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A sequential design for maximizing the probability of a favourable response
Authors:S.D. Durham  N. Flournoy  W. Li
Abstract:Consider the situation in which subjects arrive sequentially for a treatment and in which there are two distinct ways in which the treatment may fail. Treatments are given at different dosages, and the probabilities of the two failure types vary with dose. Assuming that decreasing the chances of one failure type increases the chances of the other, we say the failures oppose each other. Also assume that one failure type is primary in that, if it occurs, it censors the trial, so that observation of the secondary failure type is contingent on no failure of the primary type. We are interested in designs that provide information about the dose that maximizes the probability of success, i.e., the optimal dose, while treating very few subjects at dosages that have high risks of failure. Assuming that dosages belong to a discrete set, we show that a randomized version of the Pólya urn scheme causes dose selection to be progressively biased so as to favour those doses that produce success with higher probability.
Keywords:Adaptive designs  bivariate binary random variables  branching processes  Phase I/II clinical trials  optimal dosages  dose-response experiments  randomized Pó  lya urn  sequential maximum likelihood  stochastic approximation  Yule processes
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