Hemophilia is a rare, inherited bleeding disorder affecting an estimated 400,000 people worldwide (1). Characterized by spontaneous bleeding and long-term, irreversible joint damage, persons with hemophilia are often limited in normal day-to-day activities, including work/school, and require comprehensive care at specialized treatment centers. With replacement therapies extending survival by decades and vastly improving quality of life (QoL), routine prophylaxis is considered the standard-of-care in developed countries. However, due to the cost of replacement factor, access to treatment remains a challenge, and increased scrutiny over funding has been augmented by growing demands on healthcare budgets (2). Thus, the hemophilia community shares a unified goal of objectively defining patient-centered value in hemophilia care.

Using a three-tiered outcomes hierarchy model initially described by Porter (3), an international, multidisciplinary panel of health economics outcomes researchers and hemophilia experts developed a value framework for decision makers to assess value of various healthcare interventions in hemophilia.

The three tiers for assessing value are: (i) Health status achieved/retained; (ii) Process of recovery; and (iii) Sustainability of health. Tier one measures survival, quality of life (QoL), and hemophilia-specific outcomes of bleeding frequency, musculoskeletal complications, and severe bleeds, as well as function/activity (that is, lifestyle impairment). Tier two measures time to initial treatment or recovery and time missed at education/work, as well as disutility of care (that is, inhibitor development, pathogen transmission/infections, orthopedic intervention, and venous access). Tier three measures avoidance of bleeds, maintenance of productive lives, and long-term health, while capturing long-term consequences of insufficient therapy or age-related complications. Applicability of the framework can be demonstrated in areas of healthcare delivery, treatment regimen, and innovation for new therapies.

This value framework represents an initial collaboration with stakeholders to define and organize an array of patient-centric outcomes of importance in hemophilia into a practical tool that can influence treatment and funding decisions in hemophilia care.

The experience of implementing a hospital-based health technology assessment (HB-HTA) system in Kazakhstan is currently represented by only one organization, an independent HB-HTA unit established in 2015 in the Medical Center Hospital of the President's Affairs Administration (the Hospital). Despite the demonstrated positive experience of the Hospital, the widespread implementation of the HB-HTA system in Kazakhstan has experienced some barriers that must be considered before further development can occur.

To determine the barriers to developing and implementing HB-HTA in Kazakhstani hospitals, data from the Hospital's experience were obtained through a survey of Kazakhstan hospitals, conducted on behalf of the Ministry of Health Care. An official response was received from 29 hospitals. During the survey and discussions with hospital staff using the “brainstorming” method, several barriers to the development of HB-HTA in Kazakhstan were identified.

Barriers at the system level included the lack of monitoring of the HB-HTA system at the national and regional levels and a lack of methodological support. Organizational barriers included a critically small number of HTA experts and the need for additional logistical support and funding from hospitals. The subjective factors we attributed to the rejection of the HB-HTA system by hospital management were the underestimation of lost profits and that HTA is a tool for promoting a transparent and open system for making managerial decisions.

Despite some barriers, the development of HB-HTA in Kazakhstan is a promising area. The heads of key hospitals in Kazakhstan demonstrated a readiness and understanding of the need to use the principles of health technology assessment and clinical and economic analysis to promote the active transfer and implementation of innovative medical technologies.

Dry eye disease (DED) is a common condition that significantly impacts patients’ quality of life. Previous studies have explored the impact of DED on patients’ lives qualitatively; however, patients’ preference structures have not been thoroughly explored quantitatively.

A targeted literature review and social media listening project guided design of a discussion guide for in-depth patient interviews (n=12). These, in turn, guided construction of a quantitative questionnaire administered to moderate to severe DED patients, 40 per country in Australia, Germany, United States and United Kingdom (total n=160). Patients’ preference structures were explored through an online survey using a self-explicated conjoint methodology, because of its high respondent-friendliness. Additionally, we administered the EQ5D-5L instrument to determine the health states/utilities of patients. Reaction to a hypothetical novel treatment was further obtained to check for convergent validity with the self-explicated conjoint. Finally, we asked respondents to rate the ease and relevance of the questionnaire to them.

Qualitative research uncovered important patient perspectives that were built into the quantitative survey. For example, patients seek medical advice when their symptoms are not improving. Patients’ lives are most affected by sensitivity to light, itchy and tired eyes and an inability to perform computer/screen work; however, of most concern/worrying to them is that their DED will get worse and they go blind. Results from the quantitative preference research will also be shared and its implications for future clinical trials in DED outlined. The results of the patient research and preference study are to be shared with health technology assessment (HTA) bodies and regulators through the early dialogue scientific advice process.

A process of using qualitative research to determine what matters to patients and then quantification through respondent-friendly preference research can identify outcomes that are most patient-relevant, to inform future drug development strategies.

Health Technology Assessment (HTA) Process assists decision-making in health policies. The COVID-19 pandemic caused a high demand on protocol or guideline updates and incorporation of new drugs or therapies, overwhelming local agencies. A recent study reported that major HTA bodies in England, Scotland, Germany, and Canada reduced their number of drug recommendations in 2020, due to reprioritization of resources and COVID-related challenges. The present study aimed to evaluate the impact of the COVID-19 pandemic at the Brazilian National Committee for Health Technology Incorporation (Conitec) recommendation process.

This descriptive study evaluated all official recommendation reports available on the Government website in 2020 and 2021, extracting the data of disease category, technology type, the aim of the report, Public Involvement, and final result for the recommendation. The results were presented in tabular and graphical form using the machine learning, through the software R studio and excel.

A total of 168 documents were evaluated, including guidelines and recommendation reports, with no reduction in the number of evaluations considering 2019. In 2020, there was a more significant evaluation of guidelines, and in 2021, a report on the non-incorporation of technologies. There were four specific documents about COVID 19, including vaccines and hospital care guidelines. The most incorporated and non-incorporated technologies were medication, targeting rare and highly prevalent diseases in balance. The Brazilian government was the main proposer. These results are part of the study “A Survey about the core methods of the recommendation reports for Brazilian Ministry of Health carried out by Brazilian Health Technology Assessment Centers”, which will characterize and analyze the core methods of the recommendation reports conducted by the Brazilian HTA Centers.

The pandemic had a low impact on demands in the routine of the Conitec. Establish indicators and technological norms applicable to health services, contribute to the identification of possible new practices, methods or criteria.

Early identification of innovative medicines is crucial for timely health technology assessment (HTA) and efficient patient access. The National Institute for Health Research Innovation Observatory (NIHRIO) identifies, monitors and notifies key HTA stakeholders in England of ‘technologies’ (innovative medicines) within three to five years of regulatory approval. Increasing numbers of innovative medicines and significant uncertainties in clinical and regulatory pathways are major challenges in the monitoring and notification process. An active monitoring framework using pre-defined predictive criteria has previously been developed. This framework provides a standardized and consistent process, but is highly resource-intensive, requiring manual review of individual records.

Using the previous active monitoring framework, a scoring matrix was calculated and used to prioritize individual technologies using available data in the NIHRIO database: estimated regulatory timelines, regulatory awards/designations, innovative medicine type (for example gene therapies) and clinical trial phase, completion dates and results. A threshold for automatic and manual reviewing of technologies was developed and tested by NIHRIO analysts.

The scoring system identified approximately ninety percent of technologies meeting the threshold for semi-automated reviewing. The review period for these technologies are set automatically according to predefined criteria depending on data availability. The review periods are updated automatically until the record reaches the threshold that triggers manual reviewing. The remaining ten percent had estimated regulatory timelines necessitating the need for manual reviewing and early engagement with companies to verify regulatory timelines and/or notify HTA stakeholders.

Preliminary analysis indicates that each technology is routinely and automatically updated. The semi-automatic updating represents a significant improvement in the efficiency of the monitoring of the large volume of technologies on the NIHRIO database. Ongoing work is being undertaken to further refine, pilot and test the system.

This project is funded by the NIHR [(HSRIC-2016-10009)/Innovation Observatory]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

For the assessment of videorasterstereography compared with radiography for monitoring idiopathic scoliosis, new tools given by the INTEGRATE-HTA methodology were included within the frame set by the authority. In contrast to the usual linear approach by covering the single domains' safety and efficacy, costs, and ethical, legal, socio-cultural and organizational issues (ELSOI) separately, the methodology is based on the assumption of interactions of different aspects of the domains. From the very beginning, these interactions are captured systematically using various tools and are repeatedly discussed with stakeholders.

Relevant databases were systematically searched for studies and question catalogues were processed in order to be able to search for specific aspects in orienting bibliographic research. An initial logic model was developed and successively expanded. A synoptic table showing multiple mapping of aspects to domains, a complexity checklist, and a semantic complex highlighting the socio-cultural impact of the disease were newly developed.

Four diagnostic studies with high risk of bias were included. For the clinical outcome, Cobb angle standard deviations up to 8.2 degrees and average measurement differences up to 8.8 degrees were determined. These differences in measurement accuracy correspond to those observed for purely radiographic measurements in other studies. In addition to freedom from radiation as the greatest advantage, there were clear arguments in favor of videorasterstereography when considering ELSOI, for example less harm.

Using INTEGRATE-HTA contributes to identify interactions between domains and to significantly expand the perspective on a technology. It improves patient-centered understanding and facilitates discussions.

Involving patients in defining the scope of health technology assessments is recognized as a valuable strategy that ensures that patient-relevant outcomes are considered.

The aim of this project was to pilot the focus group approach with cardiac patients in a European rapid assessment on the wearable cardioverter defibrillator, to improve involvement processes, to identify neglected outcomes, and to explore the potential of this methodology for eliciting the patients views on their disease and the wearable cardioverter defibrillator therapy.

An e-mail was sent to members of the nine regional associations of the Austrian Organization for Heart and Lung Transplant Patients to identify eligible participants. Guiding questions for the discussion were developed based upon a hand search of patient involvement initiatives and a review of appropriate literature. The 4-hour meeting was moderated by a patient support expert and recorded upon approval of participants. The anonymized transcript was analyzed using framework analysis.

Ten eligible patients responded, of which five men, aged between 55 and 73 years (mean 65 years) from Austria and Germany, were able to participate. All respondents experienced heart transplantation, and four had received an implantable cardioverter defibrillator before.

Participants reported that experiencing a sense of security was crucial to them and that they expected to do sports and live a life with few limitations, despite receiving a therapy. A wearable cardioverter defibrillator was hence not considered a long-term solution due to expected restrictions in living a ‘normal’ life.

Challenges included the identification of participants representative of this patient group and the complexity of patient histories.

The focus group approach proved useful in the wearable cardioverter defibrillator assessment. Gathered results informed the inclusion of outcomes relevant to the target group and revealed patients views on health-related quality of life. Lessons learned guide us in further improving patient involvement processes within the European Network for HTA (EUnetHTA) project.

We aimed to develop and validate machine learning (ML) -based algorithms to predict COVID-19 diagnosis as well as to identify new biomarkers associated with the disease.

Initially, 96 blood samples of patients diagnosed with COVID-19 (Thaizhou Hospital, China) were analyzed through liquid chromatography coupled to mass spectrometry. Samples of patients presenting other pneumonias or severe acute respiratory syndrome, but with negative RT-PCR for SARS-CoV-2, were used as positive controls. Samples from healthy volunteers were used as negative controls. The final database included around 1000 metabolites. Exploratory analyses for the development of ML-based models using principal component analysis (PCA) were performed. Leverage plot versus studentized residuals method was used to detect outliers. Three supervised ML-based models were developed: discriminant analysis by partial least squares (PLS-DA), artificial neural networks discriminant analysis (ANNDA) and k-nearest neighbors (KNN). Samples for the training (70%) and testing sets (30%) were randomly selected using the Kenrad Stone algorithm. Models’ performance was evaluated considering accuracy, sensitivity and specificity. Analyses were conducted in SOLO (Eigenvector-Research).

The PCA model was able to distinguish the three classes of patients’ samples (positive for COVID-19, negative controls, positive controls) with an overall accumulated variance of 94.27 percent. The PLS-DA model presented the best performance (accuracy, sensitivity, and specificity of 93%, 98% and 88%, respectively). Increased levels of the biomarkers uridine (linked to glucose homeostasis, lipid, and amino acid metabolisms), 4-hydroxyphenylacetoylcarnitine (metabolite from the tyrosine metabolism; probably associated with anorexia) and ribothymidine (resulting from oral and fecal microbiota alterations) were significantly associated with COVID-19.

Three different and updated ML-based algorithms were developed to predict COVID-19 diagnosis; PLS-DA led to the most accurate results. High levels of some metabolites were found as potentially predictors of the disease. These biomarkers should be further evaluated as potential therapeutic targets in well-designed clinical trials. These ML-based models can help the early diagnosis of COVID-19 and guide the development of tailored interventions.

Uveitis is inflammation inside the eye whose underlying cause may be infectious or non-infectious. The objective of our study was to assess the cost-effectiveness of the dexamethasone implant and adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or pan-uveitis.

A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the relevant evidence. Quality of life data collected in three key randomized-controlled trials (1-3) was used to estimate the interventions effectiveness compared with the trials comparator arms, which consisted of placebo plus limited current practice (LCP). An indirect treatment comparison between adalimumab and dexamethasone was considered inappropriate due to lack of necessary evidence. For adalimumab, patients with active and inactive uveitis were considered separately. Due to the short duration of the trials, the rate of blindness, an important complication of uveitis, was highly uncertain. Substantial exploratory analyses were therefore undertaken. The analysis was performed from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). Costs were calculated based on standard United Kingdom sources.

The estimated incremental cost-effectiveness (ICER) of dexamethasone compared with LCP was GBP19,509 per quality-adjusted life year (QALY) gained. The estimated ICER of adalimumab compared with LCP was GBP94,523 and GBP317,547 per QALY in patients with active and inactive uveitis respectively. The factors with the largest impact upon the ICERs were the rate of blindness and the proportion of cases of blindness avoided by interventions.

Dexamethasone and adalimumab resulted in health gains, but at significant extra costs, especially adalimumab which is unlikely to be considered a cost-effective use of NHS resources. The results of the analysis are highly uncertain due to the limited availability of evidence on: the comparative effectiveness of dexamethasone, adalimumab and current practice; the effectiveness of treatments in avoiding blindness; and, the effectiveness of interventions in different subgroups.

Written patient evidence is submitted to the National Institute for Health and Care Excellence (NICE) by patient organizations and their nominated patient experts. We reviewed the impact that patient evidence had on the committee's decision making. This local learning can help generate global opportunities for Health Technology Assessment (HTA) bodies and patient groups to further develop their understanding and methodology about how patient evidence can support HTA decision making for ultra-orphan conditions.

There were two phases.

Phase one was an online questionnaire about the impact of patient evidence on the committee's decision making for ultra-orphan HTA evaluations. It was sent to the committee chair, lay committee members and selected other committee members.

Phase 2 developed the initial questionnaire findings using in-depth interviews with the committee chair and the lay members. These gained further understanding of the impact of patient evidence and the themes raised.

Key findings showed patient evidence was helpful to understand the:

• • Burden of disease

• • Patient population

• • Likely uptake of new medicines

• • Impact on carers.

For ultra-orphan conditions, where other forms of evidence are scarcer, patient evidence is fundamental to understanding patient needs, the impact of the disease, patient population and preferences.

Patient evidence was useful for the committee in different ways; it provided the committee with new evidence and it helped the committee understand and interpret the evidence submitted by others. Both are key to committee decision making. It was clear that due to the very small patient population, patient groups knew the patient population, their stage of disease, and their preferences in detail.

The findings will be used to inform an updated patient submission template for ultra-orphan HTAs, and supporting guide. These will be available on the NICE website and offered to the HTAi Interest Group on Patient and Citizen Involvement so they can be shared globally.

The National Institute for Health and Care Excellence (NICE) may recommend temporary funding through managed access agreements (MAAs) for oncology drugs (via the Cancer Drugs Fund [CDF]) and highly specialized therapies for rare diseases. MAAs allow for the collection of evidence to address key areas of clinical uncertainty, while providing access of medicines to patients, prior to re-appraisal by NICE. Observational data and other real-world evidence (RWE) are crucial requirements for all MAAs and herein we examine the extent these data are being used to inform HTA decisions at re-appraisal.

Existing MAAs entered into between the National Health Service (NHS) England and manufacturers as of 30 October 2018 were identified; for drug:indication pairings with NICE re-appraisals, all information was reviewed and the key data extracted.

Of the twenty-two MAAs identified, only two drug:indication pairings have been subsequently re-appraised by NICE: BV(brentuximab vedotin):non-Hodgkin lymphoma (’recommended’) and pembrolizumab:relapsed or refractory classical Hodgkin lymphoma (’recommended’). Data from a retrospective questionnaire regarding the proportion of patients that received curative stem cell transplant (SCT) post-BV (from patients who received BV in the old CDF) were accepted to provide sufficient evidence on the post-BV SCT rate by NICE. Meanwhile, for pembrolizumab, long-term survival benefit was the key clinical uncertainty; the primary data collection source was updated phase III randomized controlled trial data. At re-appraisal no reference was made to the observational data component; more mature survival data reduced uncertainty over survival benefits and were sufficient to support a positive NICE recommendation.

Of the twenty-two MAAs to date, only two drugs have been re-appraised thus far, with both receiving positive NICE recommendations. Observational data were successfully used to address key clinical uncertainties regarding subsequent real-world treatment patterns for BV, but observational data were not referred to in the NICE recommendation for pembrolizumab. The re-appraisal of more drugs in the future will clarify the importance being placed on observational data collection requested by NICE for existing MAAs.

Social engagement in health encompasses the idea of involving (parts of) society as full partners in the decision-making regarding both development and implementation of health technologies. Evidence shows that patient engagement is linked with fewer adverse events, better patient self-management, fewer diagnostic tests, decreased use of healthcare services and shorter lengths of stay in hospitals. Matching the escalating healthcare requirements to face the ongoing societal and economic challenges regarding access and coverage to (new) health technologies is not an easy task for health providers.

We conducted a systematic review (CRD42017068714) designed to address the institutional implementation of social engagement by the Brazilian Ministry of Health. All systematic reviews were evaluated using the new version of AMSTAR and, once all findings are synthesized, we will use the GRADE-CERQual approach to assess for confidence.

From 399 publications that met the inclusion criteria, 80 described the implementation of social engagement during the development and implementation of (new) health technologies at various levels (local, regional, national, supranational), countries and for different health technologies and social actors. The remaining 319 publications constitute case studies describing barriers and enablers to implementing social engagement in HTA and coverage decision-making processes. By mapping barriers and facilitators, we explored effectiveness and sustainability, further observing how citizen science-based strategies can ultimately reform health service delivery by innovating the social engagement in health technology development and implementation.

This systematic review addresses the know-do gap on social engagement in health technology development and implementation, from a global perspective, as a way of improving the Brazilian Ministry of Health's HTA activities and enabling a Brazilian strategy to reform health service delivery. Enabling social engagement as early as possible, during all the stages of the development cycle, grants a more effective and sustainable health care system.

The Health Technology Assessment (HTA) process aims to optimize health system funding of technologies. In recent years there has been an increase in what is known as Real-World Evidence (RWE) as a complement to clinical trials. The objective of Health Technology Assessment International’s Latin American Policy Forum 2022 was to explore the utility of incorporating RWE into HTA and decision-making processes in the region.

This article is based on a background document, survey, and the deliberative work of the country representatives who participated in the Forum.

There is a growing interest in the use of Real-World Data / Real-World Evidence in HTA processes in Latin America, although currently there are no specific local guidelines for RWE use by HTA agencies. At present, its use is limited to certain areas such as adding context to HTA reports, the evaluation of adverse events, or cost estimation.

Potential future uses of RWE were identified, including the creation of risk-sharing agreements, the assessment of technology performance in routine practice, providing information on outcomes that are not so easily evaluated in clinical trials (e.g., the identification of specific subpopulations or quality of life), and the estimation of input parameters for economic evaluations.

The participants agreed that there are several areas presenting significant potential to expand the application of RWD/RWE and that the development of normative frameworks for its use could be helpful.

The Patient-Centered Outcomes Research Institute (PCORI) horizon scanning system is an early warning system for healthcare interventions in development that could disrupt standard care. We report preliminary findings from the patient engagement process.

The system involves broadly scanning many resources to identify and monitor interventions up to 3 years before anticipated entry into U.S. health care. Topic profiles are written on included interventions with late-phase trial data and circulated with a structured review form for stakeholder comment to determine disruption potential. Stakeholders include patients and caregivers recruited from credible community sources. They view an orientation video, comment on topic profiles, and take a survey about their experience.

As of March 2020, 312 monitored topics (some of which were archived) were derived from 3,500 information leads; 121 met the criteria for topic profile development and stakeholder comment. We invited fifty-four patients and caregivers to participate; thirty-nine reviewed at least one report. Their perspectives informed analyst nominations for fourteen topics in two 2019 High Potential Disruption Reports. Thirty-four patient stakeholders completed the user-experience survey. Most agreed (68 percent) or somewhat agreed (26 percent) that they were confident they could provide useful comments. Ninety-four percent would recommend others to participate.

The system has successfully engaged patients and caregivers, who contributed unique and important perspectives that informed the selection of topics deemed to have high potential to disrupt clinical care. Most participants would recommend others to participate in this process. More research is needed to inform optimal patient and caregiver stakeholder recruitment and engagement methods and reduce barriers to participation.

Appropriate resource utilization is crucial for cancer screening programs. Overscreening is defined as screening provided beyond the upper age limit of the target age or at a shorter interval than recommended in national programs. In Japan, there are no upper age limits set for cancer screening programs, and the recommended screening interval for cervical and breast cancer screening is 2 years. To examine the efficient use of resources for cervical and breast cancer screening, we investigated how often overscreening occurred in both programs.

The target age for this study was defined as 20-69 years for cervical cancer screening and 40-69 years for breast cancer screening. We used the national report for cancer screening in 2017 in Japan and estimated the number of participants over 70 years old or those who participated in screening annually. The percentage of overscreening was compared between cervical cancer and breast cancer screening by chi-square test.

The number of participants was 4,294,127 for cervical cancer screening and 3,087,781 for breast cancer screening in 2017. The percentage of overscreening in total participants was 38.0 percent for cervical cancer screening and 35.7 percent for breast cancer screening (p<0.01). The percentage of screening at overage was higher in breast cancer screening than in cervical cancer screening (21.1% vs. 13.9%, p<0.01), whereas more frequent screening was seen more often in cervical cancer screening than in breast cancer screening (29.7% vs. 19.6%, p<0.01). If the resources used in overscreening could be used for the target population, it was estimated that the participation rate could increase by 4.1% for cervical cancer screening and 4.3% for breast cancer screening.

In Japan, screening for overage participants and short intervals may have contributed to unnecessary screening for cervical cancer and breast cancer. These resources used for overscreening could be allocated to screening for the target population.

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in CFTR gene. In Italy, reported prevalence is approximately .70 per 10,000 inhabitants (1). The practice and recommendations for Cystic Fibrosis carrier screening are very heterogeneous in Europe. A proposal of a carrier genetic test in the general population raises many questions. Health Technology Assessment (HTA) could offer a sound methodological basis for this evaluation. The aim of this work was to summarize the available evidence, using the HTA approach, on the genetic tests for Cystic Fibrosis carrier screening.

A systematic literature search was used to find the best available international and national evidence on genetics test for CF carrier screening. In this report, we specifically addressed the health problem of disease, description and technical characteristics of tests – its analytic and clinical validity, and clinical utility. Economic evaluation of different scenarios was synthesized from the literature. Ethical, organizational, and social aspects of CF and genetic screening were also considered.

Several screening strategies have been evaluated in the literature and screening options can be characterized by different timing, model and place of screening (2). The reported cost of a screening test ranged from EUR25 to EUR212 (3). Estimated life time cost of care for CF patients ranged from EUR291,048 to EUR1,105,452. Ethical analysis emphasized that the use of these tests is an advantage in terms of the acquisition of knowledge and of responsible management of choices, but at the same time raises many ethical questions. Social considerations reported among patients and their families an overall positive attitude toward population CF carrier screening.

The advances in the molecular genetics technology have made CF carrier testing reliable and affordable. The multidisciplinary approach of this HTA provided an evidence-based evaluation of genetic tests and offers a firm scientific background for the decision-makers to consider the implementation of a screening for Cystic Fibrosis carriers into the Italian health care system.