghanaian National Health Insurance Scheme (NHIS) has been a policy discussion recently. To improve priority setting, Ghana introduced and used health technology assessment (HTA) processes to guide the resource allocation. To understand the role of stakeholders throughout the HTA lifecycle and for this decision, a stakeholder mapping and engagement was undertaken. We share our results of this mapping and analysis for improving management and financing of childhood cancers in Ghana. Methods We used two main approaches; first, we undertook a systematic policy documents and literature review of stakeholders relevant in childhood cancer management and financing in Ghana. This was followed by a stakeholder engagement workshop of key stakeholders from the Ministry of Health, Ghana Health Service (GHS), National Health Insurance Authority (NHIA), academia, non-governmental organizations (NGOs), private sector, teaching hospitals, patient groups, and civil society organizations. Participation was done in- person and virtual. Questions were moderated using a focus group discussion approach where responses were recorded. Data were analysed using synthesis and development of themes. Mapping of stakeholders was done using Mendelow’s power-interest grid. Results The mapping identified eight key stakeholders in different roles: policy makers (Ministry of Health), payer (NHIA), healthcare providers (teaching hospitals, GHS, private hospitals), pharmaceutical companies, patient group (Ghana Parents Association for Childhood Cancers), and advocacy group (NGOs). Analysis showed that power and interest are concentrated with Ministry of Health and NHIA primarily because of control over resources. Also, while healthcare providers, patient groups, and advocacy groups have high interest, their power ranges from low to moderate. Further analysis of data from the workshop revealed that inability to pay for high cost of treatment leads to treatment abandonment. Payment for treatment was mainly out-of- pocket and by donation from philanthropist. Conclusions There was a strong will from stakeholders to extend coverage of the NHIS to childhood cancers in Ghana. Stakeholder engagement is a powerful tool and should be an integral part of every HTA process.

Oral Presenta�on Number: OP52 Abstract Title: Health Technology Assessment Of Pain-Free Blood Draw Devices In Pediatrics Author Names: Ilaria Cristiano ([email protected]), Francesco Faggiano, Maria Teresa Esposito, Ottavia Porzio, Matteo Ritrovato Introduction Blood collection in a pediatric population is a time-consuming activity and an unpleasant experience. Moreover, many laboratory tests require only small amounts of blood while larger quantity of blood is usually drawn, generating excess waste that must be properly disposed of. To solve patient concerns and workflow inefficiencies biomedical companies developed Pain-Free Blood Draw (PFBD) devices. The aim of this health technology assessment (HTA) study is to compare the performances of PFBD devices with the standard venipuncture to evaluate the potential benefits of introducing PFBD devices into clinical practice. Methods PFBD devices use microneedles that breach the stratum corneum, significantly reducing the pain perception due to the superficial skin penetration. Decision-oriented HTA method, was applied to conduct the HTA process. It is an analytical instrument that integrates the EunetHTA CoreModel with the analytic hierarchy process, to choose the best technology solution by identifying the main evaluation criteria and defining the weightsof system and performance values. Eight professionals have been involved to define the evaluation criteria and to measure the two technologies’ performance. As the method requires, a literature review was conducted to define the evaluation scheme represented by a multilevel decision tree composed of evaluation areas (domains) and key performance indicators (KPI). Results Five evaluation domains were included in the analysis (clinical effectiveness, safety, costs, organizational aspects, and technical characteristics), described by 35 KPIs. Preliminary clinical effectiveness results showed diagnostic concordance between blood samples obtained with PFBD and venipuncture. Even if the additional costs of PFBD, these devices seem to improve the safety by reducing the biological risks for operators. Moreover, considering pediatric patients, organizational aspects would benefit by the use of PFBD in terms of ease of use, compliance of patients, and time reduction for blood collection. Conclusions Results showed that PFBD not only have great repercussions in terms of clinical benefits, especially for pediatric patients, but also a significant impact in terms of organizational aspects.

Oral Presentation Number: OP54 Abstract Title: The Early Detection And Warning System ‘SINTESIS-New Technologies’: A Horizon Scanning Experience In Spain Author Names: Ana Isabel Hijas-Gómez ([email protected]), Setefilla Luengo-Matos, Amparo Arias-Pacheco, Begoña Rodriguez-Ortiz-de-Salazar, Luis Maria Sánchez-Gómez, Maria del Mar Polo-de-Santos Introduction SINTESIS-new technologies is the early warning system for new and emerging technologies of the Agencia de Evaluación de Tecnologías Sanitarias, Instituto de Salud Carlos III. SINTESIS is part of the Action Plan for the Early Detection of New and Emerging Technologies of the Spanish Network of Health Technology Assessment Agencies (RedETS). In RedETS, four agencies are responsible for the identification of innovative technologies. These agencies have been collaborating since 2016 according to the early awareness methods contained in the EuroScan Methods Toolkit. SINTESIS focuses on secondary information sources (i.e., experts and literature). This study describes the experience of SINTESIS in identifying and filtering new technologies in recent years. Methods Retrospective analysis of all new and emerging technologies notified by SINTESIS to RedETS since 2018. Technologies were analyzed on a year-by-year basis for their source of information, the clinical specialties involved, and whether technologies found in the identification phase were selected for further assessment. Results Between 2018–2020, SINTESIS identified 69 emerging and new technologies. Most of the information came from medical press news (35%), and medical web news (22%); other sources included experts (15%), licensing news search (12%), general press (12%), and scientific websites (6%). Almost 37 technologies (54%) were selected for further analysis. Reasons for exclusion included too early identification of technologies/prototypes without enough evidence (52%), technologies already implemented (28%), overlapping technologies between agencies (17%), and not being medical technologies (3%). Conclusions Experience suggests that news sections of general and medical journals, websites, and expert consultation are useful sources to identify new and emerging health technologies. The main limitation is that the technologies identified are often at too early a stage of development for further assessment. SINTESIS contributes, within a national horizon scanning system with other agencies, to broaden the information sources and provide useful data on early awareness of innovative technologies. Further studies are needed to assess the impact of emerging technologies detection on healthcare delivery.

Oral Presentation Number: OP55 Abstract Title: Classification System For Innovative Medicines In The Pipeline: New Or Repurposed? Author Names: Dapo Ogunbayo, Diarmuid Coughlan, Ross Fairbairn, Sola Akinbolade ([email protected]) Introduction While various criteria exist to define or categorize innovative medicines as new or repurposed, to our knowledge there are no standardized systems that sufficiently capture the range of pipeline products. The National Institute for Health and Care Research Innovation Observatory (NIHR IO) undertakes routine horizon scanning to support health technology assessment (HTA) in England and maintains a comprehensive Medicines Innovation Database (MInD). The aim of this project is to develop a ‘technology type’ (new versus repurposed) classification system for application within the MInD and to provide a high-level analysis of the emergent data. Methods We reviewed gray literature, regulatory websites, and drug repositories to identify existing ‘technology type’ classification criteria. Preliminary definitions and classifications for use on the MInD were discussed, refined, and agreed by consensus. Innovative medicines on the MInD were classified as either new or repurposed based on their regulatory approval status (Marketing Authorization) using data from the electronic medicines compendium. For repurposed medicines, further classification was undertaken using abbreviated new drug application (ANDA) data from the FDA Orange Book to identify generic medicines (patency and exclusivity status). We combined a range of semi-automated and manually derived data during this process. Results Six technology types were identified and applied to the MInD: (i) new technology; (ii) repurposed technology (on-patent/branded); (iii) repurposed drug (off-patent/generic); (iv) repurposed technology (never commercialized); (v) new and repurposed technology (combinations); and (vi) repurposed technology (combinations). Preliminary analysis of a subset of MInD records identified in July 2021 (n = 113) found mainly 52 percent new technologies, 27 percent new and repurposed technologies (combinations) and 14 percent repurposed technology (never commercialized). Further analysis of approximately 7000 MInD records are ongoing and will report temporal trends, regulatory status, and key challenges. Conclusions Our novel evidence-based approach to developing classifications for technology types of innovative medicines resulted in six mutually exclusive states that can be applied to a larger dataset. We believe this offers HTA stakeholders a mechanism to gain valuable insights into the innovation trends, gaps, and areas of unmet need.

Oral Presentation Number: OP56 Abstract Title: A Life Cycle Approach To Horizon Scanning Outputs - From Signals To Guidelines Author Names: Sonia Garcia Gonzalez Moral, Sarah Khalid Khan ([email protected]), Katherine Lanyi, Dapo Ogunbayo, Dawn Craig Introduction The National Institute for Health and Care Research Innovation Observatory (IO) is a horizon scanning centre based at Newcastle University, United Kingdom. The IO provides horizon scanning intelligence on new and innovative medicinal products to the National Institute for Health and Care Excellence (NICE) as technology briefing notifications (TBNs). We present an analysis of how TBNs produced between April 2017 and October 2021 feed into the NICE HTA process and used to inform their Technology Appraisal (TA) programme. Methods TBNs were mapped to relevant published NICE TA guidance and time from horizon scanning identification to NICE recommendation was studied. For mapping technologies undergoing appraisal, provisional guidance-in- development (GID) identification numbers (IDs) were used. For technologies that had not reached the NICE scoping stage yet, the NICE Topic Selection decision and ID was used. Results 693 TBNs were submitted to NICE between April 2017 and October 2021; 653 were prioritised for TA. Of those, eleven percent mapped to a published NICE TA guidance; forty-three percent to a GID, twenty-two percent were undergoing consultation, and three percent were not traced. Further twenty-one percent mapped to a suspended or terminated TA. Reasons for this included HTA timeliness, regulatory issues or companies unwilling to submit evidence to NICE. Time from technology identification to TA guidance publication ranged from twenty-two to 115 months. The average time from TBN submission to NICE recommendation was thirty months. Conclusions Timely notification is key in achieving TA recommendation aligned with market authorization but not the only influencing factor. After issuing a TBN, the NICE appraisal process might be terminated, suspended or withdrawn due to unforeseen factors. Horizon scanning plays a key role triggering the NICE TA process; understanding factors that influence the successful TA completion would streamline processes and find efficiencies.