Statistical analysis of sparse infection data and its implications for retroviral treatment trials in primates.
Reports on retroviral primate trials rarely publish any statistical analysis. Present statistical methodology lacks appropriate tests for these trials and effectively discourages quantitative assessment. This paper describes the theory behind VACMAN, a user-friendly computer program that calculates statistics for in vitro and in vivo infectivity data. VACMAN's analysis applies to many retroviral trials using i.v. challenges and is valid whenever the viral dose-response curve has a particular shape. Statistics from actual i.v. retroviral trials illustrate some unappreciated principles of effective animal use: dilutions other than 1:10 can improve titration accuracy; infecting titration animals at the lowest doses possible can lower challenge doses; and finally, challenging test animals in small trials with more virus than controls safeguards against false successes, "reuses" animals, and strengthens experimental conclusions. The theory presented also explains the important concept of viral saturation, a phenomenon that may cause in vitro and in vivo titrations to agree for some retroviral strains and disagree for others.
Spouge
J L
JL
National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894.
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008433:Mathematics; D015233:Models, Statistical; D011323:Primates; D011336:Probability; D012190:Retroviridae; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000503:physiopathology; D012984:Software
D000998:Antiviral Agents