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David Louis Borchers, Martin James Cox
Conventional distance sampling (CDS) methods assume that animals are uniformly distributed in the vicinity of lines or points. But when animals move in response to observers before detection, or when lines or points are not located randomly, this assumption may fail. By formulating distance sampling models as survival models, we show that using time to first detection in addition to perpendicular distance (line transect surveys) or radial distance (point transect surveys) allows estimation of detection probability, and hence density, when animal distribution in the vicinity of lines or points is not uniform and is unknown...
October 17, 2016: Biometrics
Chenguang Wang, Daniel O Scharfstein, Elizabeth Colantuoni, Timothy D Girard, Ying Yan
In randomized studies involving severely ill patients, functional outcomes are often unobserved due to missed clinic visits, premature withdrawal, or death. It is well known that if these unobserved functional outcomes are not handled properly, biased treatment comparisons can be produced. In this article, we propose a procedure for comparing treatments that is based on a composite endpoint that combines information on both the functional outcome and survival. We further propose a missing data imputation scheme and sensitivity analysis strategy to handle the unobserved functional outcomes not due to death...
October 17, 2016: Biometrics
Cécile Chauvel, John O'Quigley
Survival model construction can be guided by goodness-of-fit techniques as well as measures of predictive strength. Here, we aim to bring together these distinct techniques within the context of a single framework. The goal is how to best characterize and code the effects of the variables, in particular time dependencies, when taken either singly or in combination with other related covariates. Simple graphical techniques can provide an immediate visual indication as to the goodness-of-fit but, in cases of departure from model assumptions, will point in the direction of a more involved and richer alternative model...
October 5, 2016: Biometrics
Ruoqing Zhu, Ying-Qi Zhao, Guanhua Chen, Shuangge Ma, Hongyu Zhao
We propose a subgroup identification approach for inferring optimal and interpretable personalized treatment rules with high-dimensional covariates. Our approach is based on a two-step greedy tree algorithm to pursue signals in a high-dimensional space. In the first step, we transform the treatment selection problem into a weighted classification problem that can utilize tree-based methods. In the second step, we adopt a newly proposed tree-based method, known as reinforcement learning trees, to detect features involved in the optimal treatment rules and to construct binary splitting rules...
October 4, 2016: Biometrics
Paul R Rosenbaum, Dylan S Small
In a sensitivity analysis in an observational study with a binary outcome, is it better to use all of the data or to focus on subgroups that are expected to experience the largest treatment effects? The answer depends on features of the data that may be difficult to anticipate, a trade-off between unknown effect-sizes and known sample sizes. We propose a sensitivity analysis for an adaptive test similar to the Mantel-Haenszel test. The adaptive test performs two highly correlated analyses, one focused analysis using a subgroup, one combined analysis using all of the data, correcting for multiple testing using the joint distribution of the two test statistics...
October 4, 2016: Biometrics
Shuling Liu, Amita K Manatunga, Limin Peng, Michele Marcus
In many biomedical studies that involve correlated data, an outcome is often repeatedly measured for each individual subject along with the number of these measurements, which is also treated as an observed outcome. This type of data has been referred as multivariate random length data by Barnhart and Sampson (1995). A common approach to handling such type of data is to jointly model the multiple measurements and the random length. In previous literature, a key assumption is the multivariate normality for the multiple measurements...
October 4, 2016: Biometrics
Gang Han, Michael J Schell, Heping Zhang, Daniel Zelterman, Lajos Pusztai, Kerin Adelson, Christos Hatzis
Personalized cancer therapy requires clinical trials with smaller sample sizes compared to trials involving unselected populations that have not been divided into biomarker subgroups. The use of exponential survival modeling for survival endpoints has the potential of gaining 35% efficiency or saving 28% required sample size (Miller, 1983), making personalized therapy trials more feasible. However, the use of exponential survival has not been fully accepted in cancer research practice due to uncertainty about whether or not the exponential assumption holds...
September 26, 2016: Biometrics
Thierry Chekouo, Francesco C Stingo, James D Doecke, Kim-Anh Do
Integration of genomic data from multiple platforms has the capability to increase precision, accuracy, and statistical power in the identification of prognostic biomarkers. A fundamental problem faced in many multi-platform studies is unbalanced sample sizes due to the inability to obtain measurements from all the platforms for all the patients in the study. We have developed a novel Bayesian approach that integrates multi-regression models to identify a small set of biomarkers that can accurately predict time-to-event outcomes...
September 26, 2016: Biometrics
Peijie Hou, Joshua M Tebbs, Christopher R Bilder, Christopher S McMahan
Group testing, where individuals are tested initially in pools, is widely used to screen a large number of individuals for rare diseases. Triggered by the recent development of assays that detect multiple infections at once, screening programs now involve testing individuals in pools for multiple infections simultaneously. Tebbs, McMahan, and Bilder (2013, Biometrics) recently evaluated the performance of a two-stage hierarchical algorithm used to screen for chlamydia and gonorrhea as part of the Infertility Prevention Project in the United States...
September 22, 2016: Biometrics
Yang Liu, Francesca Chiaromonte, Bing Li
In many scientific and engineering fields, advanced experimental and computing technologies are producing data that are not just high dimensional, but also internally structured. For instance, statistical units may have heterogeneous origins from distinct studies or subpopulations, and features may be naturally partitioned based on experimental platforms generating them, or on information available about their roles in a given phenomenon. In a regression analysis, exploiting this known structure in the predictor dimension reduction stage that precedes modeling can be an effective way to integrate diverse data...
September 20, 2016: Biometrics
Ruosha Li, Yu Cheng, Qingxia Chen, Jason Fine
Bivariate survival data arise frequently in familial association studies of chronic disease onset, as well as in clinical trials and observational studies with multiple time to event endpoints. The association between two event times is often scientifically important. In this article, we examine the association via a novel quantile association measure, which describes the dynamic association as a function of the quantile levels. The quantile association measure is free of marginal distributions, allowing direct evaluation of the underlying association pattern at different locations of the event times...
September 9, 2016: Biometrics
Joshua Habiger, David Watts, Michael Anderson
Standard false discovery rate (FDR) procedures can provide misleading inference when testing multiple null hypotheses with heterogeneous multinomial data. For example, in the motivating study the goal is to identify species of bacteria near the roots of wheat plants (rhizobacteria) that are moderately or strongly associated with productivity. However, standard procedures discover the most abundant species even when their association is weak and fail to discover many moderate and strong associations when the species are not abundant...
September 6, 2016: Biometrics
Jian Zhang
This article proposes a method to address the problem that can arise when covariates in a regression setting are not Gaussian, which may give rise to approximately mixture-distributed errors, or when a true mixture of regressions produced the data. The method begins with non-Gaussian mixture-based marginal variable screening, followed by fitting a full but relatively smaller mixture regression model to the selected data with help of a new penalization scheme. Under certain regularity conditions, the new screening procedure is shown to possess a sure screening property even when the population is heterogeneous...
September 6, 2016: Biometrics
Leandro García Barrado, Els Coart, Tomasz Burzykowski
Estimating biomarker-index accuracy when only imperfect reference-test information is available is usually performed under the assumption of conditional independence between the biomarker and imperfect reference-test values. We propose to define a latent normally-distributed tolerance-variable underlying the observed dichotomous imperfect reference-test results. Subsequently, we construct a Bayesian latent-class model based on the joint multivariate normal distribution of the latent tolerance and biomarker values, conditional on latent true disease status, which allows accounting for conditional dependence...
September 6, 2016: Biometrics
Yingwei Peng, Jeremy M G Taylor
Model diagnosis, an important issue in statistical modeling, has not yet been addressed adequately for cure models. We focus on mixture cure models in this work and propose some residual-based methods to examine the fit of the mixture cure model, particularly the fit of the latency part of the mixture cure model. The new methods extend the classical residual-based methods to the mixture cure model. Numerical work shows that the proposed methods are capable of detecting lack-of-fit of a mixture cure model, particularly in the latency part, such as outliers, improper covariate functional form, or nonproportionality in hazards if the proportional hazards assumption is employed in the latency part...
September 6, 2016: Biometrics
Ying Liu, Yuanjia Wang, Donglin Zeng
Sequential multiple assignment randomization trial (SMART) is a powerful design to study Dynamic Treatment Regimes (DTRs) and allows causal comparisons of DTRs. To handle practical challenges of SMART, we propose a SMART with Enrichment (SMARTER) design, which performs stage-wise enrichment for SMART. SMARTER can improve design efficiency, shorten the recruitment period, and partially reduce trial duration to make SMART more practical with limited time and resource. Specifically, at each subsequent stage of a SMART, we enrich the study sample with new patients who have received previous stages' treatments in a naturalistic fashion without randomization, and only randomize them among the current stage treatment options...
September 6, 2016: Biometrics
John D Rice, Alex Tsodikov
In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one...
August 24, 2016: Biometrics
Peter Sasieni, Adam R Brentnall
Cancer survival comparisons between cohorts are often assessed by estimates of relative or net survival. These measure the difference in mortality between those diagnosed with the disease and the general population. For such comparisons methods are needed to standardize cohort structure (including age at diagnosis) and all-cause mortality rates in the general population. Standardized non-parametric relative survival measures are evaluated by determining how well they (i) ensure the correct rank ordering, (ii) allow for differences in covariate distributions, and (iii) possess robustness and maximal estimation precision...
August 23, 2016: Biometrics
Rebecca Yates Coley, Aaron J Fisher, Mufaddal Mamawala, Herbert Ballentine Carter, Kenneth J Pienta, Scott L Zeger
In this article, we present a Bayesian hierarchical model for predicting a latent health state from longitudinal clinical measurements. Model development is motivated by the need to integrate multiple sources of data to improve clinical decisions about whether to remove or irradiate a patient's prostate cancer. Existing modeling approaches are extended to accommodate measurement error in cancer state determinations based on biopsied tissue, clinical measurements possibly not missing at random, and informative partial observation of the true state...
August 22, 2016: Biometrics
Diego Tomassi, Liliana Forzani, Efstathia Bura, Ruth Pfeiffer
Motivated by a study conducted to evaluate the associations of 51 inflammatory markers and lung cancer risk, we propose several approaches of varying computational complexity for analyzing multiple correlated markers that are also censored due to lower and/or upper limits of detection, using likelihood-based sufficient dimension reduction (SDR) methods. We extend the theory and the likelihood-based SDR framework in two ways: (i) we accommodate censored predictors directly in the likelihood, and (ii) we incorporate variable selection...
August 9, 2016: Biometrics
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