Decisive Evidence Research Articles

GRADE evidence to decision framework in genomics guidelines: systematic review & appraisal

Abstract Background Transparent development of clinical practice guidelines (CPGs) is important for genomic medicine, as this field promises to partially challenge the traditional hierarchies of evidence. The GRADE Evidence to Decision (EtD) framework has recently emerged as a transparent and rigorous tool to produce recommendations. Our aim was to survey the genomic CPGs that used the GRADE EtD and appraise the applicability of its criteria and the quality of produced CPGs. Methods We systematically searched PubMed, Scopus, Web of Science and the gray literature till 2023 for relevant CPGs. From each eligible CPG, we extracted the reporting of the GRADE EtD criteria: benefits, harms, resource use, cost-effectiveness, acceptability, feasibility, equity and values. The quality of the CPGs were appraised across various domains using the (AGREE) II instrument. Results Among 1,144 records, 15 CPGs met inclusion criteria between 2018 and 2023, comprising 66 recommendations. Reporting of GRADE EtD criteria varied. Benefits, harms and their balance were addressed in approximately half of the recommendations 48% and 52% respectively. Feasibility, acceptability and values were also 52%, 47% and 40% respectively, resource use 39%, cost-effectiveness 23%. Equity was addressed in 36% of the recommendations. Quality appraisal of the CPGs also varied, domains were reported as follows: scope and purpose, clarity of presentation, editorial independence 86%, 85% and 84% respectively, rigor of development 77%, stakeholder involvement 72%, while applicability was 59%. Conclusions GRADE EtD is applied heterogeneously in genomic medicine CPGs, with difficulty in applying all of its criteria, including benefits and harms. Quality varied across domains with applicability of the CPGs less demonstrated. Key messages • Transparent approaches are needed in developing CPGs for genomic medicine. • Current genomic CPGs fail to address crucial aspects for producing recommendations, including benefits and harms.

Analysis Of Differences In Evidence In District Court Decisions And Supreme Court Decisions: A Case Study On The Judicial Review Process

A judicial review (PK) is a legal mechanism given to parties who are dissatisfied with a decision that has permanent legal force, either in the District Court or the Supreme Court. In Indonesia, a PK application can only be submitted once, as regulated in Article 268 paragraph (3) of the Criminal Procedure Code, and often involves new evidence (novum) as a basis for requesting a judicial review. The objective to be achieved in this study is to analyze the differences related to the evidence in the District Court decision and the Supreme Court decision in the review process. The method used in this study is juridical normative where the legal material used covers the theory, concept, legal principles and some regulations in accordance with the discussion of research. The method of data collection used is literature study where secondary data are used such as books, laws and related journals. The results of this study indicate that the difference in evidence in conducting judicial review becomes one of the considerations for the acceptance or rejection of PK by the Supreme Court. However, in fact, the specification of the quality of evidence is still not clearly explained where it will only create a blur of norms. Therefore, it is not surprising when the Supreme Court rejected many of the judicial review considering that there was no eligibility for the quality of the evidence received

The INPHET- a global approach to Environmental Public Health Tracking

Abstract Environment and health monitoring and information systems are fundamental infrastructure for evidence provision for policy making. The International Network for Public Health and Environment Tracking (INPHET) was formed by a community of environmental public health practitioners to address common interests and activities that advance environmental public health surveillance (EPHS) and data systems, and their uses to inform public health actions. Its main goal is to address the vast inequalities across countries and communities in their ability to monitor, assess, inform and mitigate environmental and health issues. INPHET supports the relevant role of environmental epidemiology as the pillar science providing evidence for decision making and interventions aiming at reducing and preventing environmental related diseases and contributes to an overall vision for public health. As a “Community of Practice”, INPHET focuses on sharing experiences and expertise; addressing common challenges for implementing and enhancing the science of EPHS/tracking; improving understanding of the link between the environment and health; and providing the appropriate evidence that informs public policy. The network, initiated in conference meetings in 2012-13 and formally launched in Modena, Italy in 2014, has carried out several activities which aim at sharing expertise and learning from different models of environmental and health data integration and surveillance systems that directly inform policy. These include Twinning cooperation with Euro-Asian and Balkan countries and sharing of expertise with African Public Health Agencies. Some experiences are presented in this workshop and highlight the EPHS/EPHT model adopted by several national public health agencies. It promotes that such integration and uses of environmental and health data is key for EPHS, including their accessibility and usability for communities of public health researchers, practitioners and policy makers.

9.L. Round table: “What” and “How” for building competencies for effective policy making in and for public health

Abstract Policymakers operating within the field of public health must regularly draw on their skills or competencies to facilitate engagement in and between policy sectors and with the public, to navigate the larger landscape of public health institutions and governance levels across the policy cycle, to generate, understand, and apply evidence for decision making, as well as to negotiate the demands of diverse stakeholders. What exactly are the competencies needed and how can they be cultivated to enhance the collective capacity of policymaking institutions? The increasing strain placed on public health systems worldwide, owing specially to challenges in population ageing, the burden of non-communicable diseases, and the exigencies introduced by pandemics, environmental disasters, and geo-political instabilities push us to expand the scope of public health. A look to the policy environs and outcomes seen within and across countries demonstrates that the quality of policy is both highly variable and exceedingly subject to the quality of public health leadership itself. These developments shed light on the need for greater investment in the development of competencies needed by policymakers to engage in effective decision making on key issues impacting population health and the resilience of public health systems. This includes efforts to strengthen the abilities of policymakers to identify problems, recognize opportunities, and put forth solutions in line with robust data and evidence, principles of public health ethics, gaps and priorities in public health needs, and in accordance with financial and political realities. The proposed roundtable will examine the state-of-the-art on policymaking competencies in public health, and how to build them by examining the barriers and opportunities. The panel will convene leading experts in the field of public health research and practice to explore: 1) the conceptual definition of competencies for policymaking at different levels of governance and across the policy cycle; 2) the strengths and limits of competency frameworks and their utility in guiding assessment and training tools, as well as policy practice; 3) the challenges associated with developing, maintaining and transferring competencies in fast-changing, multi-level policy making environments; 4) the challenges for public health experts and institutions to be trusted advisors both by policy makers and other stakeholders and the population; and 5) the opportunities to harness the unexploited power of professional networks in some countries of Europe. Key messages • An enhanced research agenda and investment are needed for the development of competencies - individual and collective - for effective public health policy-making and stronger governance. • Innovative approaches to policy-making are needed, and this requires building competencies, including leadership, for addressing the complex nature of public health.

Italian guidelines for age range and test interval in breast cancer screening programmes: GRADE-ADOLOPMENT of the European guidelines.

A guideline panel formulated a set of recommendations for breast cancer screening and diagnosis to implement clinical activities in Italy in alignment with the European Breast Cancer Guidelines on Screening and Diagnosis (European Commission Initiative on Breast Cancer-ECIBC). The panel issued national recommendations through adopting, adapting, and/or developing recommendations from the European guidelines (ADOLOPMENT approach). This process utilizes the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence to decision (EtD) framework. An additional PubMed search was conducted using search terms specific to Italy to tailor the EU guidelines to the national context. Nine articles were included as contextual evidence in the EtD. A total of 13 recommendations were finalized, either adapted or adopted to suit the national context. Organized breast cancer screening is strongly recommended for women aged 50-69 every 2 years, and it is conditionally recommended every 3 years for women aged 70-74, as well as every 1 or 2 years for women aged 45-49. Annual mammography received a strong recommendation against for women aged 50 and older. Developing shared national guidelines for the management of mammography screening will improve the standardization of processes across all settings, thereby promoting health equity.

Ambient air pollution and risk of allergic respiratory diseases in European and East Asian populations: A Mendelian randomization study

BackgroundAmbient air pollution has become a challenging global health issue since industrialization, especially affecting respiratory diseases. However, the causal link between air pollution and allergic respiratory diseases (ARDs) remains unclear due to confounding factors in conventional epidemiological studies across different populations. Thus, we aimed to clarify the causal associations between air pollution and ARDs in European and East Asian populations using Mendelian randomization (MR). MethodsMR utilizes genetic variants and provides a satisfactory level of causal evidence. Genetic data for exposures (PM2.5, PM2.5 absorbance, PM10, PMcoarse, NO2 and NOx) and outcomes (allergic rhinitis, chronic rhinosinusitis, asthma, and obesity related asthma) were obtained from genome-wide association studies. Instrumental variables were strictly filtered based on core assumptions. Two-sample MR and sensitivity analyses were conducted separately for European and East Asian populations. ResultsPMcoarse was causally associated with an increased risk of chronic rhinosinusitis (OR = 1.588 [1.002–2.518]; p = 0.049) and obesity related asthma (OR = 1.956 [1.012–3.780]; p = 0.046) in European population, and PM10 was associated with a decreased risk of allergic rhinitis in East Asian population (OR = 0.882 [0.798–0.974]; p = 0.013). No heterogeneity or pleiotropy was detected in any significant causal association. ConclusionOur findings indicate that ambient air pollution has opposite impacts on the etiology of ARDs in European and East Asian populations, which provides evidence for decisions on public policies and suggests that different responses to environmental factors such as air pollution may contribute to racial heterogeneity of ARDs.

Prior probability biases perceptual choices by modulating the accumulation rate, rather than the baseline, of decision evidence

Abstract The prior probability of an upcoming stimulus has been shown to influence the formation of perceptual decisions. Computationally these effects have typically been attributed to changes in the starting point (i.e. baseline) of evidence accumulation in sequential sampling models. More recently, it has also been proposed that prior probability might additionally lead to changes in the rate of evidence accumulation. Here, we introduce a neurally-informed behavioural modelling approach to understand whether prior probability influences the starting point, the rate of evidence accumulation or both. To this end, we employ a well-established visual object categorization task for which two neural components underpinning participants’ choices have been characterised using single-trial analysis of the electroencephalogram. These components are reliable measures of trial-by-trial variability in the quality of the relevant decision evidence, which we use to constrain the estimation of a hierarchical drift diffusion model of perceptual choice. We find that, unlike previous computational accounts, constraining the model with the endogenous variability in the relevant decision evidence, results in prior probability effects being explained primarily by changes in the rate of evidence accumulation rather than changes in the starting point or a combination of both. Ultimately, our neurally-informed modelling approach helps disambiguate the mechanistic effect of prior probability on perceptual decision formation, suggesting that prior probability biases primarily the interpretation of sensory evidence towards the most likely stimulus.

Mapping interpretations of the law in online content moderation in Germany

Content moderation is a vital condition that online platforms must facilitate, according to the law, to create suitable online environments for their users. By the law, we mean national or European laws that require the removal of content by online platforms, such as EU Regulation 2021/784, which addresses the dissemination of terrorist content online. Content moderation required by these national or European laws, summarised here as ‘the law’, is different from the moderation of pieces of content that is not directly required by law but instead is conducted voluntarily by the platforms. New regulatory requests create an additional layer of complexity of legal grounds for the moderation of content and are relevant to platforms’ daily decisions. The decisions made are either grounded in reasons stemming from different sources of law, such as international or national provisions, or can be based on contractual grounds, such as the platform's Terms of Service and Community Standards. However, how to empirically measure these essential aspects of content moderation remains unclear. Therefore, we ask the following research question: How do online platforms interpret the law when they moderate online content?To understand this complex interplay and empirically test the quality of a platform's content moderation claims, this article develops a methodology that facilitates empirical evidence of the individual decisions taken per piece of content while highlighting the subjective element of content classification by human moderators. We then apply this methodology to a single empirical case, an anonymous medium-sized German platform that provided us access to their content moderation decisions. With more knowledge of how platforms interpret the law, we can better understand the complex nature of content moderation, its regulation and compliance practices, and to what degree legal moderation might differ from moderation due to contractual reasons in dimensions such as the need for context, information, and time.Our results show considerable divergence between the platform's interpretation of the law and ours. We believe that a significant number of platform legal interpretations are incorrect due to divergent interpretations of the law and that platforms are removing legal content that they falsely believe to be illegal (‘overblocking’) while simultaneously not moderating illegal content (‘underblocking’). In conclusion, we provide recommendations for content moderation system design that takes (legal) human content moderation into account and creates new methodological ways to test its quality and effect on speech in online platforms.

Financing green innovation startups: a systematic literature review on early-stage SME funding

ABSTRACT This paper investigates the critical issue of financing early-stage green startups, examining the types of investors and finance models available, the challenges these startups face, and how the green finance ecosystem can better support early-stage investment. Utilizing a systematic literature review (SLR) methodology, we provide a comprehensive analysis of the current landscape. Our findings reveal a significant paucity of data and a bias towards well-established North American and European ecosystems, while highlighting an emerging diversity in private finance sources post-Global financial crisis (GFC), including grants, equity, and crowdfunding. Despite this, there remains a heavy reliance on public funding and a lack of evidence regarding its impact. The inherent characteristics of cleantech – high capital expenditure, long investment horizons, and disruptive nature – necessitate innovative public financing instruments and policies to reduce risk and attract private investment. Our theoretical contribution highlights the necessity for interdisciplinary research and policy collaboration to develop a holistic entrepreneurial finance (entfin) ecosystem. This approach should integrate quantitative economic and qualitative behavioural finance research to address information asymmetries and improve the green economy policy mix. Such a framework will support public-private co-financing, enhance stakeholder engagement, and provide evidence for policy decisions, facilitating more rapid commercialization of cleantech innovations for environmental sustainability.

A Review and Comparative Case Study Analysis of Real-World Evidence in European Regulatory and Health Technology Assessment Decision Making for Oncology Medicines

ObjectivesReal-world evidence (RWE) is valuable in supporting regulatory and health technology assessment (HTA) decisions; however, the actual contribution to approvals remains elusive. This study aimed to review RWE approaches and use in oncology medicine approvals in Europe and understand cohesion and discrepancy in the acceptance of the RWE by the European Medicines Agency (EMA) and European HTA bodies. MethodsThis scoping review involved a search of the EMA database, National Institute for Health and Care Excellence (NICE), Gemeinsamer Bundesausschuss (G-BA), and Haute Autorité de Santé (HAS) websites to identify final reports and appraisals for oncology medicines with references to RWE. The selection was guided by research terms associated with RWE study designs, data sources, and outcomes. Qualitative analysis was used to systemize the data. Case studies assessed by more than one agency were selected for comparative assessment of RWE approach, use, and acceptability. ResultsRWE was mainly leveraged as an external control for indirect treatment comparisons or contextualization to support clinical trial results by the EMA, NICE, G-BA, and HAS. However, this approach was mostly rejected due to methodology biases. Comparative assessment of RWE acceptability for the same oncology medicines across agencies suggests discrepancies between EMA and European HTA bodies and among NICE, G-BA, and HAS. ConclusionsThere is diverging acceptance of RWE in EMA and European HTA bodies with no clear consensus on the most effective way to leverage RWE in approvals. With the introduction of the joint European Union Joint Clinical Assessment in 2025, it is crucial for European HTA bodies and EMA to develop synergetic standards for the use of RWE to ensure equitable and timely access to medicines.

Improving Decision-Making and Documentation on the Acute Medical Post-Take Ward Round

Abstract Background Frail Older people have a substantial presence on the Acute Medical Take. They also have a large conversion rate to hospital admission after the Post-Take Ward Round (PTWR). They decondition and deteriorate with long delays in the Emergency Department. The PTWR is a particularly important part of the patient journey particularly for capturing senior decision-maker input around key clinical and patient flow parameters. PTWR documentation in Irish hospitals is currently largely captured in an open freehand manner. Decisions made on the PTWR have implications across several domains including quality of care, patient safety, medico-legal outcomes as well as informing patient flow metrics. A structured & standardised approach to PTWR decision-making is anticipated to improve outcomes across these respective domains. Methods A standardised PTWR tool (1) was used to replace freehand PTWR case-note entries. All medical consultants were invited to use the tool on their PTWRs. All auditors were trained in gathering data consistently. Spot audits were undertaken on all wards before and two weeks after the introduction of a Standardised PTWR clerking tool. Capture of Key PTWR documentation and evidence of decisions made were identified. The Chi2 test was used to compare outcomes before and after introducing the intervention tool. Results 138 PTWR patients (number >65y: 124) documentation were assessed before the introduction of the PTWR tool and 74 patients afterwards. Significant improvement was found across 12/16 domains including decisions made relating to Investigations reviewed, Diagnoses made, Thrombo-prophylaxis considered, Ceilings of care reviewed, Discussions with patients and/or advocates and Predicted Date of Discharge (p<0.001). Conclusion A standardised PTWR tool significantly improves the capture of key documentation and decisions made on the Acute Medical Take above conventional freehand case-note entries. This may have significant implications for the care of older people clinically both from an individual and overall patient flow perspective.

Qualitative assessment of evidence-informed adolescent mental health policymaking in India: insights from project SAMA

BackgroundThe importance of evidence-informed health policymaking is widely recognized. However, many low- and middle-income countries lack evidence-informed mental health policies due to insufficient data, stigma or lack of resources. Various policies address adolescent mental health in India, but published knowledge on their evidence-informed nature is limited. In this paper, we report results of our analysis of the role of evidence in adolescent mental health policymaking in India.MethodsThis paper reports findings from the document analysis of key policy documentation (n = 10) and in-depth interviews with policy actors including policymakers, researchers, practitioners and intermediaries (n = 13). Framework analysis was used, informed by the components of a conceptual framework adapted from the literature: actors, policy and evidence processes, nature of evidence itself and contextual influences.ResultsResults show that adolescent mental health policies in India were generally evidence-informed, with more key evidence becoming generally available from 2010 onwards. Both formal and informal evidence informed mental health policies, particularly agenda-setting and policy development. Mental health policymaking in India is deemed important yet relatively neglected due to competing policy priorities and structural barriers such as stigma. Use of evidence in mental health policymaking reflected differing values, interests, relative powers and ideologies of policy actors. Involvement of government officials in evidence generation often resulted in successful evidence uptake in policy decisions. Policy actors often favoured formal and quantitative evidence, with a tendency to accept global evidence that aligns with personal values.ConclusionsThere is a need to ensure a balanced and complementary combination of formal and informal evidence for policy decisions. Evidence generation, dissemination and use for policy processes should recognize evidence preferences by key stakeholders, while prioritizing locally available evidence where possible. To help this, a balanced involvement of policy actors can ensure complementary perspectives in evidence production and policy agendas. This continued generation and promotion of evidence can also help reduce societal stigma around mental health and promote mental health as a key policy priority.

Long-term quality of life and influencing factors in elderly patients after vertebroplasty based on the EQ-5D-3L Chinese utility scoring system: a retrospective study

BackgroundThe quality of life of elderly patients after vertebroplasty is influenced by various factors. Although the EuroQol 5-Dimension 3-Level (EQ-5D-3L) scale has been widely used to assess quality of life, the factors affecting the long-term postoperative quality of life of elderly vertebroplasty patients in China have not been thoroughly studied.MethodsThis retrospective study included 519 patients aged 65 years and older who underwent elective vertebroplasty. We collected baseline data from these patients and conducted telephone follow-ups 12 months postoperation to evaluate their EQ-5D-3L health utility scores and EuroQol Visual Analogue Scale (EQ-VAS) scores. Univariate and multivariate linear regression models were used to analyse the factors affecting quality of life.ResultsOf the 519 patients, the majority were female (78.0%), aged 65 to 95 years, with an average age of 75.2 years. Twelve months postoperation, pain/discomfort was the most commonly reported issue for 68.4% of patients. The median EQ-5D-3L health utility score was 0.783, with a range between 0.450 and 0.887; the median EQ-VAS score was 75, ranging from 60 to 85. Multivariate linear regression analysis indicated that older age, hormone use, higher American Society of Anesthesiologists (ASA) grades, nondrinking habits, and low albumin levels were found to be independent risk factors affecting long-term quality of life in elderly patients after vertebroplasty. Additionally, a history of tumours, the number of vertebral compression fractures, and bone mineral density were also crucial influencing factors.ConclusionsBased on the use of the EQ-5D-3L Chinese utility scoring system, we evaluated the quality of life of patients aged 65 and above 12 months after vertebroplasty. This study identified several factors related to postoperative quality of life in elderly vertebroplasty patients, providing crucial evidence for further clinical decisions and patient education.

Latin American panelists find GRADE-ADOLOPMENT useful and important to contextualize recommendations in their region

Background and ObjectiveGrading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT is widely applied to efficiently use existing credible guidelines and contextualize them to a target setting. To highlight the experiences of a Latin American Guideline Development Group (GDG) applying GRADE-ADOLOPMENT to adapt the American Society of Hematology's clinical practice guideline on managing venous thromboembolisms (VTEs) in Latin America. Study Design and SettingWe employed a mixed-method postevaluation using self-administered surveys and semistructured interviews. We assessed the Latin American GDG (1) general satisfaction and confidence using the approach, (2) their ratings on the usefulness, appropriateness, and importance of GRADE-ADOLOPMENT and its tools to inform their judgements, and (3) any additional facilitators and barriers to refine the process. ResultsEleven of the 14 GDG members, including nine panelists and two methodologists, provided survey responses and eight participated in the interview. Respondents felt “mostly” or “completely” satisfied with the adapted guideline. Eight panelists who were surveyed agree that GRADE-ADOLOPMENT is useful in countries with limited resources. Although panelists expressed initial apprehensions in their understanding of the process, they demonstrated enhanced confidence in their capacity to apply GRADE after completing workshop training and by acquiring experience. Panelists reiterated the importance of considering evidence-to-decision (EtD) criteria (ie, resources, feasibility, and cost-effectiveness) when adapting recommendations. The GDG encountered challenges with collecting local and regional data, prioritizing recommendations while considering intraregional diversity, and the lengthy publication period, although the latter stemmed from procedures not related to GRADE-ADOLOPMENT. ConclusionsGRADE-ADOLOPMENT is an important tool to facilitate the adaptation and uptake of clinical practice guidelines in novel settings. The GDG felt satisfied with their overall experience using the GRADE-ADOLOPMENT approach. However, their experience could have been optimized if they had access to robust regional evidence, more recommendations to adapt from, and worked with more efficient guideline production timelines.

Exploring the Influence of Financial Literacy on Mobile Financial Service Usage: An Ordered Probit Analysis

Mobile financial service, an emerging form of financial services that has developed alongside the internet and mobile devices, are becoming increasingly significant in the global financial market. Financial literacy is crucial for safely and effectively using these services, as it equips individuals with the necessary knowledge and skills to navigate the digital financial landscape, make informed decisions, and manage their finances responsibly. This study explores the link between financial literacy and the use of mobile financial services, aiming to promote financial inclusion and help users benefit from mobile banking technologies. The results indicate that the impact of objective financial literacy varies significantly across different types of mobile financial services. It boosts the utilization of mobile banking services, with coefficient 0.025 (p<0.01), while simultaneously reducing the frequency of mobile payments and transfers, with coefficients -0.041 and -0.012 respectively (p<0.01). The results also show that subjective financial literacy always positively relate to the use of mobile banking, mobile payments and mobile transfers, with coefficients 0.038, 0.044 and 0.03 respectively (p<0.01). Further, this paper investigates how financial literacy miscalibration affects the use of mobile financial services. The results show that individuals who over-evaluated their financial literacy are more likely to use mobile financial services than individuals who under-evaluated or correct-evaluated their financial literacy. The results serve as decisive evidence for policymakers to enhance consumer financial literacy, thereby improving their use of mobile financial services. Future studies could delve deeper into the underlying reasons for the differential impact of objective financial literacy on various MFS types.

The Influence of Emotional Response and Aesthetic Perception of Shopping Mall Facade Color on Entry Decisions—Evidence from the Yangtze River Delta Region of China

The Influence of Emotional Response and Aesthetic Perception of Shopping Mall Facade Color on Entry Decisions—Evidence from the Yangtze River Delta Region of China

Procedural closure of the patent ductus arteriosus in preterm infants: a clinical practice guideline.

Transcatheter closure of the patent ductus arteriosus (PDA) is being increasingly adopted as an alternative to surgical PDA closure in preterm infants. To develop rigorous clinical practice guideline recommendations on procedural PDA closure in preterm infants. The principles of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence-to-Decision (EtD) framework were used to develop the guideline recommendations. An e-Delphi survey of 45 experts was conducted and recommendations that reached ≥75% agreement were accepted as consensus. Procedural PDA closure may be considered in extremely preterm infants (<28 weeks gestational age) requiring invasive mechanical ventilation >10 postnatal days and confirmed to have a large hemodynamically significant PDA, at centers with high local rates of death and/or bronchopulmonary dysplasia (conditional recommendation). If sufficient institutional expertise is available and patient characteristics are suitable, transcatheter PDA closure may be considered as the preferred approach over PDA ligation (conditional recommendation).

The STAR Compass to Guide Future Pharmacovigilance Based on a 10-Year Review of the Strengthened EU System.

This article reflects on the 2010 pharmacovigilance legislation of the European Union (EU). Its legislative aim of better patient and public health protection through new responsibilities for pharmaceutical companies and regulatory bodies is considered to have been achieved and is well supported by the good pharmacovigilance practices 'EU-GVP'. For future progress, we set out a vision for high-quality pharmacovigilance in a world of ongoing medical, technological and social changes. To deliver this vision, four principles are proposed to guide actions for further progressing the EU pharmacovigilance system: synergistic interactions with healthcare systems; trustworthy evidence for regulatory decisions; adaptive process efficiency; and readiness for emergency situations (the 'STAR principles'). Like a compass, these principles should guide actions for building capacity, technology and methods; improving regulatory processes; and expanding policies, frameworks and research agendas. Fit for the future, the EU system should achieve further improved outputs in terms of safe, effective and trusted use of medicines and positive health outcomes within patient-centred healthcare.

Real-World Evidence to Support EU Regulatory Decision Making-Results From a Pilot of Regulatory Use Cases.

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory-led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real-world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit-for-purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory-led RWE generation.

Accurate segmentation of liver tumor from multi-modality non-contrast images using a dual-stream multi-level fusion framework

The use of multi-modality non-contrast images (i.e., T1FS, T2FS and DWI) for segmenting liver tumors provides a solution by eliminating the use of contrast agents and is crucial for clinical diagnosis. However, this remains a challenging task to discover the most useful information to fuse multi-modality images for accurate segmentation due to inter-modal interference. In this paper, we propose a dual-stream multi-level fusion framework (DM-FF) to, for the first time, accurately segment liver tumors from non-contrast multi-modality images directly. Our DM-FF first designs an attention-based encoder–decoder to effectively extract multi-level feature maps corresponding to a specified representation of each modality. Then, DM-FF creates two types of fusion modules, in which a module fuses learned features to obtain a shared representation across multi-modality images to exploit commonalities and improve the performance, and a module fuses the decision evidence of segment to discover differences between modalities to prevent interference caused by modality’s conflict. By integrating these three components, DM-FF enables multi-modality non-contrast images to cooperate with each other and enables an accurate segmentation. Evaluation on 250 patients including different types of tumors from two MRI scanners, DM-FF achieves a Dice of 81.20%, and improves performance (Dice by at least 11%) when comparing the eight state-of-the-art segmentation architectures. The results indicate that our DM-FF significantly promotes the development and deployment of non-contrast liver tumor technology.