title: Design questions for Streptococcus pneumoniae vaccine trials with a colonisation endpoint.
abstract: Evaluation of vaccine efficacy for protection against colonisation (VEcol) with Streptococcus pneumoniae and other bacterial pathogens is often based on a cross-sectional study design, in which only one nasopharyngeal sample is obtained per study subject. Here we investigate the feasibility of this study design by investigating a number of practical design problems. Specific questions are related to the timing of colonisation measurement with respect to the time of vaccination, the adjustment for the within-host replacement of vaccine-type colonisation by the non-vaccine type pneumococci, and the impact of multiple serotype colonisation on VEcol estimation. We also discuss the issue of choosing the control vaccine, including comparison of two active pneumococcal vaccines, as well as the sample size and the statistical power of colonisation endpoint trials. In addition, the statistical design with the specific aim to include information about VEcol in the licensure process of new pneumococcal vaccine products is discussed.
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland. Electronic address: kari.auranen@thl.fi.
authors.forename: Kari
authors.initials: K
authors.lastname: Auranen
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rinta-Kokko
authors.affiliation: University College London Medical School, Institute of Child Health, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Nohynek
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
authors.affiliation: Pneumococcal Research and Infectious Diseases and Microbiology, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Satzke
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland.
authors.forename: Birgit
authors.initials: B
authors.lastname: Simell
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Käyhty
mesh_terms: D002986:Clinical Trials as Topic; D003430:Cross-Sectional Studies; D006801:Humans; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D017063:Outcome Assessment, Health Care; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D013997:Time Factors; D014611:Vaccination
chemical_list: D022242:Pneumococcal Vaccines
keywords: Multiple colonisation; NVT; Nasopharyngeal colonisation; PCV; Pneumococcus; Sample size; VE(T); VE(acq); VE(col); VT; Vaccine efficacy; combined vaccine efficacy against acquisition and duration of colonisation; non-vaccine (sero)type(s); pneumococcal conjugate vaccine; vaccine (sero)type(s); vaccine efficacy against acquisition of colonisation; vaccine efficacy against colonisation