ICT Toolkit for Integrated Prevention, Testing and Linkage to Care Across HIV, Hepatitis, STIs and Tuberculosis in Europe.

Online digital tools are considered an innovative method to promote HIV, hepatitis and STIs prevention, testing and treatment services, overcoming individual and social barriers, especially for younger people and other, possibly hard-to-reach, target population groups. In this paper, we introduce INTEGRATE RiskRadar, a web and mobile application developed in the scope of the EU-supported INTEGRATE Joint Action (JA), that aims to enhance the integration of combination prevention, testing and linkage to care for HIV, hepatitis, STIs and tuberculosis by providing integrated information and digital tools regarding all four diseases to population groups at increased risk, aiming to eliminate the individual and social barriers to effective adoption of prevention practices, testing and linkage to care, and thus reduce the incidence and burden of these diseases in the European Region.

Development of a ePRO-Based Palliative Care Intervention for Cancer Patients: A Participatory Design Approach.

This paper describes a qualitative study conducted in the context of developing a novel ePRO (electronic Patient Reported Outcome) based palliative care intervention for cancer patients. The aim of the study was to elicit end-users' needs, judgements of the MyPal system and recommendations for improvement. A participatory design was chosen as the value of this approach has been well established in eHealth systems' design as well as the development of novel healthcare services. Focus groups with Chronic Lymphocytic Leukemia (CLL) patients were conducted at the Centre for Research and Technology (CERTH) in Greece using specially designed vignettes and discussion guides. Findings revealed that patients saw MyPal offering increased, direct contact with the healthcare team, freedom of physical and psychological symptom reporting as well as valid and reliable information. However, they had concerns about the appropriate use of data collected by MyPal, the efficiency of data analysis and data security adopted for sensitive personal information. The participatory design approach used has been very useful in encouraging the genuine involvement of participants, a factor which over time can empower and promote participants' long-term engagement.

Citizen Perspectives on Cross-Border eHealth Data Exchange: A European Survey.

Efficient and secure cross-border eHealth data exchange has been recently identified by the European Commission as one of the top-three priorities for the digital transformation of health and care in the European Union. To this end, various organizational, legal, ethical, and technical challenges, related to citizens' privacy and health data security arise. This paper discusses an online survey that was conducted with the participation of European citizens, aiming to identify how they feel about exchanging their health data with healthcare professionals or eHealth service providers and to what extent they are aware of the privacy, legal, security, and technology acceptance issues (e.g. use of biometrics, mobile apps, etc.). The survey rationale, structure, and results are presented, while potential barriers and facilitators regarding cross-border health data exchange and the adoption of eHealth solutions at large are discussed.

Mining Social Media for Perceptions and Trends on HIV Pre-Exposure Prophylaxis.

Pre-Exposure Prophylaxis (PrEP) is an approach for preventing the human immunodeficiency virus (HIV), which entails the administration of antiretroviral medication to high-risk seronegative persons. If taken correctly, PrEP can reduce HIV infection risk by more than 90%. The aim of this study was to identify and examine PrEP-related perceptions and trends discussed on Twitter. Using open-source technologies, text-mining and interactive visualisation techniques, a comprehensive data gathering and analytics Web-based platform was developed to facilitate the study objectives. Our results demonstrate that monitoring of PrEP-related discussions on Twitter can be detected over time and valuable insights can be obtained concerning issues of PrEP awareness, expressed opinions, perceived barriers and key discussion points on its adoption. The proposed platform could support public-health professionals and policy makers in PrEP monitoring, facilitating informed decision making and strategy planning for efficient HIV combination prevention.

A Knowledge-Based Platform for Assessing Potential Adverse Drug Reactions at the Point of Care: User Requirements and Design.

Even though Adverse Drug Reactions (ADRs) constitute a significant public health issue, there is a lack of Information & Communication Technologies (ICT) tools supporting Pharmacovigilance activities at the point of care. In this paper, we present the rationale of a Web-based platform to address this need. The driving user scenario of the proposed platform refers to a clinician who investigates information for a possible ADR as part of a specific patient treatment. The goal is to facilitate this assessment through appropriate tools for searching various relevant data sources, analysing the acquired data, aggregating the obtained evidence, and offering follow-up ADR monitoring over time in a systematic and user-friendly way. In this regard, we describe the adopted user requirements engineering methodology and illustrate the use of Knowledge Engineering (KE) as the platform's main technical paradigm to enable heterogeneous data integration and handle the complexity of the underlying information processing workflow.

Contributions on Clinical Decision Support from the 2018 Literature.

OBJECTIVES: To summarize recent research and select the best papers published in 2018 in the field of computerized clinical decision support for the Decision Support section of the International Medical Informatics Association (IMIA) yearbook. METHODS: A literature review was performed by searching two bibliographic databases for papers referring to clinical decision support systems (CDSSs). The aim was to identify a list of candidate best papers from the retrieved bibliographic records, which were then peer-reviewed by external reviewers. A consensus meeting of the IMIA editorial team finally selected the best papers on the basis of all reviews and the section editors' evaluation. RESULTS: Among 1,148 retrieved articles, 15 best paper candidates were selected, the review of which resulted in the selection of four best papers. The first paper introduces a deep learning model for estimating short-term life expectancy (>3 months) of metastatic cancer patients by analyzing free-text clinical notes in electronic medical records, while maintaining the temporal visit sequence. The second paper takes note that CDSSs become routinely integrated in health information systems and compares statistical anomaly detection models to identify CDSS malfunctions which, if remain unnoticed, may have a negative impact on care delivery. The third paper fairly reports on lessons learnt from the development of an oncology CDSS using artificial intelligence techniques and from its assessment in a large US cancer center. The fourth paper implements a preference learning methodology for detecting inconsistencies in clinical practice guidelines and illustrates the applicability of the proposed methodology to antibiotherapy. CONCLUSIONS: Three of the four best papers rely on data-driven methods, and one builds on a knowledge-based approach. While there is currently a trend for data-driven decision support, the promising results of such approaches still need to be confirmed by the adoption of these systems and their routine use.

Computational Advances in Drug Safety: Systematic and Mapping Review of Knowledge Engineering Based Approaches.

Drug Safety (DS) is a domain with significant public health and social impact. Knowledge Engineering (KE) is the Computer Science discipline elaborating on methods and tools for developing "knowledge-intensive" systems, depending on a conceptual "knowledge" schema and some kind of "reasoning" process. The present systematic and mapping review aims to investigate KE-based approaches employed for DS and highlight the introduced added value as well as trends and possible gaps in the domain. Journal articles published between 2006 and 2017 were retrieved from PubMed/MEDLINE and Web of Science® (873 in total) and filtered based on a comprehensive set of inclusion/exclusion criteria. The 80 finally selected articles were reviewed on full-text, while the mapping process relied on a set of concrete criteria (concerning specific KE and DS core activities, special DS topics, employed data sources, reference ontologies/terminologies, and computational methods, etc.). The analysis results are publicly available as online interactive analytics graphs. The review clearly depicted increased use of KE approaches for DS. The collected data illustrate the use of KE for various DS aspects, such as Adverse Drug Event (ADE) information collection, detection, and assessment. Moreover, the quantified analysis of using KE for the respective DS core activities highlighted room for intensifying research on KE for ADE monitoring, prevention and reporting. Finally, the assessed use of the various data sources for DS special topics demonstrated extensive use of dominant data sources for DS surveillance, i.e., Spontaneous Reporting Systems, but also increasing interest in the use of emerging data sources, e.g., observational healthcare databases, biochemical/genetic databases, and social media. Various exemplar applications were identified with promising results, e.g., improvement in Adverse Drug Reaction (ADR) prediction, detection of drug interactions, and novel ADE profiles related with specific mechanisms of action, etc. Nevertheless, since the reviewed studies mostly concerned proof-of-concept implementations, more intense research is required to increase the maturity level that is necessary for KE approaches to reach routine DS practice. In conclusion, we argue that efficiently addressing DS data analytics and management challenges requires the introduction of high-throughput KE-based methods for effective knowledge discovery and management, resulting ultimately, in the establishment of a continuous learning DS system.

"OPTImAL": an ontology for patient adherence modeling in physical activity domain.

BACKGROUND: Maintaining physical fitness is a crucial component of the therapeutic process for patients with cardiovascular disease (CVD). Despite the known importance of being physically active, patient adherence to exercise, both in daily life and during cardiac rehabilitation (CR), is low. Patient adherence is frequently composed of numerous determinants associated with different patient aspects (e.g., psychological, clinical, etc.). Understanding the influence of such determinants is a central component of developing personalized interventions to improve or maintain patient adherence. Medical research produced evidence regarding factors affecting patients' adherence to physical activity regimen. However, the heterogeneity of the available data is a significant challenge for knowledge reusability. Ontologies constitute one of the methods applied for efficient knowledge sharing and reuse. In this paper, we are proposing an ontology called OPTImAL, focusing on CVD patient adherence to physical activity and exercise training. METHODS: OPTImAL was developed following the Ontology Development 101 methodology and refined based on the NeOn framework. First, we defined the ontology specification (i.e., purpose, scope, target users, etc.). Then, we elicited domain knowledge based on the published studies. Further, the model was conceptualized, formalized and implemented, while the developed ontology was validated for its consistency. An independent cardiologist and three CR trainers evaluated the ontology for its appropriateness and usefulness. RESULTS: We developed a formal model that includes 142 classes, ten object properties, and 371 individuals, that describes the relations of different factors of CVD patient profile to adherence and adherence quality, as well as the associated types and dimensions of physical activity and exercise. 2637 logical axioms were constructed to comprise the overall concepts that the ontology defines. The ontology was successfully validated for its consistency and preliminary evaluated for its appropriateness and usefulness in medical practice. CONCLUSIONS: OPTImAL describes relations of 320 factors originated from 60 multidimensional aspects (e.g., social, clinical, psychological, etc.) affecting CVD patient adherence to physical activity and exercise. The formal model is evidence-based and can serve as a knowledge tool in the practice of cardiac rehabilitation experts, supporting the process of activity regimen recommendation for better patient adherence.

The European cross-border health data exchange roadmap: Case study in the Italian setting.

Health data exchange is a major challenge due to the sensitive information and the privacy issues entailed. Considering the European context, in which health data must be exchanged between different European Union (EU) Member States, each having a different national regulatory framework as well as different national healthcare structures, the challenge appears even greater. Europe has tried to address this challenge via the epSOS ("Smart Open Services for European Patients") project in 2008, a European large-scale pilot on cross-border sharing of specific health data and services. The adoption of the framework is an ongoing activity, with most Member States planning its implementation by 2020. Yet, this framework is quite generic and leaves a wide space to each EU Member State regarding the definition of roles, processes, workflows and especially the specific integration with the National Infrastructures for eHealth. The aim of this paper is to present the current landscape of the evolving eHealth infrastructure for cross-border health data exchange in Europe, as a result of past and ongoing initiatives, and illustrate challenges, open issues and limitations through a specific case study describing how Italy is approaching its adoption and accommodates the identified barriers. To this end, the paper discusses ethical, regulatory and organizational issues, also focusing on technical aspects, such as interoperability and cybersecurity. Regarding cybersecurity aspects per se, we present the approach of the KONFIDO EU-funded project, which aims to reinforce trust and security in European cross-border health data exchange by leveraging novel approaches and cutting-edge technologies, such as homomorphic encryption, photonic Physical Unclonable Functions (p-PUF), a Security Information and Event Management (SIEM) system, and blockchain-based auditing. In particular, we explain how KONFIDO will test its outcomes through a dedicated pilot based on a realistic scenario, in which Italy is involved in health data exchange with other European countries.

Comprehensive user requirements engineering methodology for secure and interoperable health data exchange.

BACKGROUND: Increased digitalization of healthcare comes along with the cost of cybercrime proliferation. This results to patients' and healthcare providers' skepticism to adopt Health Information Technologies (HIT). In Europe, this shortcoming hampers efficient cross-border health data exchange, which requires a holistic, secure and interoperable framework. This study aimed to provide the foundations for designing a secure and interoperable toolkit for cross-border health data exchange within the European Union (EU), conducted in the scope of the KONFIDO project. Particularly, we present our user requirements engineering methodology and the obtained results, driving the technical design of the KONFIDO toolkit. METHODS: Our methodology relied on four pillars: (a) a gap analysis study, reviewing a range of relevant projects/initiatives, technologies as well as cybersecurity strategies for HIT interoperability and cybersecurity; (b) the definition of user scenarios with major focus on cross-border health data exchange in the three pilot countries of the project; (c) a user requirements elicitation phase containing a threat analysis of the business processes entailed in the user scenarios, and (d) surveying and discussing with key stakeholders, aiming to validate the obtained outcomes and identify barriers and facilitators for HIT adoption linked with cybersecurity and interoperability. RESULTS: According to the gap analysis outcomes, full adherence with information security standards is currently not universally met. Sustainability plans shall be defined for adapting existing/evolving frameworks to the state-of-the-art. Overall, lack of integration in a holistic security approach was clearly identified. For each user scenario, we concluded with a comprehensive workflow, highlighting challenges and open issues for their application in our pilot sites. The threat analysis resulted in a set of 30 user goals in total, documented in detail. Finally, indicative barriers of HIT acceptance include lack of awareness regarding HIT risks and legislations, lack of a security-oriented culture and management commitment, as well as usability constraints, while important facilitators concern the adoption of standards and current efforts for a common EU legislation framework. CONCLUSIONS: Our study provides important insights to address secure and interoperable health data exchange, while our methodological framework constitutes a paradigm for investigating diverse cybersecurity-related risks in the health sector.

OpenPVSignal: Advancing Information Search, Sharing and Reuse on Pharmacovigilance Signals via FAIR Principles and Semantic Web Technologies.

Signal detection and management is a key activity in pharmacovigilance (PV). When a new PV signal is identified, the respective information is publicly communicated in the form of periodic newsletters or reports by organizations that monitor and investigate PV-related information (such as the World Health Organization and national PV centers). However, this type of communication does not allow for systematic access, discovery and explicit data interlinking and, therefore, does not facilitate automated data sharing and reuse. In this paper, we present OpenPVSignal, a novel ontology aiming to support the semantic enrichment and rigorous communication of PV signal information in a systematic way, focusing on two key aspects: (a) publishing signal information according to the FAIR (Findable, Accessible, Interoperable, and Re-usable) data principles, and (b) exploiting automatic reasoning capabilities upon the interlinked PV signal report data. OpenPVSignal is developed as a reusable, extendable and machine-understandable model based on Semantic Web standards/recommendations. In particular, it can be used to model PV signal report data focusing on: (a) heterogeneous data interlinking, (b) semantic and syntactic interoperability, (c) provenance tracking and (d) knowledge expressiveness. OpenPVSignal is built upon widely-accepted semantic models, namely, the provenance ontology (PROV-O), the Micropublications semantic model, the Web Annotation Data Model (WADM), the Ontology of Adverse Events (OAE) and the Time ontology. To this end, we describe the design of OpenPVSignal and demonstrate its applicability as well as the reasoning capabilities enabled by its use. We also provide an evaluation of the model against the FAIR data principles. The applicability of OpenPVSignal is demonstrated by using PV signal information published in: (a) the World Health Organization's Pharmaceuticals Newsletter, (b) the Netherlands Pharmacovigilance Centre Lareb Web site and (c) the U.S. Food and Drug Administration (FDA) Drug Safety Communications, also available on the FDA Web site.

ARCOCT: Automatic detection of lumen border in intravascular OCT images.

BACKGROUND AND OBJECTIVE: Intravascular optical coherence tomography (OCT) is an invaluable tool for the detection of pathological features on the arterial wall and the investigation of post-stenting complications. Computational lumen border detection in OCT images is highly advantageous, since it may support rapid morphometric analysis. However, automatic detection is very challenging, since OCT images typically include various artifacts that impact image clarity, including features such as side branches and intraluminal blood presence. This paper presents ARCOCT, a segmentation method for fully-automatic detection of lumen border in OCT images. METHODS: ARCOCT relies on multiple, consecutive processing steps, accounting for image preparation, contour extraction and refinement. In particular, for contour extraction ARCOCT employs the transformation of OCT images based on physical characteristics such as reflectivity and absorption of the tissue and, for contour refinement, local regression using weighted linear least squares and a 2nd degree polynomial model is employed to achieve artifact and small-branch correction as well as smoothness of the artery mesh. Our major focus was to achieve accurate contour delineation in the various types of OCT images, i.e., even in challenging cases with branches and artifacts. RESULTS: ARCOCT has been assessed in a dataset of 1812 images (308 from stented and 1504 from native segments) obtained from 20 patients. ARCOCT was compared against ground-truth manual segmentation performed by experts on the basis of various geometric features (e.g. area, perimeter, radius, diameter, centroid, etc.) and closed contour matching indicators (the Dice index, the Hausdorff distance and the undirected average distance), using standard statistical analysis methods. The proposed method was proven very efficient and close to the ground-truth, exhibiting non statistically-significant differences for most of the examined metrics. CONCLUSIONS: ARCOCT allows accurate and fully-automated lumen border detection in OCT images.

A Survey of Mobile Phone Sensing, Self-Reporting, and Social Sharing for Pervasive Healthcare.

The current institution-based model for healthcare service delivery faces enormous challenges posed by an aging population and the prevalence of chronic diseases. For this reason, pervasive healthcare, i.e., the provision of healthcare services to individuals anytime anywhere, has become a major focus for the research community. In this paper, we map out the current state of pervasive healthcare research by presenting an overview of three emerging areas in personalized health monitoring, namely: 1) mobile phone sensing via in-built or external sensors, 2) self-reporting for manually captured health information, such as symptoms and behaviors, and 3) social sharing of health information within the individual's community. Systems deployed in a real-life setting as well as proofs-of-concept for achieving pervasive health are presented, in order to identify shortcomings and increase our understanding of the requirements for the next generation of pervasive healthcare systems addressing these three areas.

IT-CARES: an interactive tool for case-crossover analyses of electronic medical records for patient safety.

BACKGROUND: The significant risk of adverse events following medical procedures supports a clinical epidemiological approach based on the analyses of collections of electronic medical records. Data analytical tools might help clinical epidemiologists develop more appropriate case-crossover designs for monitoring patient safety. OBJECTIVE: To develop and assess the methodological quality of an interactive tool for use by clinical epidemiologists to systematically design case-crossover analyses of large electronic medical records databases. MATERIAL AND METHODS: We developed IT-CARES, an analytical tool implementing case-crossover design, to explore the association between exposures and outcomes. The exposures and outcomes are defined by clinical epidemiologists via lists of codes entered via a user interface screen. We tested IT-CARES on data from the French national inpatient stay database, which documents diagnoses and medical procedures for 170 million inpatient stays between 2007 and 2013. We compared the results of our analysis with reference data from the literature on thromboembolic risk after delivery and bleeding risk after total hip replacement. RESULTS: IT-CARES provides a user interface with 3 columns: (i) the outcome criteria in the left-hand column, (ii) the exposure criteria in the right-hand column, and (iii) the estimated risk (odds ratios, presented in both graphical and tabular formats) in the middle column. The estimated odds ratios were consistent with the reference literature data. DISCUSSION: IT-CARES may enhance patient safety by facilitating clinical epidemiological studies of adverse events following medical procedures. The tool's usability must be evaluated and improved in further research.

Association of global and local low endothelial shear stress with high-risk plaque using intracoronary 3D optical coherence tomography: Introduction of 'shear stress score'.

AIMS: The association of low endothelial shear stress (ESS) with high-risk plaque (HRP) has not been thoroughly investigated in humans. We investigated the local ESS and lumen remodelling patterns in HRPs using optical coherence tomography (OCT), developed the shear stress score, and explored its association with the prevalence of HRPs and clinical outcomes. METHODS AND RESULTS: A total of 35 coronary arteries from 30 patients with stable angina or acute coronary syndrome (ACS) were reconstructed with three dimensional (3D) OCT. ESS was calculated using computational fluid dynamics and classified into low, moderate, and high in 3-mm-long subsegments. In each subsegment, (i) fibroatheromas (FAs) were classified into HRPs and non-HRPs based on fibrous cap (FC) thickness and lipid pool size, and (ii) lumen remodelling was classified into constrictive, compensatory, and expansive. In each artery the shear stress score was calculated as metric of the extent and severity of low ESS. FAs in low ESS subsegments had thinner FC compared with high ESS (89 ± 84 vs.138 ± 83 µm, P < 0.05). Low ESS subsegments predominantly co-localized with HRPs vs. non-HRPs (29 vs. 9%, P < 0.05) and high ESS subsegments predominantly with non-HRPs (9 vs. 24%, P < 0.05). Compensatory and expansive lumen remodelling were the predominant responses within subsegments with low ESS and HRPs. In non-stenotic FAs, low ESS was associated with HRPs vs. non-HRPs (29 vs. 3%, P < 0.05). Arteries with increased shear stress score had increased frequency of HRPs and were associated with ACS vs. stable angina. CONCLUSION: Local low ESS and expansive lumen remodelling are associated with HRP. Arteries with increased shear stress score have increased frequency of HRPs and propensity to present with ACS.

Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

OBJECTIVE: Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. METHODS: Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. RESULTS: The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. CONCLUSIONS: This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

Framework of sensor-based monitoring for pervasive patient care.

Sensor-based health systems can often become difficult to use, extend and sustain. The authors propose a framework for designing sensor-based health monitoring systems aiming to provide extensible and usable monitoring services in the scope of pervasive patient care. The authors' approach relies on a distributed system for monitoring the patient health status anytime-anywhere and detecting potential health complications, for which healthcare professionals and patients are notified accordingly. Portable or wearable sensing devices measure the patient's physiological parameters, a smart mobile device collects and analyses the sensor data, a Medical Center system receives notifications on the detected health condition, and a Health Professional Platform is used by formal caregivers in order to review the patient condition and configure monitoring schemas. A Service-oriented architecture is utilised to provide extensible functional components and interoperable interactions among the diversified system components. The framework was applied within the REMOTE ambient-assisted living project in which a prototype system was developed, utilising Bluetooth to communicate with the sensors and Web services for data exchange. A scenario of using the REMOTE system and preliminary usability results show the applicability, usefulness and virtue of our approach.

Integrated Care and Connected Health Approaches Leveraging Personalised Health through Big Data Analytics.

Integrated care and connected health are two fast evolving concepts that have the potential to leverage personalised health. From the one side, the restructuring of care models and implementation of new systems and integrated care programs providing coaching and advanced intervention possibilities, enable medical decision support and personalized healthcare services. From the other side, the connected health ecosystem builds the means to follow and support citizens via personal health systems in their everyday activities and, thus, give rise to an unprecedented wealth of data. These approaches are leading to the deluge of complex data, as well as in new types of interactions with and among users of the healthcare ecosystem. The main challenges refer to the data layer, the information layer, and the output of information processing and analytics. In all the above mentioned layers, the primary concern is the quality both in data and information, thus, increasing the need for filtering mechanisms. Especially in the data layer, the big biodata management and analytics ecosystem is evolving, telemonitoring is a step forward for data quality leverage, with numerous challenges still left to address, partly due to the large number of micro-nano sensors and technologies available today, as well as the heterogeneity in the users' background and data sources. This leads to new R&D pathways as it concerns biomedical information processing and management, as well as to the design of new intelligent decision support systems (DSS) and interventions for patients. In this paper, we illustrate these issues through exemplar research targeting chronic patients, illustrating the current status and trends in PHS within the integrated care and connected care world.

A Multiagent System for Integrated Detection of Pharmacovigilance Signals.

Pharmacovigilance is the scientific discipline that copes with the continuous assessment of the safety profile of marketed drugs. This assessment relies on diverse data sources, which are routinely analysed to identify the so-called "signals", i.e. potential associations between drugs and adverse effects, that are unknown or incompletely documented. Various computational methods have been proposed to support domain experts in signal detection. However, recent comparative studies illustrated that current methods exhibit high false-positive rates, significantly variable performance across different datasets used for analysis and events of interest, but also complementarity in their outcomes. In this regard, in order to reinforce accurate and timely signal detection, we elaborated through an agent-based approach towards systematic, joint exploitation of multiple heterogeneous signal detection methods, data sources and other drug-related resources under a common, integrated framework. The approach relies on a multiagent system operating based on a collaborative agent interaction protocol, aiming to implement a comprehensive workflow that comprises of method selection and execution, as well as outcomes' aggregation, filtering, ranking and annotation. This paper presents the design of the proposed multiagent system, discusses implementation issues and demonstrates the applicability of the proposed solution in an example signal detection scenario. This work constitutes a step towards large-scale, integrated and knowledge-intensive computational signal detection.