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This seems to be an example of terms only having meaning in the context that they were meant. In the original e-mail, Markus wrote about "SAD and MAD studies as they are done in early drug development". I interpreted this to refer to 'single ascending dose' and 'multiple ascending dose' studies. These are terms that are used at AstraZeneca but whether they are standard remains to be seen. In my opinion, these studies seldom have clear objectives and it is unclear what criteria is used on the basis to choose doses for subsequent study. I recommend the conduct of a SAD study to follow a decision theoretic approach such as: Zhou Y, Whitehead J. Practical implementation of Bayesian dose-escalation procedures. DIJ 2003 37: 59 Whitehead J, Zhou Y, Stevens JW, Blakey G, Price J, Leadbetter J. Bayesian decision procedures for dose escalation based on evidence of undesirable events and therapeutic benefit. Submitted to Statistics in Medicine Whitehead J, Zhou, Stevens JW, Blakey G. An evaluation of a Bayesian method of dose-escalation based on bivariate binary responses. Submitted to Journal of Biopharmaceutical Statistics Whitehead J, Zhou Y. Easy to implement Bayesian methods for dose-escalation studies in healthy volunteers. Biostatistics 2001 2: 47-61 John Bayesian Statistics Focus Team Leader _________________________________________________________ John W Stevens AstraZeneca R&D Charnwood Clinical Sciences, Bakewell Road, Loughborough, Leics LE11 5RH, England Tel: +44 (0) 1509 645044 Fax: +44 (0) 1509 645503 [log in to unmask]