The early use of Antibiotics for at Risk CHildren with InfluEnza in primary care (the ARCHIE programme).

Aims and objectives The overall aim of the ARCHIE programme is to produce an evidence base to inform NHS policy for the use of antibiotics in at risk children with influenza/influenza-like illness (ILI). At risk children are more prone to influenza-related clinical deterioration (bacterial complications and hospitalisation) than otherwise healthy children. The programme will be delivered in five workpackages designed to: refine the definition of at risk , explore the views of GPs and parents who will be key to implementing policy, test the effectiveness of early antibiotics delivered in primary care, determine the effect of antibiotics on bacterial carriage and antibiotic resistance, and construct clinical and economic models to inform NHS policy. Background and rationale Influenza/ILI in children create a considerable burden on NHS resources each winter. Influenza immunisation is only partially effective, coverage amongst at risk children is currently low and antiviral medications are of modest clinical benefit. Because of concern about NHS capacity to manage complications during influenza epidemics and pandemics there are national government stockpiles of co-amoxiclav held for use in primary care. Research environment The programme will be co-ordinated by the University of Oxford, which has an established primary care research environment of excellence (top rated in 2008 Research Assessment Exercise and founder member of the National School of Primary Care Research). The programme will benefit from pre-agreed collaboration between the PCRN and MCRN. Research plan Workpackage A will provide a refined, evidence-based definition of at risk children through conducting a prognostic systematic review. This definition will inform a more precise definition of at risk for entry into our clinical trial (workpackage C) and for future influenza immunisation policy. Workpackage B will explore factors which influence GPs antibiotic prescribing decisions as well as parental experiences and consulting attitudes in relation to at risk children with influenza/ILI using qualitative methodology. The results will help us design materials for our clinical trial and understand the factors likely to influence the implementation of our research findings. We will also develop a website to improve public understanding of the importance of influenza and its complications. Workpackage C will determine the effectiveness of the early co-amoxiclav use for at risk children with influenza/ILI by conducting a double-blind randomised placebo-controlled trial involving 600 children in Thames Valley, Liverpool, Bristol and Southampton. We will perform exploratory subgroup analyses in children with different influenza subtypes (A, B, A/H1N1 2009), influenza and bacteria co-infections and prescribed concurrent antiviral medication. Workpackage D will determine the impact of co-amoxiclav on bacterial carriage and the development of antibiotic resistance by conducting a nested prospective longitudinal study of children participating in the trial, sampling with interval throat swabs over the course of a year. Workpackage E will conduct a systematic review, develop and validate multivariable risk scores to estimate levels of risk in at risk children with influenza/ILI and determine which children are likely to gain greatest clinical benefit from antibiotics. We will assess and compare health care resource utilisation and costs, and explore the cost-effectiveness of different potential strategies for early antibiotic use. Projected Outputs & Dissemination plans The programme will provide an evidence base to underpin NHS policy for primary care antibiotic prescribing during the influenza season. Outputs will include peer- reviewed presentations and publications in multidisciplinary fields and a website of parents experiences of children with influenza. We will disseminate our findings to the Department of Healt