The European Regimen Accelerator for Tuberculosis (ERA4TB) has the explicit goal of developing a new combination therapy to treat all forms of TB starting from ~20 leads and drug candidates provided by EFPIA. Since details of these are as yet unavailable, we will implement an agile drug development algorithm that entails profiling and portfolio construction. Profiling involves characterisation and ranking molecules in preclinical studies comprising in vitro drug combination assays, hollow fiber and single cell analysis, innovative murine and non-human primate models, PK/PD studies, combined with biomarker discovery and non-invasive NIR or PET/CT imaging to monitor disease progression and response to treatment. Modelling, simulation and artificial intelligence tools will help progress compounds from early preclinical to clinical development and to predict drug exposure, human doses and the best combinations. After extensive preclinical profiling, selected compounds will enter portfolio development for first time in human tests and phase I clinical trials in order to ensure that they are safe, well-tolerated and bioavailable with negligible drug-drug interactions. If needed, formulation studies will be conducted to improve pharmacological properties. ERA4TB has assembled the best expertise and resources available in Europe, to build a highly effective and sustainable drug development consortium with a flexible and dynamic management system to execute the profiling and portfolio strategy, aided by clearly defined go/no-go decision points. The expected outcome of ERA4TB is a series of highly active, bactericidal, orally available drugs to constitute two or more new combination regimens with treatment-shortening potential ready for Phase II clinical evaluation. These regimens will be compatible with drugs used to treat common comorbidities, such as HIV-AIDS and diabetes, and should impact UN Sustainable Development Goal 3, namely, ending TB by 2030.

COMPAR-EU aims to identify, compare, and rank the most effective and cost-effective self-management interventions (SMIs) for adults in Europe within four high-priority chronic conditions: type 2 diabetes, obesity, chronic obstructive pulmonary disease, and heart failure. This project addresses an important gap in current knowledge applying network meta-analysis, an extension of meta-analysis methodology that allows multiple (rather than pairwise) comparisons of intervention effectiveness, to randomised controlled trials (RCTs) that meet the study inclusion criteria. This centralised analysis of an estimated 4000 RCTs will substantially help to overcome current problems associated with the dispersion and duplication of evidence. The work will be based on a validated taxonomy of SMIs and will prioritise outcomes from the patients’ perspective. In addition, a cost-effectiveness of the most effective SMIs will be estimated to provide insights into the economic consequences of adopting SMIs for societies, healthcare budgets, and patients. Contextual factors associated with successful interventions will also be studied. Drawing on our results, we will develop and pilot decision-making tools to facilitate access to evidence-based information on the most effective SMIs to key users through a user-friendly interactive platform. A multiprong strategy for exploitation of the research findings will lead to clear business cases for implementing it in different contexts within the heterogeneous EU health system. The end goal of the project is to have an impact in supporting policy-makers, guideline developers, researchers, industry, professionals and patients to make informed decisions on the identification and implementation of the most suitable SMIs, therefore contributing to the diffusion of the knowledge, healthcare sustainability and equity and promoting EU competitiveness in a globally emerging market.