@booklet {davidazriel-ttvedids2010,
	title = {Treatment Versus Experimentation Dilemma in Dose-Finding Studies, The},
	howpublished = {Discussion Papers},
	year = {2010},
	month = {9},
	publisher = {Journal of Statistical Planning and Inference 141, 2759{\textendash}2768. (2011).},
	abstract = {Phase I clinical trials are conducted in order to find the maximum tolerated dose (MTD) of a given drug from a finite set of doses. For ethical reasons, these studies are usually sequential, treating patients or group of patients with the best available dose according to the current knowledge. However, it is proved here that such designs, and, more generally, designs that concentrate on one dose from some time on, cannot provide consistent estimators for the MTD unless very strong parametric assumptions hold. We describe a family of sequential designs that treat individuals with one of the two closest doses to the estimated MTD, and prove that such designs, under general conditions, concentrate eventually on the two closest doses to the MTD and estimate the MTD consistently. It is shown that this family contains randomized designs that assign the MTD with probability that approaches 1 as the size of the experiment goes to infinity. We compare several designs by simulations, studying their performances in terms of correct estimation of the MTD and the proportion of individuals treated with the MTD.},
	url = {/files/dp559.pdf},
	author = {David Azriel, Micha Mandel and Yosef Rinott}
}
