A key problem in Mental Health is that up to one third of patients suffering from major mental disorders develop resistance against drug therapy. However, patients showing early signs of treatment resistance (TR) do not receive adequate early intensive pharmacological treatment but instead they undergo a stepwise trial-and-error treatment approach. This situation originates from three major knowledge and translation gaps: i.) we lack effective methods to identify individuals at risk for TR early in the disease process, ii.) we lack effective, personalized treatment strategies grounded in insights into the biological basis of TR, and iii.) we lack efficient processes to translate scientific insights about TR into clinical practice, primary care and treatment guidelines. It is the central goal of PSYCH-STRATA to bridge these gaps and pave the way for a shift towards a treatment decision-making process tailored for the individual at risk for TR. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for TR across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression. PSYCH-STRATA will i.) dissect the biological basis of TR and establish criteria to enable early detection of individuals at risk for TR based on the integrated analysis of an unprecedented collection of genetic, biological, digital mental health, and clinical data. ii.) Moreover, we will determine effective treatment strategies of individuals at risk for TR early in the treatment process, based on pan-European clinical trials in SCZ, BD and MDD. These efforts will enable the establishment of novel multimodal machine learning models to predict TR risk and treatment response. Lastly, iii.) we will enable the translation of these findings into clinical practice by prototyping the integration of personalized treatment decision support and patient-oriented decision-making mental health boards.

ImpleMentAll will develop, apply, and evaluate tailored implementation strategies in the context of on-going eHealth implementation initiatives in the EU and beyond. Common mental health disorders account for an alarming proportion of the global burden of disease. Being regarded as an evidence-based psychotherapeutic eHealth intervention, Internet-based Cognitive Behavioural Therapy (iCBT), has the potential to answer to this societal challenge by providing an efficacious and efficient treatment from which more people can benefit. As a result, various iCBT implementation projects are currently conducted across the world. We propose to use this natural laboratory to develop and evaluate a toolkit for tailored implementation strategies that is expected to make implementation trajectories more efficient. The objectives for ImpleMentAll are: 1) To develop a generic Integrated Theory-based Framework for Intervention Tailoring Strategies (the ItFits-toolkit) for data-driven tailored implementation of evidence-based eHealth services. 2) To demonstrate the impact of the ItFits toolkit on the implementation of eHealth for common mental disorders, in 9 European countries, 2 LMIC, and Australia. 3) To disseminate the validated toolkit in various healthcare contexts across Europe. ImpleMentAll is a true multidisciplinary international collaboration that unites key experts in clinical practice, health innovation, clinical research, and implementation science. Combined with it’s unique setup, ImpleMentAll will be able to test if tailoring implementation strategies lead to more efficient implementation. The resulting ItFits-toolkit will enable data driven evaluation of eHealth implementation projects in terms key performance indicators for process, effectiveness, and efficiency outcomes. Its methods, materials, and strategies will provide concrete guidance on tuning implementation interventions to local determinant of practice across a variety of health care systems.

In the EU, about 165 million people are affected each year by mental disorders, and estimates indicate that mental disorders will become the number 1 economic cost factor in medicine in 2030. Schizophrenia alone affects approximately 1% of the world's population. The clinical effectiveness of the antipsychotics on the market remains limited with 30 to 50% of schizophrenic patients showing an insufficient response to treatment. Several factors, from genetic to psychological and social, may lie behind poor treatment outcomes or side effects and varies from patient to patient. Therefore, the central aim of the VIRTUAL BRAIN TWIN project is to create an ecosystem for generating virtual brain twins for psychiatric patients, by leveraging the consortium’s detailed knowledge and expertise in neuronal microcircuit simulation, mathematical analysis, innovative AI tools, and psychiatric care and clinical studies. This ecosystem will guide clinicians to optimise medication type and dosage, and to evaluate alternative treatments, such as brain stimulation and lifestyle changes. Multiscale cause-effect simulations and virtual brain simulations based on fMRI or sMRI data from the individual patient, will bridge the gap between molecules and the patient's brain. At the centre of this ecosystem will be the Virtual Brain Twin platform, which will make use of big data, multiscale modelling, and high-performance computing (HPC) that will be secured by appropriate data safety and protection. The platform will be embedded in the European digital neuroscience research infrastructure EBRAINS and will be initially accessible to neuroscientists, clinical researchers, and mathematical modellers, and in the future, to clinicians, and patients as well. This ground-breaking project will pave the way for personalised treatment of psychiatric disorders, with the potential to significantly improve the quality of life of patients suffering from these conditions.

SYNCHROS (SYNergies for Cohorts in Health: integrating the ROle of all Stakeholders) coordination and support action aims to establish a sustainable European strategy for the development of the next generation of integrated population, patient and clinical trial cohorts, thereby contributing to an international strategic agenda for enhanced coordination of cohorts globally. This will address the practical, ethical and legal, and the methodological challenge to optimising the exploitation of current and future cohort data, towards the development of stratified and personalised medicine as well as facilitating health policy. In order to achieve this objective, SYNCHROS will map the cohort landscape in Europe and large international initiatives, identify the best methods for integrating cohort data, identify solutions for addressing practical, ethical and legal challenges in integrating data across patient, clinical trial and population cohorts, and evaluate the use of emerging and new data collection technologies and types of data. Together with intensive stakeholder involvement (researchers, patients, funding bodies, clinicians, coordinators of previous harmonization and integration exercises), strategy briefs will be written and used to conduct stakeholder dialogues to generate consensus following a deliberative process and implementation science methods. We aim to make sustainable recommendations on standards to improve future sample, data collection and data sharing methods and disseminate this information so as to contribute to defining an international strategic agenda for better coordination of cohorts globally. SYNCHROS partners include a large range of expertise from epidemiology and clinical research to legal/ethical issues and anthropology, international organizations such as WHO and European infrastructures such as ECRIN.