Decision-making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts

The aim of a phase H clinical trial is to decide whether or not to develop an experimental therapy further through phase III clinical evaluation. In this paper, we present a Bayesian approach to the phase H trial, although we assume that subsequent phase III clinical trials will hat,e standard frequentist analyses. The decision whether to conduct the phase III trial is based on the posterior predictive probability of a significant result being obtained. This fusion of Bayesian and frequentist techniques accepts the current paradigm for expressing objective evidence of therapeutic value, while optimizing the form of the phase II investigation that leads to it. By using prior information, we can assess whether a phase II study is needed at all, and how much or what sort of evidence is required. The proposed approach is illustrated by the design of a phase II clinical trial of a multi-drug resistance modulator used in combination with standard chemotherapy in the treatment of metastatic breast cancer. Copyright (c) 2005 John Wiley & Sons, Ltd.

Skilloscopy: Bayesian modeling of decision makers' skill

This paper proposes and demonstrates an approach, Skilloscopy, to the assessment of decision makers. In an increasingly sophisticated, connected and information-rich world, decision making is becoming both more important and more difficult. At the same time, modelling decision-making on computers is becoming more feasible and of interest, partly because the information-input to those decisions is increasingly on record. The aims of Skilloscopy are to rate and rank decision makers in a domain relative to each other: the aims do not include an analysis of why a decision is wrong or suboptimal, nor the modelling of the underlying cognitive process of making the decisions. In the proposed method a decision-maker is characterised by a probability distribution of their competence in choosing among quantifiable alternatives. This probability distribution is derived by classic Bayesian inference from a combination of prior belief and the evidence of the decisions. Thus, decision-makers’ skills may be better compared, rated and ranked. The proposed method is applied and evaluated in the gamedomain of Chess. A large set of games by players across a broad range of the World Chess Federation (FIDE) Elo ratings has been used to infer the distribution of players’ rating directly from the moves they play rather than from game outcomes. Demonstration applications address questions frequently asked by the Chess community regarding the stability of the Elo rating scale, the comparison of players of different eras and/or leagues, and controversial incidents possibly involving fraud. The method of Skilloscopy may be applied in any decision domain where the value of the decision-options can be quantified.

Crossbred cow adoption and milk market participation in a multivariate count data framework

Cross-bred cow adoption is an important and potent policy variable precipitating subsistence household entry into emerging milk markets. This paper focuses on the problem of designing policies that encourage and sustain milkmarket expansion among a sample of subsistence households in the Ethiopian highlands. In this context it is desirable to measure households’ ‘proximity’ to market in terms of the level of deficiency of essential inputs. This problem is compounded by four factors. One is the existence of cross-bred cow numbers (count data) as an important, endogenous decision by the household; second is the lack of a multivariate generalization of the Poisson regression model; third is the censored nature of the milk sales data (sales from non-participating households are, essentially, censored at zero); and fourth is an important simultaneity that exists between the decision to adopt a cross-bred cow, the decision about how much milk to produce, the decision about how much milk to consume and the decision to market that milk which is produced but not consumed internally by the household. Routine application of Gibbs sampling and data augmentation overcome these problems in a relatively straightforward manner. We model the count data from two sites close to Addis Ababa in a latent, categorical-variable setting with known bin boundaries. The single-equation model is then extended to a multivariate system that accommodates the covariance between crossbred-cow adoption, milk-output, and milk-sales equations. The latent-variable procedure proves tractable in extension to the multivariate setting and provides important information for policy formation in emerging-market settings

Bayesian estimation of the double hurdle model in the presence of fixed costs

We present a model of market participation in which the presence of non-negligible fixed costs leads to random censoring of the traditional double-hurdle model. Fixed costs arise when household resources must be devoted a priori to the decision to participate in the market. These costs, usually of time, are manifested in non-negligible minimum-efficient supplies and supply correspondence that requires modification of the traditional Tobit regression. The costs also complicate econometric estimation of household behavior. These complications are overcome by application of the Gibbs sampler. The algorithm thus derived provides robust estimates of the fixed-costs, double-hurdle model. The model and procedures are demonstrated in an application to milk market participation in the Ethiopian highlands.

A comprehensive benchmarking system for evaluating global vegetation models.

We present a benchmark system for global vegetation models. This system provides a quantitative evaluation of multiple simulated vegetation properties, including primary production; seasonal net ecosystem production; vegetation cover, composition and 5 height; fire regime; and runoff. The benchmarks are derived from remotely sensed gridded datasets and site-based observations. The datasets allow comparisons of annual average conditions and seasonal and inter-annual variability, and they allow the impact of spatial and temporal biases in means and variability to be assessed separately. Specifically designed metrics quantify model performance for each process, 10 and are compared to scores based on the temporal or spatial mean value of the observations and a “random” model produced by bootstrap resampling of the observations. The benchmark system is applied to three models: a simple light-use efficiency and water-balance model (the Simple Diagnostic Biosphere Model: SDBM), and the Lund-Potsdam-Jena (LPJ) and Land Processes and eXchanges (LPX) dynamic global 15 vegetation models (DGVMs). SDBM reproduces observed CO2 seasonal cycles, but its simulation of independent measurements of net primary production (NPP) is too high. The two DGVMs show little difference for most benchmarks (including the interannual variability in the growth rate and seasonal cycle of atmospheric CO2), but LPX represents burnt fraction demonstrably more accurately. Benchmarking also identified 20 several weaknesses common to both DGVMs. The benchmarking system provides a quantitative approach for evaluating how adequately processes are represented in a model, identifying errors and biases, tracking improvements in performance through model development, and discriminating among models. Adoption of such a system would do much to improve confidence in terrestrial model predictions of climate change 25 impacts and feedbacks.

A comprehensive benchmarking system for evaluating global vegetation models

We present a benchmark system for global vegetation models. This system provides a quantitative evaluation of multiple simulated vegetation properties, including primary production; seasonal net ecosystem production; vegetation cover; composition and height; fire regime; and runoff. The benchmarks are derived from remotely sensed gridded datasets and site-based observations. The datasets allow comparisons of annual average conditions and seasonal and inter-annual variability, and they allow the impact of spatial and temporal biases in means and variability to be assessed separately. Specifically designed metrics quantify model performance for each process, and are compared to scores based on the temporal or spatial mean value of the observations and a "random" model produced by bootstrap resampling of the observations. The benchmark system is applied to three models: a simple light-use efficiency and water-balance model (the Simple Diagnostic Biosphere Model: SDBM), the Lund-Potsdam-Jena (LPJ) and Land Processes and eXchanges (LPX) dynamic global vegetation models (DGVMs). In general, the SDBM performs better than either of the DGVMs. It reproduces independent measurements of net primary production (NPP) but underestimates the amplitude of the observed CO2 seasonal cycle. The two DGVMs show little difference for most benchmarks (including the inter-annual variability in the growth rate and seasonal cycle of atmospheric CO2), but LPX represents burnt fraction demonstrably more accurately. Benchmarking also identified several weaknesses common to both DGVMs. The benchmarking system provides a quantitative approach for evaluating how adequately processes are represented in a model, identifying errors and biases, tracking improvements in performance through model development, and discriminating among models. Adoption of such a system would do much to improve confidence in terrestrial model predictions of climate change impacts and feedbacks.

Regression Models with Heteroscedasticity using Bayesian Approach

In this paper, we compare the performance of two statistical approaches for the analysis of data obtained from the social research area. In the first approach, we use normal models with joint regression modelling for the mean and for the variance heterogeneity. In the second approach, we use hierarchical models. In the first case, individual and social variables are included in the regression modelling for the mean and for the variance, as explanatory variables, while in the second case, the variance at level 1 of the hierarchical model depends on the individuals (age of the individuals), and in the level 2 of the hierarchical model, the variance is assumed to change according to socioeconomic stratum. Applying these methodologies, we analyze a Colombian tallness data set to find differences that can be explained by socioeconomic conditions. We also present some theoretical and empirical results concerning the two models. From this comparative study, we conclude that it is better to jointly modelling the mean and variance heterogeneity in all cases. We also observe that the convergence of the Gibbs sampling chain used in the Markov Chain Monte Carlo method for the jointly modeling the mean and variance heterogeneity is quickly achieved.

On estimation and influence diagnostics for log-Birnbaum-Saunders Student-t regression models: Full Bayesian analysis

The purpose of this paper is to develop a Bayesian approach for log-Birnbaum-Saunders Student-t regression models under right-censored survival data. Markov chain Monte Carlo (MCMC) methods are used to develop a Bayesian procedure for the considered model. In order to attenuate the influence of the outlying observations on the parameter estimates, we present in this paper Birnbaum-Saunders models in which a Student-t distribution is assumed to explain the cumulative damage. Also, some discussions on the model selection to compare the fitted models are given and case deletion influence diagnostics are developed for the joint posterior distribution based on the Kullback-Leibler divergence. The developed procedures are illustrated with a real data set. (C) 2010 Elsevier B.V. All rights reserved.

Bayesian Analysis for Nonlinear Regression Model Under Skewed Errors, with Application in Growth Curves

We have considered a Bayesian approach for the nonlinear regression model by replacing the normal distribution on the error term by some skewed distributions, which account for both skewness and heavy tails or skewness alone. The type of data considered in this paper concerns repeated measurements taken in time on a set of individuals. Such multiple observations on the same individual generally produce serially correlated outcomes. Thus, additionally, our model does allow for a correlation between observations made from the same individual. We have illustrated the procedure using a data set to study the growth curves of a clinic measurement of a group of pregnant women from an obstetrics clinic in Santiago, Chile. Parameter estimation and prediction were carried out using appropriate posterior simulation schemes based in Markov Chain Monte Carlo methods. Besides the deviance information criterion (DIC) and the conditional predictive ordinate (CPO), we suggest the use of proper scoring rules based on the posterior predictive distribution for comparing models. For our data set, all these criteria chose the skew-t model as the best model for the errors. These DIC and CPO criteria are also validated, for the model proposed here, through a simulation study. As a conclusion of this study, the DIC criterion is not trustful for this kind of complex model.