Clinical Trials Commons^™

Cross-Calibration Of Stroke Disability Measures: Bayesian Analysis Of Longitudinal Ordinal Categorical Data Using Negative Dependence, Giovanni Parmigiani, Heidi W. Ashih, Gregory P. Samsa, Pamela W. Duncan, Sue Min Lai, David B. Matchar

Johns Hopkins University, Dept. of Biostatistics Working Papers

It is common to assess disability of stroke patients using standardized scales, such as the Rankin Stroke Outcome Scale (RS) and the Barthel Index (BI). The Rankin Scale, which was designed for applications to stroke, is based on assessing directly the global conditions of a patient. The Barthel Index, which was designed for general applications, is based on a series of questions about the patient’s ability to carry out 10 basis activities of daily living. As both scales are commonly used, but few studies use both, translating between scales is important in gaining an overall understanding of the efficacy of …

An Extended General Location Model For Causal Inference From Data Subject To Noncompliance And Missing Values, Yahong Peng, Rod Little, Trivellore E. Raghuanthan

The University of Michigan Department of Biostatistics Working Paper Series

Noncompliance is a common problem in experiments involving randomized assignment of treatments, and standard analyses based on intention-to treat or treatment received have limitations. An attractive alternative is to estimate the Complier-Average Causal Effect (CACE), which is the average treatment effect for the subpopulation of subjects who would comply under either treatment (Angrist, Imbens and Rubin, 1996, henceforth AIR). We propose an Extended General Location Model to estimate the CACE from data with non-compliance and missing data in the outcome and in baseline covariates. Models for both continuous and categorical outcomes and ignorable and latent ignorable (Frangakis and Rubin, 1999) …

Adjusting For Non-Ignorable Verification Bias In Clinical Studies For Alzheimer’S Disease, Xiao-Hua Zhou, Pete Castelluccio

UW Biostatistics Working Paper Series

A common problem for comparing the relative accuracy of two screening tests for Alzheimer’s disease (D) in a two-stage design study is verification bias. If the verification bias can be assumed to be ignorable, Zhou and Higgs (2000) have proposed a maximum likelihood approach to compare the relative accuracy of screening tests in a two-stage design study. However, if the verification mechanism also depends on the unobserved disease status, the ignorable assumption does not hold. In this paper, we discuss how to use a profile likelihood approach to compare the relative accuracy of two screening tests for AD without assuming …

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 …

Constrained Boundary Monitoring For Group Sequential Clinical Trials, Bart E. Burington, Scott S. Emerson

UW Biostatistics Working Paper Series

Group sequential stopping rules are often used during the conduct of clinical trials in order to attain more ethical treatment of patients and to better address efficiency concerns. Because the use of such stopping rules materially affects the frequentist operating characteristics of the hypothesis test, it is necessary to choose an appropriate stopping rule during the planning of the study. It is often the case, however, that the number and timing of interim analyses are not precisely known at the time of trial design, and thus the implementation of a particular stopping rule must allow for flexible determination of 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 …

Estimating Causal Parameters In Marginal Structural Models With Unmeasured Confounders Using Instrumental Variables, Tanya A. Henneman, Mark Johannes Van Der Laan, Alan E. Hubbard

U.C. Berkeley Division of Biostatistics Working Paper Series

For statisticians analyzing medical data, a significant problem in determining the causal effect of a treatment on a particular outcome of interest, is how to control for unmeasured confounders. Techniques using instrumental variables (IV) have been developed to estimate causal parameters in the presence of unmeasured confounders. In this paper we apply IV methods to both linear and non-linear marginal structural models. We study a specific class of generalized estimating equations that is appropriate to these data, and compare the performance of the resulting estimator to the standard IV method, a two-stage least squares procedure. Our results are applied to …

Mixture Hazards Models With Additive Random Effects Accounting For Treatment Effectiveness Lag Time, Ying Qing Chen, C. A. Rohde, M.-C. Wang

U.C. Berkeley Division of Biostatistics Working Paper Series

In many clinical trials to evaluate treatment efficacy, it is believed that there may exist latent treatment effectiveness lag times after which medical treatment procedure or chemical compound would be in full effect. In this article, semiparametric regression models are proposed and studied for estimating the treatment effect accounting for such latent lag times. The new models take advantage of the invariance property of the additive hazards model in marginalising over an additive latent variable; parameters in the models are thus easily estimated and interpreted, while the flexibility of not having to specify the baseline hazard function is preserved. Monte …

Probabilities Of Transition Among Health States For Older Adults, Paula Diehr, Donald L. Patrick

UW Biostatistics Working Paper Series

Goal: To estimate the probabilities of transition among self-rated health states for older adults, and examine how they vary by age and sex. Methods: We used self-rated health (Excellent, Very Good, Good, Fair, Poor, Dead) collected in two longitudinal studies of older adults (Mean age 75) to estimate the probability of transition in two years. We used the estimates to project future health for selected cohorts.

Findings: These older adults were most likely to be in the same health state 2 years later, but a substantial proportion changed in both directions. Transition probabilities varied by initial health state, age and …

A Class Of Semiparametric Scale-Change Hazards Regression Models And Its Adequacy For Censored Survival Data, Ying Qing Chen

U.C. Berkeley Division of Biostatistics Working Paper Series

A class of semiparametric hazards regression models called the accelerated hazards models was introduced to identify the covariate effect characterized by the scale-change between hazard functions. In this article, we compare the accelerated hazards models with several other popular classes of regression models in statistical literature for censored survival data. We also propose and study some test statistics to assess the models' adequacy. Simulation studies are conducted to evaluate the performance of the test statistics. Actual clinical trials data are analyzed to demonstrate the proposed models and test statistics.

Does The Oswestry Or Sf-36 Help A Therapist To Predict Treatment Classification, Amy Crawford, Denese D. Kaufeldt-Soliz

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine the relationship of two disability questionnaires, the Oswestry Low Back Pain Disability Questionnaire (Oswestry) and the Medical Outcome Study Short Form-36 (SF-36), and a standardized physical examination and diagnostic classification system. The physical examination was performed by the evaluating therapists from the clinic and classification was determined by the evaluating therapists and the investigators to ensure correct subject placement into treatment Stages la, lb, or II. Data collection occurred at an outpatient physical therapy clinic in a metropolitan area health maintenance organization, where a sample of 221 subjects with low back pain …

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.

A Non-Human Primate Model For Evaluating A Fenestration Corticotomy Technique, Philip G. M. Khng

Loma Linda University Electronic Theses, Dissertations & Projects

A study model has been designed to evaluate the effectiveness of a new fenestration corticotomy procedure in two non-human primates Macaca fasicularis.

The objective of this study was to evaluate the efficacy of a new conservative corticotomy procedure to facilitate dental translation using fenestrations. This pilot study compared treatment and control quadrants of each individual animal's maxilla and mandible with both having the same retraction appliance and force on the 2nd premolar following extraction of the 1st molars. The null hypothesis stated that there was no significant statistical difference between the new conservative corticotomy procedure (fenestrations) when compared with …

Tracking Plasma Lactate Concentration In Vivo With A Catheter-Tip L-Lactate Sensor, Brett T. Weinzapfel, Mark D. Ball, Lee R. Waite, Nacer E. Abrouk, Shun P. Lim

Mathematical Sciences Technical Reports (MSTR)

To circumvent the problems of repeated blood sampling for in vitro analysis, a catheter-tip L-lactate sensor has been developed. The sensor was tested in anesthetized pigs (n=6). The sensor in vivo tracked the lactate concentration non-linearly, seeming to obey Michaelis-Menten kinetics. Calibration time was short, typically 1.5 min per lactate standard. Furthermore, time drift was small, typically -1.3% to -3.3% per hour of in vivo use.

A Modified Nance Unilateral Molar Distalizer, Tracy J. Reiner

Loma Linda University Electronic Theses, Dissertations & Projects

This clinical study evaluated a modified Nance appliance designed by the author to distalize molars unilaterally for Class II correction. This fixed appliance did not rely upon extraoral traction or intraoral elastics. Twelve unilateral Class II patients aged 13 to 17 were treated nonextraction with the appliance. Pretreatment and posttreatment photographs were taken of the palatal soft tissue and did not reveal any untoward changes as a result of the Nance acrylic button. All molars were corrected to an Angle's Class I relationship. Molar correction was evaluated visually and molar distalization was measured using an acrylic jig fitted to the …