Animal study designs
non-anthrax-related
Two studies were conducted: one in New Zealand white rabbits and one in cynomolgus macaques. Both were randomized, blinded and placebo-controlled studies conducted in compliance with Good Laboratory Practices (GLP, 21 CFR 58) [The rabbit study included an IGIV (control) group, an ANTHRASIL-treated group (N = 50/group) and an untreated group of 10 animals. A sample size of 50 animals per group was selected to ensure that at least 40 animals per group would be bacteremic prior to treatment, providing more than 80% power to detect a difference between the group survival rates of 0% and 20% in IGIV and ANTHRASIL groups, respectively at a significance level of 5%. For the primary efficacy analysis, the test statistic used was the Fisher’s Exact test; as this study was the pivotal study for licensure, a more stringent two-tailed version of this test was used.The NHP study included four groups that received either IGIV or one of three doses of ANTHRASIL (N = 16/group). A sample size of 16 animals per group provided 80% power at a significance level of 5%, assuming a 15% survival rate in the control group and a 65% survival rate in the treatment group. This sample size also provides 80% power assuming a 10% survival rate in the control group and a 55% survival rate in the treatment group. Power calculations were performed using StatXact (version 8.0). For the primary efficacy analysis, a comparison of the survival rates was performed between each treatment group (groups 2, 3 and 4) and the control group (group 1) using a Fisher’s Exact test. As this study was exploratory in nature and a survival rate of less than 15% in the treatment group was not reasonably expected, the less stringent one-tailed version of this test was used.For statistical analysis, the intent-to-treat (ITT) set of animals included those animals that were confirmed to be toxemic prior to treatment and received a full dose of either placebo or ANTHRASIL. The modified intent to treat (MITT) set of animals included those in the ITT group that were confirmed to be bacteremic at any time point prior to the treatment. Any animal that died due to non-anthrax-related causes was excluded from the analysis.