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Resource modeling aims to explicitly quantify the effects of adopting new health care technologies in settings with capacity-related constraints. The aim of this analysis was to use resource modeling to explore the effects of the uptake of first-line treatment with daratumumab on wait lists and wait times in patients with untreated multiple myeloma. Two formulations were compared: the standard IV formulation (DARA-IV) and a recently approved SC formulation (DARA-SC).First, semi-structured interviews at six oncologic centers were used to retrieve data on the management of patients given a DARA-IV regimen. Second, a discrete event simulation (DES) model was built to estimate the effects on resource consumption, wait lists, and wait times in scenarios with different incident numbers of patients treated with either DARA-IV or DARA-SC.In all of the simulated scenarios with more incident patients initiated on first-line treatment with DARA-IV, the actual capacity of infusion chairs was not enough to meet the demand, leading to increases in wait times and wait lists. In the highest-demand scenario, 17 more infusion chairs per center would be required to avoid such increases. Treatment with DARA-SC would allow centers to meet the demand with their actual capacity.DES modeling can effectively be used to formally explore the effects of different formulations on the use of limited resources, wait lists, and wait times at the facility level. Based on the findings from this analysis, DARA-SC may free up resources and prevent short- and long-term costs to infusion centers.

Introduction: The incidence of foot fractures is increasing. These types of fractures represent the most expensive group of diagnoses in the emergency department. Next to this, the need for economic evaluation studies is growing fast. The aim of this article is to provide healthcare professionals with an introduction to economic evaluation studies in the field of foot fractures.Types of economic evaluation studies: Four types of economic evaluation studies exist: cost-minimization analysis (CMA), cost-benefit analysis (CBA), cost-effectiveness analysis (CEA), and cost-utility analysis (CUA). An economic evaluation study can be either trial- or model-based.Cost assessment: When assessing costs in an economic evaluation study, three steps need to be made: identification of costs, measurement of costs, and valuation of costs.Perspective of analysis: Two main perspectives exist in economic evaluation studies. When using a healthcare perspective, only the potential costs and benefits of an intervention for the healthcare sector are included. The societal perspective includes all potential costs, including societal costs.Synthesis of costs and effects and uncertainty analysis: The level of cost-effectiveness can be objectively expressed using the incremental cost-effectiveness ratio (ICER). This measure can be plotted in a cost-effectiveness plane and can be compared with existing regional ceiling ratios.Conclusion: Although this article is not a guideline for economic evaluations, we do want to present five tips to consider when performing an economic evaluation. Firstly, when measuring resource use, consult the Database of Instruments for Resource Use Measurements (DIRUM) to find an appropriate instrument. Secondly, when measuring utility values, use the EuroQol questionnaire if possible. Thirdly, when setting up an economic evaluation study, consult the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) database for the appropriate pharmacoeconomic guidelines. Fourthly, consult international guidelines to decide which study design is most appropriate. Finally, when performing an economic evaluation, consult a heath technology assessment (HTA) specialist from the start to ensure methodological quality. (C) 2022 The Author(s). Published by Elsevier Ltd.

Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.

Background Health Technology Assessment (HTA), which can support public drug reimbursement decisions will play a core function in the planned national Pharmacare program in Canada. To address existing barriers to the use of HTA, these must be ranked in order of priority. The goal of this study was to access the relative importance of known facilitators and barriers to the use of HTA in the context of the Canadian health care system, with attention to differences between regions and stakeholder groups. Methods We used the best-worst scaling object case approach to elicit a quantitative ranking of a list of 20 facilitators and 22 barriers. A sample of 68 Canadian HTA stakeholders, including members of expert committees, decision/policymakers, researchers/academics, and others participated in the study. Their task was to identify the most important and the least important item in 12 sub-sets of five facilitators and 14 sub-sets of five barriers. Findings Relative Importance Scores derived via hierarchical Bayes analysis revealed relations, engagement, and contact between stakeholders as most important on both the barrier and facilitator sides. Other top-ranked facilitators included the availably of credible and relevant research. Other top-ranked barriers included inconsistencies in the evidence and limited generalizability. The availability of HTA guidelines did not rank highly on either side. The main limitation of the study was the challenge with reaching the relevant respondents; this was mitigated by involving the national HTA agency in the research. Conclusion Canadian stakeholders consider the relationships within the HTA network among the most important. Policies should focus on strengthening these relationships. Future research should focus on the connectivity and distribution of knowledge and power within the HTA network.

Due to uncertainty regarding the potential impact of unmeasured confounding, health technology assessment (HTA) agencies often disregard evidence from nonrandomized studies when considering new technologies. Quantitative bias analysis (QBA) methods provide a means to quantify this uncertainty but have not been widely used in the HTA setting, particularly in the context of cost–effectiveness modelling (CEM). This study demonstrated the application of an aggregate and patient-level QBA approach to quantify and adjust for unmeasured confounding in a simulated nonrandomized comparison of survival outcomes. Application of the QBA output within a CEM through deterministic and probabilistic sensitivity analyses and under different scenarios of knowledge of an unmeasured confounder demonstrates the potential value of QBA in HTA.

Evidence generated from nonrandomized studies (NRS) is increasingly submitted to health technology assessment (HTA) agencies. Unmeasured confounding is a primary concern with this type of evidence, as it may result in biased treatment effect estimates, which has led to much criticism of NRS by HTA agencies. Quantitative bias analyses are a group of methods that have been developed in the epidemiological literature to quantify the impact of unmeasured confounding and adjust effect estimates from NRS. Key considerations for application in HTA proposed in this article reflect the need to balance methodological complexity with ease of application and interpretation, and the need to ensure the methods fit within the existing frameworks used to assess nonrandomized evidence by HTA bodies.

Background and aims: There is an alarming delay in Europe for anticancer medicines becoming accessible for children. Following a paediatric European Union marketing authorisation, national Health Technology Assessment (HTA) agencies evaluate effectiveness, and safety of medicines to support decision on their cost and reimbursement. This study (a SIOPE Access to Medicines project) aimed to evaluate how these HTA evaluations take place for anticancer medicines indicated for paediatric use in Europe and to explore where the delays for market access originate. Methods: We obtained HTA reports from the public domain for nine European countries for blinatumomab, dinutuximab beta and tisagenlecleucel. We evaluated the time elapsed between marketing authorisation for a paediatric indication and a national HTA decision and the nature of the decision. Results: Out of 23 HTA decisions (four countries without blinatumomab report), 18 were positive, two with restrictions, three negative. For blinatumomab, tisagenlecleucel and dinutuximab beta, the median time to an HTA decision after regulatory approval for paediatric use was 353 days (range 193–751), 141 days (range 77–517) and 515 days (range 0–780), respectively, with variability between countries. Dinutuximab beta and tisagenlecleucel were first introduced in children, but did not result in shorter time to HTA decision. For blinatumomab, marketing authorisation followed 1008 days after the indication in adults, with HTA applications submitted a median of 167 days later, and a recommendation after 145 days. Conclusions: This study reveals ample variability in HTA decision making in nine European Union countries. Collaboration and alignment of required evidence is needed to facilitate robust scientific HTA assessments, also considering methodological challenges in paediatric oncology.

Introduction The use of oral FTC/TDF for pre-exposure prophylaxis (PrEP) among high-risk people without HIV is emerging as an innovative strategy to decrease HIV epidemic. The study aims at evaluating the implications related to PrEP introduction, from a multidimensional point of view, with particular attention to the sustainability of its implementation. Methods To achieve this objective a Health Technology Assessment was conducted, within 35 Italian Infectious Disease Departments. Data were collected from literature review and using validated questionnaires and literature evidence. The introduction of PrEP (applied as “add-on” and “substitute” prevention strategy) into the clinical practice was compared with a baseline scenario (use of condoms among men who have sex with men and serodiscordant couples, and the use of Needle Syringe Programme among injection drugs users). Results Despite the improvement in patients’ quality of life, PrEP would generate a decrease of patient safety, and an increase in staff workflow, with investment in medical supplies and training courses. PrEP would lead to significant economic investments both for the NHS, and for citizens (40% and 2,377% respectively) if used as an add-on strategy, assuming FTC/TDF patent cost. With the off-patent drug, the NHS would benefit from an advantage (37%) and a shrink of the patients’ expenditure emerged (+682%). More economic resources are required if PrEP is applied as a substitute strategy, considering both the patent (NHS: 212%; citizens: 3,423%) and the off-patent drug (NHS: 73%; citizens: 1,077%). Conclusions The most cost-containing strategy would be the use of PrEP, as an add-on strategy, assuming the off-patent drugs, even if safety and organisational aspects would be deeply considered., Journal of Preventive Medicine and Hygiene, Vol. 61 No. 3 (2020): 2020613

In the drive towards faster patient access to treatments, health technology assessment (HTA) agencies are increasingly faced with reliance on evidence from surrogate endpoints, leading to increased decision uncertainty. This study undertook an updated survey of methodological guidance for using surrogate endpoints across international HTA agencies. We reviewed HTA and economic evaluation methods guidance from European, Australian and Canadian HTA agencies. We considered how guidelines addressed the methods for handling surrogate endpoints, including (1) level of evidence, (2) methods of validation, and (3) thresholds of acceptability. Across the 73 HTA agencies surveyed, 29 (40%) had methodological guidelines that made specific reference to consideration of surrogate outcomes. Of the 45 methods documents analysed, the majority [27 (60%)] were non-technology specific, 15 (33%) focused on pharmaceuticals and three (7%) on medical devices. The principles of the European network for Health Technology Assessment (EUnetHTA) guidelines published in 2015 on the handling of surrogate endpoints appear to have been adopted by many European HTA agencies, i.e. preference for final patient-relevant outcomes and reliance on surrogate endpoints with biological plausibility and epidemiological evidence of the association between the surrogate and final endpoint. Only a small number of HTA agencies (UK National Institute for Care and Excellence; the German Institute for Medical Documentation and Information and Institute for Quality and Efficiency in Health Care; the Australian Pharmaceutical Benefits Advisory Committee; and the Canadian Agency for Drugs and Technologies in Health) have developed more detailed prescriptive criteria for the acceptance of surrogate endpoints, e.g. meta-analyses of randomised controlled trials showing strong association between the treatment effect on the surrogate and final outcomes. As the decision uncertainty associated with reliance on surrogate endpoints carries a risk to patients and society, there is a need for HTA agencies to develop more detailed methodological guidance for consistent selection and evaluation of health technologies that lack definitive final patient-relevant outcome evidence at the time of the assessment.

Digital health and mobile medical apps (MMAs) have shown great promise in transforming health care, but their adoption in clinical care has been unsatisfactory, and regulatory guidance and coverage decisions have been lacking or incomplete. A multidimensional assessment framework for regulatory, policymaking, health technology assessment, and coverage purposes based on the MMA lifecycle is needed. A targeted review of relevant policy documents from international sources was conducted to map current MMA assessment frameworks, to formulate 10 recommendations, subsequently shared amongst an expert panel of key stakeholders. Recommendations go beyond economic dimensions such as cost and economic evaluation and also include MMA development and update, classification and evidentiary requirements, performance and maintenance monitoring, usability testing, clinical evidence requirements, safety and security, equity considerations, organizational assessment, and additional outcome domains (patient empowerment and environmental impact). The COVID-19 pandemic greatly expanded the use of MMAs, but temporary policies governing their use and oversight need consolidation through well-developed frameworks to support decision-makers, producers and introduction into clinical care processes, especially in light of the strong international, cross-border character of MMAs, the new EU medical device and health technology assessment regulations, and the Next Generation EU funding earmarked for health digitalization.

Objectives To conduct a formative evaluation of applying the VALIDATE approach in practice by (i) assessing how students appreciated the e-learning course, (ii) exploring how, for what purposes and with what outcomes the acquired VALIDATE competences subsequently were used in internships in different institutional contexts, and how this was shaped by these contexts, and (iii) what this shows on real-world use of VALIDATE. Methods Comparative discussion of experiences of applying the VALIDATE approach via a semistructured survey and oral feedback from e-course students; final reports on internships in health technology assessment (HTA) practice, followed by semistructured interviews with interns and supervisors to complement and interpret results. Results All students considered the VALIDATE approach an enlightening and important addition to current HTA knowledge, especially regarding understanding the relation between empirical analysis and normative inquiry, identifying policy relevant questions and using the method of reconstructing interpretive frames for scoping. The latter appeared intellectually challenging and requiring some prior HTA knowledge. The use the VALIDATE approach in practice shows that interns productively redefined the HTA problem, based on appreciation of different stakeholders’ definition of the issue; they experienced constraints from retrieving all relevant perspectives from existing literature as well as from institutional rules and routines. Conclusions Some challenges in applying the VALIDATE approach deserve attention for its future use: currently used research approaches often assume a problem as “given”; and the data needed on different perspectives is often not reported in scientific literature. Finally, data gathering on and evaluation of value dimensions was experienced as challenging.

Three directly acting antivirals (DAAs) demonstrated substantial reduction in COVID-19 hospitalizations and deaths in clinical trials. However, these agents did not completely prevent severe illness and are associated with cases of rebound illness and viral shedding. Combination regimens can enhance antiviral potency, reduce the emergence of drug-resistant variants, and lower the dose of each component in the combination. Concurrently targeting virus entry and virus replication offers opportunities to discover synergistic drug combinations. While combination antiviral drug treatments are standard for chronic RNA virus infections, no antiviral combination therapy has been approved for SARS-CoV-2. Here, we demonstrate that combining host-targeting antivirals (HTAs) that target TMPRSS2 and hence SARS-CoV-2 entry, with the DAA molnupiravir, which targets SARS-CoV-2 replication, synergistically suppresses SARS-CoV-2 infection in Calu-3 lung epithelial cells. Strong synergy was observed when molnupiravir, an oral drug, was combined with three TMPRSS2 (HTA) oral or inhaled inhibitors: camostat, avoralstat, or nafamostat. The combination of camostat plus molnupiravir was also effective against the beta and delta variants of concern. The pyrimidine biosynthesis inhibitor brequinar combined with molnupiravir also conferred robust synergistic inhibition. These HTA+DAA combinations had similar potency to the synergistic all-DAA combination of molnupiravir plus nirmatrelvir, the protease inhibitor found in paxlovid. Pharmacodynamic modeling allowed estimates of antiviral potency at all possible concentrations of each agent within plausible therapeutic ranges, suggesting possible in vivo efficacy. The triple combination of camostat, brequinar, and molnupiravir further increased antiviral potency. These findings support the development of HTA+DAA combinations for pandemic response and preparedness. IMPORTANCE Imagine a future viral pandemic where if you test positive for the new virus, you can quickly take some medicines at home for a few days so that you do not get too sick. To date, only single drugs have been approved for outpatient use against SARS-CoV-2, and we are learning that these have some limitations and may succumb to drug resistance. Here, we show that combinations of two oral drugs are better than the single ones in blocking SARS-CoV-2, and we use mathematical modeling to show that these drug combinations are likely to work in people. We also show that a combination of three oral drugs works even better at eradicating the virus. Our findings therefore bode well for the development of oral drug cocktails for at home use at the first sign of an infection by a coronavirus or other emerging viral pathogens.

BackgroundHealth Technology Assessment (HTA) is a multidisciplinary process that synthesizes, with a systematic, transparent, impartial and robust methodological approach, the main information on the medical, economic, ethical and social implications of the use and dissemination of a health technology. Its aim is to support decision-makers in identifying safe, effective, patient-centered and best-value health policies, in order to promote an equitable, efficient, and high-quality health system. Given the continued application of innovative technologies into clinical practice, healthcare professionals need to be able to adequately evaluate these technologies using evidence-based approaches such as HTA. Therefore, the implementation of training in HTA is crucial. The aim of this study was to investigate existing HTA training initiatives for healthcare professionals provided by international HTA agencies and organizations around the world.MethodsFrom March to November 2020, the websites of HTA agencies and organizations belonging to the European network for HTA (EUnetHTA) and to the International Network of Agencies for HTA (INAHTA), and the website of the HTA International (HTAi), were explored for identifying the HTA training initiatives directed to healthcare professionals. In addition, we screened the training initiatives proposed at European level by EUnetHTA as part of its Joint Actions and conducted in collaboration with its public-private partners. Specific keywords were searched in English and adapted to French, Portuguese, Spanish, Italian and German. Data extraction of the retrieved training initiatives was conducted from November 2020 to February 2021 and considered the following information: agency, country, website, coordinator, type of initiative, target, topic, main contents, and language.ResultsOut of 124 agencies/organizations/EUnetHTA public-private partners screened, only 21 provided training initiatives for healthcare professionals. A total of 55 training initiatives were analyzed, 85.5% of which were delivered at the European level and 14.5% at the international level. The countries with a greater number of courses were: Austria, Argentina, Spain, Portugal, and the United Kingdom. Twenty-one training initiatives focused on HTA application and methodology while 34 on specific HTA domains, particularly on the economic one. The technologies covered were mainly drugs.ConclusionsOur study revealed a limited number of HTA training programs targeting healthcare professionals. HTA supports the decision-making processes concerning the use and application of health technologies with scientific evidence. Indeed, training of healthcare professionals in this field should be a key driver in implementing evidence-based healthcare choices and through rigorous methodological approaches such as HTA, in order to ensure proper health governance and value-based application of technological innovations in clinical practice. Therefore, capacity building of healthcare professionals in this area should be enhanced by using appropriate and effective training initiatives and educational strategies.

Background Health care coverage decisions deal with health care technology provision or reimbursement at a national level. The coverage decision report, i.e., the publicly available document giving reasons for the decision, may contain various elements: quantitative calculations like cost and clinical effectiveness analyses and formalised and non-formalised qualitative considerations. We know little about the process of combining these heterogeneous elements into robust decisions. Methods This study describes a model for combining different elements in coverage decisions. We build on two qualitative cases of coverage appraisals at the Dutch National Health Care Institute, for which we analysed observations at committee meetings (n = 2, with field notes taken) and the corresponding audio files (n = 3), interviews with appraisal committee members (n = 10 in seven interviews) and with Institute employees (n = 5 in three interviews), and relevant documents (n = 4). Results We conceptualise decisions as combinations of elements, specifically (quantitative) findings and (qualitative) arguments and values. Our model contains three steps: 1) identifying elements; 2) designing the combinations of elements, which entails articulating links, broadening the scope of designed combinations, and black-boxing links; and 3) testing these combinations and choosing one as the final decision. Conclusions Based on the proposed model, we suggest actively identifying a wider variety of elements and stepping up in terms of engaging patients and the public, including facilitating appeals. Future research could explore how different actors perceive the robustness of decisions and how this relates to their perceived legitimacy.

Background Organizational aspects in Health Technology Assessment (HTA) reports play a significant role in managing policies and strategies to implement new health technologies. The organizational domain, however, is often under-represented in HTA reports. This study explored how organizational assessment is carried out in HTA reports and designed a new perspective through an empirical approach after the comparison with EUnetHTA's Core Model 3.0. Methods Full HTA reports were extracted from the websites of members of International Network of Agencies for HTA and the aspects relating to the organizational assessment were analysed. HTA reports were classified into 4 typologies of technologies (device, diagnosis/screening, intervention and organizational procedures) and organizational aspects described were explored through a framework of 5 domains and 15 subdomains from Core Model. Specific Multiple Correspondence Analyses were carried out to identify technology-related domains for organizational assessment in reports. Results The analysis showed that domains and subdomains of Core Model were not covered homogeneously by the organizational assessments in the HTA reports. Through Multiple Correspondence Analyses, four new technology-related dimensions were identified and named according to the Core Model’s subdomains in the four new clusters. Conclusions This study analyzed the significance of organizational assessments in current literature and the challenges of improving this domain in HTA reports. Through an empirical analysis, we proposed a new methodology to cover the most relevant aspects of organizational appraisal according to new domains to promote support to the assessment of organizational issues in reports and fulfil the needs of future HTA research.

Context The National Institute of Excellence in Health and Social Services (INESSS), which functions as the Québec health technology assessment (HTA) agency, tested a new way to engage patients along with health‐care professionals in the co‐construction of recommendations regarding implantable cardioverter‐defibrillator replacement. Objective The objective of this article was to describe the process of co‐construction of recommendations and to propose methods of building best practices for patient involvement (PI) in HTA. Design Throughout the process, documents were collected and participant observations were made. Individual interviews were conducted with patients, health‐care professionals and the INESSS scientific team, from January to March 2018. Results Three committees were established: an expert patient committee to reflect on patient experience literature; an expert health professional committee to reflect on medical literature; and a co‐construction committee through which both patients and health‐care professionals contributed to develop the recommendations. The expert patients validated and contextualized a literature review produced by the scientific team. This allowed the scientists to consider aspects related to the patient experience and to integrate the feedback from patients into HTA recommendations. The most important factor contributing to a positive PI experience was the structured methodology for selecting patient participants, and a key factor that inhibited the process was a lack of training in PI on the part of the scientific team. Conclusions This experience demonstrates that it is possible to co‐construct recommendations, even for technically complex HTA subjects, through a more democratic process than usual which led to more patient‐focused guidance.

Standard outcome sets developed by the International Consortium for Health Outcomes Measurement (ICHOM) facilitate value‐based health care in healthcare practice and have gained traction from regulators and Health Technology Assessment (HTA) agencies that regularly assess the value of new medicines. We aimed to assess the extent to which the outcomes used by regulators and HTA agencies are patient‐relevant, by comparing these to ICHOM standard sets. We conducted a cross‐sectional comparative analysis of ICHOM standard sets, and publicly available regulatory and HTA assessment guidelines. We focused on oncology due to many new medicines being developed, which are accompanied by substantial uncertainty regarding the relevance of these treatments for patients. A comparison of regulatory and HTA assessment guidelines, and ICHOM standard sets showed that both ICHOM and regulators stress the importance of disease‐specific outcomes. On the other hand, HTA agencies have a stronger focus on generic outcomes in order to allow comparisons across disease areas. Overall, similar outcomes are relevant for market access, reimbursement, and in ICHOM standard sets. However, some differences are apparent, such as the acceptability of intermediate outcomes. These are recommended in ICHOM standard sets, but regulators are more likely to accept intermediate outcomes than HTA agencies. A greater level of alignment in outcomes accepted may enhance the efficiency of regulatory and HTA processes, and increase timely access to new medicines. ICHOM standard sets may help align these outcomes. However, some differences in outcomes used may remain due to the different purposes of regulatory and HTA decision‐making., The extent to which the outcomes used for market access and reimbursement decision making are patient relevant were assessed, by comparing these to standardized outcome sets developed by the International Consortium for Health Outcomes Measurement (ICHOM).

The COVID-19 pandemic is challenging how healthcare technologies are evaluated, as new, more dynamic methods are required to test the cost effectiveness of alternative interventions during use rather than before initial adoption. Currently, health technology assessment (HTA) tends to be static and a priori: alternatives are compared before launch, and little evaluation occurs after implementation. We suggest a method that builds upon the current pre-launch HTA procedures by conceptualizing a mean-variance approach to the continuous evaluation of attainable portfolios of interventions in health systems. Our framework uses frontier analysis to identify the desirability of available health interventions so decision makers can choose diverse portfolios based upon information about expected returns and risks. This approach facilitates the extension of existing methods and assessments beyond the traditional concern with pre-adoption data, a much-needed innovation given the challenges posed by COVID-19.

Introduction: The unparalleled surge in digital health adoption during the COVID-19 pandemic has emphasized the potential of mHealth apps. However, the quality of available evidence is generally low, and regulatory frameworks have focused on apps with medical purposes only, overlooking apps with significant interactions with patients that may require stronger oversight. Areas covered: To support this expanded evidence generation process, we identified the reasons that distinguish mHealth apps compared to medical devices at large and that should differentially feature their assessment. mHealth apps are characterized by the iterative nature of the corresponding interventions, frequent user interactions with a non-linear relationship between technology usage, engagement and outcomes, significant organizational implications, as well as challenges associated with genericization, their broad diagnostic potential, and price setting. Expert Opinion: The renewed reliance experienced during the pandemic and the unprecedented injection of resources through recovery instruments can further boost the development of apps. Only robust evidence of the benefits of mHealth apps will persuade health-care professionals and beneficiaries to systematically deploy them. Regulatory bodies will need to question their current approaches by adopting comprehensive evaluation processes that adequately consider the specific features of mHealth apps.

In June 2021, the US Food and Drug Administration granted accelerated approval to aducanumab for treating Alzheimer’s disease based on the drug’s amyloid reducing effects. This was despite evidence from several earlier studies that shrinkage of β-amyloid protein plaques does not predictably delay cognitive impairment.1 The controversial decision has drawn attention to the use of surrogate endpoints—laboratory values, radiographic images, or other physical measures that may serve as indicators of clinical outcomes such as symptom control or mortality—in clinical trials of new drugs.2 In fact, the approval of aducanumab is only the latest example of growing regulatory reliance on surrogate endpoints, even though their use can cause problems for patients, clinicians, drug regulators, and health technology assessment bodies. We argue for more selective use of surrogate endpoints when evaluating new drugs, restricting their use to chronic diseases, especially when collecting data on patient relevant clinical outcomes requires trials with unattainably long follow up.

ObjectivesThere is no consensus on who might be qualified to conduct ethical analysis in the field of health technology assessment (HTA). Is there a specific expertise or skill set for doing this work? The aim of this article is to (i) clarify the concept of ethics expertise and, based on this, (ii) describe and specify the characteristics of ethics expertise in HTA.MethodsBased on the current literature and experiences in conducting ethical analysis in HTA, a group of members of the Health Technology Assessment International (HTAi) Interest Group on Ethical Issues in HTA critically analyzed the collected information during two face-to-face workshops. On the basis of the analysis, working definitions of “ethics expertise” and “core competencies” of ethics experts in HTA were developed. This paper reports the output of the workshop and subsequent revisions and discussions online among the authors.ResultsExpertise in a domain consists of both explicit and tacit knowledge and is acquired by formal training and social learning. There is a ubiquitous ethical expertise shared by most people in society; nevertheless, some people acquire specialist ethical expertise. To become an ethics expert in the field of HTA, one needs to acquire general knowledge about ethical issues as well as specific knowledge of the ethical domain in HTA. The core competencies of ethics experts in HTA consist of three fundamental elements: knowledge, skills, and attitudes.ConclusionsThe competencies described here can be used by HTA agencies and others involved in HTA to call attention to and strengthen ethical analysis in HTA.

Introduction: The new European Union (EU) Regulations on medical devices and on in vitro diagnostics provide manufacturers and Notified Bodies with new tools to improve pre-market and post-market clinical evidence generation especially for high-risk products but fail to indicate what type of clinical evidence is appropriate at each stage of the whole lifecycle of medical devices. In this paper we address: i) the appropriate level and timing of clinical evidence throughout the lifecycle of high-risk implantable medical devices; and ii) how the clinical evidence generation ecosystem could be adapted to optimize patient access. Areas covered: The European regulatory and health technology assessment (HTA) contexts are reviewed, in relation to the lifecycle of high-risk medical devices and clinical evidence generation recommended by international network or endorsed by regulatory and HTA agencies in different jurisdictions. Expert opinion: Four stages are relevant for clinical evidence generation: i) pre-clinical, pre-market; ii) clinical, pre-market; iii) diffusion, post-market; and iv) obsolescence & replacement, post-market. Each stage has its own evaluation needs and specific studies are recommended to generate the appropriate evidence. Effective lifecycle planning requires anticipation of what evidence will be needed at each stage

Background: Increasingly, multi-criteria decision analysis has gained importance as a method by which to assess the value of orphan drugs. However, very little attention has been given to the weight (relative preferences) of the individual criteria used in a framework.Aims: This study sought to gain an understanding of the preferential weights that should be allocated in a multi-criteria decision analysis framework for orphan drugs, from a multi-stakeholder perspective.Method: Using key MCDA criteria for orphan drugs reported in the literature, we developed an interactive web-based survey tool to capture preferences for different criteria from a general stakeholder sample who were requested to assign weights from a reimbursement perspective. Each criterion could be assigned a weight on a sliding scale from 0 to 100% as long as the sum of all the criteria was 100%. We subsequently used the interactive tool with an expert focus group, followed up with a group discussion regarding each criterion and their perspectives on the weight that each criterion should be allocated when assessing an orphan drug. The expert focus group participants were then able to adjust their weights, if the group discussion had changed their perspectives.Results: The interactive tool was completed by 120 general stakeholder sample from a wide range of countries and professional backgrounds and an expert focus group of ten members. The results showed the differences in perspectives on the importance of criteria. Both groups considered Treatment efficacy to be the most important criterion. The general stakeholder sample weighted Treatment safety at 12.03% compared to the expert focus group's average of 20%. The results also demonstrated the value of the group discussion, which provided additional insights into the perspectives on the importance of criteria in assessing orphan drugs.Conclusion: This study aimed to contribute to the important aspect of preferences for different criteria in MCDA. This study sheds light on the important aspect of the preferences of the different criteria. All respondents agreed on the relative importance of Treatment efficacy and Treatment safety, criteria that are captured in conventional cost-effectiveness studies, but they also expressed the view that in addition to those, several disease-related and drug-related criteria should be included in MCDA frameworks for assessing orphan drugs.

There has been continuous development in the field of health technology assessment (HTA) owing to the added value of HTA in supporting healthcare reimbursement decisions. Collaboration and engagement among countries in Asia has been carried out to share experiences and learning on the barriers and factors facilitating the implementation and use of HTA in policy making. A symposium on the topic of Health Technology Assessment (HTA): Selecting the Highest Value Care was held on January 10, 2019 at the National University of Singapore, during which 3 major challenges confronting HTA development in Asia were identified. The symposium also offered possible ways to overcome the challenges., Highlights • Countries in Asia increasingly recognize and adopt health technology assessment (HTA) in setting priorities for healthcare. Nevertheless, 2 common challenges can be identified, namely, lack of infrastructure and technical capacity to cope with the increasing demand for HTA, and the inadequate involvement of stakeholders in the HTA process. • Solutions identified at the HTA symposium in Singapore to overcome these challenges were that countries should implement a tailored and transparent mechanism for using HTA, promote existing HTA capacity, and strengthen the understanding of HTA among the stakeholders. • Health technology assessment symposia such as the one organized in Singapore provide a platform for countries to share knowledge and challenges, and bring different views to build into something greater and overcome the challenges. Such symposia should be organized regularly.

Introduction: Public health (PH) interventions are crucial for ensuring sustainable healthcare services. Nevertheless, they represent a neglected area in the field of health technology assessment (HTA) due to various methodological issues and their complex design that goes beyond clinical setting. The present study provides an environmental scan of HTA initiatives related to the assessment of PH technologies on a global level. Methods: We conducted a cross-sectional survey among 85 HTA-related European and international societies, health bodies, and networks from September 2018 to January 2019. The questionnaire contained four sections and 18 questions regarding activities related to the evaluation of PH technologies, information on existing PH technologies, and methodologies of assessment as well as barriers and facilitators to reaching a decision and implementing a PH technology. Results: Among 52 survey responses, the majority of the respondents came from European countries (35%), followed by North American (27%), and South American (19%) countries. The main type of organizations covered by our survey included HTA agencies, public administrations, and research institutes. Seventy-one % of the institutions reported engagement in any aspect of HTA in the area of PH (N = 37). Among those, 81% evaluated less than 5 PH technologies from 2013 to 2018. The most common barriers for reaching a decision on PH technologies were lack of data, conflicting stakeholder priorities, and methodological issues. A total of 76 PH interventions were reported, and most cited initiatives were related to chronic disease screening, prevention of infectious diseases, and maternal, prenatal, and neonatal screening. Conclusion: Our survey reported a rather limited involvement of HTA in the evaluation of PH technologies. In particular, an evaluation of behavioral and lifestyle interventions remains extremely rare. The implementation of collaborative HTA approaches in the setting of PH practice and policy needs to be prioritized and further strengthened. Moreover, ensuring reliable data structures and consolidation of HTA methods for the evaluation of PH technologies will be crucial for tackling the enormous burden of non-communicable diseases in societies.

All health economics reviews on chronic and episodic migraine published to date underline the heterogeneity of results. Currently, the need for the generalizability of economic evaluations across different jurisdictions is considered a key issue to avoid unnecessary overlaps and to minimize the time to reimbursement decisions. The aim of this study was to review the economic evaluations on the prophylaxis and treatments for migraine published in the previous 10 years (since 2009) and to perform a critical assessment of their generalizability. We searched PubMed, EMBASE, and EconLit databases. Articles underwent a three-stage selection process. To assess the level of generalizability, we used the checklist implemented by Augustovski et al. Studies were classified as: (1) generalizable; (2) transferable; and (3) context specific. In total, 227 articles were identified after running the search string and 11 studies were included in our review. Overall, none of the studies was judged as generalizable and three were judged transferable according to the established criteria. Our review suggests that no evidence on the economic value of either acute or prophylactic treatments against migraine is generalizable to different jurisdictions. However, the majority of studies reporting results about prophylactic treatments were found to be transferable.

Background Depending on the health system context and the demands of relevant stakeholders in countries, the need, organizational structure, and prerequisites for enabling capacity building and development in health technology assessment (HTA) will vary. Core competencies are instrumental in this and include essential knowledge, skills, and attitudes (KSAs). They provide building blocks for delivering high-quality and effective practices of HTA. We aimed to systematically explore and develop an overview of the core competencies necessary for HTA. Methods This study was conducted during 2016–19 using different methods in a structured manner. We drew concepts of KSAs from various literature sources, surveyed universities and HTA professionals, and conducted expert workshops to arrive at a common understanding of the required competencies. Results The terminology for KSAs defining competencies in HTA programs has been clarified. In addition, a list of competencies offered through different educational and training programs has been created. The surveys provided clarity on a common understanding of KSAs among HTA stakeholders. Thereafter, a set of competencies was described and classified according to the HTA domains. Conclusions Our study shows that there is diversity in HTA programs offered by educational institutions. The content of the programs varies due to differences between countries regarding the level of HTA development and the need for HTA, including the understanding of what HTA is. The preparation of a competency checklist or a “menu” of options mirroring the diversity of HTA will ensure that the specific needs of the HTA community will be covered.

Introduction Allergic rhino-conjunctivitis (ARC) is an IgE-mediated disease that occurs after exposure to indoor or outdoor allergens, or to non-specific triggers. Effective treatment options for seasonal ARC are available, but the economic aspects and burden of these therapies are not of secondary importance, also considered that the prevalence of ARC has been estimated at 23% in Europe. For these reasons, we propose a novel flexible cost-effectiveness analysis (CEA) model, intended to provide healthcare professionals and policymakers with useful information aimed at cost-effective interventions for grass-pollen induced allergic rhino-conjunctivitis (ARC). Methods Treatments compared are: 1. no AIT, first-line symptomatic drug-therapy with no allergoid immunotherapy (AIT). 2. SCIT, subcutaneous immunotherapy. 3. SLIT, sublingual immunotherapy. The proposed model is a non-stationary Markovian model, that is flexible enough to reflect those treatment-related problems often encountered in real-life and clinical practice, but that cannot be adequately represented in randomized clinical trials (RCTs). At the same time, we described in detail all the structural elements of the model as well as its input parameters, in order to minimize any issue of transparency and facilitate the reproducibility and circulation of the results among researchers. Results Using the no AIT strategy as a comparator, and the Incremental Cost Effectiveness Ratio (ICER) as a statistic to summarize the cost-effectiveness of a health care intervention, we could conclude that: SCIT systematically outperforms SLIT, except when a full societal perspective is considered. For example, for T = 9 and a pollen season of 60 days, we have ICER = €16,729 for SCIT vs. ICER = €15,116 for SLIT (in the full societal perspective).For longer pollen seasons or longer follow-up duration the ICER decreases, because each patient experiences a greater clinical benefit over a larger time span, and Quality-adjusted Life Year (QALYs) gained per cycle increase accordingly.Assuming that no clinical benefit is achieved after premature discontinuation, and that at least three years of immunotherapy are required to improve clinical manifestations and perceiving a better quality of life, ICERs become far greater than €30,000.If the immunotherapy is effective only at the peak of the pollen season, the relative ICERs rise sharply. For example, in the scenario where no clinical benefit is present after premature discontinuation of immunotherapy, we have ICER = €74,770 for SCIT vs. ICER = €152,110 for SLIT.The distance between SCIT and SLIT strongly depends on under which model the interventions are meta-analyzed. Conclusions Even though there is a considerable evidence that SCIT outperforms SLIT, we could not state that both SCIT and SLIT (or only one of these two) can be considered cost-effective for ARC, as a reliable threshold value for cost-effectiveness set by national regulatory agencies for pharmaceutical products is missing. Moreover, the impact of model input parameters uncertainty on the reliability of our conclusions needs to be investigated further.

Objectives Universal healthcare coverage in low- and middle-income countries requires challenging resource allocation decisions. Health technology assessment is one important tool to support such decision making. The International Decision Support Initiative worked with the Ghanaian Ministry of Health to strengthen health technology assessment capacity building, identifying hypertension as a priority topic area for a relevant case study. Methods Based on guidance from a national technical working group of researchers and policy makers, an economic evaluation and budget impact analysis were undertaken for the main antihypertensive medicines used for uncomplicated, essential hypertension. The analysis aimed to address specific policy questions relevant to the National Health Insurance Scheme. Results The evaluation found that first-line management of essential hypertension with diuretics has an incremental cost per disability-adjusted life-year avoided of GH¢ 276 ($179 in 2017, 4% of gross national income per capita) compared with no treatment. Calcium channel blockers were more effective than diuretics but at a higher incremental cost: GH¢ 11 061 per disability-adjusted life-year avoided ($7189 in 2017; 160% of gross national income per capita). Diuretics provide better health outcomes at a lower cost than angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Budget impact analysis highlighted the potential for cost saving through enhanced price negotiation and increased use of better-value drugs. We also illustrate how savings could be reinvested to improve population health. Conclusions Economic evaluation enabled decision makers to assess hypertension medicines in a Ghanaian context and estimate the impact of using such evidence to change policy. This study contributes to addressing challenges associated with the drive for universal healthcare coverage in the context of constrained budgets., Highlights • This article provides details of a technical modeling work collaboratively built in Ghana with a high-level policy orientation. • Recent developments in Ghana further highlight the constraints imposed on current resources available for health. • This is the first national health technology assessment study to be commissioned and conducted under Ghanaian government supervision. There are no other studies that offer the same level of contextualized information to support the National Health Insurance Authority and the Ghanaian Ministry of Health in their policy-making efforts toward improving value for money in hypertension management. • A range of cost-saving and health-improving policy scenarios were identified that could have a major impact on reducing the burden of hypertension and contribute to the financial sustainability of the National Health Insurance Scheme.

Objectives This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments (HTA) and guideline developers can rate the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables. Study Design and Setting We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Results Supplemented by practical examples, we describe how raters of the evidence can apply the GRADE domains inconsistency, imprecision, and publication bias to a body of evidence of TA studies. Conclusions Using GRADE in Cochrane and other reviews as well as World Health Organization and other guidelines helped refining the GRADE approach for rating the certainty of a body of evidence from TA studies. While several of the GRADE domains (e.g., imprecision and magnitude of the association) require further methodological research to help operationalize them, judgments need to be made on the basis of what is known so far.

Objectives The primary objective of this study was to compare the availability and access of orphan medicinal products (OMPs) in the devolved nations in the United Kingdom (UK), France, Germany, Italy and Spain. Availability is defined as the possibility to prescribe OMPs. Access refers to their full or partial reimbursement by the public health service. Methods Data were collated on: marketing authorisations, Health Technology Assessment (HTA) decisions, commissioning, and reimbursement decisions, and respective dates of these events for all the OMPs centrally authorised. Indicators of availability of and access to OMPs were calculated in each country and compared. Results We found that since the implementation of the OMPs Regulation in 2000 to end of May 2016, 143 OMPs obtained a marketing authorisation in the European Union. These OMPs are most widely accessible in Germany and France. In the other countries between 30 and 60% of OMPs are reimbursed. In particular in England, less than 50% of centrally authorised OMPs are routinely funded by the NHS, with one-third of these recommended by NICE. In Germany reimbursement is automatically granted to all medicines which receive a marketing authorisation, immediately after authorisation – but since 2011, there is an evaluation and potentially a pricing negotiation between companies and sickness funds (third party payers). In the other countries, the shortest time from authorisation to a reimbursement decision is observed in Italy and France where it takes 18.6 and 19.5 months respectively on average. Conclusions Marketing authorisation granted to OMPs is only the first step, as medicines reach patients when reimbursement decisions are implemented by national health systems (this applies to non-OMPs too). We found that more than a half of centrally authorised OMPs were available in the five selected countries, but that access to patients was further restricted by different national reimbursement policies, especially in the UK, Italy and Spain. Electronic supplementary material The online version of this article (10.1186/s13023-019-1078-5) contains supplementary material, which is available to authorized users.

Economic models are used in health technology assessments (HTAs) to evaluate the cost-effectiveness of competing medical technologies and inform the efficient use of healthcare resources. Historically, these models have been developed with specialized commercial software (such as TreeAge) or more commonly with spreadsheet software (almost always Microsoft Excel). Although these tools may be sufficient for relatively simple analyses, they put unnecessary constraints on the analysis that may ultimately limit its credibility and relevance. In contrast, modern programming languages such as R, Python, Matlab, and Julia facilitate the development of models that are (i) clinically realistic, (ii) capable of quantifying decision uncertainty, (iii) transparent and reproducible, and (iv) reusable and adaptable. An HTA environment that encourages use of modern software can therefore help ensure that coverage and pricing decisions confer greatest possible benefit and capture all scientific uncertainty, thus enabling correct prioritization of future research.

This article provides a practical overview of cost-effectiveness analyses and their application in respiratory medicine. It serves as a guide to explain non-health economists the key concepts and methods of cost-effectiveness analyses. The case for health economics is made, some key methodological issues are explained, using non-expert terminology and easy to understand examples from the fields of asthma, COPD, tuberculosis, lung cancer and other respiratory diseases. The current state-of-the-art as well as a future perspective is provided.

Background The relevance of studies focusing on patient satisfaction becomes imperative for patients with cancer, who often face major changes in their lifestyles. Their perceived uncertainty in illness and their personal experiences with the services received are crucial factors for a qualitatively adequate assistance. Objectives To assess the determinants of patient satisfaction, using a sample of 306 Bulgarian oncology outpatients. Methods The hypotheses tested concern the extent to which patient satisfaction depends on the uncertainty in illness; the patients' assessment of technical and interpersonal skills of nurses and medical staff; the information provision; and some organizational aspects. Patients were asked to answer a questionnaire composed of internationally validated scales assessing the determinants of patient satisfaction (measured through the European Organization for Research and Treatment of Cancer), uncertainty in illness (assessed through the Mishel Uncertainty in Illness Scale), and patients' health status (assessed through the EuroQol 5-dimensional questionnaire and the visual analogue scale). An ordered logit model was run, using the level of overall patient satisfaction as a dependent variable. Results This is one of the first studies carried out in Bulgaria for oncology patient satisfaction of subjective factors related to the frailty of the oncology patient status such as age, self-assessed health-related quality of life, and uncertainty in illness. Nevertheless, other determinants, reflecting the quality of the care provided, also have an impact on patient satisfaction, namely, the assessment of the nonmedical personnel, the perception of medical technical skills, and the access to a medical center. Conclusions Results stress the relevance of reducing uncertainty in illness in patients with cancer by implementing a satisfactory patient-physician relationship in the management of the disease.

Background Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer’s dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany. Electronic supplementary material The online version of this article (doi:10.1186/s12913-016-1902-8) contains supplementary material, which is available to authorized users.

The aim of this study is to analyze the potential advantages of emtricitabine/tenofovir alafenamide (FTC/TAF) introduction, creating evidence-based information to orient strategies to reduce costs, thus preserving effectiveness and appropriateness. An Health Technology Assessment (HTA) was implemented in the years 2017&ndash, 2018 comparing the dual backbones available in the Italian market: FTC/TAF, FTC/TDF (tenofovir disoproxil fumarate/emtricitabine) and ABC/3TC (abacavir/lamivudine). From an efficacy point of view, FTC/TAF ensured a higher percentage of virologic control and a better safety impact than FTC/TDF (improving the renal and bone safety profile, as well as the lipid picture). From an economic point of view, the results revealed a 4% cost saving for the Italian National Healthcare Service NHS with FTC/TAF introduction compared with the baseline scenario. Qualitative perceptions&rsquo, results showed that FTC/TAF would decrease the burden of adverse events management, increasing the accessibility of patients to healthcare providers (FTC/TAF: 0.95, FTC/TDF: 0.10, ABC/3TC: 0.28, p-value: 0.016) and social costs (FTC/TDF: &minus, 0.23, FTC/TAF: 1.04, ABC/3TC: 0.23, p-value &lt, 0.001), improving patient quality of life (FTC/TDF: 0.31, FTC/TAF: 1.85, ABC/3TC: 0.38, 0.001). Healthcare services may consider the evidence provided by the present study as an opportunity to include HIV patients in a more adequate antiretroviral treatment arm, guaranteeing a personalized clinical pathway, thus becoming more efficient and effective over time.

Background: This paper presents a generic Multi-Criteria Decision Analysis (MCDA) model for Health Technology Assessment (HTA) decision-making, which can be applied to a wide range of HTA studies, regardless of the healthcare technology type under consideration. Methods: The HTA Core Model&reg, of EUnetHTA was chosen as a basis for the development of the MCDA model because of its common acceptance among European Union countries. Validation of MCDA4HTA was carried out by an application with the HTA study group of the Turkish Ministry of Health. The commitment of the decision-making group is completed via an online application of 10 different questionnaires. The Analytic Hierarchy Process (AHP) is used to determine the weights. Scores of the criteria in MCDA4HTA are gathered directly from the HTA report. The performance matrix in this application is run with fuzzy Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), fuzzy Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR), and goal programming MCDA techniques. Results: Results for fuzzy VIKOR, fuzzy TOPSIS, and goal programming are 0.018, 0.309, and 0.191 for peritoneal dialysis and 0.978, 0.677, and 0.327 for hemodialysis, respectively. Conclusions: Peritoneal dialysis is found to be the best choice under the given circumstances, despite its higher costs to society. As an integrated decision-making model for HTA, MCDA4HTA supports both evidence-based decision policy and the transparent commitment of multi-disciplinary stakeholders.

Background When designing a randomised controlled trial (RCT), an important consideration is the sample size required. This is calculated from several components; one of which is the target difference. This study aims to review the currently reported methods of elicitation of the target difference as well as to quantify the target differences used in Health Technology Assessment (HTA)-funded trials. Methods Trials were identified from the National Institute of Health Research Health Technology Assessment journal. A total of 177 RCTs published between 2006 and 2016 were assessed for eligibility. Eligibility was established by the design of the trial and the quality of data available. The trial designs were parallel-group, superiority RCTs with a continuous primary endpoint. Data were extracted and the standardised anticipated and observed effect size estimates were calculated. Exclusion criteria was based on trials not providing enough detail in the sample size calculation and results, and trials not being of parallel-group, superiority design. Results A total of 107 RCTs were included in the study from 102 reports. The most commonly reported method for effect size derivation was a review of evidence and use of previous research (52.3%). This was common across all clinical areas. The median standardised target effect size was 0.30 (interquartile range: 0.20–0.38), with the median standardised observed effect size 0.11 (IQR 0.05–0.29). The maximum anticipated and observed effect sizes were 0.76 and 1.18, respectively. Only two trials had anticipated target values above 0.60. Conclusion The most commonly reported method of elicitation of the target effect size is previous published research. The average target effect size was 0.3. A clear distinction between the target difference and the minimum clinically important difference is recommended when designing a trial. Transparent explanation of target difference elicitation is advised, with multiple methods including a review of evidence and opinion-seeking advised as the more optimal methods for effect size quantification.

Background A recent study by Page et al. (PLoS Med. 2016;13(5):e1002028) claimed that increasing numbers of reviews are being published and many are poorly-conducted and reported. The aim of the present study was to assess how well reporting standards of systematic reviews produced in a Health Technology Assessment (HTA) context compare with reporting in Cochrane and other ‘non-Cochrane’ systematic reviews from the same years (2004 and 2014), as reported by Page et al. (PLoS Med. 2016;13(5):e1002028). Methods All relevant UK HTA programme systematic reviews published in 2004 and 2014 were identified. After piloting of the form, two reviewers each extracted relevant data on conduct and reporting from these reviews. These data were compared with data for Cochrane and “non-Cochrane” systematic reviews, as published by Page et al. (PLoS Med. 2016;13(5):e1002028). All data were tabulated and summarized. Results There were 30 UK HTA programme systematic reviews and 300 other systematic reviews, including Cochrane reviews (n = 45). The percentage of HTA reviews with required elements of conduct and reporting was frequently very similar to Cochrane and much higher than all other systematic reviews, e.g. availability of protocols (90, 98 and 16% respectively); the specification of study design criteria (100, 100, 79%); the reporting of outcomes (100, 100, 78%), quality assessment (100, 100, 70%); the searching of trial registries for unpublished data (70, 62, 19%); reporting of reasons for excluding studies (91, 91 and 70%) and reporting of authors’ conflicts of interests (100, 100, 87%). HTA reviews only compared less favourably with Cochrane and other reviews in assessments of publication bias. Conclusions UK HTA systematic reviews are often produced within a specific policy-making context. This context has implications for timelines, tools and resources. However, UK HTA systematic reviews still tend to present standards of conduct and reporting equivalent to “gold standard” Cochrane reviews and superior to systematic reviews more generally. Electronic supplementary material The online version of this article (10.1186/s12874-018-0498-6) contains supplementary material, which is available to authorized users.

Decision-making in healthcare should rely on evidence-based approaches able to make possible a transparent and robust assessment of all the aspects related to health technologies. One of the assessment elements is represented by the efficiency that is the specific objective of economic evaluations and also of Health Technology Assessment (HTA). The collection and synthesis of evidence is the first indispensable step in order to foster a proper convey of scientific knowledge to the decision-makers. This work, carried out within a broader project on the transfer of evidence from the scientific to the decision making world, is aimed to release an overview of economic evaluations and HTA on vaccines conducted in Italy. The project was carried out within the activities of the ISPOR Italy-Rome Chapter.A systematic review of Italian economic evaluations and HTA performed on vaccines and published up to May 2015 was carried out. PubMed, Scopus and the NIHR HTA databases were queried and a hand-search was performed on key journals in the field (GlobalRegional Health Technology Assessment; PharmacoEconomics Italian Research Articles; Giornale italiano di HTA; Politiche Sanitarie; HTA Focus - Pills of Clinical Governance; Pillole di Farmacoeconomia; Giornale Italiano di Farmacoeconomia e Farmacoutilizzazione; IJPH; Quaderni dell'IJPH). Studies were considered eligible if showing the results of a full economic evaluations and if performed in Italy.The literature search yielded 10 HTA reports and 33 economic evaluations. Among the latter, 20 (60,6%) were cost-effectiveness analyses. Ten studies (23,3%) assessed the vaccination against S. pneumoniae figuring out that it is cost-effectiveness and even costsaving in cases of newborns and subjects at risk. Nine studies (20,9%) addressed influenza vaccination and demonstrated its dominance on non-vaccination in the elderly. Eight studies (18,6%) evaluated the HPV vaccines concluding that they are cost-effective. Five studies (11,6%) devoted to anti-rotavirus vaccination showing its dominance on non-vaccination, in particular from the society perspective. Vaccination against pertussis, hepatitis B, chicken pox, measles, rubella, mumps were eventually shown cost-saving. The vaccine against Neisseria meningitidis was considered potentially cost-effective.The Italian scientific evidence on efficiency of vaccination is broad and allows concluding that vaccinations are value for money interventions.

Background: Resource allocation in health is universally challenging, but especially so in resource-constrained contexts in the Global South. Pursuing a strategy of evidence-based decision-making and using tools such as Health Technology Assessment (HTA), can help address issues relating to both affordability and equity when allocating resources. Three BRICS and Global South countries, China, India and South Africa have committed to strengthening HTA capacity and developing their domestic HTA systems, with the goal of getting evidence translated into policy. Through assessing and comparing the HTA journey of each country it may be possible to identify common problems and shareable insights. Objectives: This collaborative paper aimed to share knowledge on strengthening HTA systems to enable enhanced evidence-based decision-making in the Global South by: Identifying common barriers and enablers in three BRICS countries in the Global South; and Exploring how South-South collaboration can strengthen HTA capacity and utilisation for better healthcare decision-making. Methods: A descriptive and explorative comparative analysis was conducted comprising a Within-Case analysis to produce a narrative of the HTA journey in each country and an Across-Case analysis to explore both knowledge that could be shared and any potential knowledge gaps. Results: Analyses revealed that China, India and South Africa share many barriers to strengthening and developing HTA systems such as: (1) Minimal HTA expertise; (2) Weak health data infrastructure; (3) Rising healthcare costs; (4) Fragmented healthcare systems; and (5) Significant growth in non-communicable diseases. Stakeholder engagement and institutionalisation of HTA were identified as two conducive factors for strengthening HTA systems. Conclusion: China, India and South Africa have all committed to establishing robust HTA systems to inform evidence-based priority setting and have experienced similar challenges. Engagement among countries of the Global South can provide a supportive platform to share knowledge that is more applicable and pragmatic.

Mild cognitive impairment and Alzheimer's dementia involve a grey matter disease, quantifiable by 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), but also white matter damage, evidenced by diffusion tensor magnetic resonance imaging (DTI), which may play an additional pathogenic role. This study aimed to determine whether such DTI and PET variations are also interrelated in a high-risk population of older hypertensive patients with only subjective memory complaints (SMC). Sixty older hypertensive patients (75 ± 5 years) with SMC were referred to DTI and FDG-PET brain imaging, executive and memory tests, as well as peripheral and central blood pressure (BP) measurements. Mean apparent diffusion coefficient (ADCmean) was determined in overall white matter and correlated with the grey matter distribution of the metabolic rate of glucose (CMRGlc) using whole-brain voxel-based analyses of FDG-PET images. ADCmean was variable between individuals, ranging from 0.82 to 1.01.10− 3 mm2 sec− 1, and mainly in relation with CMRGlc of areas involved in Alzheimer's disease such as internal temporal areas, posterior associative junctions, posterior cingulum but also insulo-opercular areas (global correlation coefficient: − 0.577, p, Highlights • Changes in grey and white matter are interrelated in elderly hypertensive patients. • They can be documented in the absence of any objective memory complaint. • These interrelationships are associated with cognitive test results. • The interrelated grey matter areas are likely to define an Alzheimer-like pattern. • These interrelationships are linked to the level of central blood pressure.

Objectives:Evaluation is crucial for integration of e-Health/m-Health into healthcare systems and health technology assessment (HTA) could offer sound methodological basis for these evaluations. Aim of this study was to look for HTA reports on e-Health/m-Health technologies and to analyze their transparency, consistency and thoroughness, with the goal to detect areas that need improvement.Methods:PubMed, ISI-WOS, and University of York – Centre for Reviews and Dissemination–electronic databases were searched to identify reports on e-Health/m-Health technologies, published up until April 1, 2016. The International Network of Agencies for Health Technology Assessment (INAHTA) checklist was used to evaluate transparency and consistency of included reports. Thoroughness was assessed by checking the presence of domains suggested by the European network for Health Technology Assessment (EUnetHTA) HTA Core Model.Results:Twenty-eight reports published between 1999 and 2015 were included. Most were delivered by non-European countries (71.4 percent) and only 35.7 percent were classified as full reports. All the HTA reports defined the scope of research whereas more than 80 percent provided author details, summary, discussed findings, and conclusion. On the contrary, policy and research questions were clearly defined in around 30 percent and 50 percent of reports. With respect to the EUnetHTA Core Model, around 70 percent of reports dealt with effectiveness and economic evaluation, more than 50 percent described health problem and approximately 40 percent organizational and social aspects.Conclusions:E-Health/m-Health technologies are increasingly present in the field of HTA. Yet, our review identified several missing elements. Most of the reports failed to respond to relevant assessment components, especially ethical, social and organizational implications.

The article by Daniels and colleagues on expanding the scope of health technology assessment (HTA) to embrace ethical analysis has received endorsement and criticism from commentators in this journal. Referring to this debate, we examine in this article the extent and locus of ethical analysis in HTA processes. An expansion/no-expansion framing of HTA is, in our view, not very fruitful. We argue that meaningfulness and relevance to the needs of the population are what should determine the extent of ethics in HTA. Once 'relevance' is the guiding principle, engaging in ethical analysis becomes inevitable as values are all over the place in HTA, also in how assessors frame research questions. We also challenge dividing the locus of ethical analysis into assessment and appraisal as this would detach HTA from its purpose, ie, supporting legitimate decision-making. Ethical analysis should therefore be considered integral to the HTA process.

[zum vollständigen Text gelangen Sie über die oben angegebene URL], Schriftenreihe Health Technology Assessment (HTA) in der Bundesrepublik Deutschland; 135; ISSN 1864-9645

Health political background: The current assessment procedures of care needs and its underlying general notion have long been a subject of debate. The crux of the critique lies particularly in the narrowly defined, operation-oriented and unilateral focus on somatic aspects of the term care needs. A further point of criticism as an issue in the debate is the deficit orientation. A greater consideration of intra- and interpersonal resources is regarded as desirable. A third point of criticism manifests itself in the lacking patient orientation. This Health Technology Assessment should contribute to a realistic determination of the individual care need. In particular the question arises which aspects of care need beyond solely somatic and operation-oriented needs can be adequately addressed. Scientific background: Multifaceted methods and instruments are implemented to assess care needs. Several types of assessment instruments can be distinguished. E. g. instruments for self-assessment and external assessment as well as combination of these exist. Moreover, instruments differ with respect to the assessed area of care need. A further difference lies in the application target group. On the one side instruments exist that enable a disease-independent and/or an age-independent assessment, on the other side instruments exist that are intended for specific diseases or malfunctions... (see hta342_abstract_en.pdf)., Gesundheitspolitischer Hintergrund: Das derzeitige Begutachtungsverfahren und der diesem zugrunde liegende Pflegebedürftigkeitsbegriff befinden sich seit längerer Zeit in der Kritik. Der Kern dieser Kritik richtet sich insbesondere auf einen zu engen, verrichtungsbezogenen und einseitig somatisch definierten Pflegebedürftigkeitsbegriff. Ein weiterer Kritikpunkt im Fokus der Diskussion ist die Defizitorientierung. Als erstrebenswert wird eine stärkere Berücksichtigung intra- wie auch interpersoneller Ressourcen erachtet. Ein dritter wesentlicher Kritikpunkt manifestiert sich in einer fehlenden Patientenorientierung. Dieser Health Technology Assessment soll einen Beitrag dazu leisten, wie der individuelle Pflegebedarf realistisch festgestellt werden kann. Insbesondere stellt sich die Frage, wie Aspekte der Pflegebedürftigkeit, die über eine rein somatische und verrichtungsbezogene Betrachtung hinausgehen, adäquat berücksichtigt werden können. Wissenschaftlicher Hintergrund: Zur Erfassung des Pflegebedarfs werden vielfältige Methoden und Instrumente genutzt. Hierbei lassen sich mehrere Erhebungsarten unterscheiden. So gibt es Instrumente zur Fremd- und zur Selbsteinschätzung bzw. Kombinationen dieser Erhebungsmethoden. Weiterhin unterscheiden sich die Instrumente durch den Bereich für den Pflegebedarfs erhoben wurde. Ein weiterer Unterschied liegt in der Anwendungszielgruppe. Es gibt zum einen Instrumente, die eine erkrankungs- und/oder altersunabhängige Einschätzung ermöglichen, zum anderen gibt es Instrumente, die für die Anwendung bei bestimmten Erkrankungen oder Funktionsstörungen vorgesehen sind... (siehe hta342_zusammenfassung_de.pdf)., Schriftenreihe Health Technology Assessment (HTA) in der Bundesrepublik Deutschland; 134; ISSN 1864-9645

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Objectives: Several studies have reported multiple barriers to and facilitators for the uptake of health technology assessment (HTA) information by policy makers. This study elicited, using best-worst scaling (BWS), the most important barriers and facilitators and their relative weight in the use of HTA by policy makers.Methods: Two BWS object case surveys (one for barriers, one for facilitators) were conducted among sixteen policy makers and thirty-three HTA experts in the Netherlands. A list of twenty-two barriers and nineteen facilitators was included. In each choice task, participants were asked to choose the most important and the least important barrier/facilitator from a set of five. We used Hierarchical Bayes modeling to generate the mean relative importance score (RIS) for each factor and a subgroup analysis was conducted to assess differences between policy makers and HTA experts.Results: The five most important barriers (RIS > 6.00) were “no explicit framework for decision-making process,” “insufficient support by stakeholders,” “lack of support,” “limited generalizability,” and “absence of appropriate incentives.” The six most important facilitators were: “availability of explicit framework for decision making,” “sufficient support by stakeholders,” “appropriate incentives,” “sufficient quality,” “sufficient awareness,” and “sufficient support within the organization.” Overall, perceptions did not differ markedly between policy makers and HTA experts.Conclusions: Our study suggests that barriers and facilitators related to “policy characteristics” and “organization and resources” were particularly important. It is important to stimulate a pulse at the national level to create an explicit framework for including HTA in the decision-making context.

Background:Although value issues are increasingly addressed in health technology assessment (HTA) reports, HTA is still seen as a scientific endeavor and sometimes contrasted with value judgments, which are considered arbitrary and unscientific. This article aims at illustrating how numerous value judgments are at play in the HTA process, and why it is important to acknowledge and address value judgments.Methods:A panel of experts involved in HTA, including ethicists, scrutinized the HTA process with regard to implicit value judgments. It was analyzed whether these value judgments undermine the accountability of HTA results. The final results were obtained after several rounds of deliberation.Results:Value judgments are identified before the assessment when identifying and selecting health technologies to assess, and as part of assessment. They are at play in the processes of deciding on how to select, frame, present, summarize or synthesize information in systematic reviews. Also, in economic analysis, value judgments are ubiquitous. Addressing the ethical, legal, and social issues of a given health technology involves moral, legal, and social value judgments by definition. So do the appraisal and the decision-making process.Conclusions:HTA by and large is a process of value judgments. However, the preponderance of value judgments does not render HTA biased or flawed. On the contrary they are basic elements of the HTA process. Acknowledging and explicitly addressing value judgments may improve the accountability of HTA.