Designing a precision-medicine platform trial to improve the nutritional care and intestinal health of very preterm babies: the COLLABORATE study

Background Nutrition is essential for preterm brain development. Optimal nutrition is dependent upon gastrointestinal health. Primary objective To form a multiprofessional collaboration to design the world’s first neonatal precision-medicine platform trial to test new and existing nutritional interventions for very preterm infants, to prevent and treat the serious gastrointestinal inflammatory disease necrotising enterocolitis and improve brain health and development. Participants Infants born very preterm (< 32 weeks gestation). Data sources Published literature; United Kingdom National Neonatal Research Database. Methods Engagement with parents, patients, clinical teams, and industry; literature reviews; simulation studies; mechanistic study design; collaborative study development. Results There was strong stakeholder support for the platform; seven interventions were selected from those proposed, four for immediate evaluation (pasteurised human donor milk; cow milk- and human milk-derived macronutrient fortifiers; probiotic), and three for subsequent incorporation (enteral arginine; enteral insulin; fluorescence image-guided surgery). We involved Australia/New Zealand neonatal units to shorten recruitment time, designed a precision-medicine platform trial, specified operational requirements and costs, developed engagement materials, and established parent–patient, independent scientific advisory and emerging investigator groups. Limitations National Institute for Health and Care Research processes required stage 1 application submission 8 months into the Accelerated Development Award. This was unsuccessful and did not include an opportunity to respond to feedback. Conclusions Stakeholders consider a neonatal precision-medicine platform trial a high priority, providing an efficient approach to establish the efficacy of treatments and the gestational age range of infants most likely to benefit, and to speed the pace of evidence generation to improve clinical care. Future work Reapplication, requiring a further stage 1 application. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR153935.