Public Health Commons^™

On Corrected Score Approach For Proportional Hazards Model With Covariate Measurement Error, Xiao Song, Yijian Huang

UW Biostatistics Working Paper Series

In the presence of covariate measurement error with the proportional hazards model, several functional modeling methods have been proposed. These include the conditional score estimator (Tsiatis and Davidian, 2001), the parametric correction estimator (Nakamura, 1992) and the nonparametric correction estimator (Huang and Wang, 2000, 2003) in the order of weaker assumptions on the error. Although they are all consistent, each suffers from potential difficulties with small samples and substantial measurement error. In this article, upon noting that the conditional score and parametric correction estimators are asymptotically equivalent in the case of normal error, we investigate their relative finite sample performance …

Investigation And Calculation Of Dose Coefficients For Radionuclides Produced In A Spallation Neutron Source Using The Ensdf And Nubase Nuclear Databases, Yayun Song

UNLV Theses, Dissertations, Professional Papers, and Capstones

Dose coefficients are useful for risk assessment during the design and siting of accelerator-driven nuclear facilities including the Spallation Neutron Source. There are seventy-two radionuclides with half-lives equal to or greater than one minute that will be produced by the spallation of a mercury target for which no published dose coefficients exist. Out of these seventy-two, twenty-four currently have conflicting published nuclear data in the Evaluated Nuclear Structure Data Files (ENSDF) and the NUBASE data files. In this research these twenty-four radionuclides have been studied. Because of missing ENSDF records, internal and external dose coefficients were determined for only six …

Evaluating Markers For Selecting A Patient's Treatment, Xiao Song, Margaret S. Pepe

UW Biostatistics Working Paper Series

Selecting the best treatment for a patient's disease may be facilitated by evaluating clinical characteristics or biomarker measurements at diagnosis. We consider how to evaluate the potential of such measurements to impact on treatment selection algorithms. For example, magnetic resonance neurographic imaging is potentially useful for deciding whether a patient should be treated surgically for carpal tunnel syndrome or if he/she should receive less invasive conservative therapy. We propose a graphical display, the selection impact (SI) curve, that shows the population response rate as a function of treatment selection criteria based on the marker. The curve can be useful for …

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. …

A Bayesian Hierarchical Approach To Multirater Correlated Roc Analysis, Tim Johnson, Valen Johnson

The University of Michigan Department of Biostatistics Working Paper Series

In a common ROC study design, several readers are asked to rate diagnostics of the same cases processed under different modalities. We describe a Bayesian hierarchical model that facilitates the analysis of this study design by explicitly modeling the three sources of variation inherent to it. In so doing, we achieve substantial reductions in the posterior uncertainty associated with estimates of the differences in areas under the estimated ROC curves and corresponding reductions in the mean squared error (MSE) of these estimates. Based on simulation studies, both the widths of confidence intervals and MSE of estimates of differences in the …

A Bayesian Chi-Squared Test For Goodness Of Fit, Valen Johnson

The University of Michigan Department of Biostatistics Working Paper Series

This article describes an extension of classical x 2 goodness-of-fit tests to Bayesian model assessment. The extension, which essentially involvesevaluating Pearson's goodness-of-fit statistic at a parameter value drawn from its posterior distribution, has the important property that it is asymptoti-cally distributed as a x2 random variable on K-1 degrees of freedom, indepen-dently of the dimension of the underlying parameter vector. By averaging over the posterior distribution of this statistic, a global goodness-of-fit diagnostic is obtained. Advantages of this diagnostic{which may be interpreted as the area under an ROC curve{include ease of interpretation, computational conve-nience, and favorable power properties. The proposed …

Individualized Predictions Of Disease Progression Following Radiation Therapy For Prostate Cancer., Jeremy Taylor, Menggang Yu, Howard M. Sandler

The University of Michigan Department of Biostatistics Working Paper Series

Background: Following treatment for localized prostate cancer, men are monitored with serial PSA measurements. Refining the predictive value of post-treatment PSA determinations may add to clinical management and we have developed a model that predicts for an individual patient future PSA values and estimates the time to future clinical recurrence.

Methods: Data from 934 patients treated for prostate cancer between 1987 and 2000 were used to develop a comprehensive statistical model to fit the clinical recurrence events and pattern of PSA data. A logistic regression model was used for the probability of cure, non-linear hierarchical mixed models were used for …

Incorporating Death Into Health-Related Variables In Longitudinal Studies, Paula Diehr, Laura Lee Johnson, Donald L. Patrick, Bruce Psaty

UW Biostatistics Working Paper Series

Background: The aging process can be described as the change in health-related variables over time. Unfortunately, simple graphs of available data may be misleading if some people die, since they may confuse patterns of mortality with patterns of change in health. Methods have been proposed to incorporate death into self-rated health (excellent to poor) and the SF-36 profile scores, but not for other variables.

Objectives: (1) To incorporate death into the following variables: ADLs, IADLs, mini-mental state examination, depressive symptoms, body mass index (BMI), blocks walked per week, bed days, hospitalization, systolic blood pressure, and the timed walk. (2) To …

Overlap Bias In The Case-Crossover Design, With Application To Air Pollution Exposures, Holly Janes, Lianne Sheppard, Thomas Lumley

UW Biostatistics Working Paper Series

The case-crossover design uses cases only, and compares exposures just prior to the event times to exposures at comparable control, or “referent” times, in order to assess the effect of short-term exposure on the risk of a rare event. It has commonly been used to study the effect of air pollution on the risk of various adverse health events. Proper selection of referents is crucial, especially with air pollution exposures, which are shared, highly seasonal, and often have a long term time trend. Hence, careful referent selection is important to control for time-varying confounders, and in order to ensure that …

Development Of Dose Coefficients For Radionuclides Produced In Spallation Targets, Phillip W. Patton, Mark Rudin

Transmutation Sciences Physics (TRP)

Dose coefficients permit simple determination of radiation dose associated with various exposure scenarios, and ultimately permit radiation safety personnel to assess the health risks to workers in a nuclear facility. Specifically, radiation safety personnel use dose coefficients to determine the radiation dose incurred to a tissue or organ system from a given exposure. These parameters are often expressed in terms of Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs).

Results from this study will be used to produce ALIs and DACs for these rare radionuclides created by spallation target systems that are not included in Federal Guidance Report …

Detecting Spatiotemporal Clusters Of Accidental Poisoning Mortality Among Texas Counties, Us, 1980 – 2001, Ella T. Nkhoma, Chiehwen E. Hsu, Victoria I. Hunt, Ann M. Harris

Faculty, Staff and Student Publications

Background Accidental poisoning is one of the leading causes of injury in the United States, second only to motor vehicle accidents. According to the Centers for Disease Control and Prevention, the rates of accidental poisoning mortality have been increasing in the past fourteen years nationally. In Texas, mortality rates from accidental poisoning have mirrored national trends, increasing linearly from 1981 to 2001. The purpose of this study was to determine if there are spatiotemporal clusters of accidental poisoning mortality among Texas counties, and if so, whether there are variations in clustering and risk according to gender and race/ethnicity. The Spatial …

Uncertainty And The Value Of Diagnostic Information With Application To Axillary Lymph Node Dissection In Breast Cancer, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

In clinical decision making, it is common to ask whether, and how much, a diagnostic procedure is contributing to subsequent treatment decisions. Statistically, quantification of the value of the information provided by a diagnostic procedure can be carried out using decision trees with multiple decision points, representing both the diagnostic test and the subsequent treatments that may depend on the test's results. This article investigates probabilistic sensitivity analysis approaches for exploring and communicating parameter uncertainty in such decision trees. Complexities arise because uncertainty about a model's inputs determines uncertainty about optimal decisions at all decision nodes of a tree. We …

Survival Model Predictive Accuracy And Roc Curves, Patrick Heagerty, Yingye Zheng

UW Biostatistics Working Paper Series

The predictive accuracy of a survival model can be summarized using extensions of the proportion of variation explained by the model, or R^2, commonly used for continuous response models, or using extensions of sensitivity and specificity which are commonly used for binary response models.

In this manuscript we propose new time-dependent accuracy summaries based on time-specific versions of sensitivity and specificity calculated over risk sets. We connect the accuracy summaries to a previously proposed global concordance measure which is a variant of Kendall's tau. In addition, we show how standard Cox regression output can be used to obtain estimates of …

Semiparametric Estimation Of Time-Dependent: Roc Curves For Longitudinal Marker Data, Yingye Zheng, Patrick Heagerty

UW Biostatistics Working Paper Series

One approach to evaluating the strength of association between a longitudinal marker process and a key clinical event time is through predictive regression methods such as a time-dependent covariate hazard model. For example, a time-varying covariate Cox model specifies the instantaneous risk of the event as a function of the time-varying marker and additional covariates. In this manuscript we explore a second complementary approach which characterizes the distribution of the marker as a function of both the measurement time and the ultimate event time. Our goal is to flexibly extend the standard diagnostic accuracy concepts of sensitivity and specificity to …

Optimization Of Breast Cancer Screening Modalities, Yu Shen, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

Mathematical models and decision analyses based on microsimulations have been shown to be useful in evaluating relative merits of various screening strategies in terms of cost and mortality reduction. Most investigations regarding the balance between mortality reduction and costs have focused on a single modality, mammography. A systematic evaluation of the relative expenses and projected benefit of combining clinical breast examination and mammography is not at present available. The purpose of this report is to provide methodologic details including assumptions and data used in the process of modeling for complex decision analyses, when searching for optimal breast cancer screening strategies …

Data Analysis In The Antes System, Yavuz Tor

Theses and Dissertations - UTB/UTPA

Acanthosis nigricans is a skin condition that can be used as an indicator for the risk of developing type 2 diabetes in the future. Border Health Office, in University of Texas - Pan American, organizes screenings in schools for acanthosis nigricans. Screening results are, then, collected and evaluated in the Border Health Office. The ANTES System is a computer system that stores and manages the data collected in those screenings.

This study is on the analysis of those collected data to track the progress of data entry, to evaluate the progress on obesity and related problems, and to discover the …

Antes: A Web-Based Acanthosis Nigricans And Other Obesity Related Information System, Chunyue Wang

Theses and Dissertations - UTB/UTPA

Acanthosis nigricans is a cutaneous marker associated with systemic disorders and may serve as an indicator for risk of Type 2 diabetes. Acanthosis nigricans screening can help identify children who have high insulin levels and who may be at-risk for developing Type 2 diabetes. The ANTES system is a computerization attempt for acanthosis nigricans control of the student population from elementary schools and secondary schools in Texas. A general description of the system and the medical and history background of the ANTES program is given. The technology applied to the system is demonstrated. An overview of the system operation status …

Development Of Dose Conversion Coefficients For Radionuclides Produced In Spallation Neutron Sources: Quarterly Progress Report 8/20/03 – 12/01/03, Phillip W. Patton, Mark Rudin

Transmutation Sciences Physics (TRP)

A research consortium comprised of representatives from several universities and national laboratories has been established as part of this project to generate internal and external dose conversion coefficients for radionuclides produced in spallation neutron sources. Information obtained from this multi-year study will be used to support the siting and licensing of future accelerator-driven nuclear initiatives within the U.S. Department of Energy complex, including the Spallation Neutron Source (SNS) and Accelerator Production of Tritium (APT) Projects. Determination of these coefficients will also fill data gaps for several hundred radionuclides that exist in Federal Guide Report No. 11 and in Publications 68 …

Time-Series Studies Of Particulate Matter, Michelle L. Bell, Jonathan M. Samet, Francesca Dominici

Johns Hopkins University, Dept. of Biostatistics Working Papers

Studies of air pollution and human health have evolved from descriptive studies of the early phenomena of large increases in adverse health effects following extreme air pollution episodes, to time-series analyses and the development of sophisticated regression models. In fact, advanced statistical methods are necessary to address the many challenges inherent in the detection of a small pollution risk in the presence of many confounders. This paper reviews the history, methods, and findings of the time-series studies estimating health risks associated with short-term exposure to particulate matter, though much of the discussion is applicable to epidemiological studies of air pollution …

Smooth Quantile Ratio Estimation With Regression: Estimating Medical Expenditures For Smoking Attributable Diseases, Francesca Dominici, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In this paper we introduce a semi-parametric regression model for estimating the difference in the expected value of two positive and highly skewed random variables as a function of covariates. Our method extends Smooth Quantile Ratio Estimation (SQUARE), a novel estimator of the mean difference of two positive random variables, to a regression model.

The methodological development of this paper is motivated by a common problem in econometrics where we are interested in estimating the difference in the average expenditures between two populations, say with and without a disease, taking covariates into account. Let Y1 and Y2 be two positive …

A Corrected Pseudo-Score Approach For Additive Hazards Model With Longitudinal Covariates Measured With Error, Xiao Song, Yijian Huang

UW Biostatistics Working Paper Series

In medical studies, it is often of interest to characterize the relationship between a time-to-event and covariates, not only time-independent but also time-dependent. Time-dependent covariates are generally measured intermittently and with error. Recent interests focus on the proportional hazards framework, with longitudinal data jointly modeled through a mixed effects model. However, approaches under this framework depend on the normality assumption of the error, and might encounter intractable numerical difficulties in practice. This motivates us to consider an alternative framework, that is, the additive hazards model, under which little has been done when time-dependent covariates are measured with error. We propose …

Smooth Quantile Ratio Estimation, Francesca Dominici, Leslie Cope, Daniel Q. Naiman, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In a study of health care expenditures attributable to smoking, we seek to compare the distribution of medical costs for persons with lung cancer or chronic obstructive pulmonary disease (cases) to those without (controls) using a national survey which includes hundreds of cases and thousands of controls. The distribution of costs is highly skewed toward larger values, making estimates of the mean from the smaller sample dependent on a small fraction of the biggest values. One approach to deal with the smaller sample is to rely on a simple parametric model such as the log-normal, but this makes the undesirable …

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) …

Analysis Of Soil Lead Levels In An Historic District Of A South Central Kentucky City, Robert Cummins

Masters Theses & Specialist Projects

Lead in soil has been shown to be a significant pathway of lead exposure in children. Several factors including age of housing units, exterior composition, and paint loading may affect the amount of lead present in the soil. The purpose of this study was to analyze soil lead levels on properties located in an historic district and relate those levels to the variables previously mentioned. A total of 30 soil samples were collected from housing units in a nationally recognized historic district. Concentrations of lead in the soil were analyzed using a NITON X-ray Fluorescence Spectrum Analyzer, following EPA Method …

Dose Coefficients For Radionuclides Produced In A Spallation Neutron Source, John P. Shanahan

Transmutation Sciences Physics (TRP)

Internal and external dose coefficient values have been calculated for 14 anthropogenic radionuclides which are not currently presented in Federal Guidance Reports No. 11, 12, and 13 or Publications 68 and 72 of the International Commission on Radiological Protection. Internal dose coefficient values are reported for inhalation and ingestion of 1 μm and 5 μm particulates along with the f1 values and absorption types for the adult worker. Internal dose coefficient values are also reported for inhalation and ingestion of 1 μm particulates as well as the f1 values and absorption types for members of the public. Additionally, external dose …

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 …

Study Of The Distribution And Variation Of The Herbicide Atrazine In Finished Drinking Water At A Small Community Water System In Kentucky, Vijay Golla

Masters Theses & Specialist Projects

This study examines the variation in the distribution of the concentration of atrazine, a triazine herbicide used in Kentucky to control weeds primarily in corn fields. Atrazine is known to have carcinogenic properties and is an endocrine disruptor in aquatic species even at low concentrations. Atrazine has the ability to be transported through the environment into water bodies due to its physical and chemical properties favoring its occurrence and distribution. Raw and Finished drinking water samples were collected from the Lewisburg water treatment plant which derives its drinking water supplies from a source water intake namely Spa Lake, which has …

A New Confidence Interval For The Difference Between Two Binomial Proportions Of Paired Data, Xiao-Hua Zhou, Gengsheng Qin

UW Biostatistics Working Paper Series

Motivated by a study on comparing sensitivities and specificities of two diagnostic tests in a paired design when the sample size is small, we first derived an Edgeworth expansion for the studentized difference between two binomial proportions of paired data. The Edgeworth expansion can help us understand why the usual Wald interval for the difference has poor coverage performance in the small sample size. Based on the Edgeworth expansion, we then derived a transformation based confidence interval for the difference. The new interval removes the skewness in the Edgeworth expansion; the new interval is easy to compute, and its coverage …

Improved Confidence Intervals For The Sensitivity At A Fixed Level Of Specificity Of A Continuous-Scale Diagnostic Test, Xiao-Hua Zhou, Gengsheng Qin

UW Biostatistics Working Paper Series

For a continuous-scale test, it is an interest to construct a confidence interval for the sensitivity of the diagnostic test at the cut-off that yields a predetermined level of its specificity (eg. 80%, 90%, or 95%). IN this paper we proposed two new intervals for the sensitivity of a continuous-scale diagnostic test at a fixed level of specificity. We then conducted simulation studies to compare the relative performance of these two intervals with the best existing BCa bootstrap interval, proposed by Platt et al. (2000). Our simulation results showed that the newly proposed intervals are better than the BCa bootstrap …