Uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group.

OBJECTIVES: Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface. METHODS: Six online discussions among WG members (Dec 2021-Sep 2022) who examined the output of a scoping review, two literature-based case studies and a survey; application of the initial guidance to a real-world case study; and two international conference panel discussions. RESULTS: The WG identified key concepts, clustered into twelve building blocks that were collectively perceived to define uncertainty: "unavailable," "inaccurate," "conflicting," "not understandable," "random variation," "information," "prediction," "impact," "risk," "relevance," "context," and "judgment." These were converted into a checklist to explain and define whether any issue constitutes a decision-relevant uncertainty. A taxonomy of domains in which uncertainty may exist within the regulatory-HTA interface was developed to facilitate categorization. The real-world case study was used to demonstrate how the guidance may facilitate deliberation between stakeholders and where additional guidance development may be needed. CONCLUSIONS: The systematic approach taken for the identification of uncertainties in this guidance has the potential to facilitate understanding of uncertainty and its management across different stakeholders involved in drug development and evaluation. This can improve consistency and transparency throughout decision processes. To further support uncertainty management, linkage to suitable mitigation strategies is necessary.

The accountability of the private sector towards citizens in times of crisis: vaccines, medicines and equipment.

In this article, we examine what the role of the private sector in times of crises is and whether the private sector is, and can be held to be, accountable. COVID-19 has amplified the difficulties with public-private partnerships and this article addresses several aspects concerning business enterprises, in particular transnational corporations, human rights and health sector activities, highlighting the key aspects to understand and address accountability issues. The article also explores accountability for the private sector, the processes to ensure accountability, and the relevance of regulation and self-regulation.

Health technology assessment applied to emergency preparedness: a new perspective.

Emergency preparedness is a continuous quality improvement process through which roles and responsibilities are defined to effectively anticipate, respond to, and recover from the impact of emergencies. This process results in documented plans that provide a backbone structure for developing the core capacities to address health threats. Nevertheless, several barriers can impair an effective preparedness planning, as it needs a 360° perspective to address each component according to the best evidence and practice. Preparedness planning shares common principles with health technology assessment (HTA) as both encompass a multidisciplinary and multistakeholder approach, follow an iterative cycle, adopt a 360° perspective on the impact of intervention measures, and conclude with decision-making support. Our "Perspective" illustrates how each HTA domain can address different component(s) of a preparedness plan that can indeed be seen as a container of multiple HTAs, which can then be used to populate the entire plan itself. This approach can allow one to overcome preparedness barriers, providing an independent, systematic, and robust tool to address the components and ensuring a comprehensive evaluation of their value in the mitigation of the impact of emergencies.

The fourth edition of the European Network for Health Technology Assessment Forum: highlights and outcomes.

The European Network for Health Technology Assessment (EUnetHTA) organizes an annual Forum with stakeholders to receive feedback on its activities, processes, and outputs produced. The fourth edition of the EUnetHTA Forum brought together representatives of HTA bodies, patient organizations, healthcare professionals (HCPs), academia, payers, regulators, and industry. The aim of this paper is to provide an overview of the highlights presented at the 2019 EUnetHTA Forum, reporting the main items and themes discussed in the plenary panel and breakout sessions. The leading topic was the concept of unmet medical need seen from different stakeholders' perspectives. Breakout sessions covered the joint production of assessment reports and engagement with payers, patients, and HCPs. Synergies, pragmatism, and inclusiveness across Member States and stakeholders were emphasized as leading factors to put in place a collaboration that serves the interest of patients and public health in a truly European spirit.

Assessing refugee healthcare needs in Europe and implementing educational interventions in primary care: a focus on methods.

The current political crisis, conflicts and riots in many Middle Eastern and African countries have led to massive migration waves towards Europe. European countries, receiving these migratory waves as first port of entry (POE) over the past few years, were confronted with several challenges as a result of the sheer volume of newly arriving refugees. This humanitarian refugee crisis represents the biggest displacement crisis of a generation. Although the refugee crisis created significant challenges for all national healthcare systems across Europe, limited attention has been given to the role of primary health care (PHC) to facilitate an integrated delivery of care by enhancing care provision to refugees upon arrival, on transit or even for longer periods. Evidence-based interventions, encompassing elements of patient-centredness, shared decision-making and compassionate care, could contribute to the assessment of refugee healthcare needs and to the development and the implementation of training programmes for rapid capacity-building for the needs of these vulnerable groups and in the context of integrated PHC care. This article reports on methods used for enhancing PHC for refugees through rapid capacity-building actions in the context of a structured European project under the auspices of the European Commission and funded under the 3rd Health Programme by the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA). The methods include the assessment of the health needs of all the people reaching Europe during the study period, and the identification, development, and testing of educational tools. The developed tools were evaluated following implementation in selected European primary care settings.

[Primary care of refugees and migrants. Lesson learnt from the EUR-HUMAN project]. / Menekültek, migránsok az alapellátásban. Mit tanulhattunk az EUR-HUMAN projekt eredményeibol?

In 2015, local wars, starvation and misery in some Middle Eastern, Asian and African countries forced millions of people to leave their homelands. Many of these people migrated toward Europe, reaching Hungary as well. The refugee crisis created significant challenges for all national healthcare systems across Europe. Limited attention has been given to the extent to which health service provision for refugees and migrants has become a task for primary health care (PHC), which has been unprepared as a profession and pressured by the enormous workload. Hungarian primary care was involved only to an extent in the refugees' health care, as most of the migrants entering Hungary wanted to move forward to other countries. The need for evidence-based patient-centred interventions to assess refugee healthcare needs, and for training programmes for rapid capacity-building for integrated PHC was addressed by the EUropean Refugees - HUman Movement and Advisory Network (EUR-HUMAN) project, which 7 European countries developed together. The overall aim of the EUR-HUMAN project is to enhance the knowledge and expertise of European member states who accept refugees and migrants in addressing their health needs, safeguarding them from risks, while at the same time to minimize cross-border health risks. This initiative focuses on addressing the early arrival period, transition and longer-term settlement of refugees in European host countries. A primary objective of this project is to identify, design and assess interventions to improve PHC delivery for refugees and migrants with a focus on vulnerable groups. The structure, the main focus and outputs of the project are described and summarized in this paper, providing relevant information and access to educational materials for Hungarian (primary care) physicians. The EUR-HUMAN project was operated in 2016 under the auspices of the European Commission and funded by the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA). Orv Hetil. 2018; 159(35): 1414-1422.

Operational integration in primary health care: patient encounters and workflows.

BACKGROUND: Despite several countrywide attempts to strengthen and standardise the primary healthcare (PHC) system, Greece is still lacking a sustainable, policy-based model of integrated services. The aim of our study was to identify operational integration levels through existing patient care pathways and to recommend an alternative PHC model for optimum integration. METHODS: The study was part of a large state-funded project, which included 22 randomly selected PHC units located across two health regions of Greece. Dimensions of operational integration in PHC were selected based on the work of Kringos and colleagues. A five-point Likert-type scale, coupled with an algorithm, was used to capture and transform theoretical framework features into measurable attributes. PHC services were grouped under the main categories of chronic care, urgent/acute care, preventive care, and home care. A web-based platform was used to assess patient pathways, evaluate integration levels and propose improvement actions. Analysis relied on a comparison of actual pathways versus optimal, the latter ones having been identified through literature review. RESULTS: Overall integration varied among units. The majority (57%) of units corresponded to a basic level. Integration by type of PHC service ranged as follows: basic (86%) or poor (14%) for chronic care units, poor (78%) or basic (22%) for urgent/acute care units, basic (50%) for preventive care units, and partial or basic (50%) for home care units. The actual pathways across all four categories of PHC services differed from those captured in the optimum integration model. Certain similarities were observed in the operational flows between chronic care management and urgent/acute care management. Such similarities were present at the highest level of abstraction, but also in common steps along the operational flows. CONCLUSIONS: Existing patient care pathways were mapped and analysed, and recommendations for an optimum integration PHC model were made. The developed web platform, based on a strong theoretical framework, can serve as a robust integration evaluation tool. This could be a first step towards restructuring and improving PHC services within a financially restrained environment.

Irrational prescribing of over-the-counter (OTC) medicines in general practice: testing the feasibility of an educational intervention among physicians in five European countries.

BACKGROUND: Irrational prescribing of over-the-counter (OTC) medicines in general practice is common in Southern Europe. Recent findings from a research project funded by the European Commission (FP7), the "OTC SOCIOMED", conducted in seven European countries, indicate that physicians in countries in the Mediterranean Europe region prescribe medicines to a higher degree in comparison to physicians in other participating European countries. In light of these findings, a feasibility study has been designed to explore the acceptance of a pilot educational intervention targeting physicians in general practice in various settings in the Mediterranean Europe region. METHODS: This feasibility study utilized an educational intervention was designed using the Theory of Planned Behaviour (TPB). It took place in geographically-defined primary care areas in Cyprus, France, Greece, Malta, and Turkey. General Practitioners (GPs) were recruited in each country and randomly assigned into two study groups in each of the participating countries. The intervention included a one-day intensive training programme, a poster presentation, and regular visits of trained professionals to the workplaces of participants. Reminder messages and email messages were, also, sent to participants over a 4-week period. A pre- and post-test evaluation study design with quantitative and qualitative data was employed. The primary outcome of this feasibility pilot intervention was to reduce GPs' intention to provide medicines following the educational intervention, and its secondary outcomes included a reduction of prescribed medicines following the intervention, as well as an assessment of its practicality and acceptance by the participating GPs. RESULTS: Median intention scores in the intervention groups were reduced, following the educational intervention, in comparison to the control group. Descriptive analysis of related questions indicated a high overall acceptance and perceived practicality of the intervention programme by GPs, with median scores above 5 on a 7-point Likert scale. CONCLUSIONS: Evidence from this intervention will estimate the parameters required to design a larger study aimed at assessing the effectiveness of such educational interventions. In addition, it could also help inform health policy makers and decision makers regarding the management of behavioural changes in the prescribing patterns of physicians in Mediterranean Europe, particularly in Southern European countries.

Improving Antibiotic Use in Nursing Homes by Infection Prevention and Control and Antibiotic Stewardship (IMAGINE): Protocol for a Before-and-After Intervention and Implementation Study.

BACKGROUND: Despite the extensive use of antibiotics and the growing challenge of antimicrobial resistance, there has been a lack of substantial initiatives aimed at diminishing the prevalence of infections in nursing homes and enhancing the detection of urinary tract infections (UTIs). OBJECTIVE: This study aims to systematize and enhance efforts to prevent health care-associated infections, mainly UTIs and reduce antibiotic inappropriateness by implementing a multifaceted intervention targeting health care professionals in nursing homes. METHODS: A before-and-after intervention study carried out in a minimum of 10 nursing homes in each of the 8 European participating countries (Denmark, Greece, Hungary, Lithuania, Poland, Slovakia, Slovenia, and Spain). A team of 4 professionals consisting of nurses, doctors, health care assistants, or health care helpers are actively involved in each nursing home. Over the initial 3-month period, professionals in each nursing home are registering information on UTIs as well as infection and prevention control measures by means of the Audit Project Odense method. The audit will be repeated after implementing a multifaceted intervention. The intervention will consist of feedback and discussion of the results from the first registration, training on the implementation of infection and prevention control techniques provided by experts, appropriateness of the diagnostic approach and antibiotic prescribing for UTIs, and provision of information materials on infection control and antimicrobial stewardship targeted to staff, residents, and relatives. We will compare the pre- and postintervention audit results using chi-square test for prescription appropriateness and Student t test for implemented hygiene elements. RESULTS: A total of 109 nursing homes have participated in the pilot study and the first registration audit. The results of the first audit registration are expected to be published in autumn of 2024. The final results will be published by the end of 2025. CONCLUSIONS: This is a European Union-funded project aimed at contributing to the battle against antimicrobial resistance through improvement of the quality of management of common infections based on evidence-based interventions tailored to the nursing home setting and a diverse range of professionals. We expect the intervention to result in a significant increase in the number of hygiene activities implemented by health care providers and residents. Additionally, we anticipate a marked reduction in the number of inappropriately managed UTIs, as well as a substantial decrease in the overall incidence of infections following the intervention. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60099.

A Mixture of Essential Oils from Three Cretan Aromatic Plants Inhibits SARS-CoV-2 Proliferation: A Proof-of-Concept Intervention Study in Ambulatory Patients.

INTRODUCTION: The need for effective therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remained largely unmet. Previous work has shown that a combination of three aromatic plants' essential oils (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticose Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care settings. METHODS: A total of 69 adult patients were included in a clinical proof-of-concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention group and control group) during three study periods (IG2020, n=13, IG2021/22, n=25, and CG2021/22, n=31). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture was administered daily for 14 days per os in the intervention group, while the control group received usual care. RESULTS: The PoC study found that the number and frequency of general symptoms, including general fatigue, weakness, fever, and myalgia, decreased following CAPeo administration. By Day 7, the average presence (number) of symptoms decreased in comparison with Day 1 in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1), representing a significant decrease in the cumulative presence in IC (-3.3 vs. -0.9, p < 0.001; η2 = 0.20) on Day 7 and on Day 14 (-4.2 vs. -2.9, p = 0.027; η2 = 0.08). DISCUSSION/CONCLUSIONS: Our findings suggest that CAPeo possesses potent antiviral activity against SARS-CoV-2 in addition tο its effect against influenza A and B and human rhinovirus HRV14 strains. The early and effective impact on alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for patients with mild COVID-19.

Inclusion of functional measures and frailty in the development and evaluation of medicines for older adults.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in people older than age 65 years, dates from 1994. Since then, the inclusion of older people in clinical trials has hardly improved, particularly for the oldest old age group (individuals older than age 75 years), which is the fastest growing demographic bracket in the EU. Even though most medications are taken by this group, relevant endpoints and safety outcomes for this cohort are rarely included and reported, both in clinical trials and regulatory approval documents. To improve the critical appraisal and the regulatory review of medicines taken by frail older adults, eight recommendations are presented and discussed in this Health Policy. These recommendations are brought together from different perspectives and experience of the treatment of older patients. On one side, the perspective of medical practitioners from various clinical disciplines, with their direct experience of clinical decision making; on the other, the perspective of regulators assessing the data submitted in medicine registration dossiers, their relevance to the risk-benefit balance for older patients, and the communication of the findings in the product information. Efforts to improve the participation of older people in clinical trials have been in place for more than a decade, with little success. The recommendations presented here are relevant for stakeholders, authorities, pharmaceutical companies, and researchers alike, as the implementation of these measures is not under the capacity of a single entity. Improving the inclusion of frail older adults requires awareness, focus, and action on the part of those who can effect a much needed change.

Measuring the Burden of Infodemics: Summary of the Methods and Results of the Fifth WHO Infodemic Management Conference.

Background: An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention. Objective: In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics. Methods: An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health-implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified. Results: The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions. Conclusions: Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers.

Risk assessment of COVID-19 epidemic resurgence in relation to SARS-CoV-2 variants and vaccination passes.

The introduction of COVID-19 vaccination passes (VPs) by many countries coincided with the Delta variant fast becoming dominant across Europe. A thorough assessment of their impact on epidemic dynamics is still lacking. Here, we propose the VAP-SIRS model that considers possibly lower restrictions for the VP holders than for the rest of the population, imperfect vaccination effectiveness against infection, rates of (re-)vaccination and waning immunity, fraction of never-vaccinated, and the increased transmissibility of the Delta variant. Some predicted epidemic scenarios for realistic parameter values yield new COVID-19 infection waves within two years, and high daily case numbers in the endemic state, even without introducing VPs and granting more freedom to their holders. Still, suitable adaptive policies can avoid unfavorable outcomes. While VP holders could initially be allowed more freedom, the lack of full vaccine effectiveness and increased transmissibility will require accelerated (re-)vaccination, wide-spread immunity surveillance, and/or minimal long-term common restrictions.

The benefits, costs and feasibility of a low incidence COVID-19 strategy.

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust.

Collaboration amongst general practitioners and gynaecologists working in primary health care in Germany: a cross-sectional study.

AIM: This cross-sectional study is the first one to explore the collaboration of the influencing factors thereof amongst general practitioners (GPs) and gynaecologists (Gyns) working in primary care in urban and rural settings in Germany. BACKGROUND: The number of women aged ≥ 50 years is predicted to increase in the next years in Germany. This coincides with the ageing of primary care specialists providing outpatient care. Whereas delegation of tasks to nurses as a form of interprofessional collaboration has been the target of recent studies, there is no data regarding collaboration amongst physicians in different specialisations working in primary care. We explored collaboration amongst GPs and Gyn regarding the healthcare provision to women aged ≥ 50 years. METHODS: A quantitative postal survey was administered to GPs and Gyns in three federal states in Germany, focusing on care provision to women aged ≥ 50 years. A total of 4545 physicians, comprising 3514 GPs (67% of the total GP population) randomly selected, and all 1031 Gyns practicing in these states received the postal survey in March 2018. A single reminder was sent in April 2018 with data collection ending in June 2018. Multiple logistic regressions were performed for collaboration, adjusted by age and sex, alongside descriptive methods. FINDINGS: The overall response rate was 31% (1389 respondents): 861 GPs (25%) and 528 Gyns (51%), with the mean respondent age being 54.4 years. Seventy-two per cent were female. Key competencies of collaboration are associated with working in rural federal states and with network participation. Physicians from rural states [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.2, 1.9] and physicians in networks (OR = 3.0, CI = 2.3, 3.9) were more satisfied with collaboration. Collaboration to deliver services for women aged ≥ 50 years is more systematic amongst GPs and Gyns who are members of a network; increased networking could improve collaboration, and ultimately, outcomes too.

Diversity in Health Informatics: Mentoring and Leadership.

Diversity, inclusion and interdisciplinary collaboration are drivers for healthcare innovation and adoption of new, technology-mediated services. The importance of diversity has been highlighted by the United Nations' in SDG5 "Achieve gender equality and empower all women and girls", to drive adoption of social and digital innovation. Women play an instrumental role in health care and are in position to bring about significant changes to support ongoing digitalization and transformation. At the same time, women are underrepresented in Science, Technology, Engineering and Mathematics (STEM). To some extent, the same holds for health care informatics. This paper sums up input to strategies for peer mentoring to ensure diversity in health informatics, to target systemic inequalities and build sustainable, intergenerational communities, improve digital health literacy and build capacity in digital health without losing the human touch.