Title: Improving childhood atopic eczema through clinical trials of prevention, education and therapy
Funder: Department of Health and Social Care

Abstract: Objectives: This application builds on the applicant's NIHR Clinician Scientist and Clinical Trials Fellowships and focuses on three high priority research areas in childhood atopic eczema (AE): dietary intervention to prevent AE, nurse-led parental AE education, and treatment with immuno-suppressive medication in children with severe recalcitrant AE. The main research questions of the three trials are: Prevention trial: Does prolonged breastfeeding reduce the risk of AE up to 16 years of age? Education trial: Does a structured nurse-led parental eczema education programme (EEP) in addition to standard care lead to a significant reduction in AE severity and improvement in child and parental quality of life? Treatment trial: Is methotrexate equally efficacious to ciclosporin in the treatment of severe recalcitrant AE, with a more favourable side effect profile? The described research programme will provide a platform for the applicant to develop further skills in clinical trials methodology and conduct, research collaboration as part of multi-centre trials, and more specifically health economics evaluation and qualitative research methods in RCTs as well as complex statistics skills. The long-term aim is to build a research portfolio that has the critical mass to support the establishment of the first centre that specialises in evidence-based clinical paediatric dermatology research. Design: Prevention trial: Analysis of the longitudinal impact of prolonged breastfeeding on AE and other allergic disease outcomes within the largest randomised controlled trial with a breastfeeding intervention (n>17,000 mother-infant pairs in Belarus; PROmotion Of Breastfeeding Intervention Trial PROBIT). Maternity units were cluster randomized to either established care or a structured breastfeeding support programme. PROBIT studies a broad range of health outcomes, including the impact on AE cumulative risk and severity. The study is already fully funded and the teenage follow up phase (age 16) is underway (PROBIT IV). I designed the AE study module for PROBIT IV and will oversee all AE-related analyses. The PhD project that forms part of this CDF application will be nested within PROBIT. Education trial: This is a national multicentre RCT, testing a standardised nurse-led parental eczema education programme (EEP trial). The main outcomes are AE severity and child and parental quality of life, as well as a cost evaluation from an NHS perspective. The outline application was submitted to the HTA main funding stream in January 2014. Treatment trial: This is a multicentre RCT that randomises children with severe recalcitrant AE to receive either oral ciclosporin or oral methotrexate for 9 months (TREatment of severe Atopic eczema in children Taskforce (TREAT) trial). Follow up is for another 6 months. Main outcomes are a reduction in disease severity and improvement in quality of life. This trial has a mechanistic component, focusing on the anti-inflammatory effect of methotrexate versus ciclosporin. An outline application was submitted to the NIHR EME call for skin disease in October 2013. Expected outcomes: All three clinical trials address high priority research areas identified in systematic reviews and a recent national research priority setting exercise for AE, coordinated by the James Lind Alliance. The results will inform national and international infant feeding policy (PROBIT) as well as treatment guidance (EEP and TREAT trials) and NHS national commissioning (EEP trial). Anticipated benefits: It is anticipated that the proposed research will aid AE prevention and also improve the quality of life of children with AE and that of their parents through patient education, and safer and more efficacious systemic anti-inflammatory treatments. In addition, the CDF will allow the applicant to develop the skills and research programme necessary to establish himself as a fully independent Senior Investigator and to build a centre of excellence for evidence-based paediatric dermatology research.

Lay abstract: Eczema affects ~20% of UK children. If moderate to severe, it has a detrimental effect on the quality of life comparable to diabetes. The economic burden is similar to asthma. This Fellowship comprises three clinical trials in children: one compares two immuno-suppressive medications in the treatment of severe eczema, one tests the impact of an educational intervention on children's eczema severity and quality of life, and the third trial assesses whether prolonged breastfeeding protects against eczema and other allergic diseases. All three trials are likely to change clinical practice in the UK and beyond.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;6.1 PHARMACEUTICALS;7.1 INDIVIDUAL CARE NEEDS
Health categories: SKIN