Title: An Individual Patient Data Prospective Meta-Analysis of Skin Care Intervention for the Prevention of Eczema and Associated Health Conditions in Children
Funder: Department of Health and Social Care

Abstract: Background: This research project is an individual patient data prospectively planned meta-analysis (PPMA) of interventions designed to enhance the infant skin barrier with the aim of preventing eczema and associated health conditions. The rationale for undertaking this PPMA is that currently individual trials are underpowered for detection of an effect of the intervention on an important secondary outcome (Allowing for 20% loss to follow up, if 8% in the BEEP control group have food allergy, the study will have 80% power at a 2-sided alpha of 0.05 to detect a 5% absolute difference in food allergy in the treatment group ie a reduction to 4%/ increase to 14%) Therefore PPMA will allow analysis of the interaction between treatment duration and participant baseline characteristics, which will help us to understand which patients benefit most from the intervention. Hypothesis: interventions that aim to enhance skin barrier function during the first year of life will lead to reduced eczema and food allergy beyond the treatment period. Methods: A search strategy will be developed, supported by the Cochrane Skin Group, to identify all ongoing trials of infant skin barrier promotion for preventing eczema or food allergy. The investigators of relevant trials will be contacted with an invitation to join the prospectively planned meta-analysis collaboration. Individual patient data meta-analysis will be undertaken, combining datasets from the first two major trials of skin barrier enhancement for preventing eczema and food allergy. Other eligible trials will only be included in the first cycle of prospective meta-analysis, if they are due to report their primary outcome within the timeline of this Fellowship. Study populations: Populations at low, high or normal risk of eczema (i.e. atopic eczema, or atopic dermatitis) and associated health conditions will be included. Study interventions and comparators: All skin care interventions that are designed to increase skin barrier function, reduce dryness and/or reduce subclinical inflammation will be included for example emollients, bathing products, advice regarding soap and bathing frequency, medicated creams or ointments, including complex interventions. Comparators are no treatment, standard care, or other active interventions that affect skin barrier function, dryness and/or inflammation. Study outcomes: Eligible outcomes are those recorded at least 4 weeks following cessation of the intervention period. The primary timepoint for analysis is age 2 years. The primary outcome is eczema, assessed using UK Working Party Criteria, subject to data availability. Secondary outcomes are longer term prevalence of eczema (over 6 months after cessation of intervention), eczema severity, time to onset of eczema, food allergy. Tertiary outcomes are health economic outcomes, and other complications of eczema such as eczema herpeticum. We will also analyse potential harms such as accidents, skin infections or other adverse effects of emollients or their components. Study impact: First this study will answer the question whether interventions designed to promote skin barrier function in infancy can prevent food allergy. Currently individual trials are not sufficiently powered to answer this question. Second this study will allow tailoring of public health advice, in the event of a positive outcome, by helping identify the population that will benefit most from the intervention.

Lay abstract: Aims The overall aim of this study is to assess whether protecting the skin barrier of babies in the first year of life can reduce their risk of developing eczema or food allergy. I will achieve this by combining the results of two major trials which are running in parallel, one funded by the NIHR HTA programme. The trials are both testing whether applying moisturisers to a baby's skin each day for the first year of life will reduce their risk of developing eczema or food allergy. By combining results from the two trials, a technique called individual patient data meta-analysis, we can find out with greater certainty whether or not moisturisers in the first year of life reduce risk of eczema or food allergy. Combining results from the two trials will also allow us to more precisely identify which babies, if any, benefit most from regular moisturisers in the first year of life - allowing any advice regarding skin barrier protection in babies to be targeted. My individual patient data meta-analysis will be planned in detail while the individual trials are running, so that the meta-analysis can be completed promptly when the trials finish. This means that the results of the trials will be capitalised on and disseminated to relevant stakeholders rapidly. Background Allergic diseases such as eczema and food allergy are the most common long-term health conditions in children and young people, with more than 1 in 3 children in England and Wales reporting at least one allergic condition (Pundekar et al). There is no cure for most children with allergic disease, and the cost to the NHS of treatment is estimated at over 1 billion pounds per annum (Gupta et al). The cost of childhood food allergy to affected families and healthcare providers has been estimated as at least $25 billion per annum in the United States of America (Gupta et al). Recent evidence, including my own higher degree work, has shown a strong association between skin barrier impairment in the first months of life and later risk of eczema and food allergy. We also know that treating babies with a moisturiser each day for the first months of life can suppress eczema during the treatment, and that eczema in the first months of life increases risk of food allergy. What we don't yet know, is whether treating babies with a moisturiser each day for the first months of life, to improve skin barrier function, leads to a longer term reduction in risk of eczema after the treatment has finished, or to reduced food allergy. Design I will collaborate with researchers in Sydney Australia, Oslo Norway and Nottingham to combine the databases from two major trials testing whether daily moisturiser during the first year of life reduces risk of eczema or food allergy at age 2 years. I will carefully create a combined dataset, and will plan and undertake statistical analysis of this combined dataset to more clearly understand the effects of early moisturiser use on risk of eczema and food allergy, and identify features of infants which are associated with greatest benefit. I will undertake a detailed training programme in parallel with this work, designed to give me high-level skills in designing and analysing clinical trials, and individual patient data meta-analysis of trial results. PPI Public and patient involvement will inform prioritisation of outcome measures, to ensure the results that are important to patients are included in the study. Patients and members of the public will also review the study protocol, monitor progress of the individual trials, and help disseminate the results of my study through patient charities, support groups and the media.

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH;SKIN