SafePolyMed is structured along five scientific work packages (WP1-5), which are flanked by project and innovation management activities (WP6 & WP7).
Work Package 1 - Patients at Risk Score
WP1 aims to develop a novel, evidence-based risk score model for individual patients using machine learning based on the analysis of large real-world datasets combining multiple factors, such as demographics, drug-drug interactions, drug-gene interactions or drug-disease interactions. The novel risk score model will be validated in clinical case studies covered in WP5. The main objectives of WP1 are: (1) the design and development of a framework for the analysis of the retrospective data in SafePolyMed, (2) the development of statistical, machine learning and deep learning models for extraction and analysis of pharmacology-enriched real-world data, (3) the development of the required mechanisms for data harmonisation and (4) the exploration of associations between genetic variation, medication use trajectories, and treatment outcomes.
Work Package 2 - Patient-Reported Outcome
WP2 focuses on patient-reported outcomes and will develop patient-reported outcome measures in close collaboration with patient organisations for assessing drug safety. To ensure a more resilient patient participation approach in Europe’s health systems, WP2 will also establish appropriate infrastructures such as a patient engagement hub and provide training for patient empowerment. In detail, WP2 aims (1) to empower patients to better understand personalised treatment and safety risks, as well as train patients in awareness of safety-related outcomes and to report on safety outcomes in drug therapy. Furthermore, the WP focuses on (2) the development and validation of a safety patient-reported outcome measure for patient care and clinical practice to enhance safety and adherence to polymedication. Lastly, it aims (3) to identify participative actions to improve quality and safety of drug treatment and related processes in health care along different fields of drug therapy.
Work Package 3 - Medication Management Center
WP3 will specify and implement system requirements for a comprehensive, sustainable medication management center able to integrate, harmonise and standardise polymedication data and empower citizens in Europe to proactively manage their own health care. The developed models and patient-reported outcome measures in WP1, WP2 and WP4, respectively, will be combined and made available as a joint framework within the medication management center with the aim (1) to integrate, harmonise and standardise medication data. The WP further aims (2) to create and provide a comprehensive, sustainable knowledge base concerning polymedication and patient safety. Furthermore, it focuses on (3) empowering citizens in health care by increasing access to health relevant information and (4) to ensure quality and comparability of health data according to ethical, legal and regulatory guidelines. This is achieved by creating and giving patients access to the medication management center, which will be tested in a clinical case study within the framework of WP5.
Work Package 4 - Model-Based Precision Dosing
The overall aim of WP4 is to develop a model-based precision dosing framework in completion to the medication management safety developed in WP3. The backbone will consist of a library of 10 mechanistic mathematical models of clinically relevant drugs selected during analysis of real-world datasets. Furthermore, data obtained from the U-PGx PREPARE study will complement the published clinical pharmacokinetics studies used to build and evaluate comprehensive mechanistic models which will be able to provide model-based dose recommendations for complex individual patient’s scenarios. A prototype of a web-based application frontend for the precision dosing models will be developed in close collaboration with clinicians to ensure model accessibility to non-pharmacometricians. Specifically, WP4 aims (1) to select compounds of interest based on their clinical relevance using pharmacology-enriched real-world data, (2) to build and evaluate whole-body physiologically-based pharmacokinetic models which are capable of describing and predicting complex drug drug-gene combinations, (3) to provide model-based dose recommendations, and lastly (4) to design and develop a prototype of a web-based model application frontend.
Work Package 5 - Clinical Case Study
In WP5, the developed tools and techniques from WP 1, 2, 3 and 4 will be tested and evaluated in a clinical pilot study called the EmPaSafe study (Empowering Patients to Improve Safety in Polymedication). The study is an observation proof-of-concept study assessing the feasibility of using the medication management center to empower citizens regarding their own medication. Four centers, including partners Leiden University Medical Center, the University of Ljubljana, the University of Patras as well as the University Hospital of RWTH Aachen, will recruit 30 patients each. These patients will get access to the medication management center as developed in WP3 and will be followed for a duration of 12 weeks during which they will receive 4 questionnaires. The primary objective is to assess the feasibility of using the developed medication management center in combination with the developed risk score algorithms, patient-reported outcome tool, and model-based precision dosing tool to empower EU citizens to improve drug safety. Secondary objectives are to investigate, if the tool is able to accurately identify patients at risk for a drug-drug-gene interaction, lower the adverse drug reaction rate compared with matched historical controls, and assess cost consequences of this approach. In detail, WP5 aims (1) to write a clinical study protocol, (2) to obtain Institutional Review Board approval for patient recruitment, (3) to train involved clinicians in the use of the developed tools, (4) to implement those tools and recruit 120 patients and lastly, (5) to analyse data to assess both the quantitative and qualitative impact of developed tools on drug safety.
Work Package 6 – Project Management and Scientific Coordination
Overall, WP6 will provide a clear organisational framework, guidance and all support mechanisms to enable a smooth project workflow in SafePolyMed and to ensure that objectives and milestones will be met in time. In detail, the WP aims (1) to quickly set up management and communication structures and processes, such as an internal project management platform and the public project website, (2) to monitor on a central level all project activities, deliverables and deadlines which ensures the timely and qualitative achievement of project results through scientific coordination and impact-oriented project management, (3) to ensure efficiency, high quality and maximum usability of the project outcomes, and lastly (4) to provide proper risk-analysis and conflict management to safeguard a smooth collaboration between all partners.
Work Package 7 - Innovation Management: Communication, Dissemination, Exploitation
WP7 focuses on innovation management, specifically with regard to communication, dissemination and exploitation. The innovation management will follow a multidimensional, integrated and impact-oriented approach: It will ensure consistent communication and dissemination, assuring optimal visibility and a wide outreach to relevant stakeholders. Strategic planning and implementation of project exploitation through dedicated innovation management will safeguard that high-quality results are captured, assessed and properly used. A proper IP management strategy will lay the foundation for further exploitation activities considering background knowledge of beneficiaries as well as newly created results. Specifically, WP7 aims (1) to engage in communication activities, creating visibility and encouraging project outreach, (2) to disseminate results to targeted stakeholders and the scientific community, and (3) to foster innovation capacity and exploitation of results – including IP management.