Models and methods: a perspective of the impact of six IMI translational data-centric initiatives for Alzheimer's disease and other neuropsychiatric disorders.

The Innovative Medicines Initiative (IMI), was a European public-private partnership (PPP) undertaking intended to improve the drug development process, facilitate biomarker development, accelerate clinical trial timelines, improve success rates, and generally increase the competitiveness of European pharmaceutical sector research. Through the IMI, pharmaceutical research interests and the research agenda of the EU are supported by academic partnership and financed by both the pharmaceutical companies and public funds. Since its inception, the IMI has funded dozens of research partnerships focused on solving the core problems that have consistently obstructed the translation of research into clinical success. In this post-mortem review paper, we focus on six research initiatives that tackled foundational challenges of this nature: Aetionomy, EMIF, EPAD, EQIPD, eTRIKS, and PRISM. Several of these initiatives focused on neurodegenerative diseases; we therefore discuss the state of neurodegenerative research both at the start of the IMI and now, and the contributions that IMI partnerships made to progress in the field. Many of the initiatives we review had goals including, but not limited to, the establishment of translational, data-centric initiatives and the implementation of trans-diagnostic approaches that move beyond the candidate disease approach to assess symptom etiology without bias, challenging the construct of disease diagnosis. We discuss the successes of these initiatives, the challenges faced, and the merits and shortcomings of the IMI approach with participating senior scientists for each. Here, we distill their perspectives on the lessons learned, with an aim to positively impact funding policy and approaches in the future.