Practical guide to sample size calculations: superiority trials

A sample size justification is a vital part of any investigation. However, estimating the number of participants required to give meaningful results is not always straightforward. A number of components are required to facilitate a suitable sample size calculation. In this paper, the steps for conducting sample size calculations for superiority trials are summarised. Practical advice and examples are provided illustrating how to carry out the calculations by hand and using the app SampSize. Copyright © 2015 John Wiley & Sons, Ltd.     

Practical guide to sample size calculations: non‐inferiority and equivalence trials

A sample size justification is a vital part of any trial design. However, estimating the number of participants required to give a meaningful result is not always straightforward. A number of components are required to facilitate a suitable sample size calculation. In this paper, the steps for conducting sample size calculations for non‐inferiority and equivalence trials are summarised. Practical advice and examples are provided that illustrate how to carry out the calculations by hand and using the app SampSize. Copyright © 2015 John Wiley & Sons, Ltd.     

Approximations for a fixed sample size selection procedure for negative binomial populations

A large sample approximation of the least favorable configuration for a fixed sample size selection procedure for negative binomial populations is proposed. A normal approximation of the selection procedure is also presented. Optimal sample sizes required to be drawn from each population and the bounds for the sample sizes are tabulated. Sample sizes obtained using the approximate least favorable configuration are compared with those obtained using the exact least favorable configuration. Alternate form of the normal approximation to the probability of correct selection is also presented. The relation between the required sample size and the number of populations involved is studied.     

Sample size determination for cluster randomization phase II trials of dichotomous data

One of the main goals for a phase II trial is to screen and select the best treatment to proceed onto further studies in a phase III trial. Under the flexible design proposed elsewhere, we discuss for cluster randomization trials sample size calculation with a given desired probability of correct selection to choose the best treatment when one treatment is better than all the others. We develop exact procedures for calculating the minimum required number of clusters with a given cluster size (or the minimum number of patients with a given number of repeated measurements) per treatment. An approximate sample size and the evaluation of its performance for two arms are also given. To help readers employ the results presented here, tables are provided to summarize the resulting minimum required sample sizes for cluster randomization trials with two arms and three arms in a variety of situations. Finally, to illustrate the sample size calculation procedures developed here, we use the data taken from a cluster randomization trial to study the association between the dietary sodium and the blood pressure.     

Graphical displays for clarifying how allocation ratio affects total sample size for the two sample logrank test

For time‐to‐event data, the power of the two sample logrank test for the comparison of two treatment groups can be greatly influenced by the ratio of the number of patients in each of the treatment groups. Despite the possible loss of power, unequal allocations may be of interest due to a need to collect more data on one of the groups or to considerations related to the acceptability of the treatments to patients. Investigators pursuing such designs may be interested in the cost of the unbalanced design relative to a balanced design with respect to the total number of patients required for the study. We present graphical displays to illustrate the sample size adjustment factor, or ratio of the sample size required by an unequal allocation compared to the sample size required by a balanced allocation, for various survival rates, treatment hazards ratios, and sample size allocation ratios. These graphical displays conveniently summarize information in the literature and provide a useful tool for planning sample sizes for the two sample logrank test. Copyright © 2010 John Wiley & Sons, Ltd.     

A modified least-failures sampling procedure for bernoulli subset selection

We restrict attention to a class of Bernoulli subset selection procedures which take observations one-at-a-time and can be compared directly to the Gupta-Sobel single-stage procedure. For the criterion of minimizing the expected total number of observations required to terminate experimentation, we show that optimal sampling rules within this class are not of practical interest. We thus turn to procedures which, although not optimal, exhibit desirable behavior with regard to this criterion. A procedure which employs a modification of the so-called least-failures sampling rule is proposed, and is shown to possess many desirable properties among a restricted class of Bernoulli subset selection procedures. Within this class, it is optimal for minimizing the number of observations taken from populations excluded from consideration following a subset selection experiment, and asymptotically optimal for minimizing the expected total number of observations required. In addition, it can result in substantial savings in the expected total num¬ber of observations required as compared to a single-stage procedure, thus it may be de¬sirable to a practitioner if sampling is costly or the sample size is limited.     

Sample size determination for testing equality in Poisson frequency data under an AB/BA crossover trial

Assuming that the frequency of occurrence follows the Poisson distribution, we develop sample size calculation procedures for testing equality based on an exact test procedure and an asymptotic test procedure under an AB/BA crossover design. We employ Monte Carlo simulation to demonstrate the use of these sample size formulae and evaluate the accuracy of sample size calculation formula derived from the asymptotic test procedure with respect to power in a variety of situations. We note that when both the relative treatment effect of interest and the underlying intraclass correlation between frequencies within patients are large, the sample size calculation based on the asymptotic test procedure can lose accuracy. In this case, the sample size calculation procedure based on the exact test is recommended. On the other hand, if the relative treatment effect of interest is small, the minimum required number of patients per group will be large, and the asymptotic test procedure will be valid for use. In this case, we may consider use of the sample size calculation formula derived from the asymptotic test procedure to reduce the number of patients needed for the exact test procedure. We include an example regarding a double‐blind randomized crossover trial comparing salmeterol with a placebo in exacerbations of asthma to illustrate the practical use of these sample size formulae. Copyright © 2013 John Wiley & Sons, Ltd.     

Sample Size and Power Calculations for Left-Truncated Normal Distribution

Abstract

Sample size calculation is an important component in designing an experiment or a survey. In a wide variety of fields—including management science, insurance, and biological and medical science—truncated normal distributions are encountered in many applications. However, the sample size required for the left-truncated normal distribution has not been investigated, because the distribution of the sample mean from the left-truncated normal distribution is complex and difficult to obtain. This paper compares an ad hoc approach to two newly proposed methods based on the Central Limit Theorem and on a high degree saddlepoint approximation for calculating the required sample size with the prespecified power. As shown by use of simulations and an example of health insurance cost in China, the ad hoc approach underestimates the sample size required to achieve prespecified power. The method based on the high degree saddlepoint approximation provides valid sample size and power calculations, and it performs better than the Central Limit Theorem. When the sample size is not too small, the Central Limit Theorem also provides a valid, but relatively simple tool to approximate that sample size.     

On the Bayesian analysis of the mixture of power function distribution using the complete and the censored sample

The power function distribution is often used to study the electrical component reliability. In this paper, we model a heterogeneous population using the two-component mixture of the power function distribution. A comprehensive simulation scheme including a large number of parameter points is followed to highlight the properties and behavior of the estimates in terms of sample size, censoring rate, parameters size and the proportion of the components of the mixture. The parameters of the power function mixture are estimated and compared using the Bayes estimates. A simulated mixture data with censored observations is generated by probabilistic mixing for the computational purposes. Elegant closed form expressions for the Bayes estimators and their variances are derived for the censored sample as well as for the complete sample. Some interesting comparison and properties of the estimates are observed and presented. The system of three non-linear equations, required to be solved iteratively for the computations of maximum likelihood (ML) estimates, is derived. The complete sample expressions for the ML estimates and for their variances are also given. The components of the information matrix are constructed as well. Uninformative as well as informative priors are assumed for the derivation of the Bayes estimators. A real-life mixture data example has also been discussed. The posterior predictive distribution with the informative Gamma prior is derived, and the equations required to find the lower and upper limits of the predictive intervals are constructed. The Bayes estimates are evaluated under the squared error loss function.     

Sample size recalculation for binary data in internal pilot study designs

For binary endpoints, the required sample size depends not only on the known values of significance level, power and clinically relevant difference but also on the overall event rate. However, the overall event rate may vary considerably between studies and, as a consequence, the assumptions made in the planning phase on this nuisance parameter are to a great extent uncertain. The internal pilot study design is an appealing strategy to deal with this problem. Here, the overall event probability is estimated during the ongoing trial based on the pooled data of both treatment groups and, if necessary, the sample size is adjusted accordingly. From a regulatory viewpoint, besides preserving blindness it is required that eventual consequences for the Type I error rate should be explained. We present analytical computations of the actual Type I error rate for the internal pilot study design with binary endpoints and compare them with the actual level of the chi‐square test for the fixed sample size design. A method is given that permits control of the specified significance level for the chi‐square test under blinded sample size recalculation. Furthermore, the properties of the procedure with respect to power and expected sample size are assessed. Throughout the paper, both the situation of equal sample size per group and unequal allocation ratio are considered. The method is illustrated with application to a clinical trial in depression. Copyright © 2004 John Wiley & Sons Ltd.     

A Bayesian sequential design with adaptive randomization for 2‐sided hypothesis test

Bayesian sequential and adaptive randomization designs are gaining popularity in clinical trials thanks to their potentials to reduce the number of required participants and save resources. We propose a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms. In this paper, we consider 2‐arm clinical trials. Patients are allocated to the 2 arms with a randomization rate to achieve minimum variance for the test statistic. Algorithms are presented to calculate the optimal randomization rate, critical values, and power for the proposed design. Sensitivity analysis is implemented to check the influence on design by changing the prior distributions. Simulation studies are applied to compare the proposed method and traditional methods in terms of power and actual sample sizes. Simulations show that, when total sample size is fixed, the proposed design can obtain greater power and/or cost smaller actual sample size than the traditional Bayesian sequential design. Finally, we apply the proposed method to a real data set and compare the results with the Bayesian sequential design without adaptive randomization in terms of sample sizes. The proposed method can further reduce required sample size.     

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.     

Bayesian Estimation of a Multidimensional Additive Graded Response Model for Correlated Traits

The aim of the article is to propose a Bayesian estimation through Markov chain Monte Carlo of a multidimensional item response theory model for graded responses with an additive structure with correlated latent traits. A simulation study is conducted to evaluate the model parameter recovery under different conditions (sample size, test and subtest length, number of response categories, and correlation structure). The results show that the parameters are well reproduced when the sample size is sufficiently large (n = 1, 000), while the worst recovery is observed for small sample size (n = 500), and four response categories with a short number of test items.     

Selection of Variables in Multivariate Regression Models for Large Dimensions

The Akaike information criterion, AIC, and Mallows’ C _p statistic have been proposed for selecting a smaller number of regressors in the multivariate regression models with fully unknown covariance matrix. All of these criteria are, however, based on the implicit assumption that the sample size is substantially larger than the dimension of the covariance matrix. To obtain a stable estimator of the covariance matrix, it is required that the dimension of the covariance matrix is much smaller than the sample size. When the dimension is close to the sample size, it is necessary to use ridge-type estimators for the covariance matrix. In this article, we use a ridge-type estimators for the covariance matrix and obtain the modified AIC and modified C _p statistic under the asymptotic theory that both the sample size and the dimension go to infinity. It is numerically shown that these modified procedures perform very well in the sense of selecting the true model in large dimensional cases.     

Sample design for observing classes of objects

We consider optimal sample designs for observing classes of objects. Suppose we will take a simple random sample of equal-sized sectors from a study population and observe the classes existing on these sectors. The classes might be many different things, for example, herbaceous plant species (in sampling quadrats), microinvertebrate species (in sampling cores), and side effects from a drug (in conducting medical trials). Under a nonparametric mixture model and data from a previous related study, we first estimate the optimal number of sample sectors of a given size. Then for negative binomial dispersions of individuals with a common aggregation parameter k, we consider the optimal size as well as number of sample sectors. A simple test exists to check our common k assumption and our optimal size method requires far less data than would be required by a grid method or other method which utilizes data from sample sectors of several different sizes.     

Rényi statistics for testing hypotheses in mixed linear regression models

Rényi divergences are used to propose some statistics for testing general hypotheses in mixed linear regression models. The asymptotic distribution of these tests statistics, of the Kullback–Leibler and of the likelihood ratio statistics are provided, assuming that the sample size and the number of levels of the random factors tend to infinity. A simulation study is carried out to analyze and compare the behavior of the proposed tests when the sample size and number of levels are small.     

Optimal One-Way Random Effects Designs for the Intraclass Correlation Based on Confidence Intervals

ABSTRACT

Confidence intervals for the intraclass correlation coefficient (ρ) are used to determine the optimal allocation of experimental material in one-way random effects models. Designs that produce narrow intervals are preferred since they provide greater precision to estimate ρ. Assuming the total cost and the relative cost of the two stages of sampling are fixed, the authors investigate the number of classes and the number of individuals per class required to minimize the expected length of confidence intervals. We obtain results using asymptotic theory and compare these results to those obtained using exact calculations. The best design depends on the unknown value of ρ. Minimizing the maximum expected length of confidence intervals guards against worst-case scenarios. A good overall recommendation based on asymptotic results is to choose a design having classes of size 2 + √4 + 3r, where r is the relative cost of sampling at the class-level compared to the individual-level. If r = 0, then the overall cost is the sample size and the recommendation reduces to a design having classes of size 4.     

Monte Carlo Approximations of the Quantiles of a Sample Statistic

We consider in this article the problem of numerically approximating the quantiles of a sample statistic for a given population, a problem of interest in many applications, such as bootstrap confidence intervals. The proposed Monte Carlo method can be routinely applied to handle complex problems that lack analytical results. Furthermore, the method yields estimates of the quantiles of a sample statistic of any sample size though Monte Carlo simulations for only two optimally selected sample sizes are needed. An analysis of the Monte Carlo design is performed to obtain the optimal choices of these two sample sizes and the number of simulated samples required for each sample size. Theoretical results are presented for the bias and variance of the numerical method proposed. The results developed are illustrated via simulation studies for the classical problem of estimating a bivariate linear structural relationship. It is seen that the size of the simulated samples used in the Monte Carlo method does not have to be very large and the method provides a better approximation to quantiles than those based on an asymptotic normal theory for skewed sampling distributions.     

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.     

A modified subset selection formulation with special reference to one-way and two-way layout experiments

The usual formulation of subset selection due to Gupta (1956) requires a minimum guaranteed probability of a correct selection. The modified formulation of the present paper includes an additional requirement that the expected number of the nonbest populations be bounded above by a specified constant when the best and the next best populations are ‘sufficiently’ apart. A class of procedures is defined and the determination of the minimum sample size required is discussed. The specific problems discussed for normal populations include selection in terms of means and variances, and selection in terms of treatment effects in a two-way layout.