Comparison of sample size formulae for 2x2 cross-over designs applied to bioequivalence studies

We consider the comparison of two formulations in terms of average bioequivalence using the 2 × 2 cross-over design. In a bioequivalence study, the primary outcome is a pharmacokinetic measure, such as the area under the plasma concentration by time curve, which is usually assumed to have a lognormal distribution. The criterion typically used for claiming bioequivalence is that the 90% confidence interval for the ratio of the means should lie within the interval (0.80, 1.25), or equivalently the 90% confidence interval for the differences in the means on the natural log scale should be within the interval (-0.2231, 0.2231). We compare the gold standard method for calculation of the sample size based on the non-central t distribution with those based on the central t and normal distributions. In practice, the differences between the various approaches are likely to be small. Further approximations to the power function are sometimes used to simplify the calculations. These approximations should be used with caution, because the sample size required for a desirable level of power might be under- or overestimated compared to the gold standard method. However, in some situations the approximate methods produce very similar sample sizes to the gold standard method. Copyright © 2005 John Wiley & Sons, Ltd.

Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline

The International Citicoline Trial in acUte Stroke is a sequential phase III study of the use of the drug citicoline in the treatment of acute ischaemic stroke, which was initiated in 2006 in 56 treatment centres. The primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow-up. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well-established scales: the Barthel Index, the modified Rankin scale and the National Institutes of Health Stroke Scale. This approach was previously used in the analysis of the influential National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator in stroke. The purpose of this paper is to describe how this trial was designed, and in particular how the simultaneous objectives of taking into account three assessment scales, performing a series of interim analyses and conducting treatment allocation and adjusting the analyses to account for prognostic factors, including more than 50 treatment centres, were addressed. Copyright (C) 2008 John Wiley & Sons, Ltd.

Quantitative pulsed phase thermography applied to steel plates

Pulsed Phase Thermography (PPT) has been proven effective on depth retrieval of flat-bottomed holes in different materials such as plastics and aluminum. In PPT, amplitude and phase delay signatures are available following data acquisition (carried out in a similar way as in classical Pulsed Thermography), by applying a transformation algorithm such as the Fourier Transform (FT) on thermal profiles. The authors have recently presented an extended review on PPT theory, including a new inversion technique for depth retrieval by correlating the depth with the blind frequency fb (frequency at which a defect produce enough phase contrast to be detected). An automatic defect depth retrieval algorithm had also been proposed, evidencing PPT capabilities as a practical inversion technique. In addition, the use of normalized parameters to account for defect size variation as well as depth retrieval from complex shape composites (GFRP and CFRP) are currently under investigation. In this paper, steel plates containing flat-bottomed holes at different depths (from 1 to 4.5 mm) are tested by quantitative PPT. Least squares regression results show excellent agreement between depth and the inverse square root blind frequency, which can be used for depth inversion. Experimental results on steel plates with simulated corrosion are presented as well. It is worth noting that results are improved by performing PPT on reconstructed (synthetic) rather than on raw thermal data.

Using bargaining-game theory for negotiating concession period for BOT-type contract

This paper extends the build-operate-transfer (BOT) concession model (BOTCcM) to a new method for identifying a concession period by using bargaining-game theory. Concession period is one of the most important decision variables in arranging a BOT-type contract, and there are few methodologies available for helping to determine the value of this variable. The BOTCcM presents an alternative method by which a group of concession period solutions are produced. Nevertheless, a typical weakness in using BOTCcM is that the model cannot recommend a specific time span for concessionary. This paper introduces a new method called BOT bargaining concession model (BOTBaC) to enable the identification of a specific concession period, which takes into account the bargaining behavior of the two parties concerned in engaging a BOT contract, namely, the investor and the government concerned. The application of BOTBaC is demonstrated through using an example case.

Semantic-driven context-aware visual information indexing and retrieval: applied in the film post-production domain

A large volume of visual content is inaccessible until effective and efficient indexing and retrieval of such data is achieved. In this paper, we introduce the DREAM system, which is a knowledge-assisted semantic-driven context-aware visual information retrieval system applied in the film post production domain. We mainly focus on the automatic labelling and topic map related aspects of the framework. The use of the context- related collateral knowledge, represented by a novel probabilistic based visual keyword co-occurrence matrix, had been proven effective via the experiments conducted during system evaluation. The automatically generated semantic labels were fed into the Topic Map Engine which can automatically construct ontological networks using Topic Maps technology, which dramatically enhances the indexing and retrieval performance of the system towards an even higher semantic level.

Clustering techniques applied to multiple-models structures

In this work a method for building multiple-model structures is presented. A clustering algorithm that uses data from the system is employed to define the architecture of the multiple-model, including the size of the region covered by each model, and the number of models. A heating ventilation and air conditioning system is used as a testbed of the proposed method.