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The expected value of the standard power function of a test, computed with respect to a design prior distribution, is often used to evaluate the probability of success of an experiment. However, looking only at the expected value might be reductive. Instead, the whole probability distribution of the power function induced by the design prior can be exploited. In this article we consider one‐sided testing for the scale parameter of exponential families and we derive general unifying expressions for cumulative distribution and density functions of the random power. Sample size determination criteria based on alternative summaries of these functions are discussed. The study sheds light on the relevance of the choice of the design prior in order to construct a successful experiment. [ABSTRACT FROM AUTHOR]

Many sample size criteria exist. These include power calculations and methods based on confidence interval widths from a frequentist viewpoint, and Bayesian methods based on credible interval widths or decision theory. Bayesian methods account for the inherent uncertainty of inputs to sample size calculations through the use of prior information rather than the point estimates typically used by frequentist methods. However, the choice of prior density can be problematic because there will almost always be different appreciations of the past evidence. Such differences can be accommodated a priori by robust methods for Bayesian design, for example, using mixtures or ϵ-contaminated priors. This would then ensure that the prior class includes divergent opinions. However, one may prefer to report several posterior densities arising from a "community of priors," which cover the range of plausible prior densities, rather than forming a single class of priors. To date, however, there are no corresponding sample size methods that specifically account for a community of prior densities in the sense of ensuring a large-enough sample size for the data to sufficiently overwhelm the priors to ensure consensus across widely divergent prior views. In this paper, we develop methods that account for the variability in prior opinions by providing the sample size required to induce posterior agreement to a prespecified degree. Prototypic examples to one- and two-sample binomial outcomes are included. We compare sample sizes from criteria that consider a family of priors to those that would result from previous interval-based Bayesian criteria. [ABSTRACT FROM AUTHOR]

In this paper, we develop a general Bayesian clinical trial design methodology, tailored for time-to-event trials with a cured fraction in scenarios where a previously completed clinical trial is available to inform the design and analysis of the new trial. Our methodology provides a conceptually appealing and computationally feasible framework that allows one to construct a fixed, maximally informative prior a priori while simultaneously identifying the minimum sample size required for the new trial so that the design has high power and reasonable type I error control from a Bayesian perspective. This strategy is particularly well suited for scenarios where adaptive borrowing approaches are not practical due to the nature of the trial, complexity of the model, or the source of the prior information. Control of a Bayesian type I error rate offers a sensible balance between wanting to use high-quality information in the design and analysis of future trials while still controlling type I errors in an equitable way. Moreover, sample size determination based on our Bayesian view of power can lead to a more adequately sized trial by virtue of taking into account all the uncertainty in the treatment effect. We demonstrate our methodology by designing a cancer clinical trial in high-risk melanoma. [ABSTRACT FROM AUTHOR]

In 1992, the US Food and Drug Administration declared that two drugs demonstrate average bioequivalence (ABE) if the log-transformed mean difference of pharmacokinetic responses lies in (-0.223, 0.223). The most widely used approach for assessing ABE is the two one-sided tests procedure. More specifically, ABE is concluded when a 100(1 - 2α) % confidence interval for mean difference falls within (-0.223, 0.223). As known, bioequivalent studies are usually conducted by crossover design. However, in the case that the half-life of a drug is long, a parallel design for the bioequivalent study may be preferred. In this study, a two-sided interval estimation - such as Satterthwaite's, Cochran-Cox's, or Howe's approximations - is used for assessing parallel ABE. We show that the asymptotic joint distribution of the lower and upper confidence limits is bivariate normal, and thus the sample size can be calculated based on the asymptotic power so that the confidence interval falls within (-0.223, 0.223). Simulation studies also show that the proposed method achieves sufficient empirical power. A real example is provided to illustrate the proposed method. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Multiple endpoints are increasingly used in clinical trials. The significance of some of these clinical trials is established if at least r null hypotheses are rejected among m that are simultaneously tested. The usual approach in multiple hypothesis testing is to control the family-wise error rate, which is defined as the probability that at least one type-I error is made. More recently, the q-generalized family-wise error rate has been introduced to control the probability of making at least q false rejections. For procedures controlling this global type-I error rate, we define a type-II r-generalized family-wise error rate, which is directly related to the r-power defined as the probability of rejecting at least r false null hypotheses. We obtain very general power formulas that can be used to compute the sample size for single-step and step-wise procedures. These are implemented in our R package rPowerSampleSize available on the CRAN, making them directly available to end users. Complexities of the formulas are presented to gain insight into computation time issues. Comparison with Monte Carlo strategy is also presented. We compute sample sizes for two clinical trials involving multiple endpoints: one designed to investigate the effectiveness of a drug against acute heart failure and the other for the immunogenicity of a vaccine strategy against pneumococcus. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In clinical studies, multiple comparisons of several treatments to a control with ordered categorical responses are often encountered. A popular statistical approach to analyzing the data is to use the logistic regression model with the proportional odds assumption. As discussed in several recent research papers, if the proportional odds assumption fails to hold, the undesirable consequence of an inflated familywise type I error rate may affect the validity of the clinical findings. To remedy the problem, a more flexible approach that uses the latent normal model with single-step and stepwise testing procedures has been recently proposed. In this paper, we introduce a step-up procedure that uses the correlation structure of test statistics under the latent normal model. A simulation study demonstrates the superiority of the proposed procedure to all existing testing procedures. Based on the proposed step-up procedure, we derive an algorithm that enables the determination of the total sample size and the sample size allocation scheme with a pre-determined level of test power before the onset of a clinical trial. A clinical example is presented to illustrate our proposed method. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]