Design of Experiments and Sample Surveys Commons^™

Non-Inferiority Testing: Kernel Estimation And Overlap Measure, Larie C. Ward

Electronic Theses and Dissertations

In non-inferiority testing, the decision of whether a proposed treatment is non-inferior to a reference treatment depends on model assumptions and choices of acceptable tolerance limits. Here, we consider a method that employs kernels to estimate the probability density functions of both the experimental and reference populations from two independent samples. Based on these densities, we introduce a quantity called the overlap coefficient or overlap measure. A bootstrap technique is helpful in exploring the distribution and variance empirically. We derive the distribution of this measure and define a hypothesis test that can be applied to the non-inferiority setting under some …

A Two-Stage Design For Comparing Binomial Treatments With A Standard, Cecelia K. Schmidt

UNF Graduate Theses and Dissertations

We propose a method for comparing success rates of several populations among each other and against a desired standard success rate. This design is appropriate for a situation in which all experimental treatments have only two outcomes that can be considered “success”and “failure” respectively. The goal is to identify which treatment has the highest rate of success that is also higher than the desired standard. The design combines elements of both hypothesis testing and statistical selection. At the first stage, if none of the samples have a number of successes above the appropriate standard for the design, the experiment is …

Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu

Electronic Theses and Dissertations

In Clinical Practice, combination drug therapy has become common in treating many disease conditions. The purpose of these combinations is often to ensure optimal efficacy and to reduce adverse effects that may arise from monotherapy. Clinical trials have also been conducted to ensure efficacy and safety of these combinations before they are introduced into the market. However, adverse effects still occur with combination therapies. The objective of this study is to (1) To determine a region of optimum doses of Drug A and Drug B in combination while focusing on efficacy alone (2) To determine a region of optimum doses …

Further Advances For The Sequential Multiple Assignment Randomized Trial (Smart), Tianjiao Dai

Dissertations & Theses (Open Access)

ABSTRACT

FURTHER ADVANCES FOR THE SEQUENTIAL MULTIPLE ASSIGNMENT RANDOMIZED TRIAL (SMART)

Tianjiao Dai, M.S.

Advisory Professor: Sanjay Shete, Ph.D.

Sequential multiple assignment randomized trial (SMART) designs have been developed these years for studying adaptive interventions. In my Ph.D. study, I mainly investigate how to further improve SMART designs and optimize the interventions for each individual in the trial. My dissertation has focused on two topics of SMART designs.

1) Developing a novel SMART design that can reduce the cost and side effects associated with the interventions and proposing the corresponding analytic methods. I have developed a time-varying SMART design in …

A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed …

When Is A Randomised Controlled Trial Health Equity Relevant? Development And Validation Of A Conceptual Framework, J. Jull, M. Whitehead, M. Petticrew, E. Kristjansson, D. Gough, Sarah Baird, +Several Additional Authors

Global Health Faculty Publications

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials.

Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials.

Results A randomised trial can …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Simulations Of A New Response-Adaptive Biased Coin Design, Aleksandra Stein

Department of Statistics: Dissertations, Theses, and Student Work

Modern medical experiments accrue and treat patients--hence obtain treatment response data--throughout a trial. Designs which prospectively plan to modify patient allocation by leveraging accumulating data are response-adaptive randomization (RAR) designs. Many such designs attempt to balance the desire to bias assignment proportions towards a treatment which is performing better against the need to maintain randomization in the face of continued equipoise.

This dissertation consists of simulated investigations into frequentist and ethical properties of an new RAR biased coin design. Chapter 2 proposes a new adaptive design for phase III clinical trials, a modification of the 2001 Bandyopadhyay and Biswas biased …

Adaptive Randomization Designs, Jenna Colavincenzo

Statistics

Adaptive design methodologies use prior information to develop a clinical trial design. The goal of an adaptive design is to maintain the integrity and validity of the study while giving the researcher flexibility in identifying the optimal treatment. An example of an adaptive design can be seen in a basic pharmaceutical trial. There are three phases of the overall trial to compare treatments and experimenters use the information from the previous phase to make changes to the subsequent phase before it begins.

Adaptive design methods have been in practice since the 1970s, but have become increasingly complex ever since. One …

Estimating The Impact Of Community-Level Interventions: The Search Trial And Hiv Prevention In Sub-Saharan Africa, Laura Balzer, Maya Petersen, Joshua Schwab, Mark Van Der Laan

Laura B. Balzer

Evaluation of community level interventions to prevent HIV infection presents significant methodological challenges. Even when it is feasible to randomly assign a treatment versus control level of the intervention to each community in a sample, measurement of incident HIV infection remains difficult. In this talk we describe an experimental design developed for the SEARCH Trial, a large community randomized trial that will evaluate the impact of expanded treatment on incident HIV and other outcomes. Regular community-wide testing campaigns are conducted and a random sample of community members who fail to attend a campaign are tracked. The data generated by this …

Why Match In Individually And Cluster Randomized Trials?, Laura B. Balzer, Maya L. Petersen, Mark J. Van Der Laan

Laura B. Balzer

The decision to match individuals or clusters in randomized trials is motivated by both practical and statistical concerns. Matching protects against chance imbalances in baseline covariate distributions and is thought to improve study credibility. Matching is also implemented to increase study power. This article compares the asymptotic efficiency of the pair-matched design, where units are matched on baseline covariates and the treatment randomized within pairs, to the independent design, where units are randomly paired and the treatment randomized within pairs. We focus on estimating the average treatment effect and use the efficient influence curve to understand the information provided by …

Why Match In Individually And Cluster Randomized Trials?, Laura Balzer, Maya Petersen, Mark Van Der Laan

Laura B. Balzer

The decision to match individuals or clusters in randomized trials is motivated by both practical and statistical concerns. Matching protects against chance imbalances in baseline covariate distributions and is thereby thought to improve study credibility. Matching is also implemented to increase study power. Analogue to Rose and van der Laan (2009), this article investigates the asymptotic efficiency of pair-matching individuals or clusters relative to not matching in randomized trials. We focus on estimating the average treatment effect. We use the efficient influence curve to understand the information provided by each design for estimation of the target causal parameter. Our approach …

Software Internationalization: A Framework Validated Against Industry Requirements For Computer Science And Software Engineering Programs, John Huân Vũ

Master's Theses

View John Huân Vũ's thesis presentation at http://youtu.be/y3bzNmkTr-c.

In 2001, the ACM and IEEE Computing Curriculum stated that it was necessary to address "the need to develop implementation models that are international in scope and could be practiced in universities around the world." With increasing connectivity through the internet, the move towards a global economy and growing use of technology places software internationalization as a more important concern for developers. However, there has been a "clear shortage in terms of numbers of trained persons applying for entry-level positions" in this area. Eric Brechner, Director of Microsoft Development Training, suggested …

New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski

COBRA Preprint Series

As the field of functional genetics and genomics is beginning to mature, we become confronted with new challenges. The constant drop in price for sequencing and gene expression profiling as well as the increasing number of genetic and genomic variables that can be measured makes it feasible to address more complex questions. The success with rare diseases caused by single loci or genes has provided us with a proof-of-concept that new therapies can be developed based on functional genomics and genetics.

Common diseases, however, typically involve genetic epistasis, genomic pathways, and proteomic pattern. Moreover, to better understand the underlying biologi-cal …

New Estimating Methods For Surrogate Outcome Data, Bin Nan

The University of Michigan Department of Biostatistics Working Paper Series

Surrogate outcome data arise frequently in medical research. The true outcomes of interest are expensive or hard to ascertain, but measurements of surrogate outcomes (or more generally speaking, the correlates of the true outcomes) are usually available. In this paper we assume that the conditional expectation of the true outcome given covariates is known up to a finite dimensional parameter. When the true outcome is missing at random, the e±cient score function for the parameter in the conditional mean model has a simple form, which is similar to the generalized estimating functions. There is no integral equation involved as in …

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

The University of Michigan Department of Biostatistics Working Paper Series

Randomized allocation of treatments is a cornerstone of experimental design, but has drawbacks when a limited set of individuals are willing to be randomized, or the act of randomization undermines the success of the treatment. Choice-based experimental designs allow a subset of the participants to choose their treatments. We discuss here causal inferences for experimental designs where some participants are randomly allocated to treatments and others receive their treatment preference. This paper was motivated by the “Women Take Pride” (WTP) study (Janevic et al., 2001), a doubly randomized preference trail (DRPT) to assess behavioral interventions for women with heart disease. …

Mixtures Of Varying Coefficient Models For Longitudinal Data With Discrete Or Continuous Non-Ignorable Dropout, Joseph W. Hogan, Xihong Lin, Benjamin A. Herman

The University of Michigan Department of Biostatistics Working Paper Series

The analysis of longitudinal repeated measures data is frequently complicated by missing data due to informative dropout. We describe a mixture model for joint distribution for longitudinal repeated measures, where the dropout distribution may be continuous and the dependence between response and dropout is semiparametric. Specifically, we assume that responses follow a varying coefficient random effects model conditional on dropout time, where the regression coefficients depend on dropout time through unspecified nonparametric functions that are estimated using step functions when dropout time is discrete (e.g., for panel data) and using smoothing splines when dropout time is continuous. Inference under the …

Design Of The Hiv Prevention Trials Network (Hptn) Protocol 054: A Cluster Randomized Crossover Trial To Evaluate Combined Access To Nevirapine In Developing Countries, Jim Hughes, Robert L. Goldenberg, Catherine M. Wilfert, Megan Valentine, Kasonde G. Mwinga, Laura A. Guay, Francis Mmiro, Jeffrey S. A. Stringer

UW Biostatistics Working Paper Series

HPTN054 is a cluster randomized trial designed to compare two approaches to providing single dose nevirapine to HIV-seropositive mothers and their infants to prevent mother-to-child transmission of HIV in resource limited settings. A number of challenging issues arose during the design of this trial. Most importantly, the need to achieve high participation rates among pregnant, HIV-seropositive women in selected prenatal care clinics led us to develop a method of collecting anonymous and unlinked information on a key surrogate endpoint instead of pursuing linked and identified information on a clinical endpoint. In addition, since group counseling is the standard model for …

Estimating Disease Prevalence In Two-Phase Studies, Todd A. Alonzo, Margaret S. Pepe

UW Biostatistics Working Paper Series

Disease prevalence is ideally estimated using a “gold standard” to ascertain true disease status on all subjects in a population of interest. In practice, however, the gold standard may be too costly or invasive to be applied to all subjects, in which case a two-phase design is often employed. Phase 1 data consisting of inexpensive and non-invasive screening tests on all study subjects are used to determine the subjects that receive the gold standard in the second phase. Naïve estimates of prevalence in two-phase studies can be biased (verification bias). Imputation and re-weighting estimators are often used to avoid this …

Sources Of Epidemiological Equivocacy, Timothy Sly

RISK: Health, Safety & Environment (1990-2002)

Mr. Sly discusses five sources of uncertainty and ambiguity in health and medical research that can interfere with decision making.