title: Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.
abstract: The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity.
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. richard.reeve@glasgow.ac.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Reeve
authors.forename: Sarah
authors.initials: S
authors.lastname: Cox
authors.forename: Eliana
authors.initials: E
authors.lastname: Smitsaart
authors.forename: Claudia Perez
authors.initials: CP
authors.lastname: Beascoechea
authors.forename: Bernd
authors.initials: B
authors.lastname: Haas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Maradei
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Haydon
authors.forename: Paul
authors.initials: P
authors.lastname: Barnett
mesh_terms: D032761:Animal Experimentation / Q000706:statistics & numerical data*; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D005536:Foot-and-Mouth Disease / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D015233:Models, Statistical; D012680:Sensitivity and Specificity; D013020:South America; D013678:Technology, Pharmaceutical / Q000379:methods*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D014765:Viral Vaccines