Biostatistical assessment of mutagenicity studies: A stepwise confidence procedure

Abstract

The paper addresses the issue of identifying the maximum safe dose in the context of non-inferiority trials where several doses of toxicological compounds exist. Statistical methodology for identifying the maximum safe dose is available for three-arm non inferiority designs with only one experimental drug treatment. Extension of this methodology for several experimental groups exists but with multiplicity adjustment. However, if the experimental or the treatment groups can be ordered a priori according to their treatment effect, then multiplicity adjustment is unneeded. Assuming homogeneity of variances across dose group in normality settings, we employed the generalized Fieller’s confdence interval method in a multiple comparison stepwise procedure by incorporating the partitioning principle in order to control the family wise error rate (FWER). Simulation results revealed that the procedure properly controlled the FWER in strong sense. Also, the power of our procedure increases with increasing sample size and the ratio of mean differences. We illustrate our procedure with mutagenicity dataset from a clinical study