The construction of optimal designs for dose-escalation studies

Methods for the construction of A-,MV -,Dand E-optimal designs for dose-escalation studies are presented. Algebraic results proved elusive and explicit expressions for the requisite optimal designs are only given for a restricted class of traditional designs. Recourse to numerical procedures and heuristics is therefore made. Complete enumeration of all possible designs is discussed but is, as expected, highly computer intensive. Two exchange algorithms, one based on block exchanges and termed the Block Exchange Algorithm and the other a candidate-set-free algorithm based on individual exchanges and termed the Best Move Algorithm, are therefore introduced. Of these the latter is the most computationally effective. The methodology is illustrated by means of a range of carefully selected examples.