During the last two decades, Professor Valerii Fedorov was involved in developing methods of optimal design of pharmaceutical research working at ICON plc, VP, Innovation Center
In the present state of the development of theory and experimental techniques many investigations... more In the present state of the development of theory and experimental techniques many investigations in physics, especially those concerning the properties of elementary particles, require, sophisticated, expensive, and extended experiments to be performed. Actual experience shows that the design of such experiments by the methods of mathematical statistics allows, in most cases, to use the available means (e. g. time, money, and material) more effectively than in passive (non-planned) experiments. In view of this a more extensive application of the mathematical methods for designing experiments becomes necessary. In this review the existing methods of designing experiments are described in a universally accessible form. Examples concerning mainly experiments on the phase shift analysis of elastic scattering and measurements of differential effective cross sections are considered in this review. For simplicity, these examples are presented schematically. The examples are selected from the domain of nuclear physics not by chance but because experiments in this region are specially expensive. In comparison with the book by KLEPIKOV and SOKOLOV (1961) containing one chapter on the planning of physical experiments, the present paper embraces a wider variety of problems.
We applaud the authors for their innovative approach to design augmentation. There are three key ... more We applaud the authors for their innovative approach to design augmentation. There are three key concepts we especially like and want to emphasize. First is the simple but powerful idea of using the previous responses to guide the choice of new design points. We find the ...
Journal of statistical theory and practice, Dec 23, 2013
ABSTRACT Randomized discontinuation trial (RDT) has gained popularity across a number of therapeu... more ABSTRACT Randomized discontinuation trial (RDT) has gained popularity across a number of therapeutic areas. Oncology is one of the most known. In the simplest case, at the initial open-label stage all patients are treated with the experimental treatment to identify a population of responders. This stage is followed by a randomized two-arm trial to compare two conditions, for example, treatment versus placebo. Potentially RDT increases the efficiency of trials relatively to traditional designs gaining information from a sensitized population if the open-label stage provides a reliable separation of responders from nonresponders. Often a sensitized population is called an enriched population, and respectively, the RDT is called “enrichment experiment.” We compare RDT with the traditional two-arm randomized clinical trials (RCT) for binary outcomes assuming that the population of interest consists of three groups: placebo responders, treatment-only responders, and nonresponders. Our results are derived in the “parameter estimation” setting and they are based on the comparison of estimator variances. We identify conditions under which RDT is either superior or inferior to RCT in terms of response rates, misclassification rates, and clinical ethics. Extension of our results to design optimization, hypothesis testing, and sample size calculation is rather straightforward.
In this section we assume that the independent variables xl… x k (and the response variable y) ar... more In this section we assume that the independent variables xl… x k (and the response variable y) are observed in the space of variables t that are out of the experimenter’s control but are known. Typically, t stands for time; but t may correspond to temperature, atmospheric pressure, wind direction in environmental studies; to age, living conditions, gender in biological studies, etc. We associate t with time because time-dependent models are of great practical relevance. But no specific features of “time” are crucial for the following. The reader may adapt the results to other situations.
In the present state of the development of theory and experimental techniques many investigations... more In the present state of the development of theory and experimental techniques many investigations in physics, especially those concerning the properties of elementary particles, require, sophisticated, expensive, and extended experiments to be performed. Actual experience shows that the design of such experiments by the methods of mathematical statistics allows, in most cases, to use the available means (e. g. time, money, and material) more effectively than in passive (non-planned) experiments. In view of this a more extensive application of the mathematical methods for designing experiments becomes necessary. In this review the existing methods of designing experiments are described in a universally accessible form. Examples concerning mainly experiments on the phase shift analysis of elastic scattering and measurements of differential effective cross sections are considered in this review. For simplicity, these examples are presented schematically. The examples are selected from the domain of nuclear physics not by chance but because experiments in this region are specially expensive. In comparison with the book by KLEPIKOV and SOKOLOV (1961) containing one chapter on the planning of physical experiments, the present paper embraces a wider variety of problems.
We applaud the authors for their innovative approach to design augmentation. There are three key ... more We applaud the authors for their innovative approach to design augmentation. There are three key concepts we especially like and want to emphasize. First is the simple but powerful idea of using the previous responses to guide the choice of new design points. We find the ...
Journal of statistical theory and practice, Dec 23, 2013
ABSTRACT Randomized discontinuation trial (RDT) has gained popularity across a number of therapeu... more ABSTRACT Randomized discontinuation trial (RDT) has gained popularity across a number of therapeutic areas. Oncology is one of the most known. In the simplest case, at the initial open-label stage all patients are treated with the experimental treatment to identify a population of responders. This stage is followed by a randomized two-arm trial to compare two conditions, for example, treatment versus placebo. Potentially RDT increases the efficiency of trials relatively to traditional designs gaining information from a sensitized population if the open-label stage provides a reliable separation of responders from nonresponders. Often a sensitized population is called an enriched population, and respectively, the RDT is called “enrichment experiment.” We compare RDT with the traditional two-arm randomized clinical trials (RCT) for binary outcomes assuming that the population of interest consists of three groups: placebo responders, treatment-only responders, and nonresponders. Our results are derived in the “parameter estimation” setting and they are based on the comparison of estimator variances. We identify conditions under which RDT is either superior or inferior to RCT in terms of response rates, misclassification rates, and clinical ethics. Extension of our results to design optimization, hypothesis testing, and sample size calculation is rather straightforward.
In this section we assume that the independent variables xl… x k (and the response variable y) ar... more In this section we assume that the independent variables xl… x k (and the response variable y) are observed in the space of variables t that are out of the experimenter’s control but are known. Typically, t stands for time; but t may correspond to temperature, atmospheric pressure, wind direction in environmental studies; to age, living conditions, gender in biological studies, etc. We associate t with time because time-dependent models are of great practical relevance. But no specific features of “time” are crucial for the following. The reader may adapt the results to other situations.
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Papers by Valerii Fedorov