First in Human Dose Calculation

The other day, I got an opportunity to teach students of MS in Drug Development course about procedures used in calculating first human dose for Phase I clinical trials. I started out explaining the objectives of Phase I studies, various study designs and the need to estimate safe starting doses. The process outlined in the FDA guidance document for estimating the MRSD (Maximum Recommended Starting Dose) is based on doses administerd to different animal species, observed toxicities and a proposed algorithm (as mentioned below) . Additional methods reported include PK guided approach based on AUC and clearance. You can find my slides here.

Let me know your thoughts on these methods. All comments, suggestions, criticism will be highly appreciated.