Bayesian decision procedures for dose-escalation based on evidence of undesirable events and therapeutic benefit.

In this paper, Bayesian decision procedures are developed for dose-escalation studies based on bivariate observations of undesirable events and signs of therapeutic benefit. The methods generalize earlier approaches taking into account only the undesirable outcomes. Logistic regression models are used to model the two responses, which are both assumed to take a binary form. A prior distribution for the unknown model parameters is suggested and an optional safety constraint can be included. Gain functions to be maximized are formulated in terms of accurate estimation of the limits of a therapeutic window or optimal treatment of the next cohort of subjects, although the approach could be applied to achieve any of a wide variety of objectives. The designs introduced are illustrated through simulation and retrospective implementation to a completed dose-escalation study. Copyright © 2006 John Wiley & Sons, Ltd.

Gaining acceptability for the Bayesian decision-theoretic approach in dose-escalation studies

There has recently been increasing demand for better designs to conduct first-into-man dose-escalation studies more efficiently, more accurately and more quickly. The authors look into the Bayesian decision-theoretic approach and use simulation as a tool to investigate the impact of compromises with conventional practice that might make the procedures more acceptable for implementation. Copyright © 2005 John Wiley & Sons, Ltd.

Bayesian decision procedures for binary and continuous bivariate dose-escalation studies

In this paper, Bayesian decision procedures are developed for dose-escalation studies based on binary measures of undesirable events and continuous measures of therapeutic benefit. The methods generalize earlier approaches where undesirable events and therapeutic benefit are both binary. A logistic regression model is used to model the binary responses, while a linear regression model is used to model the continuous responses. Prior distributions for the unknown model parameters are suggested. A gain function is discussed and an optional safety constraint is included. Copyright (C) 2006 John Wiley & Sons, Ltd.

PDM 2006: Proceedings of the International Workshop on Data Mining

Recently major processor manufacturers have announced a dramatic shift in their paradigm to increase computing power over the coming years. Instead of focusing on faster clock speeds and more powerful single core CPUs, the trend clearly goes towards multi core systems. This will also result in a paradigm shift for the development of algorithms for computationally expensive tasks, such as data mining applications. Obviously, work on parallel algorithms is not new per se but concentrated efforts in the many application domains are still missing. Multi-core systems, but also clusters of workstations and even large-scale distributed computing infrastructures provide new opportunities and pose new challenges for the design of parallel and distributed algorithms. Since data mining and machine learning systems rely on high performance computing systems, research on the corresponding algorithms must be on the forefront of parallel algorithm research in order to keep pushing data mining and machine learning applications to be more powerful and, especially for the former, interactive. To bring together researchers and practitioners working in this exciting field, a workshop on parallel data mining was organized as part of PKDD/ECML 2006 (Berlin, Germany). The six contributions selected for the program describe various aspects of data mining and machine learning approaches featuring low to high degrees of parallelism: The first contribution focuses the classic problem of distributed association rule mining and focuses on communication efficiency to improve the state of the art. After this a parallelization technique for speeding up decision tree construction by means of thread-level parallelism for shared memory systems is presented. The next paper discusses the design of a parallel approach for dis- tributed memory systems of the frequent subgraphs mining problem. This approach is based on a hierarchical communication topology to solve issues related to multi-domain computational envi- ronments. The forth paper describes the combined use and the customization of software packages to facilitate a top down parallelism in the tuning of Support Vector Machines (SVM) and the next contribution presents an interesting idea concerning parallel training of Conditional Random Fields (CRFs) and motivates their use in labeling sequential data. The last contribution finally focuses on very efficient feature selection. It describes a parallel algorithm for feature selection from random subsets. Selecting the papers included in this volume would not have been possible without the help of an international Program Committee that has provided detailed reviews for each paper. We would like to also thank Matthew Otey who helped with publicity for the workshop.

eRules: a modular adaptive classification rule learning algorithm for data streams

Advances in hardware and software in the past decade allow to capture, record and process fast data streams at a large scale. The research area of data stream mining has emerged as a consequence from these advances in order to cope with the real time analysis of potentially large and changing data streams. Examples of data streams include Google searches, credit card transactions, telemetric data and data of continuous chemical production processes. In some cases the data can be processed in batches by traditional data mining approaches. However, in some applications it is required to analyse the data in real time as soon as it is being captured. Such cases are for example if the data stream is infinite, fast changing, or simply too large in size to be stored. One of the most important data mining techniques on data streams is classification. This involves training the classifier on the data stream in real time and adapting it to concept drifts. Most data stream classifiers are based on decision trees. However, it is well known in the data mining community that there is no single optimal algorithm. An algorithm may work well on one or several datasets but badly on others. This paper introduces eRules, a new rule based adaptive classifier for data streams, based on an evolving set of Rules. eRules induces a set of rules that is constantly evaluated and adapted to changes in the data stream by adding new and removing old rules. It is different from the more popular decision tree based classifiers as it tends to leave data instances rather unclassified than forcing a classification that could be wrong. The ongoing development of eRules aims to improve its accuracy further through dynamic parameter setting which will also address the problem of changing feature domain values.

A scalable expressive ensemble learning using Random Prism: a MapReduce approach

The induction of classification rules from previously unseen examples is one of the most important data mining tasks in science as well as commercial applications. In order to reduce the influence of noise in the data, ensemble learners are often applied. However, most ensemble learners are based on decision tree classifiers which are affected by noise. The Random Prism classifier has recently been proposed as an alternative to the popular Random Forests classifier, which is based on decision trees. Random Prism is based on the Prism family of algorithms, which is more robust to noise. However, like most ensemble classification approaches, Random Prism also does not scale well on large training data. This paper presents a thorough discussion of Random Prism and a recently proposed parallel version of it called Parallel Random Prism. Parallel Random Prism is based on the MapReduce programming paradigm. The paper provides, for the first time, novel theoretical analysis of the proposed technique and in-depth experimental study that show that Parallel Random Prism scales well on a large number of training examples, a large number of data features and a large number of processors. Expressiveness of decision rules that our technique produces makes it a natural choice for Big Data applications where informed decision making increases the user’s trust in the system.

An evaluation of Bayesian designs for dose-escalation studies in healthy volunteers

In this paper, Bayesian decision procedures previously proposed for dose-escalation studies in healthy volunteers are reviewed and evaluated. Modifications are made to the expression of the prior distribution in order to make the procedure simpler to implement and a more relevant criterion for optimality is introduced. The results of an extensive simulation exercise to establish the proper-ties of the procedure and to aid choice between designs are summarized, and the way in which readers can use simulation to choose a design for their own trials is described. The influence of the value of the within-subject correlation on the procedure is investigated and the use of a simple prior to reflect uncertainty about the correlation is explored. Copyright (c) 2005 John Wiley & Sons, Ltd.

Decision-theoretic designs for phase II clinical trials allowing for competing studies

This article describes an approach to optimal design of phase II clinical trials using Bayesian decision theory. The method proposed extends that suggested by Stallard (1998, Biometrics54, 279–294) in which designs were obtained to maximize a gain function including the cost of drug development and the benefit from a successful therapy. Here, the approach is extended by the consideration of other potential therapies, the development of which is competing for the same limited resources. The resulting optimal designs are shown to have frequentist properties much more similar to those traditionally used in phase II trials.

Implementation of a Bayesian design in a dose-escalation study of an experimental agent in healthy volunteers

Bayesian decision procedures have recently been developed for dose escalation in phase I clinical trials concerning pharmacokinetic responses observed in healthy volunteers. This article describes how that general methodology was extended and evaluated for implementation in a specific phase I trial of a novel compound. At the time of writing, the study is ongoing, and it will be some time before the sponsor will wish to put the results into the public domain. This article is an account of how the study was designed in a way that should prove to be safe, accurate, and efficient whatever the true nature of the compound. The study involves the observation of two pharmacokinetic endpoints relating to the plasma concentration of the compound itself and of a metabolite as well as a safety endpoint relating to the occurrence of adverse events. Construction of the design and its evaluation via simulation are presented.

A Bayesian approach for dose-escalation in a phase I clinical trial incorporating pharmacodynamic endpoints

Bayesian decision procedures have already been proposed for and implemented in Phase I dose-escalation studies in healthy volunteers. The procedures have been based on pharmacokinetic responses reflecting the concentration of the drug in blood plasma and are conducted to learn about the dose-response relationship while avoiding excessive concentrations. However, in many dose-escalation studies, pharmacodynamic endpoints such as heart rate or blood pressure are observed, and it is these that should be used to control dose-escalation. These endpoints introduce additional complexity into the modeling of the problem relative to pharmacokinetic responses. Firstly, there are responses available following placebo administrations. Secondly, the pharmacodynamic responses are related directly to measurable plasma concentrations, which in turn are related to dose. Motivated by experience of data from a real study conducted in a conventional manner, this paper presents and evaluates a Bayesian procedure devised for the simultaneous monitoring of pharmacodynamic and pharmacokinetic responses. Account is also taken of the incidence of adverse events. Following logarithmic transformations, a linear model is used to relate dose to the pharmacokinetic endpoint and a quadratic model to relate the latter to the pharmacodynamic endpoint. A logistic model is used to relate the pharmacokinetic endpoint to the risk of an adverse event.

Increasing detection rate of user-to-root attacks using genetic algorithms

An extensive set of machine learning and pattern classification techniques trained and tested on KDD dataset failed in detecting most of the user-to-root attacks. This paper aims to provide an approach for mitigating negative aspects of the mentioned dataset, which led to low detection rates. Genetic algorithm is employed to implement rules for detecting various types of attacks. Rules are formed of the features of the dataset identified as the most important ones for each attack type. In this way we introduce high level of generality and thus achieve high detection rates, but also gain high reduction of the system training time. Thenceforth we re-check the decision of the user-to- root rules with the rules that detect other types of attacks. In this way we decrease the false-positive rate. The model was verified on KDD 99, demonstrating higher detection rates than those reported by the state- of-the-art while maintaining low false-positive rate.