Stochastic Approximation and Modern Model-Based Designs for Dose-Finding Clinical Trials

In 1951 Robbins and Monro published the seminal article on stochastic approximation and made a specific reference to its application to the "estimation of a quantal using response, nonresponse data." Since the 1990s, statistical methodology for dose-finding studies has grown into an active area of research. The dose-finding problem is at its core a percentile estimation problem and is in line with what the Robbins--Monro method sets out to solve. In this light, it is quite surprising that the dose-finding literature has developed rather independently of the older stochastic approximation literature. The fact that stochastic approximation has seldom been used in actual clinical studies stands in stark contrast with its constant application in engineering and finance. In this article, I explore similarities and differences between the dose-finding and the stochastic approximation literatures. This review also sheds light on the present and future relevance of stochastic approximation to dose-finding clinical trials. Such connections will in turn steer dose-finding methodology on a rigorous course and extend its ability to handle increasingly complex clinical situations.Comment: Published in at http://dx.doi.org/10.1214/10-STS334 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Recursive Parameter Estimation: Convergence

We consider estimation procedures which are recursive in the sense that each successive estimator is obtained from the previous one by a simple adjustment. We propose a wide class of recursive estimation procedures for the general statistical model and study convergence.Comment: 25 pages with 1 postscript figur

Truncated Stochastic Approximation with Moving Bounds: Convergence

In this paper we propose a wide class of truncated stochastic approximation procedures with moving random bounds. While we believe that the proposed class of procedures will find its way to a wider range of applications, the main motivation is to accommodate applications to parametric statistical estimation theory. Our class of stochastic approximation procedures has three main characteristics: truncations with random moving bounds, a matrix valued random step-size sequence, and dynamically changing random regression function. We establish convergence and consider several examples to illustrate the results

Design Issues for Generalized Linear Models: A Review

Generalized linear models (GLMs) have been used quite effectively in the modeling of a mean response under nonstandard conditions, where discrete as well as continuous data distributions can be accommodated. The choice of design for a GLM is a very important task in the development and building of an adequate model. However, one major problem that handicaps the construction of a GLM design is its dependence on the unknown parameters of the fitted model. Several approaches have been proposed in the past 25 years to solve this problem. These approaches, however, have provided only partial solutions that apply in only some special cases, and the problem, in general, remains largely unresolved. The purpose of this article is to focus attention on the aforementioned dependence problem. We provide a survey of various existing techniques dealing with the dependence problem. This survey includes discussions concerning locally optimal designs, sequential designs, Bayesian designs and the quantile dispersion graph approach for comparing designs for GLMs.Comment: Published at http://dx.doi.org/10.1214/088342306000000105 in the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Conditionally conjugate mean-field variational Bayes for logistic models

Variational Bayes (VB) is a common strategy for approximate Bayesian inference, but simple methods are only available for specific classes of models including, in particular, representations having conditionally conjugate constructions within an exponential family. Models with logit components are an apparently notable exception to this class, due to the absence of conjugacy between the logistic likelihood and the Gaussian priors for the coefficients in the linear predictor. To facilitate approximate inference within this widely used class of models, Jaakkola and Jordan (2000) proposed a simple variational approach which relies on a family of tangent quadratic lower bounds of logistic log-likelihoods, thus restoring conjugacy between these approximate bounds and the Gaussian priors. This strategy is still implemented successfully, but less attempts have been made to formally understand the reasons underlying its excellent performance. To cover this key gap, we provide a formal connection between the above bound and a recent P\'olya-gamma data augmentation for logistic regression. Such a result places the computational methods associated with the aforementioned bounds within the framework of variational inference for conditionally conjugate exponential family models, thereby allowing recent advances for this class to be inherited also by the methods relying on Jaakkola and Jordan (2000)