Vladimir P. Dragalin

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— The problem of sequential testing of multiple hypotheses is considered, and two candidate sequential test procedures are studied. Both tests are multihypothesis versions of the binary sequential probability ratio test (SPRT), and are referred to as MSPRT's. The first test is motivated by Bayesian optimality arguments, while the second corresponds to a(More)
We propose a new adaptive procedure for dose-finding in clinical trials with combination of two drugs when both efficacy and toxicity responses are available. We model the distribution of this bivariate binary endpoint using the bivariate probit model. The analytic formulae for the Fisher information matrix are obtained, that form the basis for derivation(More)
{ In a companion paper 13], we proved that two speciic constructions of mul-tihypothesis sequential tests, which we refer to as Multihypothesis Sequential Probability Ratio Tests (MSPRT's), are asymptotically optimal as the decision risks (or error probabilities) go to zero. The MSPRT's asymptotically minimize not only the expected sample size but also any(More)
Adaptive designs learn from accumulating trial data in real time and apply this knowledge to optimize subsequent study execution. A set of design rules define a priori which modifications may be incorporated into the trial design. Judicious use of adaptive designs may increase the information value per resource unit invested by avoiding allocation of(More)
We propose a correlated beta-binomial model for the binary response in multi-centre trials. The likelihood function in this case has a closed-form and we avoid multivariate numerical integrations in determining the maximum likelihood estimator. Based on derived asymptotic variance-covariance matrix of the MLE, we obtain relatively simple formulae that(More)
This paper uses a recently completed study to illustrate how adaptive trial designs can increase efficiency of psychiatric drug development. The design employed allowed a continuous reassessment of the estimated dose-response such that patients were randomized in a double-blind fashion to one of seven doses of the investigational drug, placebo, or active(More)
There is a growing interest amongst clinical investigators in the conduct of single trials combining the safety exploration of phase I with the initial investigations of efficacy usually made during phase II. This is being made increasingly possible through the use of biomar-kers that show early signs of physiological changes that are associated with a(More)
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