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Dan Jackson, Sylwia Bujkiewicz, Martin Law, Richard D Riley, Ian R White
Random-effects meta-analyses are very commonly used in medical statistics. Recent methodological developments include multivariate (multiple outcomes) and network (multiple treatments) meta-analysis. Here, we provide a new model and corresponding estimation procedure for multivariate network meta-analysis, so that multiple outcomes and treatments can be included in a single analysis. Our new multivariate model is a direct extension of a univariate model for network meta-analysis that has recently been proposed...
August 14, 2017: Biometrics
Veronika Skrivankova, Patrick J Heagerty
Clinical practice may be enhanced by use of person-level information that could guide treatment choice and lead to better outcomes for both treated individuals and for the population. The scientific challenge is to identify and validate those factors that can reliably be used to target treatment, and to accurately quantify the expected treatment benefit as a function of candidate markers. Our proposal is to explicitly focus on smooth non-parametric evaluation of a canonical single index score that estimates the expected treatment benefit associated with patient characteristics...
August 7, 2017: Biometrics
Sehee Kim, Douglas E Schaubel, Keith P McCullough
We propose a C-index (index of concordance) applicable to recurrent event data. The present work addresses the dearth of measures for quantifying a regression model's ability to discriminate with respect to recurrent event risk. The data which motivated the methods arise from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a long-running prospective international study of end-stage renal disease patients on hemodialysis. We derive the theoretical properties of the measure under the proportional rates model (Lin et al...
August 3, 2017: Biometrics
Qingning Zhou, Jianwen Cai, Haibo Zhou
Epidemiologic studies and disease prevention trials often seek to relate an exposure variable to a failure time that suffers from interval-censoring. When the failure rate is low and the time intervals are wide, a large cohort is often required so as to yield reliable precision on the exposure-failure-time relationship. However, large cohort studies with simple random sampling could be prohibitive for investigators with a limited budget, especially when the exposure variables are expensive to obtain. Alternative cost-effective sampling designs and inference procedures are therefore desirable...
August 3, 2017: Biometrics
Yuping Zhang, Zhengqing Ouyang
We consider a research scenario motivated by integrating multiple sources of information for better knowledge discovery in diverse dynamic biological processes. Given two longitudinal high-dimensional datasets for a group of subjects, we want to extract shared latent trends and identify relevant features. To solve this problem, we present a new statistical method named as joint principal trend analysis (JPTA). We demonstrate the utility of JPTA through simulations and applications to gene expression data of the mammalian cell cycle and longitudinal transcriptional profiling data in response to influenza viral infections...
July 31, 2017: Biometrics
You Wu, Jeremy Gaskins, Maiying Kong, Susmita Datta
Phosphorylated proteins provide insight into tumor etiology and are used as diagnostic, prognostic, and therapeutic markers of complex diseases. However, pre-analytic variations, such as freezing delay after biopsy acquisition, often occur in real hospital settings and potentially lead to inaccurate results. The objective of this work is to develop statistical methodology to assess the stability of phosphorylated proteins under short-time cold ischemia. We consider a hierarchical model to determine if phosphorylation abundance of a protein at a particular phosphorylation site remains constant or not during cold ischemia...
July 25, 2017: Biometrics
Emily L Butler, Eric B Laber, Sonia M Davis, Michael R Kosorok
Precision medicine seeks to provide treatment only if, when, to whom, and at the dose it is needed. Thus, precision medicine is a vehicle by which healthcare can be made both more effective and efficient. Individualized treatment rules operationalize precision medicine as a map from current patient information to a recommended treatment. An optimal individualized treatment rule is defined as maximizing the mean of a pre-specified scalar outcome. However, in settings with multiple outcomes, choosing a scalar composite outcome by which to define optimality is difficult...
July 25, 2017: Biometrics
Karl Mertens, Stijn Vansteelandt
Structural nested failure time models (SNFTMs) are models for the effect of a time-dependent exposure on a survival outcome. They have been introduced along with so-called G-estimation methods to provide valid adjustment for time-dependent confounding induced by time-varying variables. Adjustment for informative censoring in SNFTMs is possible via inverse probability of censoring weighting (IPCW). In the presence of considerable dropout, this can imply substantial information loss and consequently imprecise effect estimates...
July 25, 2017: Biometrics
Weining Shen, Jing Ning, Ying Yuan, Anna S Lok, Ziding Feng
There is an increasing need to construct a risk-prediction scoring system for survival data and identify important risk factors (e.g., biomarkers) for patient screening and treatment recommendation. However, most existing methodologies either rely on strong model assumptions (e.g., proportional hazards) or only handle binary outcomes. In this article, we propose a flexible method that simultaneously selects important risk factors and identifies the optimal linear combination of risk factors by maximizing a pseudo-likelihood function based on the time-dependent area under the receiver operating characteristic curve...
July 25, 2017: Biometrics
Tian Dai, Ying Guo, Limin Peng, Amita K Manatunga
Assessing agreement is often of interest in biomedical and clinical research when measurements are obtained on the same subjects by different raters or methods. Most classical agreement methods have been focused on global summary statistics, which cannot be used to describe various local agreement patterns. The objective of this work is to study the local agreement pattern between two continuous measurements subject to censoring. In this article, we propose a new agreement measure based on bivariate hazard functions to characterize the local agreement pattern between two correlated survival outcomes...
July 19, 2017: Biometrics
Qianchuan He, Yang Liu, Ulrike Peters, Li Hsu
Somatic mutations are the driving forces for tumor development, and recent advances in cancer genome sequencing have made it feasible to evaluate the association between somatic mutations and cancer-related traits in large sample sizes. However, despite increasingly large sample sizes, it remains challenging to conduct statistical analysis for somatic mutations, because the vast majority of somatic mutations occur at very low frequencies. Furthermore, cancer is a complex disease and it is often accompanied by multiple traits that reflect various aspects of cancer; how to combine the information of these traits to identify important somatic mutations poses additional challenges...
July 19, 2017: Biometrics
Yijian Huang, Ching-Yun Wang
Many survival studies have error-contaminated covariates due to the lack of a gold standard of measurement. Furthermore, the error distribution can depend on the true covariates but the structure may be difficult to characterize; heteroscedasticity is a common manifestation. We suggest a novel dependent measurement error model with minimal assumptions on the dependence structure, and propose a new functional modeling method for Cox regression when an instrumental variable is available. This proposal accommodates much more general error contamination than existing approaches including nonparametric correction methods of Huang and Wang (2000, Journal of the American Statistical Association 95, 1209-1219; 2006, Statistica Sinica 16, 861-881)...
July 6, 2017: Biometrics
Sai H Dharmarajan, Douglas E Schaubel, Rajiv Saran
It is often of interest to compare centers or healthcare providers on quality of care delivered. We consider the setting where evaluation of center performance on multiple competing events is of interest. We propose estimating center effects through cause-specific proportional hazards frailty models that allow correlation among a center's cause-specific effects. Estimation of our model proceeds via penalized partial likelihood and is implemented in R. To evaluate center performance, we also propose a directly standardized excess cumulative incidence (ECI) measure...
July 6, 2017: Biometrics
Sofía S Villar, William F Rosenberger
We introduce a non-myopic, covariate-adjusted response adaptive (CARA) allocation design for multi-armed clinical trials. The allocation scheme is a computationally tractable procedure based on the Gittins index solution to the classic multi-armed bandit problem and extends the procedure recently proposed in Villar et al. (2015). Our proposed CARA randomization procedure is defined by reformulating the bandit problem with covariates into a classic bandit problem in which there are multiple combination arms, considering every arm per each covariate category as a distinct treatment arm...
July 6, 2017: Biometrics
Richard J Barker, Matthew R Schofield, William A Link, John R Sauer
N-mixture models describe count data replicated in time and across sites in terms of abundance N and detectability p. They are popular because they allow inference about N while controlling for factors that influence p without the need for marking animals. Using a capture-recapture perspective, we show that the loss of information that results from not marking animals is critical, making reliable statistical modeling of N and p problematic using just count data. One cannot reliably fit a model in which the detection probabilities are distinct among repeat visits as this model is overspecified...
July 3, 2017: Biometrics
Ying Huang
This article focuses on the evaluation of vaccine-induced immune responses as principal surrogate markers for predicting a given vaccine's effect on the clinical endpoint of interest. To address the problem of missing potential outcomes under the principal surrogate framework, we can utilize baseline predictors of the immune biomarker(s) or vaccinate uninfected placebo recipients at the end of the trial and measure their immune biomarkers. Examples of good baseline predictors are baseline immune responses when subjects enrolled in the trial have been previously exposed to the same antigen, as in our motivating application of the Zostavax Efficacy and Safety Trial (ZEST)...
June 26, 2017: Biometrics
Zhonghua Liu, Xihong Lin
We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics...
June 26, 2017: Biometrics
Brandon Koch, David M Vock, Julian Wolfson
The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this article, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models...
June 21, 2017: Biometrics
Richard Huggins, Jakub Stoklosa, Cameron Roach, Paul Yip
Sparse capture-recapture data from open populations are difficult to analyze using currently available frequentist statistical methods. However, in closed capture-recapture experiments, the Chao sparse estimator (Chao, 1989, Biometrics 45, 427-438) may be used to estimate population sizes when there are few recaptures. Here, we extend the Chao (1989) closed population size estimator to the open population setting by using linear regression and extrapolation techniques. We conduct a small simulation study and apply the models to several sparse capture-recapture data sets...
June 20, 2017: Biometrics
Ajit C Tamhane, Jiangtao Gou, Christopher Jennison, Cyrus R Mehta, Teresa Curto
Glimm et al. (2010) and Tamhane et al. (2010) studied the problem of testing a primary and a secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with K=2 looks. In this article, we greatly extend the previous results to multiple (K>2) looks. If the familywise error rate (FWER) is to be controlled at a preassigned α level then it is clear that the primary boundary must be of level α. We show under what conditions one α-level primary boundary is uniformly more powerful than another...
June 6, 2017: Biometrics
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