Design questions for Streptococcus pneumoniae vaccine trials with a colonisation endpoint |
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Authors: | Kari Auranen Hanna Rinta-Kokko David Goldblatt Hanna Nohynek Katherine L O’Brien Catherine Satzke Birgit Simell Antti Tanskanen Helena Käyhty |
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Institution: | 1. Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland;2. University College London Medical School, Institute of Child Health, London, UK;3. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;4. Pneumococcal Research and Infectious Diseases and Microbiology, Murdoch Childrens Research Institute, Royal Children''s Hospital, Parkville, VIC, Australia;5. Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia |
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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. |
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Keywords: | PCV pneumococcal conjugate vaccine VEcol vaccine efficacy against colonisation VEacq vaccine efficacy against acquisition of colonisation VET combined vaccine efficacy against acquisition and duration of colonisation VT vaccine (sero)type(s) NVT non-vaccine (sero)type(s) |
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