Biostatistics Commons^™

Robust Estimation Of Pure/Natural Direct Effects With Mediator Measurement Error, Eric J. Tchetgen Tchetgen, Sheng Hsuan Lin

COBRA Preprint Series

Recent developments in causal mediation analysis have offered new notions of direct and indirect effects, that formalize more traditional and informal notions of mediation analysis emanating primarily from the social sciences. The pure or natural direct effect of Robins-Greenland-Pearl quantifies the causal effect of an exposure that is not mediated by a variable on the causal pathway to the outcome, and combines with the natural indirect effect to produce the total causal effect of the exposure. Sufficient conditions for identification of natural direct effects were previously given, that assume certain independencies about potential outcomes, and a rich literature on estimation …

Robust Estimation Of Pure/Natural Direct Effects With Mediator Measurement Error, Eric J. Tchetgen Tchetgen, Sheng Hsuan Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Measuring Infertility In Populations: Constructing A Standard Definition For Use With Demographic And Reproductive Health Surveys, Maya N. Mascarenhas, Hoiwan Cheung, Colin D. Mathers, Gretchen A. Stevens

Dartmouth Scholarship

Background: Infertility is a significant disability, yet there are no reliable estimates of its global prevalence. Studies on infertility prevalence define the condition inconsistently, rendering the comparison of studies or quantitative summaries of the literature difficult. This study analyzed key components of infertility to develop a definition that can be consistently applied to globally available household survey data.

Methods: We proposed a standard definition of infertility and used it to generate prevalence estimates using 53 Demographic and Health Surveys (DHS). The analysis was restricted to the subset of DHS that contained detailed fertility information collected through the reproductive health calendar. …

Genetic Modulation Of Lipid Profiles Following Lifestyle Modification Or Metformin Treatment: The Diabetes Prevention Program, Toni I. Pollin, Tamara Isakova, Kathleen A. Jablonski, Paul I.W. De Bakker, Andrew Taylor, Jarred B. Mcateer, Qing Pan, Edward Horton, Linda M. Delahanty, David Altshuler, Alan R. Shuldiner, Ronald Goldberg, Jose C. Florez, George A. Bray

Epidemiology Faculty Publications

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, …

Targeted Learning For Causality And Statistical Analysis In Medical Research, Sherri Rose, Richard J.C.M. Starmans, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The authors present the use of targeted learning methods for medical research, prepared as a chapter for the upcoming book "Statistics: Discovering Your Future Power." The targeted learning framework involves the explicit specification of the data, model, and parameter. The estimators are double robust and efficient, and can incorporate machine learning procedures such as the super learner.

Modeling Sleep Fragmentation In Populations Of Sleep Hypnograms, Bruce J. Swihart, Naresh M. Punjabi, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

We introduce methods for the analysis of large populations of sleep architectures (hypnograms) that respect the 5-state 20-transition-type structure defined by the American Academy of Sleep Medicine. By applying these methods to the hypnograms of 5598 subjects from the Sleep Heart Health Study we: 1) provide the firrst analysis of sleep hypnogram data of such size and complexity in a community cohort with a 4-level comorbidity; 2) compare 5-state 20-transition-type sleep to 3-state 6-transition-type sleep for a check of feasibility and information-loss; 3) extend current approaches to multivariate survival data analysis to populations of time-to-transition processes; and 4) provide scalable …

A Phase I Bayesian Adaptive Design To Simultaneously Optimize Dose And Schedule Assignments Both Among And Within Patients, Thomas M. Braun, Jin Zhang

The University of Michigan Department of Biostatistics Working Paper Series

In traditional schedule or dose-schedule finding designs, patients are assumed to receive their assigned dose-schedule combination throughout the trial even though the combination may be found to have an undesirable toxicity profile, which contradicts actual clinical practice. Since no systematic approach exists to optimize intra-patient dose-schedule as- signment, we propose a Phase I clinical trial design that extends existing approaches that optimize dose and schedule solely among patients by incorporating adaptive variations to dose-schedule assignments within patients as the study proceeds. Our design is based on a Bayesian non-mixture cure rate model that incorporates multiple administrations each patient receives with …

Fitting And Interpreting Continuous-Time Latent Markov Models For Panel Data, Jane M. Lange, Vladimir N. Minin

UW Biostatistics Working Paper Series

Multistate models are used to characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses according a standard continuous-time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi-Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by …

Transitions Among Health States Using 12 Measures Of Successful Aging: Results From The Cardiovascular Health Study, Stephen Thielke, Paula Diehr

UW Biostatistics Working Paper Series

Introduction

Successful aging has many dimensions, which may manifest differently in men and women and at different ages. We sought to characterize one-year transitions in 12 measures of successful aging among a large cohort of older adults.

Methods

We analyzed twelve different measures of health in the Cardiovascular Health Study: self-rated health, ADLs, IADLs, depression, cognition, timed walk, number of days spent in bed, number of blocks walked, extremity strength, recent hospitalizations, feelings about life as a whole, and life satisfaction. We dichotomized responses for each variable into “healthy” or “sick”, and estimated the prevalence of the healthy state and …

Flexible Covariate-Adjusted Exact Tests For Randomized Studies, Alisa J. Stephens, Eric J. Tchetgen Tchetgen, Victor De Gruttola

Harvard University Biostatistics Working Paper Series

No abstract provided.

Locally Efficient Estimation Of Marginal Treatment Effects When Outcomes Are Correlated: Is The Prize Worth The Chase?, Alisa J. Stephens, Eric J. Tchetgen Tchetgen, Victor De Gruttola

Harvard University Biostatistics Working Paper Series

No abstract provided.

Fall In C-Peptide During First 2 Years From Diagnosis: Evidence Of At Least Two Distinct Phases From Composite Type 1 Diabetes Trialnet Data., Carla J. Greenbaum, Craig A. Beam, David Boulware, Stephen E. Gitelman, Peter A. Gottlieb, Kevan C. Herold, John M. Lachin, Paula L. Mcgee, Jerry P. Palmer, Mark D. Pescovitz, Heidi Krause-Steinrauf, Jay S. Skyler, Jay M. Sosenko

Epidemiology Faculty Publications

Interpretation of clinical trials to alter the decline in β-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of β-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 …

Genetic Susceptibility To Type 2 Diabetes: A Global Meta-Analysis Studying The Genetic Differences In Tunisian Populations, Rym Berhouma, S. Kouidhi, M. Ammar, H. Abid, T. Baroudi, H. Ennafaa, A. Benammar-Elgaaied

Human Biology Open Access Pre-Prints

The present study is the first meta-analysis to evaluate type 2 diabetes (T2D) - associated polymorphisms in cohorts originated from several Tunisian regions. In fact, we evaluated the effect of seven polymorphisms in the following genes; PPARg ( Pro12Ala), TNFα (-308A/G), ENPP1(K121Q), TCF7L2(rs7903146 C/T), MTHFR( C677T), ACE(I/D), CAPN10(3R/2R) on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, centre or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled ORs were computed by the fixed-effects method of Mantel-Haenszel if no heterogeneity between …

Bayesian Adaptive Designs For Early Phase Clinical Trials, Chunyan Cai

Dissertations and Theses (Open Access)

My dissertation focuses mainly on Bayesian adaptive designs for phase I and phase II clinical trials. It includes three specific topics: (1) proposing a novel two-dimensional dose-finding algorithm for biological agents, (2) developing Bayesian adaptive screening designs to provide more efficient and ethical clinical trials, and (3) incorporating missing late-onset responses to make an early stopping decision.

Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which toxicity and efficacy monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as …

Adaptive Matching In Randomized Trials And Observational Studies, Mark J. Van Der Laan, Laura Balzer, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

In many randomized and observational studies the allocation of treatment among a sample of n independent and identically distributed units is a function of the covariates of all sampled units. As a result, the treatment labels among the units are possibly dependent, complicating estimation and posing challenges for statistical inference. For example, cluster randomized trials frequently sample communities from some target population, construct matched pairs of communities from those included in the sample based on some metric of similarity in baseline community characteristics, and then randomly allocate a treatment and a control intervention within each matched pair. In this case, …

A Comparison Of Methods Of Analysis To Control For Confounding In A Cohort Study Of A Dietary Intervention, Esinhart Hali

Theses and Dissertations

Comparing samples from different populations can be biased by confounding. There are several statistical methods that can be used to control for confounding. These include; multiple linear regression, propensity score matching, propensity score/logit of propensity score as a single covariate in a linear regression model, stratified analysis using propensity score quintiles, weighted analysis using propensity scores or trimmed scores. The data were from two studies of a dietary intervention (FIBERR and RNP). The outcome variable was change from baseline to one month for eight outcome measures; fat, fiber, and fruits/ vegetables behavior, fat, fiber, and fruits/vegetables intentions, fat and fruits/vegetables …

The Effect Of Baseline Cluster Stratification On The Power Of Pre-Post Analysis, Fengjiao Hu

Theses and Dissertations

The purpose of study is to check whether the power of detecting the effect of intervention versus control in a pre- and post-study can be increased by using a stratified randomized controlled design. A stratified randomized controlled design with two study arms and two time points, where strata are determined by clustering on baseline outcomes of the primary measure, is considered. A modified hierarchical clustering algorithm is developed which guarantees optimality as well as requiring each cluster to have at least one subject per study arm. The power is calculated based on simulated bivariate normal distributed primary measures with mixture …

Does Pair-Matching On Ordered Baseline Measures Increase Power: A Simulation Study, Yan Jin

Theses and Dissertations

It has been shown that pair-matching on an ordered baseline with normally distributed measures reduces the variance of the estimated treatment effect (Park and Johnson, 2006). The main objective of this study is to examine if pair-matching improves the power when the distribution is a mixture of two normal distributions. Multiple scenarios with a combination of different sample sizes and parameters are simulated. The power curves are provided for three cases, with and without matching, as follows: analysis of post-intervention data only, adding baseline as a covariate, and classic pre-post comparison. The study shows that the additional variance reduction provided …

Analytic Programming With Fmri Data: A Quick-Start Guide For Statisticians Using R, Ani Eloyan, Shanshan Li, John Muschelli, Jim Pekar, Stewart Mostofsky, Brian S. Caffo

Johns Hopkins University, Dept. of Biostatistics Working Papers

Functional magnetic resonance imaging (fMRI) is a thriving field that plays an important role in medical imaging analysis, biological and neuroscience research and practice. This manuscript gives a didactic introduction to the statistical analysis of fMRI data using the R project along with the relevant R code. The goal is to give tatisticians who would like to pursue research in this area a quick start for programming with fMRI data along with the available data visualization tools.

Assessing Movement Of Fish Through Spectral Analysis Of Otolith Life History Scans, Renee Reilly Hoover

OES Theses and Dissertations

The ability to accurately measure movement timing across environmental gradients is fundamental for testing hypotheses in marine ecology that deal with ingress, egress, and migration of fish. Timing and patterns of movement have been estimated using life-history scans of the chemical signatures encoded in fish otoliths (ear stones). I provide a quantitative approach to examining life history scan data using spectral analysis, which retrospectively measures the movement timing for individual fish. Sagittal otoliths from juvenile Atlantic croaker (Micropogonias undulates) and adult black sea bass (Centropristis striata) were sampled using laser ablation inductively coupled plasma mass spectrometry …