Biostatistics Commons^™

A Review Of Software For Analyzing Molecular Sequences, Haema Nilakanta, Kimberly L. Drews, Suzanne Firrell, Mary A. Foulkes, Kathleen A. Jablonski

GW Biostatistics Center

Background Over the past ten years, there has been an explosion of microbiome research. Many software packages for analyzing microbial sequences such as the 16S gene from 454 sequencers and Illumina platforms are available. But for a new researcher, it is difficult to know which package to choose. We present a systematic review of packages for the analysis of molecular sequences used to describe and compare microbial communities. This review gives students and researchers information to help choose the best analytic pipeline for their project. To the best of our knowledge, this is the first review of such software.

Findings …

Constrained Bayesian Estimation Of Inverse Probability Weights For Nonmonotone Missing Data, Baoluo Sun, Eric J. Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

No abstract provided.

Testing Gene-Environment Interactions In The Presence Of Measurement Error, Chongzhi Di, Li Hsu, Charles Kooperberg, Alex Reiner, Ross Prentice

UW Biostatistics Working Paper Series

Complex diseases result from an interplay between genetic and environmental risk factors, and it is of great interest to study the gene-environment interaction (GxE) to understand the etiology of complex diseases. Recent developments in genetics field allows one to study GxE systematically. However, one difficulty with GxE arises from the fact that environmental exposures are often measured with error. In this paper, we focus on testing GxE when the environmental exposure E is subject to measurement error. Surprisingly, contrast to the well-established results that the naive test ignoring measurement error is valid in testing the main effects, we find that …

Personalized Evaluation Of Biomarker Value: A Cost-Benefit Perspective, Ying Huang, Eric Laber

UW Biostatistics Working Paper Series

For a patient who is facing a treatment decision, the added value of information provided by a biomarker depends on the individual patient’s expected response to treatment with and without the biomarker, as well as his/her tolerance of disease and treatment harm. However, individualized estimators of the value of a biomarker are lacking. We propose a new graphical tool named the subject-specific expected benefit curve for quantifying the personalized value of a biomarker in aiding a treatment decision. We develop semiparametric estimators for two general settings: i) when biomarker data are available from a randomized trial; and ii) when biomarker …

Identifying Genetic Variants For Heart Rate Variability In The Acetylcholine Pathway, Harriëtte Riese, Loretto M. Muñoz, Catharina A. Hartman, Xiuhua Ding, Shaoyong Su, Albertine J. Oldehinkel, Arie M. Van Roon, Peter J. Van Der Most, Joop Lefrandt, Ron T. Gansevoort, Pim Van Der Harst, Niek Verweij, Carmilla M. M. Licht, Dorret I. Boomsma, Jouke-Jan Hottenga, Gonneke Willemsen, Brenda W. J. H. Penninx, Ilja M. Nolte, Eco J. C. De Geus, Xiaoling Wang, Harold Snieder

Biostatistics Faculty Publications

Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a …

Cross-Design Synthesis For Extending The Applicability Of Trial Evidence When Treatment Effect Is Heterogeneous-I. Methodology, Ravi Varadhan, Carlos Weiss

Johns Hopkins University, Dept. of Biostatistics Working Papers

Randomized controlled trials (RCTs) provide reliable evidence for approval of new treatments, informing clinical practice, and coverage decisions. The participants in RCTs are often not a representative sample of the larger at-risk population. Hence it is argued that the average treatment effect from the trial is not generalizable to the larger at-risk population. An essential premise of this argument is that there is significant heterogeneity in the treatment effect (HTE). We present a new method to extrapolate the treatment effect from a trial to a target group that is inadequately represented in the trial, when HTE is present. Our method …

Cross-Design Synthesis For Extending The Applicability Of Trial Evidence When Treatment Effect Is Heterogeneous. Part Ii. Application And External Validation, Carlos Weiss, Ravi Varadhan

Johns Hopkins University, Dept. of Biostatistics Working Papers

Randomized controlled trials (RCTs) generally provide the most reliable evidence. When participants in RCTs are selected with respect to characteristics that are potential treatment effect modifiers, the average treatment effect from the trials may not be applicable to a specific target population. We present a new method to project the treatment effect from a RCT to a target group that is inadequately represented in the trial when there is heterogeneity in the treatment effect (HTE). The method integrates RCT and observational data through cross-design synthesis. An essential component is to identify HTE and a calibration factor for unmeasured confounding for …

Enhanced Precision In The Analysis Of Randomized Trials With Ordinal Outcomes, Iván Díaz, Elizabeth Colantuoni, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

We present a general method for estimating the effect of a treatment on an ordinal outcome in randomized trials. The method is robust in that it does not rely on the proportional odds assumption. Our estimator leverages information in prognostic baseline variables, and has all of the following properties: (i) it is consistent; (ii) it is locally efficient; (iii) it is guaranteed to match or improve the precision of the standard, unadjusted estimator. To the best of our knowledge, this is the first estimator of the causal relation between a treatment and an ordinal outcome to satisfy these properties. We …

Applications Of The Wei-Lachin Multivariate One-Sided Test For Multiple Outcomes On Possibly Different Scales, John M. Lachin

GW Biostatistics Center

Many studies aim to assess whether a therapy has a beneficial effect on multiple outcomes simultaneously relative to a control. Often the joint null hypothesis of no difference for the set of outcomes is tested using separate tests with a correction for multiple tests, or using a multivariate T2-like MANOVA or global test. However, a more powerful test in this case is a multivariate one-sided or one-directional test directed at detecting a simultaneous beneficial treatment effect on each outcome, though not necessarily of the same magnitude. The Wei-Lachin test is a simple 1 df test obtained from a simple …

Optimal Bayesian Adaptive Trials When Treatment Efficacy Depends On Biomarkers, Yifan Zhang, Lorenzo Trippa, Giovanni Parmigiani

Harvard University Biostatistics Working Paper Series

No abstract provided.

Hiv Testing Implementation In Two Urban Cities: Practice, Policy And Perceived Barriers, Camden J. Hallmark, Jennifer Skillicorn, Thomas P. Giordano, Jessica A. Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

Background

Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

Methods

We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

Results

In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …

Generalized Quantile Treatment Effect, Sergio Venturini, Francesca Dominici, Giovanni Parmigiani

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Bayesian Approach To Joint Modeling Of Menstrual Cycle Length And Fecundity, Kirsten J. Lum, Rajeshwari Sundaram, Germaine M. Buck-Louis, Thomas A. Louis

Johns Hopkins University, Dept. of Biostatistics Working Papers

Female menstrual cycle length is thought to play an important role in couple fecundity, or the biologic capacity for reproduction irrespective of pregnancy intentions. A complete assessment of the association between menstrual cycle length and fecundity requires a model that accounts for multiple risk factors (both male and female) and the couple's intercourse pattern relative to ovulation. We employ a Bayesian joint model consisting of a mixed effects accelerated failure time model for longitudinal menstrual cycle lengths and a hierarchical model for the conditional probability of pregnancy in a menstrual cycle given no pregnancy in previous cycles of trying, in …

Using Graphs To Characterize Nationwide Physician Referral Networks, Ding Tong, Shu-Xia Li, Isuru Ranasinghe, Sudhakar Nuti, Hongyu Zhao, Harlan Krumholz

Yale Day of Data

AIM:

Evaluating physician referral network characteristics can help to understand how physicians and hospitals interact to provide patient services within the US healthcare system and ultimately how this may influence patient outcomes.

METHOD:

We used the 2012-2013 national Physician Referral data from the Centers for Medicare & Medicaid Services (CMS), which consists of 73,071,804 pairs of referrals from one health provider to another in calendar year 2012 and the first two quarters of year 2013 within 30 days of care. These referrals are from 642,144 national-wide physicians and 4,811 hospitals. We obtained information for each provider, physician or hospital, from …

Stratified Meta-Analysis To Examine Data Biases In Lung Cancer Studies Of Refinery Workers, Sherman Selix

Yale Day of Data

Petroleum refineries employ a variety of workers who historically experienced different potentials for asbestos exposure depending on job tasks. Associations between petroleum refinery work and lung cancer related to occupational asbestos exposure have been quantified among various locations, corporations, and time periods. To combine the data from several individual refinery studies and examine an overall effect, a systematic review and stratified meta-analysis was employed. Using set search terms among four databases, 112 potential publications were identified, of which 29 qualified for meta-analysis. Risk estimates and confidence intervals were extracted from these publications to construct four separate datasets. Inverse variance weighting …

Online Targeted Learning, Mark J. Van Der Laan, Samuel D. Lendle

U.C. Berkeley Division of Biostatistics Working Paper Series

We consider the case that the data comes in sequentially and can be viewed as sample of independent and identically distributed observations from a fixed data generating distribution. The goal is to estimate a particular path wise target parameter of this data generating distribution that is known to be an element of a particular semi-parametric statistical model. We want our estimator to be asymptotically efficient, but we also want that our estimator can be calculated by updating the current estimator based on the new block of data without having to revisit the past data, so that it is computationally much …

Lung Flute Improves Symptoms And Health Status In Copd With Chronic Bronchitis: A 26 Week Randomized Controlled Trial, Sanjay Sethi, Jingjing Yin, Pamela K. Anderson

Biostatistics: Faculty Publications

Background: Chronic obstructive pulmonary disease (COPD) is characterized by mucus hypersecretion that contributes to disease related morbidity and is associated with increased mortality. The Lung Flute® is a new respiratory device that produces a low frequency acoustic wave with moderately vigorous exhalation to increase mucus clearance. We hypothesized that the Lung Flute, used on a twice daily basis will provide clinical benefit to patients with COPD with chronic bronchitis.

Methods: We performed a 26 week randomized, non-intervention controlled, single center, open label trial in 69 patients with COPD and Chronic Bronchitis. The primary endpoint was change in respiratory symptoms measured …

Estimation Of The Overall Treatment Effect In The Presence Of Interference In Cluster-Randomized Trials Of Infectious Disease Prevention, Nicole Bohme Carnegie, Rui Wang, Victor De Gruttola

Harvard University Biostatistics Working Paper Series

No abstract provided.

Cox Regression Models With Functional Covariates For Survival Data, Jonathan E. Gellar, Elizabeth Colantuoni, Dale M. Needham, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge …

Targeted Learning Of An Optimal Dynamic Treatment, And Statistical Inference For Its Mean Outcome, Mark J. Van Der Laan, Alexander R. Luedtke

U.C. Berkeley Division of Biostatistics Working Paper Series

Suppose we observe n independent and identically distributed observations of a time-dependent random variable consisting of baseline covariates, initial treatment and censoring indicator, intermediate covariates, subsequent treatment and censoring indicator, and a final outcome. For example, this could be data generated by a sequentially randomized controlled trial, where subjects are sequentially randomized to a first line and second line treatment, possibly assigned in response to an intermediate biomarker, and are subject to right-censoring. In this article we consider estimation of an optimal dynamic multiple time-point treatment rule defined as the rule that maximizes the mean outcome under the dynamic treatment, …