Three-stage designs for monitoring clinical trials

Optimal three-stage designs with equal sample sizes at each stage are presented and compared to fixed sample designs, fully sequential designs, designs restricted to use the fixed sample critical value at the final stage, and to modifications of other group sequential designs previously proposed in the literature. Typically, the greatest savings realized with interim analyses are obtained by the first interim look. More than 50% of the savings possible with a fully sequential design can be realized with a simple two-stage design. Three-stage designs can realize as much as 75% of the possible savings. Without much loss in efficiency, the designs can be modified so that the critical value at the final stage equals the usual fixed sample value while maintaining the overall level of significance, alleviating some potential confusion should a final stage be necessary. Some common group sequential designs, modified to allow early acceptance of the null hypothesis, are shown to be nearly optimal in some settings while performing poorly in others. An example is given to illustrate the use of several three-stage plans in the design of clinical trials.     

An adaptive sampling scheme guided by BART—with an application to predict processor performance

The evaluation of new processor designs is an important issue in electrical and computer engineering. Architects use simulations to evaluate designs and to understand trade‐offs and interactions among design parameters. However, due to the lengthy simulation time and limited resources, it is often practically impossible to simulate a full factorial design space. Effective sampling methods and predictive models are required. In this paper, the authors propose an automated performance predictive approach which employs an adaptive sampling scheme that interactively works with the predictive model to select samples for simulation. These samples are then used to build Bayesian additive regression trees, which in turn are used to predict the whole design space. Both real data analysis and simulation studies show that the method is effective in that, though sampling at very few design points, it generates highly accurate predictions on the unsampled points. Furthermore, the proposed model provides quantitative interpretation tools with which investigators can efficiently tune design parameters in order to improve processor performance. The Canadian Journal of Statistics 38: 136–152; 2010 © 2010 Statistical Society of Canada     

Multivariate forests with missing mixed outcomes

In this article, we propose a multivariate random forest method for multiple responses of mixed types with missing responses. Imputation is performed for each bootstrap sample used to build the individual trees that form the forest. The individual trees are built using a weighted splitting rule allowing downweighting of imputed observations. A simulation study shows the benefits of this approach over complete case analysis when missing responses are missing completely at random and missing at random (MAR). In particular, the gain in prediction accuracy of the proposed method is larger in the MAR case and also increases as the proportion of missing increases.     

Sequential confidence intervals for the number of cells in a multinomial population

A two-sided sequential confidence interval is suggested for the number of equally probable cells in a given multinomial population with prescribed width and confidence coefficient. We establish large-sample properties of the fixed-width confidence interval procedure using a normal approximation, and some comparisons are made. In addition, a simulation study is carried out in order to investigate the finite sample behaviour of the suggested sequential interval estimation procedure.     

Comparing the relative efficiency of three sequential procedures

We consider the sequential procedures developed by Robbins and Siegmund (1974), Louis (1975) and Zoubeidi (1992) for comparing the means of two treatments. We let the procedures have equal power functions and compare their Bayes and minimax risks using the invariance property of their power functions. For each of several formulations of the problem we determine the most relatively efficient procedure and compute its expected total sample size.     

On Calculations Involving the Maximum Cell Frequency

We describe a method of computing the cumulative distribution function of the maximum and minimum cell frequencies in sampling distributions commonly encountered in the analysis of categorical data.The procedure is efficient for exact or approximate calculation in both homogeneous and non-homogeneous cases, is non-recursive, and does not require Dirichlet integrals.Some related statistical problems are also discussed.     

A latent variable model for analyzing mixed longitudinal (k,l)-inflated count and ordinal responses

A random effects model for analyzing mixed longitudinal count and ordinal data is presented where the count response is inflated in two points (k and l) and an (k,l)-Inflated Power series distribution is used as its distribution. A full likelihood-based approach is used to obtain maximum likelihood estimates of parameters of the model. For data with non-ignorable missing values models with probit model for missing mechanism are used.The dependence between longitudinal sequences of responses and inflation parameters are investigated using a random effects approach. Also, to investigate the correlation between mixed ordinal and count responses of each individuals at each time, a shared random effect is used. In order to assess the performance of the model, a simulation study is performed for a case that the count response has (k,l)-Inflated Binomial distribution. Performance comparisons of count-ordinal random effect model, Zero-Inflated ordinal random effects model and (k,l)-Inflated ordinal random effects model are also given. The model is applied to a real social data set from the first two waves of the national longitudinal study of adolescent to adult health (Add Health study). In this data set, the joint responses are the number of days in a month that each individual smoked as the count response and the general health condition of each individual as the ordinal response. For the count response there is incidence of excess values of 0 and 30.     

Sequential Hypothesis Tests for Identifying the Minimum Dose with a Threshold Effect

We propose a procedure to identify a lowest dose having greater effect than a threshold dose under the assumption of monotonicity of dose mean response in dose response test. So, we use statistics based on contrasts among sample means and apply a group sequential procedure to our procedure to identify effectively the dose. If we can identify the dose at an early step in the sequential test, since we can terminate the procedure with a few observations, the procedure is useful from an economical point of view. In a simulation studies, we compare the superiority among these procedures based on three contrasts.     

THE CONVERGENCE RATE OF SEQUENTIAL FIXED-WIDTH CONFIDENCE INTERVALS FOR REGULAR FUNCTIONALS

Let X₁X₂,.be i.i.d. random variables and let U_n= (n r)^-1S?^(n,r) h (X_i1,., X_ir,) be a U-statistic with EU_n= v, v unknown. Assume that g(X₁) =E[h(X₁,.,X_r) - v |X₁]has a strictly positive variance s?². Further, let a be such that φ(a) - φ(-a) =α for fixed α, 0 < α < 1, where φ is the standard normal d.f., and let S²_n be the Jackknife estimator of n Var U_n. Consider the stopping times N(d)= min {n: S²_n: + n^-1≤²a^-2},d > 0, and a confidence interval for v of length 2d,of the form I_n,d= [U_n,-d, Un + d]. We assume that Var U_n is unknown, and hence, no fixed sample size method is available for finding a confidence interval for v of prescribed width 2d and prescribed coverage probability α Turning to a sequential procedure, let I_N(d),d be a sequence of sequential confidence intervals for v. The asymptotic consistency of this procedure, i.e. lim_{d → 0}P(v ∈ I_N(d),d)=α follows from Sproule (1969). In this paper, the rate at which |P(v ∈ I_N(d),d) converges to α is investigated. We obtain that |P(v ∈ I_N(d),d) - α| = 0 (d^{1/2-(1+k)/2(1+m)}), d → 0, where K = max {0,4 - m}, under the condition that E|h(X₁, X_r)|^m < ∞m > 2. This improves and extends recent results of Ghosh & DasGupta (1980) and Mukhopadhyay (1981).     

Parameter estimation for switched counting processes

The paper investigates parameter estimation problems in special Markov modulated counting processes. The events occuring at any state of an underlying Markov chain can be equipped with marks performing additional information on the events. Specifying the model to the case of two-state Markov chain modulation, the so-called switched counting process, some statistical problems are studied:maximum likelihood estimators, Rao-Blackwell optimal estimators, test of equality of the counting intensities of the two states and minimax estimation procedures. Tne consideration could be applied in various practical problems, in particular, in queueing and in reliability models, for example in failure-repair processes with alternatively operating repair systems.