Distance-based outlier detection for high dimension,low sample size data

Despite the popularity of high dimension, low sample size data analysis, there has not been enough attention to the sample integrity issue, in particular, a possibility of outliers in the data. A new outlier detection procedure for data with much larger dimensionality than the sample size is presented. The proposed method is motivated by asymptotic properties of high-dimensional distance measures. Empirical studies suggest that high-dimensional outlier detection is more likely to suffer from a swamping effect rather than a masking effect, thus yields more false positives than false negatives. We compare the proposed approaches with existing methods using simulated data from various population settings. A real data example is presented with a consideration on the implication of found outliers.     

Exact calculation of minimum sample size for estimating a Poisson parameter

Abstract

We develop an exact approach for the determination of the minimum sample size for estimating a Poisson parameter such that the pre-specified levels of relative precision and confidence are guaranteed. The exact computation is made possible by reducing infinitely many evaluations of coverage probability to finitely many evaluations. The theory for supporting such a reduction is that the minimum of coverage probability with respect to the parameter in an interval is attained at a discrete set of finitely many elements. Computational mechanisms have been developed to further reduce the computational complexity. An explicit bound for the minimum sample size is established.     

Geometric representation of high dimension, low sample size data

Summary.  High dimension, low sample size data are emerging in various areas of science. We find a common structure underlying many such data sets by using a non-standard type of asymptotics: the dimension tends to ∞ while the sample size is fixed. Our analysis shows a tendency for the data to lie deterministically at the vertices of a regular simplex. Essentially all the randomness in the data appears only as a random rotation of this simplex. This geometric representation is used to obtain several new statistical insights.     

A practical comparison of blinded methods for sample size reviews in survival data clinical trials

This paper presents practical approaches to the problem of sample size re-estimation in the case of clinical trials with survival data when proportional hazards can be assumed. When data are readily available at the time of the review, on a full range of survival experiences across the recruited patients, it is shown that, as expected, performing a blinded re-estimation procedure is straightforward and can help to maintain the trial's pre-specified error rates. Two alternative methods for dealing with the situation where limited survival experiences are available at the time of the sample size review are then presented and compared. In this instance, extrapolation is required in order to undertake the sample size re-estimation. Worked examples, together with results from a simulation study are described. It is concluded that, as in the standard case, use of either extrapolation approach successfully protects the trial error rates.     

Testing multiple primary endpoints in clinical trials with sample size adaptation

In this paper, we propose a design that uses a short‐term endpoint for accelerated approval at interim analysis and a long‐term endpoint for full approval at final analysis with sample size adaptation based on the long‐term endpoint. Two sample size adaptation rules are compared: an adaptation rule to maintain the conditional power at a prespecified level and a step function type adaptation rule to better address the bias issue. Three testing procedures are proposed: alpha splitting between the two endpoints; alpha exhaustive between the endpoints; and alpha exhaustive with improved critical value based on correlation. Family‐wise error rate is proved to be strongly controlled for the two endpoints, sample size adaptation, and two analysis time points with the proposed designs. We show that using alpha exhaustive designs greatly improve the power when both endpoints are effective, and the power difference between the two adaptation rules is minimal. The proposed design can be extended to more general settings. Copyright © 2015 John Wiley & Sons, Ltd.     

Ultrahigh-dimensional sufficient dimension reduction for censored data with measurement error in covariates

In this paper, we consider the ultrahigh-dimensional sufficient dimension reduction (SDR) for censored data and measurement error in covariates. We first propose the feature screening procedure based on censored data and the covariates subject to measurement error. With the suitable correction of mismeasurement, the error-contaminated variables detected by the proposed feature screening procedure are the same as the truly important variables. Based on the selected active variables, we develop the SDR method to estimate the central subspace and the structural dimension with both censored data and measurement error incorporated. The theoretical results of the proposed method are established. Simulation studies are reported to assess the performance of the proposed method. The proposed method is implemented to NKI breast cancer data.     

Type I error rate control in adaptive designs for confirmatory clinical trials with treatment selection at interim

Interest in confirmatory adaptive combined phase II/III studies with treatment selection has increased in the past few years. These studies start comparing several treatments with a control. One (or more) treatment(s) is then selected after the first stage based on the available information at an interim analysis, including interim data from the ongoing trial, external information and expert knowledge. Recruitment continues, but now only for the selected treatment(s) and the control, possibly in combination with a sample size reassessment. The final analysis of the selected treatment(s) includes the patients from both stages and is performed such that the overall Type I error rate is strictly controlled, thus providing confirmatory evidence of efficacy at the final analysis. In this paper we describe two approaches to control the Type I error rate in adaptive designs with sample size reassessment and/or treatment selection. The first method adjusts the critical value using a simulation-based approach, which incorporates the number of patients at an interim analysis, the true response rates, the treatment selection rule, etc. We discuss the underlying assumptions of simulation-based procedures and give several examples where the Type I error rate is not controlled if some of the assumptions are violated. The second method is an adaptive Bonferroni-Holm test procedure based on conditional error rates of the individual treatment-control comparisons. We show that this procedure controls the Type I error rate, even if a deviation from a pre-planned adaptation rule or the time point of such a decision is necessary.     

Review: Reversed low-rank ANOVA model for transforming high dimensional genetic data into low dimension

A general modeling procedure for analyzing genetic data is reviewed. We review ANOVA type model that can handle both the continuous and discrete genetic variables in one modeling framework. Unlike the regression type models which typically set the phenotype variable as a response, this ANOVA model treats the phenotype variable as an explanatory variable. By reversely treating the phenotype variable, usual high dimensional problem is turned into low dimension. Instead, the ANOVA model always includes interaction term between the genetic locations and phenotype variable to find potential association between them. The interaction term is designed to be low rank with the multiplication of bilinear terms so that the required number of parameters is kept in a manageable degree. We compare the performance of the reviewed ANOVA model to the other popular methods via microarray and SNP data sets.     

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.     

Blinded sample size recalculation for clinical trials with normal data and baseline adjusted analysis

Baseline adjusted analyses are commonly encountered in practice, and regulatory guidelines endorse this practice. Sample size calculations for this kind of analyses require knowledge of the magnitude of nuisance parameters that are usually not given when the results of clinical trials are reported in the literature. It is therefore quite natural to start with a preliminary calculated sample size based on the sparse information available in the planning phase and to re‐estimate the value of the nuisance parameters (and with it the sample size) when a portion of the planned number of patients have completed the study. We investigate the characteristics of this internal pilot study design when an analysis of covariance with normally distributed outcome and one random covariate is applied. For this purpose we first assess the accuracy of four approximate sample size formulae within the fixed sample size design. Then the performance of the recalculation procedure with respect to its actual Type I error rate and power characteristics is examined. The results of simulation studies show that this approach has favorable properties with respect to the Type I error rate and power. Together with its simplicity, these features should make it attractive for practical application. Copyright © 2009 John Wiley & Sons, Ltd.     

Likelihood‐based and marginal inference methods for recurrent event data with covariate measurement error

Recurrent event data arise commonly in medical and public health studies. The analysis of such data has received extensive research attention and various methods have been developed in the literature. Depending on the focus of scientific interest, the methods may be broadly classified as intensity‐based counting process methods, mean function‐based estimating equation methods, and the analysis of times to events or times between events. These methods and models cover a wide variety of practical applications. However, there is a critical assumption underlying those methods–variables need to be correctly measured. Unfortunately, this assumption is frequently violated in practice. It is quite common that some covariates are subject to measurement error. It is well known that covariate measurement error can substantially distort inference results if it is not properly taken into account. In the literature, there has been extensive research concerning measurement error problems in various settings. However, with recurrent events, there is little discussion on this topic. It is the objective of this paper to address this important issue. In this paper, we develop inferential methods which account for measurement error in covariates for models with multiplicative intensity functions or rate functions. Both likelihood‐based inference and robust inference based on estimating equations are discussed. The Canadian Journal of Statistics 40: 530–549; 2012 © 2012 Statistical Society of Canada