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A multi‐arm trial allows simultaneous comparison of multiple experimental treatments with a common control and provides a substantial efficiency advantage compared to the traditional randomized controlled trial. Many novel multi‐arm multi‐stage (MAMS) clinical trial designs have been proposed. However, a major hurdle to adopting the group sequential MAMS routinely is the computational effort of obtaining total sample size and sequential stopping boundaries. In this paper, we develop a group sequential MAMS trial design based on the sequential conditional probability ratio test. The proposed method provides analytical solutions for futility and efficacy boundaries to an arbitrary number of stages and arms. Thus, it avoids complicated computational effort for the methods proposed by Magirr et al. Simulation results showed that the proposed method has several advantages compared to the methods implemented in R package MAMS by Magirr et al. [ABSTRACT FROM AUTHOR]

We consider longitudinal discrete data that may be unequally spaced in time and may exhibit overdispersion, so that the variance of the outcome variable is inflated relative to its assumed distribution. We implement an approach that extends generalized linear models for analysis of longitudinal data and is likelihood based, in contrast to generalized estimating equations (GEE) that are semiparametric. The method assumes independence between subjects; first‐order antedependence within subjects; exponential family distributions for the first outcome on each subject and for the subsequent conditional distributions; and linearity of the expectations of the conditional distributions. We demonstrate application of the method in an analysis of seizure counts and in a study to evaluate the performance of transplant centers. Simulations for both studies demonstrate the benefits of the proposed likelihood based approach; however, they also demonstrate better than anticipated performance for GEE. [ABSTRACT FROM AUTHOR]

In oncology clinical trials, overall survival, time to progression, and progression-free survival are three commonly used endpoints. Empirical correlations among them have been published for different cancers, but statistical models describing the dependence structures are limited. Recently, Fleischer et al. proposed a statistical model that is mathematically tractable and shows some flexibility to describe the dependencies in a realistic way, based on the assumption of exponential distributions. This paper aims to extend their model to the more flexible Weibull distribution. We derived theoretical correlations among different survival outcomes, as well as the distribution of overall survival induced by the model. Model parameters were estimated by the maximum likelihood method and the goodness of fit was assessed by plotting estimated versus observed survival curves for overall survival. We applied the method to three cancer clinical trials. In the non-small-cell lung cancer trial, both the exponential and the Weibull models provided an adequate fit to the data, and the estimated correlations were very similar under both models. In the prostate cancer trial and the laryngeal cancer trial, the Weibull model exhibited advantages over the exponential model and yielded larger estimated correlations. Simulations suggested that the proposed Weibull model is robust for data generated from a range of distributions. [ABSTRACT FROM AUTHOR]

We propose a flexible parametric model to describe alternating states recurrent-event data where there is a possibility of cure with each type of event. We begin by introducing a novel cure model in which a common frailty influences both the cure probability and the hazard function given not cured. We then extend our model to data with recurring events of two alternating types. We assume that each type of event has a gamma frailty, and we link the frailties by a Clayton copula. We illustrate the model with an analysis of data from two smoking cessation trials comparing bupropion and placebo, in which each subject potentially experienced a series of lapse and recovery events. Our analysis suggests that bupropion increases the probability of permanent cure and decreases the hazard of lapse, but does not affect the distribution of time to recovery during a lapse. The data suggest a positive but non-significant association between the lapse and recovery frailties. A simulation study suggests that the estimates have little bias and that their 95 per cent confidence intervals have nearly nominal coverage in samples of practical size. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]