Sample size determination for testing equality in frequency data under an incomplete block crossover design

When there are more than two treatments under comparison, we may consider the use of the incomplete block crossover design (IBCD) to save the number of patients needed for a parallel groups design and reduce the duration of a crossover trial. We develop an asymptotic procedure for simultaneously testing equality of two treatments versus a control treatment (or placebo) in frequency data under the IBCD with two periods. We derive a sample size calculation procedure for the desired power of detecting the given treatment effects at a nominal-level and suggest a simple ad hoc adjustment procedure to improve the accuracy of the sample size determination when the resulting minimum required number of patients is not large. We employ Monte Carlo simulation to evaluate the finite-sample performance of the proposed test, the accuracy of the sample size calculation procedure, and that with the simple ad hoc adjustment suggested here. We use the data taken as a part of a crossover trial comparing the number of exacerbations between using salbutamol or salmeterol and a placebo in asthma patients to illustrate the sample size calculation procedure.     

Exact sample-size determination in testing non-inferiority under a simple crossover trial

For testing the non-inferiority (or equivalence) of an experimental treatment to a standard treatment, the odds ratio (OR) of patient response rates has been recommended to measure the relative treatment efficacy. On the basis of an exact test procedure proposed elsewhere for a simple crossover design, we develop an exact sample-size calculation procedure with respect to the OR of patient response rates for a desired power of detecting non-inferiority at a given nominal type I error. We note that the sample size calculated for a desired power based on an asymptotic test procedure can be much smaller than that based on the exact test procedure under a given situation. We further discuss the advantage and disadvantage of sample-size calculation using the exact test and the asymptotic test procedures. We employ an example by studying two inhalation devices for asthmatics to illustrate the use of sample-size calculation procedure developed here.     

Sample size calculation for testing non-inferiority and equivalence under Poisson distribution

When counting the number of chemical parts in air pollution studies or when comparing the occurrence of congenital malformations between a uranium mining town and a control population, we often assume Poisson distribution for the number of these rare events. Some discussions on sample size calculation under Poisson model appear elsewhere, but all these focus on the case of testing equality rather than testing equivalence. We discuss sample size and power calculation on the basis of exact distribution under Poisson models for testing non-inferiority and equivalence with respect to the mean incidence rate ratio. On the basis of large sample theory, we further develop an approximate sample size calculation formula using the normal approximation of a proposed test statistic for testing non-inferiority and an approximate power calculation formula for testing equivalence. We find that using these approximation formulae tends to produce an underestimate of the minimum required sample size calculated from using the exact test procedure. On the other hand, we find that the power corresponding to the approximate sample sizes can be actually accurate (with respect to Type I error and power) when we apply the asymptotic test procedure based on the normal distribution. We tabulate in a variety of situations the minimum mean incidence needed in the standard (or the control) population, that can easily be employed to calculate the minimum required sample size from each comparison group for testing non-inferiority and equivalence between two Poisson populations.     

Exact sample size determination in a weibull test plan when there is time censoring

Engineers who conduct reliability tests need to choose the sample size when designing a test plan. The model parameters and quantiles are the typical quantities of interest. The large-sample procedure relies on the property that the distribution of the t -like quantities is close to the standard normal in large samples. In this paper, we use a new procedure based on both simulation and asymptotic theory to determine the sample size for a test plan. Unlike the complete data case, the t -like quantities are not pivotal quantities in general when data are time censored. However we show that the distribution of the t -like quantities only depend on the expected proportion failing and obtain the distributions by simulation for both complete and time censoring case when data follow Weibull distribution. We find that the large-sample procedure usually underestimates the sample size even when it is said to be 200 or more. The sample size given by the proposed procedure insures the requested nominal accuracy and confidence of the estimation when the test plan results in complete or time censored data. Some useful figures displaying the required sample size for the new procedure are also presented.     

Sample size calculation based on risk ratio under multiple matching

To increase the efficiency of comparisons between treatments in clinical trials, we may consider the use of a multiple matching design, in which, for each patient receiving the experimental treatment, we match with more than one patient receiving the standard treatment. To assess the efficacy of the experimental treatment, the risk ratio (RR) of patient responses between two treatments is certainly one of the most commonly used measures. Because the probability of patient responses in clinical trial is often not small, the odds ratio (OR), of which the practical interpretation is not easily understood, cannot approximate RR well. Thus, all sample size formulae in terms of OR for case-control studies with multiple matched controls per case can be of limited use here. In this paper, we develop three sample size formulae based on RR for randomized trials with multiple matching. We propose a test statistic for testing the equality of RR under multiple matching. On the basis of Monte Carlo simulation, we evaluate the performance of the proposed test statistic with respect to Type I error. To evaluate the accuracy and usefulness of the three sample size formulae developed in this paper, we further calculate their simulated powers and compare them with those of the sample size formula ignoring matching and the sample size formula based on OR for multiple matching published elsewhere. Finally, we include an example that employs the multiple matching study design about the use of the supplemental ascorbate in the supportive treatment of terminal cancer patients to illustrate the use of these formulae.     

Sample Size Calculation and Blinded Sample Size Recalculation in Clinical Trials Where the Treatment Effect is Measured by the Relative Risk

In clinical trials with binary endpoints, the required sample size does not depend only on the specified type I error rate, the desired power and the treatment effect but also on the overall event rate which, however, is usually uncertain. The internal pilot study design has been proposed to overcome this difficulty. Here, nuisance parameters required for sample size calculation are re-estimated during the ongoing trial and the sample size is recalculated accordingly. We performed extensive simulation studies to investigate the characteristics of the internal pilot study design for two-group superiority trials where the treatment effect is captured by the relative risk. As the performance of the sample size recalculation procedure crucially depends on the accuracy of the applied sample size formula, we firstly explored the precision of three approximate sample size formulae proposed in the literature for this situation. It turned out that the unequal variance asymptotic normal formula outperforms the other two, especially in case of unbalanced sample size allocation. Using this formula for sample size recalculation in the internal pilot study design assures that the desired power is achieved even if the overall rate is mis-specified in the planning phase. The maximum inflation of the type I error rate observed for the internal pilot study design is small and lies below the maximum excess that occurred for the fixed sample size design.     

Nonlinear Lp-norm estimation: Part II: The asymptotic distribution gf the exponent,p, as a function of the sample kurtosis.

In this paper it will be shown that the exponent p in L_p,-norm P estimation as an explicit function of the sample kurtosis is asymptotically normally distributed. The asymptotic variances of p for two sllch formulae are derived. An alternative formula which implicitly relates p to the sample kurtosis is also discussed.

An adaptive procedure for the selection of p when the underlying error distribution is unknown is also suggested. This procedure is used to verify empirically that the asymptotic distribution of p is normal.     

Exact calculation of power and sample size in bioequivalence studies using two one‐sided tests

The number of subjects in a pharmacokinetic two‐period two‐treatment crossover bioequivalence study is typically small, most often less than 60. The most common approach to testing for bioequivalence is the two one‐sided tests procedure. No explicit mathematical formula for the power function in the context of the two one‐sided tests procedure exists in the statistical literature, although the exact power based on Owen's special case of bivariate noncentral t‐distribution has been tabulated and graphed. Several approximations have previously been published for the probability of rejection in the two one‐sided tests procedure for crossover bioequivalence studies. These approximations and associated sample size formulas are reviewed in this article and compared for various parameter combinations with exact power formulas derived here, which are computed analytically as univariate integrals and which have been validated by Monte Carlo simulations. The exact formulas for power and sample size are shown to improve markedly in realistic parameter settings over the previous approximations. Copyright © 2014 John Wiley & Sons, Ltd.     

Asymptotic distributions of functions of a sample covariance matrix under the elliptical distribution

This paper is concerned with asymptotic distributions of functions of a sample covariance matrix under the elliptical model. Simple but useful formulae for calculating asymptotic variances and covariances of the functions are derived. Also, an asymptotic expansion formula for the expectation of a function of a sample covariance matrix is derived; it is given up to the second-order term with respect to the inverse of the sample size. Two examples are given: one of calculating the asymptotic variances and covariances of the stepdown multiple correlation coefficients, and the other of obtaining the asymptotic expansion formula for the moments of sample generalized variance.     

Sample size determination for the parallel model in a survey with sensitive questions

Recently, a new non-randomized parallel design is proposed by Tian (2013) for surveys with sensitive topics. However, the sample size formulae associated with testing hypotheses for the parallel model are not yet available. As a crucial component in surveys, the sample size formulae with the parallel design are developed in this paper by using the power analysis method for both the one- and two-sample problems. We consider both the one- and two-sample problems. The asymptotic power functions and the corresponding sample size formulae for both the one- and two-sided tests based on the large-sample normal approximation are derived. The performance is assessed through comparing the asymptotic power with the exact power and reporting the ratio of the sample sizes with the parallel model and the design of direct questioning. We numerically compare the sample sizes needed for the parallel design with those required for the crosswise and triangular models. Two theoretical justifications are also provided. An example from a survey on ‘sexual practices’ in San Francisco, Las Vegas and Portland is used to illustrate the proposed methods.     

Sample size calculation for the one‐sample log‐rank test

In this paper, an exact variance of the one‐sample log‐rank test statistic is derived under the alternative hypothesis, and a sample size formula is proposed based on the derived exact variance. Simulation results showed that the proposed sample size formula provides adequate power to design a study to compare the survival of a single sample with that of a standard population. Copyright © 2014 John Wiley & Sons, Ltd.     

Corrected asymptotic distribution of statistics based on the multinomial law

Investigators and epidemiologists often use statistics based on the parameters of a multinomial distribution. Two main approaches have been developed to assess the inferences of these statistics. The first one uses asymptotic formulae which are valid for large sample sizes. The second one computes the exact distribution, which performs quite well for small samples. They present some limitations for sample sizes N neither large enough to satisfy the assumption of asymptotic normality nor small enough to allow us to generate the exact distribution. We analytically computed the 1/N corrections of the asymptotic distribution for any statistics based on a multinomial law. We applied these results to the kappa statistic in 2×2 and 3×3 tables. We also compared the coverage probability obtained with the asymptotic and the corrected distributions under various hypothetical configurations of sample size and theoretical proportions. With this method, the estimate of the mean and the variance were highly improved as well as the 2.5 and the 97.5 percentiles of the distribution, allowing us to go down to sample sizes around 20, for data sets not too asymmetrical. The order of the difference between the exact and the corrected values was 1/N² for the mean and 1/N³ for the variance.     

Comparison of disease prevalence in two populations under double-sampling scheme with two fallible classifiers

A disease prevalence can be estimated by classifying subjects according to whether they have the disease. When gold-standard tests are too expensive to be applied to all subjects, partially validated data can be obtained by double-sampling in which all individuals are classified by a fallible classifier, and some of individuals are validated by the gold-standard classifier. However, it could happen in practice that such infallible classifier does not available. In this article, we consider two models in which both classifiers are fallible and propose four asymptotic test procedures for comparing disease prevalence in two groups. Corresponding sample size formulae and validated ratio given the total sample sizes are also derived and evaluated. Simulation results show that (i) Score test performs well and the corresponding sample size formula is also accurate in terms of the empirical power and size in two models; (ii) the Wald test based on the variance estimator with parameters estimated under the null hypothesis outperforms the others even under small sample sizes in Model II, and the sample size estimated by this test is also accurate; (iii) the estimated validated ratios based on all tests are accurate. The malarial data are used to illustrate the proposed methodologies.     

Takacs–Fiksel Method for Stationary Marked Gibbs Point Processes

Abstract. This article studies a method to estimate the parameters governing the distribution of a stationary marked Gibbs point process. This procedure, known as the Takacs–Fiksel method, is based on the estimation of the left and right hand sides of the Georgii–Nguyen–Zessin formula and leads to a family of estimators due to the possible choices of test functions. We propose several examples illustrating the interest and flexibility of this procedure. We also provide sufficient conditions based on the model and the test functions to derive asymptotic properties (consistency and asymptotic normality) of the resulting estimator. The different assumptions are discussed for exponential family models and for a large class of test functions. A short simulation study is proposed to assess the correctness of the methodology and the asymptotic results.     

Procedure for determining sample size at each stage in group sequential test

The purpose of our study is to propose a. procedure for determining the sample size at each stage of the repeated group significance, tests intended to compare the efficacy of two treatments when a response variable is normal. It is necessary to devise a procedure for reducing the maximum sample size because a large number of sample size are often used in group sequential test. In order to reduce the sample size at each stage, we construct the repeated confidence boundaries which enable us to find which of the two treatments is the more effective at an early stage. Thus we use the recursive formulae of numerical integrations to determine the sample size at the intermediate stage. We compare our procedure with Pocock's in terms of maximum sample size and average sample size in the simulations.     

Cancer immunotherapy trial design with long-term survivors

Cancer immunotherapy often reflects the improvement in both short-term risk reduction and long-term survival. In this scenario, a mixture cure model can be used for the trial design. However, the hazard functions based on the mixture cure model between two groups will ultimately crossover. Thus, the conventional assumption of proportional hazards may be violated and study design using standard log-rank test (LRT) could lose power if the main interest is to detect the improvement of long-term survival. In this paper, we propose a change sign weighted LRT for the trial design. We derived a sample size formula for the weighted LRT, which can be used for designing cancer immunotherapy trials to detect both short-term risk reduction and long-term survival. Simulation studies are conducted to compare the efficiency between the standard LRT and the change sign weighted LRT.     

Randomized allocation procedure for testing a normal mean with known variance

This paper provides an alternative test procedure for the problem of testing normal mean against two-sided alternative with known variance for costly trials. The goal is to carry out the test procedure with a smaller sample size if the alternative is true. The sample size is determined in an adaptive fashion which takes all the previous observations into account for adaptation. Some exact and asymptotic results related to the test and design are studied.     

More powerful sign test using median ranked set sample: Finite sample power comparison

Sign test using median ranked set samples (MRSS) is introduced and investigated. We show that, this test is more powerful than the sign tests based on simple random sample (SRS) and ranked set sample (RSS) for finite sample size. It is found that, when the set size of MRSS is odd, the null distribution of the MRSS sign test is the same as the sign test obtained by using SRS. The exact null distributions and the power functions, in case of finite sample sizes, of these tests are derived. Also, the asymptotic distribution of the MRSS sign tests are derived. Numerical comparison of the MRSS sign test power with the power of the SRS sign test and the RSS sign test is given. Illustration of the procedure, using real data set of bilirubin level in Jaundice babies who stay in neonatal intensive care is introduced.     

ASYMPTOTIC EXPANSIONS APPLIED TO F-TEST CRITERIA

Using asymptotic expansions of the Kummer hypergeometric function, the sequential. F-test criterion is evaluated asymptotically in terms of the sample size. The continuation region inequalities for the test are inverted and expressed in terms of known test criteria. A rapidly converging algorithm for carrying out the sequential procedure is provided. This makes the F-test easier for the practitioner to use. Almost sure finite termination of the sequential. F-test is asserted by appealing to the continuation inequalities and a heuristic asymptotic expansion of the test criterion. Average stopping times of the sequential procedure for a variety of population means and population number configurations are tabulated. The computer symbolic manipulation program MAPLE was used to derive some formulae.     

A nonparametric test for proving noninferiority in clinical trials with ordered categorical data

We consider the problem of proving noninferiority when the comparison is based on ordered categorical data. We apply a rank test based on the Wilcoxon–Mann–Whitney effect where the asymptotic variance is estimated consistently under the alternative and a small‐sample approximation is given. We give the associated 100(1?α)% confidence interval and propose a formula for sample size determination. Finally, we illustrate the procedure and possible choices of the noninferiority margin using data from a clinical trial. Copyright © 2003 John Wiley & Sons, Ltd.