Assessing clinical benefit in the Medicare Drug Price Negotiation Program: A 2-step approach for improving transparency, consistency, and meaningful patient engagement.

In early 2024, the Centers for Medicare & Medicaid Services (CMS) will send initial price offers to the manufacturers of the first 10 drugs selected for the Medicare Drug Price Negotiation Program, established under the Inflation Reduction Act. However, CMS has not specified exactly how it will adjust the starting point for an initial price offer based on assessment of a drug's clinical benefit. This article addresses unanswered questions relating to CMS' methods for assessing clinical benefit. Specifically, we address how CMS can weigh various measures of evidence, ensure transparency and consistency, meaningfully incorporate patient and other stakeholder perspectives, and support addressing evidence gaps. We propose a 2-step approach for assessing the overall clinical benefit of a selected drug compared with its therapeutic alternatives that builds on the framework outlined by CMS. In step 1, CMS would evaluate conventional clinical benefit, defined in terms of outcomes commonly used in clinical studies for the selected drug and indications. In step 2, CMS would evaluate other outcomes broadly related to patient experience that are not adequately represented in the clinical literature. Overall, our approach incorporates the advantages of both qualitative and quantitative approaches to value assessment and decision-making. We describe a set of loose decision rules to improve transparency and consistency, recommend incorporating ranks and weights to signal to researchers and manufacturers which elements of clinical benefit and sources of data are the most important, and center meaningful deliberation with clinical experts, patients, and caregivers.

Multistakeholder Perceptions of Additional Value Elements for United States Value Assessment of Health Interventions.

OBJECTIVES: Limitations in conventional cost-effectiveness methods have led to calls for incorporation of additional value elements in assessments of health technologies. However, gaps remain in how additional value elements may inform decision making. This study aimed to prioritize additional value elements from the perspective of healthy individuals without a specific condition or indicated for a specific treatment in the United States among a multistakeholder panel and compare the importance of perspective-specific value elements. METHODS: Additional value elements were prioritized in 2 phases: (1) we identified and categorized additional value elements in a targeted literature review, and (2) we convened a multistakeholder group-based preference elicitation study (N = 28) to evaluate the description of each value element and rank and generate normalized weights of each value element for its significance in value assessment. The importance of additional value elements was also weighted relative to patient-centric value elements. RESULTS: The rank and weight of contextual value elements among 28 stakeholders were "severity of the disease" (26.2%), "disadvantaged and vulnerable target populations highly represented" (21.8%), "broader economic impact" (17.3%), "risk protection" (13.8%), "rarity of the disease" (11.3%), and "novel mechanism of action" (9.7%). Relative weight of the additional value elements versus patient-centric value elements was 52% and 48%, respectively. CONCLUSIONS: Study findings may inform priority setting for value frameworks and emerging US government assessments. The group-based elicitation method is repeatable and useful for structured deliberative processes in value assessment and may help improve the consistency and predictability of what is important to stakeholders.

Alternative approaches to measuring value: an update on innovative methods in the context of the United States Medicare drug price negotiation program.

INTRODUCTION: The United States has begun assessing the value of pharmaceuticals to inform negotiated prices in the Medicare program. Given strong political objections in the United States to the use of QALYs, Medicare will need to adopt an alternative approach to measuring value. AREAS COVERED: In this narrative review, we identified six alternative approaches to measuring value (equal value life-years, health years in total, generalized risk-adjusted cost-effectiveness, severity weighting based on absolute or proportional shortfall, comparative effectiveness based on conventional clinical endpoints, and comparative effectiveness based on both conventional endpoints and patient-centric value elements) and five criteria for assessing these approaches (responsiveness to concerns about discrimination, feasibility, transparency, flexibility, and the ability to incorporate factors beyond traditional value elements). EXPERT OPINION: Four of the alternatives are broadly aligned with the cost-effectiveness framework, but none fully addresses all aspects of the stated concerns that QALYs may be used to unintentionally implement discrimination. We note, however, that the extent to which these concerns lead to discrimination in practice is unknown. Finally, we recommend an approach for measuring value in terms of comparative effectiveness that combines quantitative ranking and weighting of distinct criteria (including patient-centric value elements) with deliberation.

Using Real-World Data to Inform Value-Based Contracts for Cell and Gene Therapies in Medicaid.

OBJECTIVE: High upfront costs and long-term benefit uncertainties of gene therapies challenge Medicaid budgets, making value-based contracts a potential solution. However, value-based contract design is hindered by cost-offset uncertainty. The aim of this study is to determine actual cost-offsets for valoctocogene roxaparvovec (hemophilia A) and etranacogene dezaparvovec (hemophilia B) from Colorado Medicaid's perspective, defining payback periods and its uncertainty from the perspective of Colorado Medicaid. METHODS: This cost analysis used 2018-2022 data from the Colorado Department of Health Care Policy & Financing to determine standard-of-care costs and employed cost simulation models to estimate the cost of Medicaid if patients switched to gene therapy versus if they did not. Data encompassed medical and pharmacy expenses of Colorado Medicaid enrollees. Identified cohorts were patients aged 18+ with ICD-10-CM codes D66 (hemophilia A) and D67 (hemophilia B). Severe hemophilia A required ≥ 6 claims per year for factor therapies or emicizumab, while moderate/severe hemophilia B necessitated ≥ 4 claims per year for factor therapies. Patients were included in the cohort in the year they first met the criteria and were subsequently retained in the cohort for the duration of the observation period. Standard-of-care included factor VIII replacement therapy/emicizumab for hemophilia A and factor IX replacement therapies for hemophilia B. Simulated patients received valoctocogene roxaparvovec or etranacogene dezaparvovec. Main measures were annual standard-of-care costs, cost offset, and breakeven time when using gene therapies. RESULTS: Colorado Medicaid's standard-of-care costs for hemophilia A and B were $426,000 [standard deviation (SD) $353,000] and $546,000 (SD $542,000) annually, respectively. Substituting standard-of-care with gene therapy for eligible patients yielded 8-year and 6-year average breakeven times, using real-world costs, compared with 5 years with published economic evaluation costs. Substantial variability in real-world standard-of-care costs resulted in a 48% and 59% probability of breakeven within 10 years for hemophilia A and B, respectively. Altering eligibility criteria significantly influenced breakeven time. CONCLUSIONS: Real-world data indicates substantial uncertainty and extended payback periods for gene therapy costs. Utilizing real-world data, Medicaid can negotiate value-based contracts to manage budget fluctuations, share risk with manufacturers, and enhance patient access to innovative treatments.

Frailty prevalence in 42 European countries by age and gender: development of the SHARE Frailty Atlas for Europe.

Comparative frailty prevalence data across European countries is sparse due to heterogeneous measurement methods. The Survey of Health, Ageing and Retirement (SHARE) initiative conducted interviews with probability sampling of non-institutionalized elderly people in several European countries. Previous frailty analyses of SHARE datasets were limited to initial SHARE countries and did not provide age- and gender-stratified frailty prevalence. Our aim was to provide age- and gender-stratified frailty prevalence estimates in all European countries, with predictions where necessary. From 29 SHARE participating countries, 311,915 individual surveys were analyzed. Frailty prevalence was estimated by country and gender in 5-year age bands using the SHARE Frailty Instrument and a frailty index. Association of frailty prevalence with age, gender, and GDP per capita (country-specific economic indicator for predictions) was investigated in multivariate mixed logistic regression models with or without multiple imputation. Female gender and increasing age were significantly associated with higher frailty prevalence. Higher GDP per capita, with or without purchasing power parity adjustment, was significantly associated with lower frailty prevalence in the 65-79 age groups in all analyses. Observed and predicted data on frailty rates by country are provided in the interactive SHARE Frailty Atlas for Europe. Our study provides age- and gender-stratified frailty prevalence estimates for all European countries, revealing remarkable between-country heterogeneity. Higher frailty prevalence is strongly associated with lower GDP per capita, underlining the importance of investigating transferability of evidence across countries at different developmental levels and calling for improved policies to reduce inequity in risk of developing frailty across European countries.

Mapping Hungarian procedure codes to SNOMED CT.

BACKGROUND: Data harmonisation is essential in real-world data (RWD) research projects based on hospital information systems databases, as coding systems differ between countries. The Hungarian hospital information systems and the national claims database use internationally known diagnosis codes, but data on medical procedures are recorded using national codes. There is no simple or standard solution for mapping the national codes to a standard coding system. Our aim was to map the Hungarian procedure codes (OENO) to SNOMED CT as part of the European Health Data Evidence Network (EHDEN) project. METHODS: We recruited 25 professionals from different specialties to manually map the procedure codes used between 2011 and 2021. A mapping protocol and training material were developed, results were regularly revised, and the challenges of mapping were recorded. Approximately 7% of the codes were mapped by more people in different specialties for validation purposes. RESULTS: We mapped 4661 OENO codes to standard vocabularies, mostly SNOMED CT. We categorized the challenges into three main areas: semantic, matching, and methodological. Semantic refers to the occasionally unclear meaning of the OENO codes, matching to the different granularity and purpose of the OENO and SNOMED CT vocabularies. Lastly, methodological challenges were used to describe issues related to the design of the above-mentioned two vocabularies. CONCLUSIONS: The challenges and solutions presented here may help other researchers to design their process to map their national codes to standard vocabularies in order to achieve greater consistency in mapping results. Moreover, we believe that our work will allow for better use of RWD collected in Hungary in international research collaborations.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) adjunctive therapy for major depressive disorder (MDD) after two antidepressant treatment failures: meta-analysis of randomized sham-controlled trials.

BACKGROUND: Several meta-analyses demonstrated the efficacy of unilateral High-Frequency Left-sided (HFL) repetitive Transcranial Magnetic Stimulation (rTMS) for individuals with Major Depressive Disorder (MDD); however, results are contradictory due to heterogeneity of the included studies. METHODS: A systematic literature review (SLR) of English language articles published since 2000 was performed in March 2022 on PubMed and Scopus databases. Empirical evidence on the relative efficacy of rTMS treatment compared with standard pharmacotherapy in Treatment-Resistant Depression (TRD) were extracted. Random effects models were used to assess the effects of rTMS on response and remission rates. RESULTS: 19 randomized double-blinded sham-controlled studies were included for quantitative analysis for response (n = 854 patients) and 9 studies for remission (n = 551 patients). The risk ratio (RR) for response and remission are 2.25 and 2.78, respectively for patients after two treatment failures using rTMS as add-on treatment compared to standard pharmacotherapy. Cochrane's Q test showed no significant heterogeneity. No publication bias was detected. CONCLUSIONS: rTMS is significantly more effective than sham rTMS in TRD in response and remission outcomes and may be beneficial as an adjunctive treatment in patients with MDD after two treatment failures. This finding is consistent with previous meta-analyses; however, the effect size was smaller than in the formerly published literature.

Recommendations to overcome barriers to the use of artificial intelligence-driven evidence in health technology assessment.

Background: Artificial intelligence (AI) has attracted much attention because of its enormous potential in healthcare, but uptake has been slow. There are substantial barriers that challenge health technology assessment (HTA) professionals to use AI-generated evidence for decision-making from large real-world databases (e.g., based on claims data). As part of the European Commission-funded HTx H2020 (Next Generation Health Technology Assessment) project, we aimed to put forward recommendations to support healthcare decision-makers in integrating AI into the HTA processes. The barriers, addressed by the paper, are particularly focusing on Central and Eastern European (CEE) countries, where the implementation of HTA and access to health databases lag behind Western European countries. Methods: We constructed a survey to rank the barriers to using AI for HTA purposes, completed by respondents from CEE jurisdictions with expertise in HTA. Using the results, two members of the HTx consortium from CEE developed recommendations on the most critical barriers. Then these recommendations were discussed in a workshop by a wider group of experts, including HTA and reimbursement decision-makers from both CEE countries and Western European countries, and summarized in a consensus report. Results: Recommendations have been developed to address the top 15 barriers in areas of (1) human factor-related barriers, focusing on educating HTA doers and users, establishing collaborations and best practice sharing; (2) regulatory and policy-related barriers, proposing increasing awareness and political commitment and improving the management of sensitive information for AI use; (3) data-related barriers, suggesting enhancing standardization and collaboration with data networks, managing missing and unstructured data, using analytical and statistical approaches to address bias, using quality assessment tools and quality standards, improving reporting, and developing better conditions for the use of data; and (4) technological barriers, suggesting sustainable development of AI infrastructure. Conclusion: In the field of HTA, the great potential of AI to support evidence generation and evaluation has not yet been sufficiently explored and realized. Raising awareness of the intended and unintended consequences of AI-based methods and encouraging political commitment from policymakers is necessary to upgrade the regulatory and infrastructural environment and knowledge base required to integrate AI into HTA-based decision-making processes better.

Prevalence, Cardiometabolic Comorbidities and Reporting of Chronic Kidney Disease; A Hungarian Cohort Analysis.

Objectives: Chronic kidney disease (CKD) implies increased comorbidity burden, disability, and mortality, becoming a significant public health problem worldwide, however, prevalence data are lacking in Hungary. Methods: We determined CKD prevalence, stage distribution, comorbidities using estimated glomerular filtration rate (eGFR), albuminuria, and international disease codes in a cohort of healthcare utilizing residents within the catchment area of the University of Pécs, in the County Baranya, Hungary, between 2011 and 2019 by database analysis. The number of laboratory-confirmed and diagnosis-coded CKD patients were compared. Results: Of the total 296,781 subjects of the region, 31.3% had eGFR tests and 6.4% had albuminuria measurements, of whom we identified 13,596 CKD patients (14.0%) based on laboratory thresholds. Distribution by eGFR was presented (G3a: 70%, G3b: 22%, G4: 6%, G5: 2%). Amongst all CKD patients 70.2% had hypertension, 41.5% diabetes, 20.5% heart failure, 9.4% myocardial infarction, 10.5% stroke. Only 28.6% of laboratory-confirmed cases were diagnosis-coded for CKD in 2011-2019. Conclusion: CKD prevalence was 14.0% in a Hungarian subpopulation of healthcare-utilizing subjects in 2011-2019, and substantial under-reporting of CKD was also found.

Guidance on using real-world evidence from Western Europe in Central and Eastern European health policy decision making.

Aim: Real-world data and real-world evidence (RWE) are becoming more important for healthcare decision making and health technology assessment. We aimed to propose solutions to overcome barriers preventing Central and Eastern European (CEE) countries from using RWE generated in Western Europe. Materials & methods: To achieve this, following a scoping review and a webinar, the most important barriers were selected through a survey. A workshop was held with CEE experts to discuss proposed solutions. Results: Based on survey results, we selected the nine most important barriers. Multiple solutions were proposed, for example, the need for a European consensus, and building trust in using RWE. Conclusion: Through collaboration with regional stakeholders, we proposed a list of solutions to overcome barriers on transferring RWE from Western Europe to CEE countries.

Time trade-off health state utility values for depression: a systematic review and meta-analysis.

PURPOSE: This study aims to systematically review the literature on health utility in depression generated by time trade-off (TTO) method and to compare health state vignettes. METHODS: Systematic literature search was conducted following PRISMA guideline in 2020 November (updated in 2022 March) in Pubmed, Web of Science, PsycInfo, and Cochrane Database of Systematic Reviews. Random effect meta-analysis was conducted to pool vignette-based utility values of mild, moderate, and severe depression and to compare the preferences of depressed and nondepressed population. RESULTS: Overall, 264 records were found, 143 screened by title and abstract after removing duplicates, 18 assessed full text, and 14 original publications included. Majority of the studies (n = 9) used conventional TTO method, and most of the studies (n = 8) applied 10-year timeframe. Eight studies evaluated self-experienced health (own-current depression). Six studies assessed vignette-based health states of remitted, mild, moderate, and severe depression, half of them applied McSad measure based health description. Altogether, 61 different utility values have been cataloged, mean utility of self-experienced depression states (n = 33) ranged between 0.89 (current-own depression) and 0.24 (worst experienced depression). Pooled utility estimates for vignette-based mild, moderate, and severe depression was 0.75, 0.66 and 0.50, respectively. Meta-regression showed that severe depression (ß = -0.16) and depressed sample populations (ß = -0.13) significantly decrease vignette-based utility scores. CONCLUSION: Our review revealed extent heterogeneity both in TTO methodology and health state vignette development. Patient's perception of depression health states was worse than healthy respondents.

Prioritization of implementation barriers related to integrated care models in Central and Eastern European countries.

The importance of integrated care will increase in future health systems due to aging populations and patients with chronic multimorbidity, however, such complex healthcare interventions are often developed and implemented in higher income countries. For Central and Eastern European (CEE) countries it is important to investigate which integrated care models are transferable to their setting and facilitate the implementation of relevant models by identifying barriers to their implementation. This study investigates the relative importance of integrated care models and the most critical barriers for their implementation in CEE countries. Experts from Croatia, Hungary, Poland, Romania and Serbia were invited to complete an online survey within the SELFIE H2020 project. 81 respondents completed the survey. Although experts indicated that some integrated care models were already being implemented in CEE countries, the survey revealed a great need for further improvement in the integration of care, especially the managed care of oncology patients, coordinated palliative care of terminally ill patients, and nursing care of elderly with multimorbidity. Lack of long-term financial sustainability as well as of dedicated financing schemes were seen the most critical implementation barriers, followed by the lack of integration between health and social care providers and insufficient availability of human resources. These insights can guide future policy making on integrated care in CEE countries.

Heterogeneous impact of the COVID-19 pandemic on lung, colorectal and breast cancer incidence in Hungary: results from time series and panel data models.

OBJECTIVE: During the COVID-19 pandemic, health system resources were reallocated to provide care for patients with COVID-19, limiting access for others. Patients themselves also constrained their visits to healthcare providers. In this study, we analysed the heterogeneous effects of the pandemic on the new diagnoses of lung, colorectal and breast cancer in Hungary. DESIGN: Time series and panel models of quarterly administrative data, disaggregated by gender, age group and district of residence. PARTICIPANTS: Data for the whole population of Hungary between the first quarter of 2017 and the second quarter of 2021. MAIN OUTCOME MEASURES: Number of patients newly diagnosed with lung, colorectal and breast cancer, defined as those who were hospitalised with the appropriate primary International Classification of Diseases Tenth Revision diagnosis code but had not had hospital encounters with such a code within the previous 5 years. RESULTS: The incidence of lung, colorectal and breast cancer decreased by 14.4% (95% CI 10.8% to 17.8%), 19.9% (95% CI 12.2% to 26.9%) and 15.5% (95% CI 2.5% to 27.0%), respectively, during the examined period of the pandemic, with different time patterns across cancer types. The incidence decreased more among people at least 65 years old than among the younger (p<0.05 for lung cancer and p<0.1 for colorectal cancer). At the district level, both the previously negative income gap in lung cancer incidence and the previously positive income gap in breast cancer incidence significantly narrowed during the pandemic (p<0.05). CONCLUSIONS: The decline in new cancer diagnoses, caused by a combination of supply-side and demand-side factors, suggests that some cancer cases have remained hidden. It calls for action by policy makers to engage individuals with high risk of cancer more in accessing healthcare services, to diagnose the disease early and to prepare for effective management of patient pathways from diagnosis to survival or end-of-life care.

Barriers to Use Artificial Intelligence Methodologies in Health Technology Assessment in Central and East European Countries.

The aim of this paper is to identify the barriers that are specifically relevant to the use of Artificial Intelligence (AI)-based evidence in Central and Eastern European (CEE) Health Technology Assessment (HTA) systems. The study relied on two main parallel sources to identify barriers to use AI methodologies in HTA in CEE, including a scoping literature review and iterative focus group meetings with HTx team members. Most of the other selected articles discussed AI from a clinical perspective (n = 25), and the rest are from regulatory perspective (n = 13), and transfer of knowledge point of view (n = 3). Clinical areas studied are quite diverse-from pediatric, diabetes, diagnostic radiology, gynecology, oncology, surgery, psychiatry, cardiology, infection diseases, and oncology. Out of all 38 articles, 25 (66%) describe the AI method and the rest are more focused on the utilization barriers of different health care services and programs. The potential barriers could be classified as data related, methodological, technological, regulatory and policy related, and human factor related. Some of the barriers are quite similar, especially concerning the technologies. Studies focusing on the AI usage for HTA decision making are scarce. AI and augmented decision making tools are a novel science, and we are in the process of adapting it to existing needs. HTA as a process requires multiple steps, multiple evaluations which rely on heterogenous data. Therefore, the observed range of barriers come as a no surprise, and experts in the field need to give their opinion on the most important barriers in order to develop recommendations to overcome them and to disseminate the practical application of these tools.

Potential Barriers of Patient Involvement in Health Technology Assessment in Central and Eastern European Countries.

Patients' perspectives are important to identify preferences, estimate values and appreciate unmet medical needs in the process of research and development and subsequent assessment of new health technologies. Patient and public involvement in health technology assessment (HTA) is essential in understanding and assessing wider implications of coverage and reimbursement decisions for patients, their relatives, caregivers, and the general population. There are two approaches to incorporating the patients' voice in HTA, preferably used in a mix. In the first one, patients, caregivers and/or their representatives directly participate at discussions in different stages of the HTA process, often at the same table with other stakeholders. Secondly, patient involvement activities can be supported by evidence on patient value and experience collected directly from patients, caregivers and/or their representatives often by patient groups Patient involvement practices, however, are limited in Central and Eastern European (CEE) countries without clear methodology or regulatory mechanisms to guide patient involvement in the HTA process. This poses the question of transferability of practices used in other countries, and might call for the development of new CEE-specific guidelines and methods. In this study we aim to map potential barriers of patient involvement in HTA in countries of the CEE region.

Repetitive transcranial magnetic stimulation may be a cost-effective alternative to antidepressant therapy after two treatment failures in patients with major depressive disorder.

BACKGROUND: The cost-effectiveness of treatment strategies for patients with Major Depressive Disorder (MDD) who have not responded to two adequate treatments with antidepressants (TRD) are still unclear. The aim of this analysis was to evaluate the cost-effectiveness of add-on repetitive Transcranial Magnetic Stimulation (rTMS) compared with standard treatment. METHODS: A Markov-model simulated clinical events over one year from the perspective of healthcare payer. Third- and fourth-line treatment pathways (augmentation, antidepressant switch or combination, and Electro-Convulsive Therapy (ECT)) were defined based on medical practice guidelines. Transition probabilities were derived from a recent meta-analysis and scientific publications. Resource utilization and cost estimates were based on the patient-level database of a large university hospital. RESULTS: Incremental Quality-Adjusted Life Years (QALYs) and costs were 0.053 and 785 €, respectively, corresponding to an Incremental Cost-Effectiveness Ratio (ICER) of 14,670 € per QALY. The difference in cost between standard treatment and rTMS is explained by the rTMS sessions used in acute (€660) and maintenance (€57/month) treatments, partly offset by lower hospital costs due to higher remission rates in the rTMS arm. Key parameters driving the ICER were incremental utility of remission, unit cost of rTMS treatment and remission rate. At a threshold of €22,243 add-on rTMS is a cost-effective alternative to pharmacotherapy. Evidence on long-term effectiveness is not yet available, so results are estimated for a one-year period. CONCLUSION: Not only does rTMS treatment have beneficial clinical effects compared with drug therapy in TRD, but it also appears to offer good value-for-money, especially in centres with larger numbers of patients where unit costs can be kept low.

Effects of lower screening activity during the COVID-19 pandemic on breast cancer patient pathways: Evidence from the age cut-off of organized screening.

We examined the effects of the COVID-19 pandemic on the screening, diagnosis and treatment of breast cancer in Hungary based on administrative data until June 2021, covering three pandemic waves. After correcting for trend and seasonality, the number of mammography examinations decreased by 68% in 2020q2, was around its usual level in 2020q3 and was reduced by 20-35% throughout 2020q4-2021q2. The reduction was caused by a combination of supply-side (temporary suspensions of screening) and demand-side (lower screening participation during the pandemic waves) factors. The number of new breast cancer diagnoses and mastectomy surgeries responded with a lag, and were below their usual level by 15-30% in all quarters between 2020q2 and 2021q2, apart from 2020q4, when there was no significant difference. Using a regression discontinuity framework, we found that the partial mastectomy rate (indicative of early diagnosis) dropped more substantially in 2020q2 in the 61-65 years old age group that was just below the age cut-off of organized screening than in the 66-70 years old age group, and this difference was partially offset in 2021q1. We suggest that policymakers need to motivate the target population (by providing both information and incentives) to catch up on missed screenings.

Using real-world evidence in healthcare from Western to Central and Eastern Europe: a review of existing barriers.

As part of the HTx (Next Generation Health Technology Assessment) project, this study was aimed at identifying the main barriers for application of real-world evidence (RWE) for the purposes of health technology assessment in the Central and Eastern European countries. A mixed methods approach was employed to identify the main barriers: a scoping review of the literature and a series of discussions with stakeholders. Based on the applied approaches, we attempted to summarize the main barriers and challenges related to transferability of RWE in five main groups: technical, regulatory, clinical, scientific and perceptional barriers. Further research should pursue the development of detailed, consensus-based guidelines to improve the harmonization and standardization of RWE.

Implementation of coverage with evidence development schemes for medical devices: A decision tool for late technology adopter countries.

Experiences with coverage with evidence development (CED) schemes are fairly limited in Central and Eastern European (CEE) countries, which are usually late adopters of new health technologies. Our aim was to put forward recommendations on how CEE health technology assessment bodies and payer organizations can apply CED to reduce decision uncertainty on reimbursement of medical devices, with a particular focus on transferring the structure and data from CED schemes in early technology adopter countries in Western Europe. Structured interviews on the practices and feasibility of transferring CED schemes were conducted and subsequently, a draft tool for the systematic classification of decision alternatives and recommendations was developed. The decision tool was reviewed in a focus group discussion and validated within a wider group of CEE experts in a virtual workshop. Transferability assessment is needed in case of (1) joint implementation of a CED scheme; (2) transferring the structure of an existing CED scheme to a CEE country; (3) reimbursement decisions that are linked to outcomes of an ongoing CED scheme in another country and (4) real-world evidence transferred from completed CED schemes. Efficient use of available resources may be improved by adequately transferring evidence and policy tools from early technology adopter countries.

Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study.

BACKGROUND/OBJECTIVES: Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP. METHODS AND ANALYSIS: The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04647097.