title: Harmonisation in study design and outcomes in paediatric antibiotic clinical trials: a systematic review.
abstract: There is no global consensus on the conduct of clinical trials in children and neonates with complicated clinical infection syndromes. No comprehensive regulatory guidance exists for the design of antibiotic clinical trials in neonates and children. We did a systematic review of antibiotic clinical trials in complicated clinical infection syndromes (including bloodstream infections and community-acquired pneumonia) in children and neonates (0-18 years) to assess whether standardised European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidance for adults was used in paediatrics, and whether paediatric clinical trials applied consistent definitions for eligibility and outcomes. We searched MEDLINE, Cochrane CENTRAL databases, and ClinicalTrials.gov between Jan 1, 2000, and Nov 18, 2015. 82 individual studies met our inclusion criteria. The published studies reported on an average of 66% of CONSORT items. Study design, inclusion and exclusion criteria, and endpoints varied substantially across included studies. The comparison between paediatric clinical trials and adult EMA and FDA guidance highlighted that regulatory definitions are only variably applicable and used at present. Absence of consensus for paediatric antibiotic clinical trials is a major barrier to harmonisation in research and translation into clinical practice. To improve comparison of therapies and strategies, international collaboration among all relevant stakeholders leading to harmonised case definitions and outcome measures is needed.
authors.affiliation: Paediatric Infectious Disease Research Group, Institute for Infection and Immunity, St George's University of London, London, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Folgori
authors.affiliation: Paediatric Infectious Disease Research Group, Institute for Infection and Immunity, St George's University of London, London, UK; Paediatric Pharmacology, University Children's Hospital Basel, Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Bielicki
authors.affiliation: Paediatric Infectious Disease Research Group, Institute for Infection and Immunity, St George's University of London, London, UK.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ruiz
authors.affiliation: University of Liverpool, Institute of Translational Medicine, Department of Women's and Children's Health, Crown Street, Liverpool, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Turner
authors.affiliation: Department of Pediatrics, University of California San Diego, San Diego, CA, USA; Rady Children's Hospital San Diego, San Diego, CA, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Bradley
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Theoklis E
authors.initials: TE
authors.lastname: Zaoutis
authors.affiliation: Institute of Medical Microbiology, University of Tartu, Tartu, Estonia.
authors.forename: Irja
authors.initials: I
authors.lastname: Lutsar
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.affiliation: University Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Paediatric Infectious Disease Research Group, Institute for Infection and Immunity, St George's University of London, London, UK. Electronic address: mike.sharland@stgeorges.nhs.uk.
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy; D002986:Clinical Trials as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy*; D003299:Cooperative Behavior; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D010372:Pediatrics; D011014:Pneumonia / Q000188:drug therapy; D012107:Research Design / Q000592:standards*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000900:Anti-Bacterial Agents