Clinical Trials Commons^™

Methodological Issues In Design And Analysis Of Studies With Correlated Data In Health Research, Jinhui Ma

Open Access Dissertations and Theses

Correlated data with complex association structures arise from longitudinal studies and cluster randomized trials. However, some methodological challenges in the design and analysis of such studies or trials have not been overcome. In this thesis, we address three of the challenges: 1) Power analysis for population based longitudinal study investigating gene-environment interaction effects on chronic disease: For longitudinal studies with interest in investigating the gene-environment interaction in disease susceptibility and progression, rigorous statistical power estimation is crucial to ensure that such studies are scientifically useful and cost-effective since human genome epidemiology is expensive. However conventional sample size calculations for longitudinal ...

An Evaluation Of Inferential Procedures For Adaptive Clinical Trial Designs With Pre-Specified Rules For Modifying The Sample Size, Greg P. Levin, Sarah C. Emerson, Scott S. Emerson

UW Biostatistics Working Paper Series

Many papers have introduced adaptive clinical trial methods that allow modifications to the sample size based on interim estimates of treatment effect. There has been extensive commentary on type I error control and efficiency considerations, but little research on estimation after an adaptive hypothesis test. We evaluate the reliability and precision of different inferential procedures in the presence of an adaptive design with pre-specified rules for modifying the sampling plan. We extend group sequential orderings of the outcome space based on the stage at stopping, likelihood ratio test statistic, and sample mean to the adaptive setting in order to compute ...

Statistical And Methodological Issues On Covariate Adjustment In Clinical Trials, Rong Chu

Open Access Dissertations and Theses

Background and objectives

We investigate three issues related to the adjustment for baseline covariates in late phase clinical trials: (1) the analysis of correlated outcomes in multicentre RCTs, (2) the assessment of the probability and implication of prognostic imbalance in RCTs, and (3) the adjustment for baseline confounding in cohort studies.

Methods

Project 1: We investigated the properties of six statistical methods for analyzing continuous outcomes in multicentre randomized controlled trials (RCTs) where within-centre clustering was possible. We simulated studies over various intraclass correlation (ICC) values with several centre combinations.

Project 2: We simulated data from RCTs evaluating a binary ...

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 ...

On Penalized Likelihood Estimation For A Non-Proportional Hazards Regression Model, Karthik Devarajan, Nader Ebrahimi

COBRA Preprint Series

The fundamental assumption of proportionality of hazards in the Cox
model sometimes does not hold in practice. In this paper, a semi-parametric generalization of the Cox model that permits crossing hazard curves is described. This model allows the interaction between covariates and the baseline hazard, and has been the subject of recent investigation. It includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach cannot be applied here to estimate the model parameters, and flexible methods based on splines and sieves for ...

Heterogeneity Issues In The Meta-Analysis Of Cluster Randomization Trials., Shun Fu Chen

Electronic Thesis and Dissertation Repository

An increasing number of systematic reviews summarize results from cluster randomization trials. Applying existing meta-analysis methods to such trials is problematic because responses of subjects within clusters are likely correlated. The aim of this thesis is to evaluate heterogeneity in the context of fixed effects models providing guidance for conducting a meta-analysis of such trials. The approaches include the adjusted Q statistic, adjusted heterogeneity variance estimators and their corresponding confidence intervals and adjusted measures of heterogeneity and their corresponding confidence intervals. Attention is limited to meta-analyses of completely randomized trials having a binary outcome. An analytic expression for power of ...