Adapting by calibration the sample size of a phase III trial on the basis of phase II data

The problem of estimating the sample size for a phase III trial on the basis of existing phase II data is considered, where data from phase II cannot be combined with those of the new phase III trial. Focus is on the test for comparing the means of two independent samples. A launching criterion is adopted in order to evaluate the relevance of phase II results: phase III is run if the effect size estimate is higher than a threshold of clinical importance. The variability in sample size estimation is taken into consideration. Then, the frequentist conservative strategies with a fixed amount of conservativeness and Bayesian strategies are compared. A new conservative strategy is introduced and is based on the calibration of the optimal amount of conservativeness – calibrated optimal strategy (COS). To evaluate the results we compute the Overall Power (OP) of the different strategies, as well as the mean and the MSE of sample size estimators. Bayesian strategies have poor characteristics since they show a very high mean and/or MSE of sample size estimators. COS clearly performs better than the other conservative strategies. Indeed, the OP of COS is, on average, the closest to the desired level; it is also the highest. COS sample size is also the closest to the ideal phase III sample size M_I, showing averages and MSEs lower than those of the other strategies. Costs and experimental times are therefore considerably reduced and standardized. However, if the ideal sample size M_I is to be estimated the phase II sample size n should be around the ideal phase III sample size, i.e. n?2M_I/3. Copyright © 2010 John Wiley & Sons, Ltd.     

A control chart based on sample ranges for monitoring the covariance matrix of the multivariate processes

For the univariate case, the R chart and the S ² chart are the most common charts used for monitoring the process dispersion. With the usual sample size of 4 and 5, the R chart is slightly inferior to the S ² chart in terms of efficiency in detecting process shifts. In this article, we show that for the multivariate case, the chart based on the standardized sample ranges, we call the RMAX chart, is substantially inferior in terms of efficiency in detecting shifts in the covariance matrix than the VMAX chart, which is based on the standardized sample variances. The user's familiarity with sample ranges is a point in favor of the RMAX chart. An example is presented to illustrate the application of the proposed chart.     

A Phase I nonparametric Shewhart-type control chart based on the median

A nonparametric Shewhart-type control chart is proposed for monitoring the location of a continuous variable in a Phase I process control setting. The chart is based on the pooled median of the available Phase I samples and the charting statistics are the counts (number of observations) in each sample that are less than the pooled median. An exact expression for the false alarm probability (FAP) is given in terms of the multivariate hypergeometric distribution and this is used to provide tables for the control limits for a specified nominal FAP value (of 0.01, 0.05 and 0.10, respectively) and for some values of the sample size (n) and the number of Phase I samples (m). Some approximations are discussed in terms of the univariate hypergeometric and the normal distributions. A simulation study shows that the proposed chart performs as well as, and in some cases better than, an existing Shewhart-type chart based on the normal distribution. Numerical examples are given to demonstrate the implementation of the new chart.     

Variable selection in partial linear regression with functional covariate

The problem of variable selection is considered in high-dimensional partial linear regression under some model allowing for possibly functional variable. The procedure studied is that of nonconcave-penalized least squares. It is shown the existence of a √n/s_n-consistent estimator for the vector of p_n linear parameters in the model, even when p_n tends to ∞ as the sample size n increases (s_n denotes the number of influential variables). An oracle property is also obtained for the variable selection method, and the nonparametric rate of convergence is stated for the estimator of the nonlinear functional component of the model. Finally, a simulation study illustrates the finite sample size performance of our procedure.     

Distribution of the range when sample size has a GPED<Subscript>1</Subscript>

The probability density function of the range R, in random sampling from a uniform distribution on (k, l) and exponential distribution with parameter λ is obtained, when the sample size is a random variable having the Generalized Polya Eggenberger Distribution of the first kind (GPED ₁). The results of Raghunandanan and Patil (1972) and Bazargan-lari (1999) follow as special cases. The p.d.f of rangeR is obtained, when the distribution of the sample sizeN belongs to Katz family of distributions, as a special case. An erratum to this article is available at .     

Goodness‐of‐fit testing based on a weighted bootstrap: A fast large‐sample alternative to the parametric bootstrap

The process comparing the empirical cumulative distribution function of the sample with a parametric estimate of the cumulative distribution function is known as the empirical process with estimated parameters and has been extensively employed in the literature for goodness‐of‐fit testing. The simplest way to carry out such goodness‐of‐fit tests, especially in a multivariate setting, is to use a parametric bootstrap. Although very easy to implement, the parametric bootstrap can become very computationally expensive as the sample size, the number of parameters, or the dimension of the data increase. An alternative resampling technique based on a fast weighted bootstrap is proposed in this paper, and is studied both theoretically and empirically. The outcome of this work is a generic and computationally efficient multiplier goodness‐of‐fit procedure that can be used as a large‐sample alternative to the parametric bootstrap. In order to approximately determine how large the sample size needs to be for the parametric and weighted bootstraps to have roughly equivalent powers, extensive Monte Carlo experiments are carried out in dimension one, two and three, and for models containing up to nine parameters. The computational gains resulting from the use of the proposed multiplier goodness‐of‐fit procedure are illustrated on trivariate financial data. A by‐product of this work is a fast large‐sample goodness‐of‐fit procedure for the bivariate and trivariate t distribution whose degrees of freedom are fixed. The Canadian Journal of Statistics 40: 480–500; 2012 © 2012 Statistical Society of Canada     

EXACT TWO-SAMPLE MEDIAN TESTS WHEN ONE "SAMPLE" VALUE POSSIBLY FROM A DIFFERENT POPULATION

Random samples are assumed for the univariate two-sample problem. Sometimes this assumption may be violated in that an observation in one “sample”, of size m, is from a population different from that yielding the remaining m—1 observations (which are a random sample). Then, the interest is in whether this random sample of size m—1 is from the same population as the other random sample. If such a violation occurs and can be recognized, and also the non-conforming observation can be identified (without imposing conditional effects), then that observation could be removed and a two-sample test applied to the remaining samples. Unfortunately, satisfactory procedures for such a removal do not seem to exist. An alternative approach is to use two-sample tests whose significance levels remain the same when a non-conforming observation occurs, and is removed, as for the case where the samples were both truly random. The equal-tail median test is shown to have this property when the two “samples” are of the same size (and ties do not occur).     

A new Markov chain approach for the economic statistical design of the VSS T2 control chart

An economic statistical design model for a T² chart which uses a variable sample size (VSS) feature is developed in this article. This study mainly differs from the others conducted in the field. In that a new approach is offered to achieve closed form of some statistical criteria. In other words, the proposed formulas can be considered as a better alternative approach in designing the VSS control charts in terms of simplicity and yet providing the users with better optimal solutions.     

Sample size determination in fixed‐dose combination drug studies

In this paper, the application of the intersection–union test method in fixed‐dose combination drug studies is discussed. An approximate sample size formula for the problem of testing the efficacy of a combination drug using intersection–union tests is proposed. The sample sizes obtained from the formula are found to be reasonably accurate in terms of attaining the target power 1?β for a specified β. Copyright © 2003 John Wiley & Sons, Ltd.     

Uniform robustness against nonnormality of the t and f tests

The size of the two-sample t test is generally thought to be robust against nonnormal distributions if the sample sizes are large. This belief is based on central limit theory, and asymptotic expansions of the moments of the t statistic suggest that robustness may be improved for moderate sample sizes if the variance, skewness, and kurtosis of the distributions are matched, particularly if the sample sizes are also equal.

It is shown that asymptotic arguments such as these can be misleading and that, in fact, the size of the t test can be as large as unity if the distributions are allowed to be completely arbitrary. Restricting the distributions to be identical or symmetric (but otherwise arbitrary) does not guarantee that the size can be controlled either, but controlling the tail-heaviness of the distributions does. The last result is proved more generally for the k-sample F test.     

Sample Size

Conventionally, sample size calculations are viewed as calculations determining the right number of subjects needed for a study. Such calculations follow the classical paradigm: “for a difference X, I need sample size Y.” We argue that the paradigm “for a sample size Y, I get information Z” is more appropriate for many studies and reflects the information needed by scientists when planning a study. This approach applies to both physiological studies and Phase I and II interventional studies. We provide actual examples from our own consulting work to demonstrate this. We conclude that sample size should be viewed not as a unique right number, but rather as a factor needed to assess the utility of a study.     

Blinded sample size re-estimation in clinical trials comparing several treatments

An important question that arises in clinical trials is how many additional observations, if any, are required beyond those originally planned. This has satisfactorily been answered in the case of two-treatment double-blind clinical experiments. However, one may be interested in comparing a new treatment with its competitors, which may be more than one. This problem is addressed in this investigation involving responses from arbitrary distributions, in which the mean and the variance are not functionally related. First, a solution in determining the initial sample size for specified level of significance and power at a specified alternative is obtained. Then it is shown that when the initial sample size is large, the nominal level of significance and the power at the pre-specified alternative are fairly robust for the proposed sample size re-estimation procedure. An application of the results is made to the blood coagulation functionality problem considered by Kropf et al. [Multiple comparisons of treatments with stable multivariate tests in a two-stage adaptive design, including a test for non-inferiority, Biom. J. 42(8) (2000), pp. 951–965].     

The Equivalence of Neyman Optimum Allocation for Sampling and Equal Proportions for Apportioning the U.S. House of Representatives

We present a surprising though obvious result that seems to have been unnoticed until now. In particular, we demonstrate the equivalence of two well-known problems—the optimal allocation of the fixed overall sample size n among L strata under stratified random sampling and the optimal allocation of the H = 435 seats among the 50 states for apportionment of the U.S. House of Representatives following each decennial census. In spite of the strong similarity manifest in the statements of the two problems, they have not been linked and they have well-known but different solutions; one solution is not explicitly exact (Neyman allocation), and the other (equal proportions) is exact. We give explicit exact solutions for both and note that the solutions are equivalent. In fact, we conclude by showing that both problems are special cases of a general problem. The result is significant for stratified random sampling in that it explicitly shows how to minimize sampling error when estimating a total T_Y while keeping the final overall sample size fixed at n; this is usually not the case in practice with Neyman allocation where the resulting final overall sample size might be near n + L after rounding. An example reveals that controlled rounding with Neyman allocation does not always lead to the optimum allocation, that is, an allocation that minimizes variance.     

Sample size determination for estimating multivariate process capability indices based on lower confidence limits

With the advent of modern technology, manufacturing processes have become very sophisticated; a single quality characteristic can no longer reflect a product's quality. In order to establish performance measures for evaluating the capability of a multivariate manufacturing process, several new multivariate capability (NMC) indices, such as NMC _p and NMC _pm , have been developed over the past few years. However, the sample size determination for multivariate process capability indices has not been thoroughly considered in previous studies. Generally, the larger the sample size, the more accurate an estimation will be. However, too large a sample size may result in excessive costs. Hence, the trade-off between sample size and precision in estimation is a critical issue. In this paper, the lower confidence limits of NMC _p and NMC _pm indices are used to determine the appropriate sample size. Moreover, a procedure for conducting the multivariate process capability study is provided. Finally, two numerical examples are given to demonstrate that the proper determination of sample size for multivariate process indices can achieve a good balance between sampling costs and estimation precision.     

ASYMPTOTIC DISTRIBUTION OF THE LARGEST EIGENVALUE

ABSTRACT

This paper studies the asymptotic distribution of the largest eigenvalue of the sample covariance matrix. The multivariate distribution for the population is assumed to be elliptical with finite kurtosis 3κ. An expression as an expectation is obtained for the distribution function of the largest eigenvalue regardless of the multiplicity, m, of the population's largest eigenvalue. The asymptotic distribution function and density function are evaluated numerically for m = 2,3,4,5. The bootstrap of the average of the m largest eigenvalues is shown to be consistent for any underlying distribution with finite fourth-order cumulants.     

Monitoring Variation in a Multivariate Process When the Dimension is Large Relative to the Sample Size

A control procedure is presented for monitoring changes in variation for a multivariate normal process in a Phase II operation where the subgroup size, m, is less than p, the number of variates. The methodology is based on a form of Wilk' statistic, which can be expressed as a function of the ratio of the determinants of two separate estimates of the covariance matrix. One estimate is based on the historical data set from Phase I and the other is based on an augmented data set including new data obtained in Phase II. The proposed statistic is shown to be distributed as the product of independent beta distributions that can be approximated using either a chi-square or F-distribution. An ARL study of the statistic is presented for a range of conditions for the population covariance matrix. Cases are considered where a p-variate process is being monitored using a sample of m observations per subgroup and m < p. Data from an industrial multivariate process is used to illustrate the proposed technique.     

Robust Confidence Intervals for the Bernoulli Parameter

Despite the simplicity of the Bernoulli process, developing good confidence interval procedures for its parameter—the probability of success p—is deceptively difficult. The binary data yield a discrete number of successes from a discrete number of trials, n. This discreteness results in actual coverage probabilities that oscillate with the n for fixed values of p (and with p for fixed n). Moreover, this oscillation necessitates a large sample size to guarantee a good coverage probability when p is close to 0 or 1.

It is well known that the Wilson procedure is superior to many existing procedures because it is less sensitive to p than any other procedures, therefore it is less costly. The procedures proposed in this article work as well as the Wilson procedure when 0.1 ≤p ≤ 0.9, and are even less sensitive (i.e., more robust) than the Wilson procedure when p is close to 0 or 1. Specifically, when the nominal coverage probability is 0.95, the Wilson procedure requires a sample size 1, 021 to guarantee that the coverage probabilities stay above 0.92 for any 0.001 ≤ min {p, 1 ?p} <0.01. By contrast, our procedures guarantee the same coverage probabilities but only need a sample size 177 without increasing either the expected interval width or the standard deviation of the interval width.     

The Estimation and Testing of the Cointegration Order Based on the Frequency Domain

ABSTRACT

This article proposes a method to estimate the degree of cointegration in bivariate series and suggests a test statistic for testing noncointegration based on the determinant of the spectral density matrix for the frequencies close to zero. In the study, series are assumed to be I(d), 0 < d ? 1, with parameter d supposed to be known. In this context, the order of integration of the error series is I(d ? b), b ∈ [0, d]. Besides, the determinant of the spectral density matrix for the dth difference series is a power function of b. The proposed estimator for b is obtained here performing a regression of logged determinant on a set of logged Fourier frequencies. Under the null hypothesis of noncointegration, the expressions for the bias and variance of the estimator were derived and its consistency property was also obtained. The asymptotic normality of the estimator, under Gaussian and non-Gaussian innovations, was also established. A Monte Carlo study was performed and showed that the suggested test possesses correct size and good power for moderate sample sizes, when compared with other proposals in the literature. An advantage of the method proposed here, over the standard methods, is that it allows to know the order of integration of the error series without estimating a regression equation. An application was conducted to exemplify the method in a real context.     

The p-Value Requires Context,Not a Threshold

Abstract

It is widely recognized by statisticians, though not as widely by other researchers, that the p-value cannot be interpreted in isolation, but rather must be considered in the context of certain features of the design and substantive application, such as sample size and meaningful effect size. I consider the setting of the normal mean and highlight the information contained in the p-value in conjunction with the sample size and meaningful effect size. The p-value and sample size jointly yield 95% confidence bounds for the effect of interest, which can be compared to the predetermined meaningful effect size to make inferences about the true effect. I provide simple examples to demonstrate that although the p-value is calculated under the null hypothesis, and thus seemingly may be divorced from the features of the study from which it arises, its interpretation as a measure of evidence requires its contextualization within the study. This implies that any proposal for improved use of the p-value as a measure of the strength of evidence cannot simply be a change to the threshold for significance.     

An Expression for Fast Computation of Sample Central Moments

An expression is provided for the expectation of sample central moments. It is practical and offers computational advantages over the original form due to Kong (The American Statistician, 65, 2011, 198–199).