MICA: Meeting global need to improve newborn care through real-world-health-data-facilitated, digital-technology-supported randomised clinical trials

AIMS AND OBJECTIVES: We aim to reduce the cost, burden, and time to conduct randomised controlled trials (RCT) to improve the care of sick and preterm babies and develop medicines, diagnostics and devices that meet their needs. RCT are the most reliable and fair way to test treatments because every patient has an equal chance of receiving the best approach. Data collection is a major cost of RCT hence we will use data recorded as part of clinical care that is already available in a high-quality repository we established, the UK National Neonatal Research Database (NNRD). We will also use digital technologies and innovative study designs. The idea for NNRD-RCT is simple but the technical processes to flow data securely, develop and implement robust, transparent operational procedures, ensure trust in processes, and deliver solutions at scale, are complex, and our principal objectives.

NEED: Neonatal care is an area of great national and global need. Newborn health sets trajectories for life; e.g. a baby born preterm, or over or underweight, is at up to 8 times greater risk of developing a chronic disease like diabetes or high blood pressure in adult life, that will decrease healthy life expectancy by as much as 15-20 years. Though improving their health has life-long benefits, newborn babies are disadvantaged in accessing biomedical innovations because of real or perceived difficulties in conducting RCT involving them. There has only ever been a single medicine specifically developed for a newborn condition, and over 90% of medicines used to treat babies have inadequate data on safety, dose, and efficacy because they have only been evaluated in older patients. This is dangerous because the way in which medicines work in babies is often very different from other age groups. Another difficulty is that reliably resolving healthcare uncertainties often requires the participation of large numbers of infants; e.g. to identify whether a treatment reduces severe retinopathy of prematurity, the major cause of childhood blindness, by 25%, would require a study involving about 14,000 infants which would be costly, difficult, and take a long time. Therefore many RCT, though needed, are never done or are too small or poor quality. The consequence is that there are many uncertainties in even routine aspects of care such as the best type of nutrition for preterm babies, and the best way to reduce the risk of infection.

WHAT WE WILL DO: We will create standard operating processes to flow data from the NNRD to RCT master-files and electronic forms and digital tools e.g. for automated reminders and staff training. We will obtain stakeholder perspectives to build understanding and trust in NNRD-RCT and develop multi-media communications and transparent, well-governanced processes for commercial RCT. We will involve stakeholders in developing two exemplar NNRD-RCT (to resolve a long-standing, priority-ranked uncertainty in clinical care and to evaluate a neonatal medicine). We will also develop statistical and design solutions that maximise NNRD-RCT efficiency. Outputs will include resources to help clinical investigators, and guidance for industry researchers.

WHY A PARTNERSHIP IS NEEDED: A partnership is needed to bring together expertise in scalable technical solutions that meet regulatory standards, develop NNRD-RCT design options, secure stakeholder involvement and engagement, and create impactful communications. Our partners are Bliss (national charity for sick and preterm babies), Health Data Research UK (national institute for health data science), Neonatal Society (clinical research society), Strategic Intelligence Alliance for Healthcare (SME supporting the NHS and industry), OpenClinica (provider of clinical trial cloud technologies) and UK Medicines and Healthcare products Regulatory Agency. The resources developed, know-how and knowledge, will be available to all clinical trials units and researchers around the world.

Our goal is to improve the evidence-base for neonatal care and the development of medicines, diagnostics, and devices targeting their requirements - areas of substantial national and global need - and bridge gaps holding back real-world data randomised controlled trials (RCT). Our principal objective is to enable delivery of efficient, cost-effective trials with the UK National Neonatal Research Database as the principal data source (NNRD-RCT). We will also maximise use of digital technologies, employ efficient statistical approaches and trial designs, and ensure understanding and trust in the new processes. The NNRD is a mature real-world data source containing detailed clinical information extracted from the Electronic Patient Records of admissions to all NHS neonatal units, quality-assured and curated to a high standard. Other aims are to develop sustained stakeholder involvement in NNRD-RCT, create a pipeline for future high-impact collaborative research, assist industry sponsors navigate requirements, grow know-how and capacity in real-world data RCT, and position the UK as a global leader

Main outputs will be standard operating procedures, technical manuals and a comprehensive "e-document suite" for NNRD-RCT; multi-media stakeholder information; guidance and design options for clinical and industry investigators; a pipeline for future NNRD-RCT; and technical specifications for two exemplar use-case NNRD-RCT, one addressing a clinical care uncertainty, and one an industry-sponsored trial. We will deliver the project in 4 work-streams over 2 years. We are academic investigators (Imperial College London; University of Liverpool), and partners Bliss (national preterm and sick newborn charity), Health Data Research UK, Medicines and Healthcare products Regulatory Agency, Neonatal Society (perinatal research society), OpenClinica (provider of clinical trial cloud technologies) and Strategic Intelligence Alliance (SME working closely with industry and the NHS).