Adverse Drug Reactions in Children and Neonates

Aim: First to provide important evidence about the incidence and nature of ADRs in children and second to develop validated methodologies for pharmacovigilance in children and neonates.Background: Unlicensed and off-label prescribing is common in paediatric practice; 25% of paediatric inpatient prescriptions and 65% of neonatal prescriptions are for medications used in this way. Extrapolation of efficacy, dosing regimes and ADRs from adult data is inappropriate due to developmental changes in physiology and drug handling. Therefore children and newborn babies are at high risk of serious and unpredictable ADRs from the use of these medications. In newborns, there are additional difficulties in distinguishing between ADRs and the diverse complications of neonatal pathology. A trend towards more adverse drug reactions when unlicensed and off-label medicines are prescribed was first reported from RLCT. However, recognition of serious ADRs generally depends on a cluster of individuals presenting with a similar pattern of unexplained clinical features and there is no systematic, pre-emptive approach to this problem in children and neonates, largely because of a dearth of good quality scientific evidence. This programme of research will address these important issues.Research Plans: (1) To characterise prospectively ADRs in children that present as acute admissions; (2) to identify and characterise prospectively ADRs in children occurring during inpatient admissions; (3) to develop systems for neonatal pharmacovigilance including applicability in the newborn of currently available tools for ADR assessment; (4) to undertake a systematic review of studies that describe previously unrecognised ADRs in children to identify common features which led to the recognition of the ADR; (5) to work with collaborators who are developing methods to ascertain parental views on reporting of ADRs in children; (6) to use the findings from 1 to 5 to develop and validate instruments that can be used to screen systematically for ADRs among hospitalised children or neonates; (7) to develop evidence-based guidelines for both the assessment of suspected ADRs and the prevention of ADRs in children and neonates.Research Team: The team comprises the necessary experience and methodological expertise to successfully complete this programme. Members of the research team have national and international standing in the areas of medicines for children, paediatric and neonatal pharmacy practice, ADR detection and reporting, qualitative research in children, secondary research methodologies and clinical guideline development and implementation. The CI is Director of the Medicines for Children Research Network (MCRN) and Head of the Division of Child Health, University of Liverpool (UoL). AN and PW are Associate Directors of MCRN. Members of the research team are members (MP, AN) of the Commission on Human Medicines (CHM) and Chairs of expert advisory groups within CHM (RLS, Paediatric; MP, Pharmacovigilance). Research Environment: The clinical setting comprises the largest children’s hospital in Western Europe and the biggest single site obstetric unit in the UK, providing unparalleled access to newborn infants and children. The two NHS trusts each have a comprehensive portfolio of paediatric and neonatal research, with collaborations with the UoL Divisions of Child Health, Perinatal Medicine, Pharmacology, Psychology and the Centre for Medical Statistics and Health Evaluation, all of which will support this programme. The host organisation is the site of the UK MCRN Coordinating Centre.Anticipated outputs, outcomes and impact of this research: This will be the largest programme of research to comprehensively identify and describe ADRs in neonates and children. Within five years this programme will improve health by generating robust pharmacovigilance systems which can be operated by front line staff for detection of ADRs in children and neonates and guidelines for th