Executive Summary

FDA final guidance on "FDL-1Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers," released July 22, provides an algorithm by which maximum recommended starting dose (MRSD) can be selected for first-in-human clinical trials. Document generally reflects draft version. The process outlined for calculating MRSD uses administered doses, observed toxicities and an algorithmic approach, although "an alternative approach could be proposed that places primary emphasis on animal pharmacokinetics and modeling rather than dose," FDA says. Merck and Bristol-Myers Squibb had requested that the process include alternate methods for deriving MRSD rather than a single approach (1"The Pink Sheet" May 12, 2003, p. 23)...