title: Design, recruitment, and microbiological considerations in human challenge studies.
abstract: Since the 18th century a wealth of knowledge regarding infectious disease pathogenesis, prevention, and treatment has been accumulated from findings of infection challenges in human beings. Partly because of improvements to ethical and regulatory guidance, human challenge studies-involving the deliberate exposure of participants to infectious substances-have had a resurgence in popularity in the past few years, in particular for the assessment of vaccines. To provide an overview of the potential use of challenge models, we present historical reports and contemporary views from experts in this type of research. A range of challenge models and practical approaches to generate important data exist and are used to expedite vaccine and therapeutic development and to support public health modelling and interventions. Although human challenge studies provide a unique opportunity to address complex research questions, participant and investigator safety is paramount. To increase the collaborative effort and future success of this area of research, we recommend the development of consensus frameworks and sharing of best practices between investigators. Furthermore, standardisation of challenge procedures and regulatory guidance will help with the feasibility for using challenge models in clinical testing of new disease intervention strategies.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Darton
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK. Electronic address: christoph.blohmke@paediatrics.ox.ac.uk.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Blohmke
authors.affiliation: Department of Immunisation, Vaccines and Biologicals, WHO, Geneva, Switzerland.
authors.forename: Vasee S
authors.initials: VS
authors.lastname: Moorthy
authors.affiliation: Department of Medicine, Imperial College London, London, UK.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Altmann
authors.affiliation: Department of Medicine, University of Virginia School of Medicine, Charlottesville VA, USA.
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hayden
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Clutterbuck
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000890:Anti-Infective Agents; D035843:Biomedical Research / Q000379:methods* / Q000592:standards; D003140:Communicable Disease Control; D003141:Communicable Diseases / Q000188:drug therapy*; D055808:Drug Discovery; D017408:Guidelines as Topic; D006805:Human Experimentation / Q000941:ethics / Q000331:legislation & jurisprudence / Q000592:standards*; D006801:Humans; D012107:Research Design / Q000592:standards*; D012449:Safety; D014612:Vaccines
chemical_list: D000890:Anti-Infective Agents; D014612:Vaccines