title: Another look at two phase I clinical trial designs.
abstract: This note is a response to a recent paper by Korn et al. in which two phase I trial designs were compared, the designs in question being the standard design and the CRM design. The authors concluded that: (i) CRM designs will take longer to complete than standard designs; and (ii) CRM designs are less safe than the standard designs. These conclusions followed from a set of simulations for three different dose toxicity situations. The first purpose of this note is to point out that these conclusions lean on false assumptions. The claims are in error. In their comparisons Korn et al. never in fact used CRM, as defined in O'Quigley, Pepe and Fisher, but a modified version. The second purpose of this note is to look at the same cases studied by Korn et al. but this time using a correctly defined CRM model. Using the same comparison tools of Korn et al. we will see that for these situations, and indeed for a very wide class of other situations not presented here, not only are (i) and (ii) not true but that the exact opposite holds.
authors.affiliation: Department of Mathematics, University of California, San Diego, La Jolla, CA 92093-0112, USA.
authors.forename: J
authors.initials: J
authors.lastname: O'Quigley
mesh_terms: D001499:Bayes Theorem; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D012107:Research Design / Q000592:standards*; D013997:Time Factors