Methodological Frameworks and Dimensions to Be Considered in Digital Health Technology Assessment: Scoping Review and Thematic Analysis.

BACKGROUND: Digital health technologies (dHTs) offer a unique opportunity to address some of the major challenges facing health care systems worldwide. However, the implementation of dHTs raises some concerns, such as the limited understanding of their real impact on health systems and people's well-being or the potential risks derived from their use. In this context, health technology assessment (HTA) is 1 of the main tools that health systems can use to appraise evidence and determine the value of a given dHT. Nevertheless, due to the nature of dHTs, experts highlight the need to reconsider the frameworks used in traditional HTA. OBJECTIVE: This scoping review (ScR) aimed to identify the methodological frameworks used worldwide for digital health technology assessment (dHTA); determine what domains are being considered; and generate, through a thematic analysis, a proposal for a methodological framework based on the most frequently described domains in the literature. METHODS: The ScR was performed in accordance with the guidelines established in the PRISMA-ScR guidelines. We searched 7 databases for peer reviews and gray literature published between January 2011 and December 2021. The retrieved studies were screened using Rayyan in a single-blind manner by 2 independent authors, and data were extracted using ATLAS.ti software. The same software was used for thematic analysis. RESULTS: The systematic search retrieved 3061 studies (n=2238, 73.1%, unique), of which 26 (0.8%) studies were included. From these, we identified 102 methodological frameworks designed for dHTA. These frameworks revealed great heterogeneity between them due to their different structures, approaches, and items to be considered in dHTA. In addition, we identified different wording used to refer to similar concepts. Through thematic analysis, we reduced this heterogeneity. In the first phase of the analysis, 176 provisional codes related to different assessment items emerged. In the second phase, these codes were clustered into 86 descriptive themes, which, in turn, were grouped in the third phase into 61 analytical themes and organized through a vertical hierarchy of 3 levels: level 1 formed by 13 domains, level 2 formed by 38 dimensions, and level 3 formed by 11 subdimensions. From these 61 analytical themes, we developed a proposal for a methodological framework for dHTA. CONCLUSIONS: There is a need to adapt the existing frameworks used for dHTA or create new ones to more comprehensively assess different kinds of dHTs. Through this ScR, we identified 26 studies including 102 methodological frameworks and tools for dHTA. The thematic analysis of those 26 studies led to the definition of 12 domains, 38 dimensions, and 11 subdimensions that should be considered in dHTA.

Synthesis of relevant information around non-core domains to support Multi-Criteria Decision Analysis (MCDA) for decision making.

Countries fundamentally base macro and micro decision making in the field of health on economic considerations, the budgetary impact of technologies being a major criterion. Nevertheless, the value of the technology of interest and its dimensions are more complex if we seek to take decisions based on the value itself. The use of structured and explicit approaches that require the assessment of multiple criteria that reflect the dimensions of this value may significantly improve the quality of the decision making. Multi-criteria decision analysis (MCDA) is a complementary decision-making tool that is able to systematically incorporate dimensions or domains such as ethical, organisational, legal, environmental and social considerations, as well as costs and benefits of medical interventions, together with the distinct perspectives of the interested parties. The objective of this article is to propose the implementation of analysis of non-core domains, in reports of Health Technology Assessment (HTA) agencies/units. To assess the scientific evidence on MCDA techniques a systematic review was conducted using structured searches in biomedical databases and websites of various HTA organisations. A consensus group was held using the nominal group technique and involving users of healthcare services, providers, managers and academics. Complementary, a survey was sent to HTA agencies to ascertain the degree of implementation of MCDA in their methods. 42 articles reporting the use of non-core criteria for the assessment of health technologies were included in the analysis. From these articles, a total of 216 non-core criteria were retrieved and categorised into domains by the researchers, and of these, 56 were classified as socioeconomic, 59 as organisational, 10 as legal, 8 as environmental and 47 as ethical, while 36 were considered to relate to other domains. The consensus group, based on the 216 non-core criteria obtained from the systematic review, proposed, and defined 26 criteria that participants considered necessary for decision making in healthcare. The consensus group did not consider that any of the domains should be given more weight than others or that any individual criteria should dominate. These approaches can serve as a framework of reference for a well-structured systematic discussion concerning the basis of individual criteria and the evidence supporting them.

Implementing the EU HTA regulation: Insights from semi-structured interviews on patient expectations, Belgian and European institutional perspectives, and industry outlooks.

Introduction: The goal of the Health Technology Assessment (HTA) Regulation 2021/2282 is to establish a more harmonized HTA framework, fostering member states cooperation and enabling equal patient access to innovative health technologies in Europe. This research aimed to assess the impact of the regulation on national HTAs, the strategic implications for health technology developers, and its influence on price and reimbursement negotiations. Methods: A scoping literature review encompassing peer-reviewed literature as well as grey literature was conducted. Between February and March 2023, semi-structured interviews (n = 20) were performed with stakeholders from Belgian governmental institutions, European institutions, advanced therapy medicinal product developers, academics, and sickness funds. The interviews were analyzed using the framework analysis method. Results: Numerous steps, such as the development of implementing acts and procedural guidelines remain to be taken. At member state level, national/regional HTA bodies and payers must act to adopt the new concepts of Joint Scientific Consultations (JSC) and Joint Clinical Assessments (JCA) within their national legislation, as well as revise their timelines and prepare for interactions at a European level. Compiling a harmonized PICO (Population, Intervention, Comparator, and Outcome), adapting local procedures, and increasing capacity to actively take part in the JSC and JCA are seen as primary barriers by several stakeholders. Training and education will help HTA bodies, payers, and health technology developers to participate in the European processes. Conclusion: While practical and legal challenges were identified, recommendations (such as actively preparing for the upcoming changes and increasing capacity while providing training) were provided to adapt national and European procedures to the needs of the HTA Regulation 2021/2282. The importance of fostering collaborations and aligning local HTA procedures with the new way of working set out by the Regulation was demonstrated with this study.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Application of Multi-Criteria Decision Analysis (MCDA) to Prioritize Real-World Evidence Studies for Health Technology Management: Outcomes and Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

Augmenting external control arms using Bayesian borrowing: a case study in first-line non-small cell lung cancer.

Aim: This study aimed to improve comparative effectiveness estimates and discuss challenges encountered through the application of Bayesian borrowing (BB) methods to augment an external control arm (ECA) constructed from real-world data (RWD) using historical clinical trial data in first-line non-small-cell lung cancer (NSCLC). Materials & methods: An ECA for a randomized controlled trial (RCT) in first-line NSCLC was constructed using ConcertAI Patient360™ to assess chemotherapy with or without cetuximab, in the bevacizumab-inappropriate subpopulation. Cardinality matching was used to match patient characteristics between the treatment arm (cetuximab + chemotherapy) and ECA. Overall survival (OS) was assessed as the primary outcome using Cox proportional hazards (PH). BB was conducted using a static power prior under a Weibull PH parameterization with borrowing weights from 0.0 to 1.0 and augmentation of the ECA from a historical control trial. Results: The constructed ECA yielded a higher overall survival (OS) hazard ratio (HR) (HR = 1.53; 95% CI: 1.21-1.93) than observed in the matched population of the RCT (HR = 0.91; 95% CI: 0.73-1.13). The OS HR decreased through the incorporation of BB (HR = 1.30; 95% CI: 1.08-1.54, borrowing weight = 1.0). BB was applied to augment the RCT control arm via a historical control which improved the precision of the observed HR estimate (1.03; 95% CI: 0.86-1.22, borrowing weight = 1.0), in comparison to the matched population of the RCT alone. Conclusion: In this study, the RWD ECA was unable to successfully replicate the OS estimates from the matched population of the selected RCT. The inability to replicate could be due to unmeasured confounding and variations in time-periods, follow-up and subsequent therapy. Despite these findings, we demonstrate how BB can improve precision of comparative effectiveness estimates, potentially aid as a bias assessment tool and mitigate challenges of traditional methods when appropriate external data sources are available.

Health-related quality of life (HRQoL) in German early benefit assessment: The importance of disease-specific instruments.

INTRODUCTION: Health-Related Quality of Life (HRQoL) data is frequently requested in early benefit assessment in Germany. To test the hypothesis that the importance of HRQoL in general and the significance of disease-specific instruments in particular has increased since the introduction of AMNOG in Germany, we analysed all early benefit assessments between 2011 and 2022. METHODS: All 793 early benefit assessments completed between 01/01/2011 and 03/11/2022 were systematically analysed. The HRQoL instruments featured in the dossier submissions were extracted for all assessments and categorized into generic and specific instruments. All G-BA resolutions were likewise assessed for consideration and acceptance of generic and specific HRQoL instruments. In addition, it was examined whether there was an association between HRQoL data and the extent of additional benefit. RESULTS: Since 2014 HRQoL data have continuously been submitted in 70% to 80% of assessments per year with the exception of 2022 (63%). Generally, disease-specific instruments are favoured, regarding submissions by industry but especially with higher acceptance by the G-BA in the resolution. Subgroup analyses revealed oncology as a major contributor to the submission and acceptance rates of disease-specific instruments. Disease-specific instruments were submitted in 81% of all oncology assessments and accepted in 53% of assessments. Overall, assessments with accepted HRQoL data tend to reach a higher overall benefit. Procedures with accepted HRQoL were most likely to receive a considerable benefit (31%), while for procedures in which HRQoL data were not accepted, a benefit was most often (65%) not proven. DISCUSSION: Industry has followed the request for submission of specific HRQoL instruments early on. Higher submission rates of specific instruments over time which at the same time meet the methodological requirements indicate that industry has learned from early assessments. A potential reason for the high submission- and acceptance rates of specific HRQoL instruments in oncology might be the particularly high relevance of HRQoL in this indication. Possible effects of changes in legislature on the future development of submission and acceptance of HRQoL data need to be monitored. CONCLUSION: In Germany, HRQoL has gained a relevant position in early benefit assessment over time. Overall specific instruments are favoured, regarding submissions by industry but especially through consideration by the G-BA in the resolution. Furthermore, HRQoL data can be supportive for benefit assessments, in particular to show that advantages in morbidity and/or mortality are reflected in HRQoL and not at the expense of HRQoL.

Access in all areas? a round up of developments in market access and health technology assessment: part 4.

In this latest update, we look at recent developments in market access including the pricing agreement of Libmeldy® by the Beneluxa Initiative, the financial impact of managed entry agreements in Italy and the restructuring of Agenzia Italiana del Farmaco (AIFA). We also highlight the collaboration between FINOSE and the New Expensive Drug (NED) section of the Nordic Pharmaceutical Forum.

Composite event-free-survival as an endpoint in oncology drug evaluation: Review and guidance perspectives from the Haute Autorité de Santé (HAS).

BACKGROUND: The use of right-censored composite endpoints, such as progression-free survival, has been questioned in haemato-oncology trials due to potential bias in estimated treatment effect. This may impact the accuracy of health technology evaluations. We hypothesized that there is heterogeneity and potential sources of bias in the reporting of composite endpoints to health technology assessment (HTA) bodies. METHODS: We reviewed the submissions for reimbursement of oncology drugs in 2021 and 2022 that used a composite endpoint in the pivotal trial, after appraisal by the French HTA body. The retrieved information included the clinical study report, protocol, and statistical analysis plan submitted by the industry. All events of the composite endpoint and all causes of censored observations were measured. The design characteristics and treatment effect estimates were recorded. FINDINGS: Seventy-six submissions were selected, including seven without a right-censored endpoint and four evaluating associations, resulting in 65 analysed records: 17 for haematological and 48 for solid tumours. Out these 65 submissions, 47 (72·3%) used a randomized controlled design, and 18 (27·7%) a non-comparative design. The most frequently used composite endpoint was progression-free survival, used in 54 (83·1%) of the submissions. Censoring was possibly informative in 51 (92·7%) cases, mostly due to the onset of new treatment (44/51, 86·3%) and/or discontinuation of follow-up (33/51, 64·7%). In contrast, 38 (58·5%) trials reported a quantification of censored observations, with only 12/51 (23·5%) quantifying the informative ones. The estimated treatment effect on the composite outcome increased with the amount of censoring, suggesting a higher benefit of the drug, but remained below that on survival with poor evidence of surrogacy (R-squared=0·23). INTERPRETATION: Clinical study reports should be improved in terms of reporting censoring, while stakeholders should be aware of this potential source of bias. At a minimum, sensitivity analysis that ignores intercurrent events should be requested.

Service Quality and Residents' Preferences for Facilitated Self-Service Fundus Disease Screening: Cross-Sectional Study.

BACKGROUND: Fundus photography is the most important examination in eye disease screening. A facilitated self-service eye screening pattern based on the fully automatic fundus camera was developed in 2022 in Shanghai, China; it may help solve the problem of insufficient human resources in primary health care institutions. However, the service quality and residents' preference for this new pattern are unclear. OBJECTIVE: This study aimed to compare the service quality and residents' preferences between facilitated self-service eye screening and traditional manual screening and to explore the relationships between the screening service's quality and residents' preferences. METHODS: We conducted a cross-sectional study in Shanghai, China. Residents who underwent facilitated self-service fundus disease screening at one of the screening sites were assigned to the exposure group; those who were screened with a traditional fundus camera operated by an optometrist at an adjacent site comprised the control group. The primary outcome was the screening service quality, including effectiveness (image quality and screening efficiency), physiological discomfort, safety, convenience, and trustworthiness. The secondary outcome was the participants' preferences. Differences in service quality and the participants' preferences between the 2 groups were compared using chi-square tests separately. Subgroup analyses for exploring the relationships between the screening service's quality and residents' preference were conducted using generalized logit models. RESULTS: A total of 358 residents enrolled; among them, 176 (49.16%) were included in the exposure group and the remaining 182 (50.84%) in the control group. Residents' basic characteristics were balanced between the 2 groups. There was no significant difference in service quality between the 2 groups (image quality pass rate: P=.79; average screening time: P=.57; no physiological discomfort rate: P=.92; safety rate: P=.78; convenience rate: P=.95; trustworthiness rate: P=.20). However, the proportion of participants who were willing to use the same technology for their next screening was significantly lower in the exposure group than in the control group (P<.001). Subgroup analyses suggest that distrust in the facilitated self-service eye screening might increase the probability of refusal to undergo screening (P=.02). CONCLUSIONS: This study confirms that the facilitated self-service fundus disease screening pattern could achieve good service quality. However, it was difficult to reverse residents' preferences for manual screening in a short period, especially when the original manual service was already excellent. Therefore, the digital transformation of health care must be cautious. We suggest that attention be paid to the residents' individual needs. More efficient man-machine collaboration and personalized health management solutions based on large language models are both needed.

Institutional Priority-Setting for Novel Drugs and Therapeutics: A Qualitative Systematic Review.

BACKGROUND: There is a lack of guidance on approaches to formulary management and funding for high-cost drugs and therapeutics by individual healthcare institutions. The objective of this review was to assess institutional approaches to resource allocation for such therapeutics, with a particular focus on paediatric and rare disease populations. METHODS: A search of Embase and MEDLINE was conducted for studies relevant to decision-making for off-formulary, high-cost drugs and therapeutics. Abstracts were evaluated for inclusion based on the Simple Multiple-Attribute Rating Techniques (SMART) criteria. A framework of 30 topics across 4 categories was used to guide data extraction and was based on findings from the initial abstract review and previous health technology assessment (HTA) publications. Reflexive thematic analysis was conducted using QSR NVivo 12 software. RESULTS: A total of 168 studies were included for analysis. Only 4 (2%) focused on paediatrics, while 21 (12%) centred on adults and the remainder (85%) did not specify. Thirty-two (19%) studies discussed the importance of high-cost therapeutics and 34 (23%) focused on rare/orphan drugs. Five themes were identified as being relevant to institutional decision-making for high-cost therapeutics: institutional strategy, substantive criteria, procedural considerations, guiding principles and frameworks, and operational activities. Each of these themes encompassed several sub-themes and was complemented by a sixth category specific to paediatrics and rare diseases. CONCLUSION: The rising cost of novel drugs and therapeutics underscores the need for robust, evidence-based, and ethically defensible decision-making processes for health technology funding, particularly at the hospital level. Our study highlights practices and themes to aid decision-makers in thinking critically about institutional, substantive, procedural, and operational considerations in support of legitimate decisions about institutional funding of high-cost drugs and therapeutics, as well as opportunities and challenges that exist for paediatric and rare disease populations.

The value of artificial intelligence for the treatment of mechanically ventilated intensive care unit patients: An early health technology assessment.

PURPOSE: The health and economic consequences of artificial intelligence (AI) systems for mechanically ventilated intensive care unit patients often remain unstudied. Early health technology assessments (HTA) can examine the potential impact of AI systems by using available data and simulations. Therefore, we developed a generic health-economic model suitable for early HTA of AI systems for mechanically ventilated patients. MATERIALS AND METHODS: Our generic health-economic model simulates mechanically ventilated patients from their hospitalisation until their death. The model simulates two scenarios, care as usual and care with the AI system, and compares these scenarios to estimate their cost-effectiveness. RESULTS: The generic health-economic model we developed is suitable for estimating the cost-effectiveness of various AI systems. By varying input parameters and assumptions, the model can examine the cost-effectiveness of AI systems across a wide range of different clinical settings. CONCLUSIONS: Using the proposed generic health-economic model, investors and innovators can easily assess whether implementing a certain AI system is likely to be cost-effective before an exact clinical impact is determined. The results of the early HTA can aid investors and innovators in deployment of AI systems by supporting development decisions, informing value-based pricing, clinical trial design, and selection of target patient groups.

Application of natural language processing to predict final recommendation of Brazilian health technology assessment reports.

INTRODUCTION: Health technology assessment (HTA) plays a vital role in healthcare decision-making globally, necessitating the identification of key factors impacting evaluation outcomes due to the significant workload faced by HTA agencies. OBJECTIVES: The aim of this study was to predict the approval status of evaluations conducted by the Brazilian Committee for Health Technology Incorporation (CONITEC) using natural language processing (NLP). METHODS: Data encompassing CONITEC's official report summaries from 2012 to 2022. Textual data was tokenized for NLP analysis. Least Absolute Shrinkage and Selection Operator, logistic regression, support vector machine, random forest, neural network, and extreme gradient boosting (XGBoost), were evaluated for accuracy, area under the receiver operating characteristic curve (ROC AUC) score, precision, and recall. Cluster analysis using the k-modes algorithm categorized entries into two clusters (approved, rejected). RESULTS: The neural network model exhibited the highest accuracy metrics (precision at 0.815, accuracy at 0.769, ROC AUC at 0.871, and recall at 0.746), followed by XGBoost model. The lexical analysis uncovered linguistic markers, like references to international HTA agencies' experiences and government as demandant, potentially influencing CONITEC's decisions. Cluster and XGBoost analyses emphasized that approved evaluations mainly concerned drug assessments, often government-initiated, while non-approved ones frequently evaluated drugs, with the industry as the requester. CONCLUSIONS: NLP model can predict health technology incorporation outcomes, opening avenues for future research using HTA reports from other agencies. This model has the potential to enhance HTA system efficiency by offering initial insights and decision-making criteria, thereby benefiting healthcare experts.

The role and impact of health economics in the optimization of patient care in osteoarthritis: insights from a practical example.

Osteoarthritis (OA) is a degenerative joint disease with a substantial global burden, causing chronic pain and reduced quality of life. Managing OA efficiently while maximizing healthcare resources is crucial. Health economics and health technology assessment (HTA) are central tools providing a framework to evaluate the clinical, economic, and ethical aspects of healthcare technologies and interventions. This article presents some insights into the role of health economics and the HTA process in OA management. It also illustrates an example of cost-effectiveness analysis in a specific healthcare context, on the basis of a recent clinical trial involving hyaluronic acid treatment for knee OA. While HTA offers valuable insights, it faces challenges like data availability and resource constraints. Integrating health economics into decision-making can enhance patient care and allocate resources effectively in OA and other healthcare domains.

A health technology assessment of personalized nutrition interventions using the EUnetHTA HTA Core Model.

OBJECTIVES: Poor nutrition links to chronic diseases, emphasizing the need for optimized diets. The EU-funded project PREVENTOMICS, introduced personalized nutrition to address this. This study aims to perform a health technology assessment (HTA) comparing personalized nutrition interventions developed through this project, with non-personalized nutrition interventions (control) for people with normal weight, overweight, or obesity. The goal is to support decisions about further development and implementation of personalized nutrition. METHODS: The PREVENTOMICS interventions were evaluated using the European Network for HTA Core Model, which includes a methodological framework that encompasses different domains for value assessment. Information was gathered via [1] different statistical analyses and modeling studies, [2] questions asked of project partners and, [3] other (un)published materials. RESULTS: Clinical trials of PREVENTOMICS interventions demonstrated different body mass index changes compared to control; differences ranged from -0.80 to 0.20 kg/m2. Long-term outcome predictions showed generally improved health outcomes for the interventions; some appeared cost-effective (e.g., interventions in UK). Ethical concerns around health inequality and the lack of specific legal regulations for personalized nutrition interventions were identified. Choice modeling studies indicated openness to personalized nutrition interventions; decisions were primarily affected by intervention's price. CONCLUSIONS: PREVENTOMICS clinical trials have shown promising effectiveness with no major safety concerns, although uncertainties about effectiveness exist due to small samples (n=60-264) and short follow-ups (10-16 weeks). Larger, longer trials are needed for robust evidence before implementation could be considered. Among other considerations, developers should explore financing options and collaborate with policymakers to prevent exclusion of specific groups due to information shortages.

A cluster-randomized study to evaluate the effectiveness and cost-effectiveness of the Assessment of Burden of Chronic Conditions (ABCC) tool in South Tyrolean primary care for patients with COPD, asthma, type 2 diabetes, and heart failure: the ABCC South Tyrol study.

BACKGROUND: Chronic diseases, such as chronic obstructive pulmonary disease (COPD), asthma, type 2 diabetes, and heart failure, often coexist and contribute to a significant burden on individuals and health systems. The Assessment of Burden of Chronic Conditions (ABCC) tool, already in routine clinical use in the Netherlands, aims to comprehensively assess and visualize disease burden, stimulate self-management, and encourage shared decision-making. This study aims to validate the German and Italian versions of the ABCC tool and evaluate its effectiveness and cost-effectiveness in the South Tyrolean Primary Care setting. METHODS: This is a cluster-randomized study involving approximately 400 patients with COPD, asthma, type 2 diabetes, and heart failure who received care from the South Tyrolean General Practices. Initially, the ABCC tool will be translated into German and Italian and validated. Subsequently, half of the participants will use the validated ABCC tool for patient-reported outcome measurement assessments, while the other half will receive usual care. The primary outcome measure is the change in the patients' perception of the quality of care after 18 months. The secondary outcomes included changes in quality of life, self-management behavior, and healthcare utilization. The missing data will be managed using multiple imputations. Additionally, a cost-effectiveness analysis that considers the direct medical costs reimbursed by the National Health Service will be conducted. DISCUSSION: This study provides insights into the application, validation, and efficacy of the ABCC tool in the South Tyrolean healthcare context. The tool's potential to enhance person-centered care, improve the quality of life, and possibly reduce healthcare costs could greatly contribute to sustainable healthcare. The challenges of implementation, such as software integration and the use of an EU data platform, will provide lessons for future international patient care data management. TRIAL REGISTRATION: ISRCTN registry, ISRCTN13531607. Registered on August 23, 2023.

R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 15.

In this latest update we discuss real-world evidence (RWE) guidance from the leading oncology professional societies, the American Society of Clinical Oncology and the European Society for Medical Oncology, and the PRINCIPLED practical guide on the design and analysis of causal RWE studies.

Methods to Include Environmental Impacts in Health Economic Evaluations and Health Technology Assessments: A Scoping Review.

OBJECTIVES: The environmental impacts of healthcare are important factors that should be considered during health technology assessments. This study aims to summarize the evidence that exists about methods to include environmental impacts in health economic evaluations and health technology assessments. METHODS: We identified records for screening using an existing scoping review and a systematic search of academic databases and gray literature up to September 2023. We screened the identified records for eligibility and extracted data using a narrative synthesis approach. The review was conducted following the JBI Manual for Evidence Synthesis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses Extension for Scoping Reviews checklist. RESULTS: We identified 2898 records and assessed the full text of 114, of which 54 were included in this review. Ten methods were identified to include environmental impacts in health economic evaluations and health technology assessments. Methods included converting environmental impacts to dollars or disability-adjusted life years and including them in a cost-effectiveness, cost-utility, or cost-benefit analysis, calculating an incremental carbon footprint effectiveness ratio or incremental carbon footprint cost ratio, incorporating impacts as one criteria of a multi-criteria decision analysis, and freely considering impacts during health technology assessment deliberation processes. CONCLUSIONS: Methods to include environmental impacts in health economic evaluations and health technology assessments exist but have not been tested for widespread use by health technology assessment agencies. Further research and implementation work is needed to determine which method can best aid decision makers to choose low environmental impact healthcare interventions.

Assessing the Performance of Alternative Methods for Estimating Long-Term Survival Benefit of Immuno-oncology Therapies.

OBJECTIVES: This study aimed to determine the accuracy and consistency of established methods of extrapolating mean survival for immuno-oncology (IO) therapies, the extent of any systematic biases in estimating long-term clinical benefit, what influences the magnitude of any bias, and the potential implications for health technology assessment. METHODS: A targeted literature search was conducted to identify published long-term follow-up from clinical trials of immune-checkpoint inhibitors. Earlier published results were identified and Kaplan-Meier estimates for short- and long-term follow-up were digitized and converted to pseudo-individual patient data using an established algorithm. Six standard parametric, 5 flexible parametric, and 2 mixture-cure models (MCMs) were used to extrapolate long-term survival. Mean and restricted mean survival time (RMST) were estimated and compared between short- and long-term follow-up. RESULTS: Predicted RMST from extrapolation of early data underestimated observed RMST in long-term follow-up for 184 of 271 extrapolations. All models except the MCMs frequently underestimated observed RMST. Mean survival estimates increased with longer follow-up in 196 of 270 extrapolations. The increase exceeded 20% in 122 extrapolations. Log-logistic and log-normal models showed the smallest change with additional follow-up. MCM performance varied substantially with functional form. CONCLUSIONS: Standard and flexible parametric models frequently underestimate mean survival for IO treatments. Log-logistic and log-normal models may be the most pragmatic and parsimonious solutions for estimating IO mean survival from immature data. Flexible parametric models may be preferred when the data used in health technology assessment are more mature. MCMs fitted to immature data produce unreliable results and are not recommended.

An Inclusive Civil Society Dialogue for Successful Implementation of the EU HTA Regulation: Call to Action to Ensure Appropriate Involvement of Stakeholders and Collaborators.

OBJECTIVES: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group. METHODS: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process. Each working group revisited the pre-convention survey results, determined key role characteristics for each stakeholder, and agreed on the most important activities to fulfill the role profile. Finally, the activities suggested per group were prioritized by plenary group. RESULTS: The prioritized actions for patients included training and capacity building, the establishment of a patient involvement committee, and the establishment of a patient unit at the EC secretariat. For clinicians, it included alignment on evidence assessment from a clinical vs. HTA point of view, capacity building, and standardization of processes. The most important actions for regulators are to develop joint regulatory-HTA guidance documents, align processes and interfaces under the regulation, and share discussions on post-licensing evidence generation. HTDs prioritized scientific advice capacity and the review of the scoping process, and further development of the scope of the assessment report fact checks. The top three actions for national HTA bodies and payers included clarification on the early HTD dialogue process, political support and commitment, and clarification on financial support. CONCLUSIONS: Addressing the activities identified as the most important for stakeholders/collaborators in the EU HTA process (e.g., in the implementation of the EU HTA Stakeholder Network and of the guidance documents developed by the EUnetHTA 21 consortium) will be key to starting an "inclusive civil society dialogue", as suggested by the European Commission's Pharmaceutical Strategy.