Accelerating the development of a perinatal platform trial to efficiently evaluate the effectiveness of multiple interventions in maternity and neonatal care

BACKGROUND Preterm birth (before 37 weeks' gestation) affects over 60,000 UK pregnancies and 15 million worldwide annually. It causes more than half of all perinatal deaths and is the leading cause of neonatal morbidity and mortality. It can have long-term sequelae evident in early childhood that persist across the lifespan. Our perinatal platform will address this area of strategic importance for the Department of Health and Social Care by focusing on interventions for pregnant women with threatened preterm labour and preterm infants. AIMS We aim to design and deliver a large ambitious perinatal platform, which will efficiently and rapidly evaluate the clinical effectiveness of multiple interventions for both pregnant women and babies. The creation of the platform depends on successful completion of several interlinked but distinct aims: 1. To build sustainable partnerships between clinicians, methodologists and statisticians with expertise in the delivery of perinatal and platform trials 2. To develop governance processes for selection of interventions by collaborative, multi-stakeholder oversight 3. To set up all aspects of project delivery 4. To develop the IT systems and framework that the data collection methods, processes and data flows will operate within 5. To work with parents, pregnant women and national charities to ensure integral public involvement in the development of the platform, including creation of a robust, inclusive PPIE strategy 6. To qualitatively explore the views of healthcare professionals about the design and conduct of a UK-wide perinatal platform trial 7. To develop and refine the most appropriate methodologies METHODS The accelerator award will enable us to conduct the necessary learning and preparation by allowing us to focus on important operational, clinical, methodological, familial and equality, diversity and inclusion aspects. The perinatal period is a unique scenario during which interventions may be aimed at pregnant women antenatally or during birth (potential for benefit/harm to the fetus), &/or intervention(s) aimed at their infants following birth. This novelty i.e., multiple sequential randomisations plus 'clustering' which will occur with potential randomisation of a mother-infant dyad plus the approach to randomising multiple births impacts directly on the design, conduct and analysis. This is unprecedented and so methodological facilitative work is required - not possible without this award. EXPERTISE Many of the co-applicants have led &/or collaborated on landmark multicentre NIHR-funded trials, and several have experience in platform trials. Clinical and methodological co-applicants are already considering research questions which cover the spectrum of pregnancy, delivery and infancy. The requisite capacity, operational and methodological aspects are ensured by partnership of 3 Clinical Trials Units. The voices of parents, pregnant women and families are central to everything that we will do, so PPIE will be strongly embedded throughout the project. OUTPUTS The main output from the 12 month accelerator award will be a Stage 1 application for a perinatal platform trial in November 2023. IMPACT We anticipate that our novel perinatal platform trial will evaluate many interventions before, during and after birth. It has the potential to improve life-long outcomes for both pregnant women and preterm infants and as a result, benefit not just them, but families, society and the NHS.