A COMPARISON OF THE IMPRECISE BETA CLASS, THE RANDOMIZED PLAY-THE-WINNER RULE AND THE TRIANGULAR TEST FOR CLINICAL TRIALS WITH BINARY RESPONSES

This paper develops clinical trial designs that compare two treatments with a binary outcome. The imprecise beta class (IBC), a class of beta probability distributions, is used in a robust Bayesian framework to calculate posterior upper and lower expectations for treatment success rates using accumulating data. The posterior expectation for the difference in success rates can be used to decide when there is sufficient evidence for randomized treatment allocation to cease. This design is formally related to the randomized play‐the‐winner (RPW) design, an adaptive allocation scheme where randomization probabilities are updated sequentially to favour the treatment with the higher observed success rate. A connection is also made between the IBC and the sequential clinical trial design based on the triangular test. Theoretical and simulation results are presented to show that the expected sample sizes on the truly inferior arm are lower using the IBC compared with either the triangular test or the RPW design, and that the IBC performs well against established criteria involving error rates and the expected number of treatment failures.     

Confidence Intervals for Difference Between Two Poisson Rates

In this article, we develop four explicit asymptotic two-sided confidence intervals for the difference between two Poisson rates via a hybrid method. The basic idea of the proposed method is to estimate or recover the variances of the two Poisson rate estimates, which are required for constructing the confidence interval for the rate difference, from the confidence limits for the two individual Poisson rates. The basic building blocks of the approach are reliable confidence limits for the two individual Poisson rates. Four confidence interval estimators that have explicit solutions and good coverage levels are employed: the first normal with continuity correction, Rao score, Freeman and Tukey, and Jeffreys confidence intervals. Using simulation studies, we examine the performance of the four hybrid confidence intervals and compare them with three existing confidence intervals: the non-informative prior Bayes confidence interval, the t confidence interval based on Satterthwait's degrees of freedom, and the Bayes confidence interval based on Student's t confidence coefficient. Simulation results show that the proposed hybrid Freeman and Tukey, and the hybrid Jeffreys confidence intervals can be highly recommended because they outperform the others in terms of coverage probabilities and widths. The other methods tend to be too conservative and produce wider confidence intervals. The application of these confidence intervals are illustrated with three real data sets.     

Coverage properties of beta estimated prediction intervals for multimodal recovery rates

In this paper we use bootstrap methodology to achieve accurate estimated prediction intervals for recovery rates. In the framework of the LossCalc model, which is the Moody's KMV model to predict loss given default, a single beta distribution is usually assumed to model the behaviour of recovery rates and, hence, to construct prediction intervals. We evaluate the coverage properties of beta estimated prediction intervals for multimodal recovery rates. We carry out a simulation study, and our results show that bootstrap versions of beta mixture prediction intervals exhibit the best coverage properties.     

Multiple comparisons of matched proportions

It is well known (see, e.g., Scheffé (1959)) that if confidence intervals are desired for several treatment comparisons of interest, especially after a preliminary test of significance, then the appropriate technique is to consider simultaneous confidence intervals with a certain joint confidence coefficient. Goodman (1964) derived such simultaneous confidence intervals for contrasts among several multinomial populations, each with the same number, say J, of classes. The special case involving simultaneous confidence intervals for contrasts among several binomial populations on the basis of independent samples follows simply by taking J=2. This paper now deals with the problem of construction of simultaneous confidence intervals among probabilities of ‘success’ on the basis of matched samples.     

Data-based interval estimation of classification error rates

Leave-one-out and 632 bootstrap are popular data-based methods of estimating the true error rate of a classification rule, but practical applications almost exclusively quote only point estimates. Interval estimation would provide better assessment of the future performance of the rule, but little has been published on this topic. We first review general-purpose jackknife and bootstrap methodology that can be used in conjunction with leave-one-out estimates to provide prediction intervals for true error rates of classification rules. Monte Carlo simulation is then used to investigate coverage rates of the resulting intervals for normal data, but the results are disappointing; standard intervals show considerable overinclusion, intervals based on Edgeworth approximations or random weighting do not perform well, and while a bootstrap approach provides intervals with coverage rates closer to the nominal ones there is still marked underinclusion. We then turn to intervals constructed from 632 bootstrap estimates, and show that much better results are obtained. Although there is now some overinclusion, particularly for large training samples, the actual coverage rates are sufficiently close to the nominal rates for the method to be recommended. An application to real data illustrates the considerable variability that can arise in practical estimation of error rates.     

Bayesian Variable Selection in Markov Mixture Models

Monte Carlo simulation is used to evaluate the actual confidence levels of five different approximations for confidence intervals for the probability of success in Markov dependent trials. The approximations involve the conditional probability of success as a nuisance parameter, and the effects of substituting Klotz's (1973), Price's (1976), and a new estimator are also evaluated. The new estimator is less biased and tends to increase the confidence level. A program for calculating the estimator and the confidence interval approximations is available.     

Estimating the grid of time-points for the piecewise exponential model

One of the greatest challenges related to the use of piecewise exponential models (PEMs) is to find an adequate grid of time-points needed in its construction. In general, the number of intervals in such a grid and the position of their endpoints are ad-hoc choices. We extend previous works by introducing a full Bayesian approach for the piecewise exponential model in which the grid of time-points (and, consequently, the endpoints and the number of intervals) is random. We estimate the failure rates using the proposed procedure and compare the results with the non-parametric piecewise exponential estimates. Estimates for the survival function using the most probable partition are compared with the Kaplan-Meier estimators (KMEs). A sensitivity analysis for the proposed model is provided considering different prior specifications for the failure rates and for the grid. We also evaluate the effect of different percentage of censoring observations in the estimates. An application to a real data set is also provided. We notice that the posteriors are strongly influenced by prior specifications, mainly for the failure rates parameters. Thus, the priors must be fairly built, say, really disclosing the expert prior opinion.     

Interval estimation for misclassification rate parameters in a complementary Poisson model

We investigate three interval estimators for binomial misclassification rates in a complementary Poisson model where the data are possibly misclassified: a Wald-based interval, a score-based interval, and an interval based on the profile log-likelihood statistic. We investigate the coverage and average width properties of these intervals via a simulation study. For small Poisson counts and small misclassification rates, the intervals can perform poorly in terms of coverage. The profile log-likelihood confidence interval (CI) is often proved to outperform the other intervals with good coverage and width properties. Lastly, we apply the CIs to a real data set involving traffic accident data that contain misclassified counts.     

Shortest prediction intervals for the birnbaum-saunders distribution

Shortest prediction intervals for a future observation from the Birnbaum-Saunders distribution are obtained from both frequentist and Bayesian perspectives. Comparisons are made with alternative intervals obtained via inversion. Monte Carlo simulations are performed to assess the approximate intervals.     

COMPARISONS AND SELECTION OF TWO-PARAMETER EXPONENTIAL POPULATIONS

For two-parameter exponential populations with the same scale parameter (known or unknown) comparisons are made between the location parameters. This is done by constructing confidence intervals, which can then be used for selection procedures. Comparisons are made with a control, and with the (unknown) “best” or “worst” population. Emphasis is laid on finding approximations to the confidence so that calculations are simple and tables are not necessary. (Since we consider unequal sample sizes, tables for exact values would need to be extensive.)     

A comparison between bootstrap methods and generalized estimating equations for correlated outcomes in generalized linear models

We discuss and evaluate bootstrap algorithms for obtaining confidence intervals for parameters in Generalized Linear Models when the data are correlated. The methods are based on a stratified bootstrap and are suited to correlation occurring within “blocks” of data (e.g., individuals within a family, teeth within a mouth, etc.). Application of the intervals to data from a Dutch follow-up study on preterm infants shows the corroborative usefulness of the intervals, while the intervals are seen to be a powerful diagnostic in studying annual measles data. In a simulation study, we compare the coverage rates of the proposed intervals with existing methods (e.g., via Generalized Estimating Equations). In most cases, the bootstrap intervals are seen to perform better than current methods, and are produced in an automatic fashion, so that the user need not know (or have to guess) the dependence structure within a block.     

A score test for monotonic trend in hazard rates for grouped survival data in stratified populations

Models for monotone trends in hazard rates for grouped survival data in stratified populations are introduced, and simple closed form score statistics for testing the significance of these trends are presented. The test statistics for some of the models understudy are shown to be independent of the assumed form of the function which relates the hazard rates to the sets of monotone scores assigned to the time intervals. The procedure is applied to test monotone trends in the recovery rates of erythematous response among skin cancer patients and controls that have been irradiated with a ultraviolent challenge.     

Wilson Confidence Intervals for the Two-Sample Log-Odds-Ratio in Stratified 2 × 2 Contingency Tables

Large-sample Wilson-type confidence intervals (CIs) are derived for a parameter of interest in many clinical trials situations: the log-odds-ratio, in a two-sample experiment comparing binomial success proportions, say between cases and controls. The methods cover several scenarios: (i) results embedded in a single 2 × 2 contingency table; (ii) a series of K 2 × 2 tables with common parameter; or (iii) K tables, where the parameter may change across tables under the influence of a covariate. The calculations of the Wilson CI require only simple numerical assistance, and for example are easily carried out using Excel. The main competitor, the exact CI, has two disadvantages: It requires burdensome search algorithms for the multi-table case and results in strong over-coverage associated with long confidence intervals. All the application cases are illustrated through a well-known example. A simulation study then investigates how the Wilson CI performs among several competing methods. The Wilson interval is shortest, except for very large odds ratios, while maintaining coverage similar to Wald-type intervals. An alternative to the Wald CI is the Agresti-Coull CI, calculated from the Wilson and Wald CIs, which has same length as the Wald CI but improved coverage.     

Some comments on a class of simultaneous inference procedures in ancova

Methods for constructing simultaneous confidence intervals for contrasts of treatment effects in analysis of covariance (ANCOVA) models are discussed and compared. A simple procedure is given by which, under a normality assumption made on the covariates, any method appropriate in an analysis of variance (ANOVA) may be applied to a corresponding ANCOVA by means of a simple adjustment of the required critical values. Some properties of this procedure are noted.     

Modified mantel-haenszel procedures for matched pairs

In the prospective study of a finely stratified population, one individual from each stratum is chosen at random for the “treatment” group and one for the “non-treatment” group. For each individual the probability of failure is a logistic function of parameters designating the stratum, the treatment and a covariate. Uniformly most powerful unbiased tests for the treatment effect are given. These tests are generally cumbersome but, if the covariate is dichotomous, the tests and confidence intervals are simple. Readily usable (but non-optimal) tests are also proposed for poly-tomous covariates and factorial designs. These are then adapted to retrospective studies (in which one “success” and one “failure” per stratum are sampled). Tests for retrospective studies with a continuous “treatment” score are also proposed.     

A class of confidence intervals for sequential phase II clinical trials with binary outcome

The phase II clinical trials often use the binary outcome. Thus, accessing the success rate of the treatment is a primary objective for the phase II clinical trials. Reporting confidence intervals is a common practice for clinical trials. Due to the group sequence design and relatively small sample size, many existing confidence intervals for phase II trials are much conservative. In this paper, we propose a class of confidence intervals for binary outcomes. We also provide a general theory to assess the coverage of confidence intervals for discrete distributions, and hence make recommendations for choosing the parameter in calculating the confidence interval. The proposed method is applied to Simon's [14] optimal two-stage design with numerical studies. The proposed method can be viewed as an alternative approach for the confidence interval for discrete distributions in general.     

A Comparison of Statistical Methods for Age-related Reference Intervals

Age-specific reference intervals are commonly used in the routine monitoring of individuals, where interest lies in the detection of extreme values, possibly indicating abnormality. Here, a review is given of the wide range of statistical techniques which have been proposed for the construction of these intervals and issues such as the estimation of confidence bands and goodness of fit are discussed. Three methods, thought to be the most widely applied approaches, are considered in more detail. Comparisons are made on the basis of reference interval estimation for three real data sets.     

Uncertain population forecasting

"Errors in population forecasts arise from errors in the jump-off population and errors in the predictions of future vital rates. The propagation of these errors through the linear (Leslie) growth model is studied, and prediction intervals for future population are developed. For U.S. national forecasts, the prediction intervals are compared with the U.S. Census Bureau's high-low intervals." In order to assess the accuracy of the predictions of vital rates, the authors "derive the predictions from a parametric statistical model and estimate the extent of model misspecification and errors in parameter estimates. Subjective, expert opinion, so important in real forecasting, is incorporated with the technique of mixed estimation. A robust regression model is used to assess the effects of model misspecification."     

Inference for functions of parameters in discrete distributions based on fiducial approach: Binomial and Poisson cases

In this article, we propose a simple method of constructing confidence intervals for a function of binomial success probabilities and for a function of Poisson means. The method involves finding an approximate fiducial quantity (FQ) for the parameters of interest. A FQ for a function of several parameters can be obtained by substitution. For the binomial case, the fiducial approach is illustrated for constructing confidence intervals for the relative risk and the ratio of odds. Fiducial inferential procedures are also provided for estimating functions of several Poisson parameters. In particular, fiducial inferential approach is illustrated for interval estimating the ratio of two Poisson means and for a weighted sum of several Poisson means. Simple approximations to the distributions of the FQs are also given for some problems. The merits of the procedures are evaluated by comparing them with those of existing asymptotic methods with respect to coverage probabilities, and in some cases, expected widths. Comparison studies indicate that the fiducial confidence intervals are very satisfactory, and they are comparable or better than some available asymptotic methods. The fiducial method is easy to use and is applicable to find confidence intervals for many commonly used summary indices. Some examples are used to illustrate and compare the results of fiducial approach with those of other available asymptotic methods.     

Convergence rates for uniform confidence intervals based on local polynomial regression estimators

We investigate the convergence rates of uniform bias-corrected confidence intervals for a smooth curve using local polynomial regression for both the interior and boundary region. We discuss the cases when the degree of the polynomial is odd and even. The uniform confidence intervals are based on the volume-of-tube formula modified for biased estimators. We empirically show that the proposed uniform confidence intervals attain, at least approximately, nominal coverage. Finally, we investigate the performance of the volume-of-tube based confidence intervals for independent non-Gaussian errors.