Yaakov Malinovsky

Pooling Designs for Outcomes under a Gaussian Random Effects Model

Due to the rising cost of laboratory assays, it has become increasingly common in epidemiological studies to pool biospecimens. This is particularly true in longitudinal studies, where the cost of performing multiple assays over time can be prohibitive. In this article, we consider the problem of estimating the parameters of a Gaussian random effects model when the repeated outcome is subject to pooling. We consider different pooling designs for the efficient maximum likelihood estimation of variance components, with particular attention to estimating the intraclass correlation coefficient. We evaluate the efficiencies of different pooling design strategies using analytic and simulation study results. We examine the robustness of the designs to skewed distributions and consider unbalanced designs. The design methodology is illustrated with a longitudinal study of premenopausal women focusing on assessing the reproducibility of F2-isoprostane, a biomarker of oxidative stress, over the menstrual cycle.

Estimation and Testing Based on Data Subject to Measurement Errors: From Parametric to Non-Parametric Likelihood Methods

Measurement error (ME) problems can cause bias or inconsistency of statistical inferences. When investigators are unable to obtain correct measurements of biological assays, special techniques to quantify MEs need to be applied. Sampling based on repeated measurements is a common strategy to allow for ME. This method has been well addressed in the literature under parametric assumptions. The approach with repeated measures data may not be applicable when the replications are complicated because of cost and/or time concerns. Pooling designs have been proposed as cost-efficient sampling procedures that can assist to provide correct statistical operations based on data subject to ME. We demonstrate that a mixture of both pooled and unpooled data (a hybrid pooled-unpooled design) can support very efficient estimation and testing in the presence of ME. Nonparametric techniques have not been well investigated to analyze repeated measures data or pooled data subject to ME. We propose and examine both the parametric and empirical likelihood methodologies for data subject to ME. We conclude that the likelihood methods based on the hybrid samples are very efficient and powerful. The results of an extensive Monte Carlo study support our conclusions. Real data examples demonstrate the efficiency of the proposed methods in practice.

Reader reaction: A note on the evaluation of group testing algorithms in the presence of misclassification

In the context of group testing screening, McMahan, Tebbs, and Bilder (2012, Biometrics 68, 287-296) proposed a two-stage procedure in a heterogenous population in the presence of misclassification. In earlier work published in Biometrics, Kim, Hudgens, Dreyfuss, Westreich, and Pilcher (2007, Biometrics 63, 1152-1162) also proposed group testing algorithms in a homogeneous population with misclassification. In both cases, the authors evaluated performance of the algorithms based on the expected number of tests per person, with the optimal design being defined by minimizing this quantity. The purpose of this article is to show that although the expected number of tests per person is an appropriate evaluation criteria for group testing when there is no misclassification, it may be problematic when there is misclassification. Specifically, a valid criterion needs to take into account the amount of correct classification and not just the number of tests. We propose, a more suitable objective function that accounts for not only the expected number of tests, but also the expected number of correct classifications. We then show how using this objective function that accounts for correct classification is important for design when considering group testing under misclassification. We also present novel analytical results which characterize the optimal Dorfman (1943) design under the misclassification.

On the Nile problem by Sir Ronald Fisher

The Nile problem by Ronald Fisher may be interpreted as the problem of making statistical inference for a special curved exponential family when the minimal sufficient statistic is incomplete. The problem itself and its versions for general curved exponential families pose a mathematical-statistical challenge: studying the subalgebras of ancillary statistics within the

A Note on the Minimax Solution for the Two-Stage Group Testing Problem

\sigma

Sequential estimation in the group testing problem

-algebra of the (incomplete) minimal sufficient statistics and closely related questions of the structure of UMVUEs. In this paper a new method is developed that, in particular, proves that in the classical Nile problem no statistic subject to mild natural conditions is a UMVUE. The method almost solves an old problem of the existence of UMVUEs. The method is purely statistical (vs. analytical) and works for any family possessing an ancillary statistic. It complements an analytical method that uses only the first order ancillarity (and thus works when the existence of ancillary subalgebras is an open problem) and works for curved exponential families with polynomial constraints on the canonical parameters of which the Nile problem is a special case.

Revisiting Nested Group Testing Procedures: New Results, Comparisons, and Robustness

Group testing is an active area of current research and has important applications in medicine, biotechnology, genetics, and product testing. There have been recent advances in design and estimation, but the simple Dorfman procedure introduced by R. Dorfman in 1943 is widely used in practice. In many practical situations, the exact value of the probability p of being affected is unknown. We present both minimax and Bayesian solutions for the group size problem when p is unknown. For unbounded p, we show that the minimax solution for group size is 8, while using a Bayesian strategy with Jeffreys’ prior results in a group size of 13. We also present solutions when p is bounded from above. For the practitioner, we propose strong justification for using a group size of between 8 and 13 when a constraint on p is not incorporated and provide useable code for computing the minimax group size under a constrained p.

On the Structure of UMVUEs

ABSTRACT Estimation using pooled sampling has long been an area of interest in the group testing literature. Such research has focused primarily on the assumed use of fixed sampling plans (i), although some recent papers have suggested alternative sequential designs that sample until a predetermined number of positive tests (ii). One major consideration, including in the new work on sequential plans, is the construction of debiased estimators that either reduce or keep the mean square error from inflating. However, whether under the above or other sampling designs unbiased estimation is in fact possible has yet to be established in the literature. In this article, we introduce a design that samples until a fixed number of negatives (iii), and show that an unbiased estimator exists under this model, whereas unbiased estimation is not possible for either of the preceding designs (i) and (ii). We present new estimators under the different sampling plans that are either unbiased or that have reduced bias relative to those already in use as well as generally improve on the mean square error. Numerical studies are done in order to compare designs in terms of bias and mean square error under practical situations with small and medium sample sizes.

Random walk designs for selecting pool sizes in group testing estimation with small samples

ABSTRACT Group testing has its origin in the identification of syphilis in the U.S. army during World War II. Much of the theoretical framework of group testing was developed starting in the late 1950s, with continued work into the 1990s. Recently, with the advent of new laboratory and genetic technologies, there has been an increasing interest in group testing designs for cost saving purposes. In this article, we compare different nested designs, including Dorfman, Sterrett and an optimal nested procedure obtained through dynamic programming. To elucidate these comparisons, we develop closed-form expressions for the optimal Sterrett procedure and provide a concise review of the prior literature for other commonly used procedures. We consider designs where the prevalence of disease is known as well as investigate the robustness of these procedures, when it is incorrectly assumed. This article provides a technical presentation that will be of interest to researchers as well as from a pedagogical perspective. Supplementary material for this article is available online.

Monitoring Distributed Data Streams through Node Clustering

Abstract In all setups when the structure of UMVUEs is known, there exists a subalgebra U