Sequential design and analysis of dose finding studies in patients with life threatening disease

We describe a recently developed approach to the design and analysis of dose finding studies in patients with life-threatening disease. Such patients may be terminally ill and, although interest is focussed on cancer, the methodology is more generally applicable. Of major interest is the identification of a dose with a given targeted toxicity level. Experimentation is carried out at a level for which all current available evidence, ie any information available before beginning the study, typically used in determining dose levels, together with information accumulated in the course of the study, indicates the best estimate of the target level. At the end of the study it is possible to obtain a statistical estimate of the probability of toxicity at the chosen level. Note that such estimation is not possible after a dose finding study carried out along traditional lines.