A pragmatic dose‐finding approach using short‐term surrogate efficacy outcomes to evaluate binary efficacy and toxicity outcomes in phase I cancer clinical trials

There is a growing need for study designs that can evaluate efficacy and toxicity outcomes simultaneously in phase I or phase I/II cancer clinical trials. Many dose‐finding approaches have been proposed; however, most of these approaches assume binary efficacy and toxicity outcomes, such as dose‐limiting toxicity (DLT), and objective responses. DLTs are often defined for short time periods. In contrast, objective responses are often defined for longer periods because of practical limitations on confirmation and the criteria used to define ‘confirmation’. This means that studies have to be carried out for unacceptably long periods of time. Previous studies have not proposed a satisfactory solution to this specific problem. Furthermore, this problem may be a barrier for practitioners who want to implement notable previous dose‐finding approaches. To cope with this problem, we propose an approach using unconfirmed early responses as the surrogate efficacy outcome for the confirmed outcome. Because it is reasonable to expect moderate positive correlation between the two outcomes and the method replaces the surrogate outcome with the confirmed outcome once it becomes available, the proposed approach can reduce irrelevant dose selection and accumulation of bias. Moreover, it is also expected that it can significantly shorten study duration. Using simulation studies, we demonstrate the positive utility of the proposed approach and provide three variations of it, all of which can be easily implemented with modified likelihood functions and outcome variable definitions. Copyright © 2013 John Wiley & Sons, Ltd.     

Testing exponentiality based on Type-I censored data

The problem of goodness-of-fit for the exponential distribution when the available data are subject to Type-I censoring is discussed here. A test procedure is proposed in this case that exhibits more power as compared to existing methods. The power of the proposed test is assessed for several alternative distributions by means of Monte Carlo simulations. Finally, the proposed test is illustrated with a real data set.     

Improved estimation of common location of two exponential populations with order restricted scale parameters using censored samples

ABSTRACT

Estimation of common location parameter of two exponential populations is considered when the scale parameters are ordered using type-II censored samples. A general inadmissibility result is proved which helps in deriving improved estimators. Further, a class of estimators dominating the MLE has been derived by an application of integrated expression of risk difference (IERD) approach of Kubokawa. A discussion regarding extending the results to a general k( ? 2) populations has been done. Finally, all the proposed estimators are compared through simulation.     

Testing the equality of several inverse Gaussian means under heterogeneity

Abstract

We consider the problem of testing the equality of several inverse Gaussian means when the scale parameters and sample sizes are possibly unequal. We propose four parametric bootstrap (PB) tests based on the uniformly minimum variance unbiased estimators of parameters. We also compare our proposed tests with the existing ones via an extensive simulation study in terms of controlling the Type I error rate and power performance. Simulation results show the merits of the PB tests.     

A Note on the Fisher Information in Exponential Distribution

ABSTRACT

It is known that the Fisher information in any set of order statistics can be simplified to a sum of double integrals. In this article, we show that it can be further simplified to a sum of single integrals for the scale parameter of an exponential distribution. Moreover, we use the result and provide a simple method of obtaining the optimal spacing of order statistics.     

Statistical Inference of Type-II Progressively Hybrid Censored Data with Weibull Lifetimes

In this article, we discuss the maximum likelihood estimators and approximate maximum likelihood estimators of the parameters of the Weibull distribution with two different progressively hybrid censoring schemes. We also present the associated expressions of the expected total test time and the expected effective sample size which will be useful for experimental planning purpose. Finally, the efficiency of the point estimation of the parameters based on the two progressive hybrid censoring schemes are compared and the merits of each censoring scheme are discussed.     

Bayesian Inference in Dependent Right Censoring

In this article, we consider dependent right censoring when the lifetime and censoring variables have a Marshall–Olkin bivariate exponential distribution and obtain MLEs, MMEs and UMVUEs of the unknown parameters. The Bayes estimators as well as the Posterior Regret Gamma Minimax (PRGM) estimators of the parameters of interest under the SEL function are also obtained and a Monte Carlo simulation study is carried out to compare these estimators.     

An M-Estimator for Estimating the Extended Burr Type III Parameters with Outliers

In this article, we present an M-estimator to estimate the parameters of the extended three-parameter Burr Type III distribution for complete data with outliers. The confidence intervals for all parameters can be obtained by the M-estimator's normal approximation. The simulation results show that the M-estimator generally outperforms the maximum likelihood and least squares methods in terms of bias and root mean square errors. We also investigate the M-estimator's impact on different quantiles and the mean for the Weibull and normal distributions with outliers. Two numerical examples are used to demonstrate the performance of our proposed method.     

Two-Sample Bayesian Prediction Intervals of Generalized Order Statistics Based on Multiply Type II Censored Data

In this article, two-sample Bayesian prediction intervals of generalized order statistics (GOS) based on multiply Type II censored data are derived. To illustrate these results, the Pareto, Weibull, and Burr-Type XII distributions are used as examples. Finally, a numerical illustration of the sequential order statistics from the Pareto distribution is presented.