Very preterm birth is a principal determinant of motor and cognitive impairment in later life. About 50 000 infants in the EU survive very preterm birth annually and are at much higher risk of cerebral palsy, visual and auditory deficits, impaired cognitive ability, psychiatric disorders and behavioural problems than infants born at term. However, the long term prognosis at initial discharge from hospital for each individual infant is unknown. Follow-up screening and prevention programmes aim to identify health problems early, enable interventions to improve outcome and to allow optimal management of health care. Despite the recognised importance of these programmes, little is known about their actual application and impact. These programmes consume significant resources because of the multidisciplinary staff required for clinical and developmental assessments and interventions, the coordination required to maintain contact with children after discharge and the time input from families. This project uses a unique resource – the EPICE cohort of 6675 babies born before 32 weeks of gestational age and surviving to discharge home in 18 geographically diverse regions in 2011/2012 – to assess the impact of these screening programmes on health, care and quality of life for very preterm infants and their families as well as on coverage, ability to meet needs, health equity and costs at the population-level. It will also generate new knowledge about assessment tools and methods. Four inter-related studies will be carried out in 11 EU countries by a multi-disciplinary consortium of clinicians (in obstetrics, paediatrics, and child development), researchers (in epidemiology, health services research and health economics) and a user organisation. Partners have the expertise to implement this project and the national and international renown to translate its result into better programmes and policies.

Building on the strong foundations of INNODIA, with its unique, Europe-wide clinical and basic research network for the study of type 1 diabetes (T1D), we propose in INNODIA HARVEST an ambitious program which aims to prevent and arrest T1D via focused objectives targeting consolidation and innovation. First, we will consolidate the INNODIA clinical network as the reference point for conducting studies to prevent or arrest T1D. We will transform our standardized clinical and bioresource platforms into a high-performance clinical trial network, running academic and industry-driven trials alongside small, mechanism-centric, biomarker-rich intervention trials to examine pathobiological pathways to T1D. INNODIA HARVEST will conduct two large studies to arrest T1D at its onset, one academia-driven, beta-cell focused (VER-A-T1D, verapamil) and one industry-driven, immune-focused (Iscalimab-study). We will exploit our original INNODIA Master Protocol allowing novel adaptive trial design to introduce combination therapies that build on complementary mechanisms. Second, we will extend our study design strategy by introducing novel biomarkers, both clinical (continuous glucose monitoring) and experimental (microbiome analysis) to deconvolute disease heterogeneity and identify new endpoints to accelerate identification of effective therapeutics. Third, we will use ‘disruptors’ in small mechanistic studies to channel innovation from clinic to basic research through a reverse immunology and reverse beta-cell biology approach. Finally, we will implement new discovery pipelines for future therapeutics, exploiting tools such as iPSC-derived islet-like cells to promote next generation target identification and drug development. As in INNODIA, the voice of people living with T1D and their families will hold a central place in INNODIA HARVEST to drive implementation of new, patient-proximal outcomes, shape our clinical trials, and bring about a meaningful change in disease perspective. A major objective of INNODIA Harvest is the execution of at least two new phase 2 trials (studying Verapamil (VER-A-T1D) or Iscalimab (CCFZ533X2207)). Considering the expected time to first patient-in as preparations for trial start can only be initiated after the start of the Action and possible fluctuating recruiting rates, due to the intercurrent COVID epidemic, there is a risk that INNODIA HARVEST will not be able to completely finalize the clinical trials, fully analyse the biomarkers collected and publish the results in the initially proposed 24 months duration. To ensure the finalization of the clinical trials and corresponding full execution of the given budget including eligibility of EFPIA in-kind contribution we propose to extend the duration of the Action from 24 to 36 months.