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)
In a companion paper [13], we proved that two specific constructions of multihypothesis 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)
A PhRMA Working Group on adaptive clinical trial designs has been formed to investigate and facilitate opportunities for wider acceptance and usage of adaptive designs and related methodologies. A White Paper summarizing the findings of the group is in preparation; this article is an Executive Summary for that full White Paper, and summarizes the findings(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)
BACKGROUND Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. OBJECTIVE To evaluate the effectiveness of oral clonidine for control of hot(More)
We introduce a two-stage design for dose-finding in the context of Phase I/II studies, where two binary correlated endpoints are available, for instance, one for efficacy and one for toxicity. The bivariate probit model is used as a working model for the dose-response relationship. Given a 'desirable point' for the marginal probabilities of efficacy and(More)
OBJECTIVE To examine whether penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis is influenced by patient age, number of days ill prior to initiation of treatment, number of prior episodes, season, total dosage (milligrams per kilogram), and frequency of administration (2 vs 3 times daily). METHODS Four hundred(More)
We introduce a new optimal design for dose finding with a continuous efficacy endpoint. This design is studied in the context of a flexible model for the mean of the dose-response. The design incorporates aspects of both D- and c-optimality and can be used when the study goals under consideration include dose-response estimation, followed by identification(More)
The study design was a multi-center, multiple-dose, randomized, open-label, 2 x 2 crossover study in patients with advanced solid tumors. Each patient was randomized to receive the test formulation or the reference formulation of the drug. The primary objective of the study was to demonstrate the bioequivalence of the test formulation T relative to the(More)
We propose an adaptive procedure for dose-finding in clinical trials when the primary efficacy endpoint is continuous. We model the mean of the efficacy endpoint, given the dose, as a four-parameter logistic function. The efficacy endpoint at each dose is distributed according to either a normal or a gamma distribution. We consider the cases of fixed(More)