Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 22 (2), 126-38

Isotonic Designs for Phase I Trials


Isotonic Designs for Phase I Trials

D H Leung et al. Control Clin Trials.


The purpose of a phase I trial in cancer is to determine the level (dose) of the treatment under study that has an acceptable level of adverse effects. Although substantial progress has recently been made in this area using parametric approaches, the method that is widely used is based on treating small cohorts of patients at escalating doses until the frequency of toxicities seen at a dose exceeds a predefined tolerable toxicity rate. This method is popular because of its simplicity and freedom from parametric assumptions. In this paper, we consider cases in which it is undesirable to assume a parametric dose-toxicity relationship. We propose a simple model-free approach by modifying the method that is in common use. The approach assumes toxicity is nondecreasing with dose and fits an isotonic regression to accumulated data. At any point in a trial, the dose given is that with estimated toxicity deemed closest to the maximum tolerable toxicity. Simulations indicate that this approach performs substantially better than the commonly used method and it compares favorably with other phase I designs. Control Clin Trials 2001;22:126-138

Comment in

Similar articles

See all similar articles

Cited by 14 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources