Defining estimands using a mix of strategies to handle intercurrent events in clinical trials

Randomized controlled trials (RCTs) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the complete data to infer the treatment effect. However, intercurrent events (ICEs) including the use of concomitant medication for unsatisfactory efficacy, treatment discontinuation due to adverse events, or lack of efficacy may lead to interventions that deviate from the original treatment assignment. Therefore, defining the appropriate estimand (the appropriate parameter to be estimated) based on the primary objective of the study is critical prior to determining the statistical analysis method and analyzing the data. The International Council for Harmonisation (ICH) E9 (R1), adopted on November 20, 2019, provided five strategies to define the estimand: treatment policy, hypothetical, composite variable, while on treatment, and principal stratum. In this article, we propose an estimand using a mix of strategies in handling ICEs. This estimand is an average of the “null” treatment difference for those with ICEs potentially related to safety and the treatment difference for the other patients if they would complete the assigned treatments. Two examples from clinical trials evaluating antidiabetes treatments are provided to illustrate the estimation of this proposed estimand and to compare it with the estimates for estimands using hypothetical and treatment policy strategies in handling ICEs.     

Revisiting the Impact of Prison Building on Job Growth: Education,Incarceration, and County‐Level Employment, 1976–2004*

Objectives. It is widely believed that prison construction offers significant economic benefits to local areas. We review the popular and scholarly literature and provide a quantitative analysis of claims. Methods. We analyze data on all existing and new prisons in the United States since 1960 to assess the impact of these prisons on the pace of public, private, and total employment growth in U.S. counties from 1976 to 2004. Results. Our results suggest that enhanced human capital is associated with employment gains and cast doubt on the assertion that prisons provide economic benefits to local areas. We provide evidence that prison construction impedes economic growth in rural counties, especially in counties that lag behind in educational attainment. Conclusions. Based on empirical results, this research casts further doubt on claims that prisons offer a viable economic development option for struggling rural communities. Possible explanations for the failure of prisons to help local areas are explored, including existing corrections officers moving to fill openings, adverse local impacts of prison labor, and paucity of local multipliers when a prison opens.     

Partitioning a weighted partial order

The problem of partitioning a partially ordered set into a minimum number of chains is a well-known problem. In this paper we study a generalization of this problem, where we not only assume that the chains have bounded size, but also that a weight w _i is given for each element i in the partial order such that w _i ≤w _j if i ≺ j. The problem is then to partition the partial order into a minimum-weight set of chains of bounded size, where the weight of a chain equals the weight of the heaviest element in the chain. We prove that this problem is -hard, and we propose and analyze lower bounds for this problem. Based on these lower bounds, we exhibit a 2-approximation algorithm, and show that it is tight. We report computational results for a number of real-world and randomly generated problem instances.     

Searching for differential expression: a non-parametric approach

Microarray experiments are being widely used in medical and biological research. The main features of these studies are the large number of variables (genes) involved and the low number of replicates (arrays). It seems clear that the most appropriate models, when looking for detecting differences in gene expression are those that exploit the most useful information to compensate for the lack of replicates. On the other hand, the control of the error in the decision process plays an important role for the high number of simultaneous statistical tests (one for each gene), so that concepts such as the false discovery rate (FDR) take a special importance. One of the alternatives for the analysis of the data in these experiments is based on the calculation of statistics derived from modifications of the classical methods used in this type of problems (moderated-t, B-statistic). Nonparametric techniques have been also proposed [B. Efron, R. Tibshirani, J.D. Storey, and V. Tusher, Empirical Bayes analysis of a microarray experiment, J. Amer. Stat. Assoc. 96 (2001), pp. 1151–1160; W. Pan, J. Lin, and C.T. Le, A mixture model approach to detecting differentially expressed genes with microarray data, Funct. Integr. Genomics 3 (2003), pp. 117–124], allowing the analysis without assuming any prior condition about the distribution of the data, which make them especially suitable in such situations. This paper presents a new method to detect differentially expressed genes based on non-parametric density estimation by a class of functions that allow us to define a distance between individuals in the sample (characterized by the coordinates of the individual (gene) in the dual space tangent to the manifold of parameters) [A. Miñarro and J.M. Oller, Some remarks on the individuals-score distance and its applications to statistical inference, Qüestiió, 16 (1992), pp. 43–57]. From these distances, we designed the test to determine the rejection region based on the control of FDR.     

Finite sample performance of frequency- and time-domain tests for seasonal fractional integration

Testing the order of integration of economic and financial time series has become a conventional procedure prior to any modelling exercise. In this paper, we investigate and compare the finite sample properties of the frequency-domain tests proposed by Robinson [Efficient tests of nonstationary hypotheses, J. Amer. Statist. Assoc. 89(428) (1994), pp. 1420–1437] and the time-domain procedure proposed by Hassler, Rodrigues, and Rubia [Testing for general fractional integration in the time domain, Econometric Theory 25 (2009), pp. 1793–1828] when applied to seasonal data. The results presented are of empirical relevance as they provide some guidance regarding the finite sample properties of these tests.     

Can we Lend?: Communicating Interlibrary Loan Rights

At the 22nd Annual North Carolina Serials Conference, focused on “Collaboration, Community, and Connection,” Linda Blake and Hilary Fredette of West Virginia University presented, ““Can we Lend?”: Communicating Interlibrary Loan Rights,” reviewing their experiences collaborating across an academic library to achieve the best possible interlibrary loan e-journal access within the bounds of sometimes inscrutable licenses.     

EBSCO Publishing

Abstract

EBSCO Publishing is an innovative company that has its roots in paper publishing. It now produces hundreds of online resources in a state-of-the-art facility located along the banks of the Ipswich River in Massachusetts. Considerable work occurs behind the scenes in Ipswich (and around the world) to produce the online databases in EBSCOhost that appear to the user at the click of a mouse. Jennifer Carroll toured the headquarters in Ipswich to learn about the processes that make these valuable resources available.     

Is It Always Necessary to Take Sample Selection into Account?

We compare a simple ordinary least squares (OLS) with the maximum likelihood estimation of the Tobit I and Tobit II regression models, in the selected sample. We propose a new measure to quantify the performance of OLS.     

Algorithmic construction of optimal block designs for two-colour cDNA microarray experiments using the linear mixed effects model

ABSTRACT

In this study, methods for efficient construction of A-, MV-, D- and E-optimal or near-optimal block designs for two-colour cDNA microarray experiments with array as the block effect are considered. Two algorithms, namely the array exchange and treatment exchange algorithms together with the complete enumeration technique are introduced. For large numbers of arrays or treatments or both, the complete enumeration method is highly computer intensive. The treatment exchange algorithm computes the optimal or near-optimal designs faster than the array exchange algorithm. The two methods however produce optimal or near-optimal designs with the same efficiency under the four optimality criteria.     

speed of covergence to the extreme value distributions on their probability ploting parers

The speed of convergence of the distribution of the normalized maximum, of a sample of independent and identically distributed random variables, to its asymptotic distribution is considered in this article. Assuming that the cumulative distribution function of the random variables is known, the error committed replacing the actual distribution of the normalized maximum by its asympotic distribution is studied. Instead of using the arithmetical scale of probabilities, we measure the difference between the actual and asympotic distribution in terms of the double-log scale used for building the probability plotting paper for the the latter. We demonstrate that the difference between the double-log values corresponding to two probabilities in the upper tail is almost exactly equal to the logarithm of the distribution may not be uniform in this double-log scale and that the difference between the actual and asymptotic distributions, on the probebility plotting paper, may be a logarithmic, power, or even exponential function in the upper tail when the latter distribution is of Fisher-Tippett type I, but that difference is at most logarithmic in the upper tail for type II and III distributions. This fact is exploited to obtain transformed variables that converge tothe asymptotic distribution faster than the original variable on the probabilites plotting paper