Disease Modeling Commons^™

Evaluating Subject-Level Incremental Values Of New Markers For Risk Classification Rule, Tianxi Cai, Lu Tian, Donald M. Lloyd-Jones, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Joint Spatial Modeling Of Recurrent Infection And Growth With Processes Under Intermittent Observation, Farouk S. Nathoo

COBRA Preprint Series

In this article we present new statistical methodology for longitudinal studies in forestry where trees are subject to recurrent infection and the hazard of infection depends on tree growth over time. Understanding the nature of this dependence has important implications for reforestation and breeding programs. Challenges arise for statistical analysis in this setting with sampling schemes leading to panel data, exhibiting dynamic spatial variability, and incomplete covariate histories for hazard regression. In addition, data are collected at a large number of locations which poses computational difficulties for spatiotemporal modeling. A joint model for infection and growth is developed; wherein, a …

Identifying Patients Who Need Additional Biomarkers For Better Prediction Of Health Outcome Or Diagnosis Of Clinical Phenotype, Lu Tian, Tianxi Cai, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Likelihood Based Method For Real Time Estimation Of The Serial Interval And Reproductive Number Of An Epidemic, Laura Forsberg White, Marcello Pagano

Harvard University Biostatistics Working Paper Series

No abstract provided.

Spatio-Temporal Analysis Of Areal Data And Discovery Of Neighborhood Relationships In Conditionally Autoregressive Models, Subharup Guha, Louise Ryan

Harvard University Biostatistics Working Paper Series

No abstract provided.

Different Public Health Interventions Have Varying Effects, Paula Diehr, Anne B. Newman, Liming Cai, Ann Derleth

UW Biostatistics Working Paper Series

Objective: To compare performance of one-time health interventions to those that change the probability of transitioning from one health state to another. Study Design and Setting: We used multi-state life table methods to estimate the impact of eight types of interventions on several outcomes. Results: In a cohort beginning at age 65, curing all the sick persons at baseline would increase life expectancy by 0.23 years and increase years of healthy life by .54 years. An equal amount of improvement could be obtained with a 12% decrease in the probability of getting sick, a 16% increase in the probability of …

Regression Analysis For The Partial Area Under The Roc Curve, Tianxi Cai, Lori E. Dodd

Harvard University Biostatistics Working Paper Series

No abstract provided.

Model Checking For Roc Regression Analysis, Tianxi Cai, Yingye Zheng

Harvard University Biostatistics Working Paper Series

The Receiver Operating Characteristic (ROC) curve is a prominent tool for characterizing the accuracy of continuous diagnostic test. To account for factors that might invluence the test accuracy, various ROC regression methods have been proposed. However, as in any regression analysis, when the assumed models do not fit the data well, these methods may render invalid and misleading results. To date practical model checking techniques suitable for validating existing ROC regression models are not yet available. In this paper, we develop cumulative residual based procedures to graphically and numerically assess the goodness-of-fit for some commonly used ROC regression models, and …

Is The Number Of Sick Persons In A Cohort Constant Over Time?, Paula Diehr, Ann Derleth, Anne Newman, Liming Cai

UW Biostatistics Working Paper Series

Objectives: To estimate the number of persons in a cohort who are sick, over time.

Methods: We calculated the number of sick persons in the Cardiovascular Health Study (CHS), a cohort study of older adults followed up to 14 years, using eight definitions of “healthy” and “sick”. We projected the number in each health state over time for a birth cohort.

Results: The number of sick persons in CHS was approximately constant for 14 years, for all definitions of “sick”. The estimated number of sick persons in the birth cohort was approximately constant from ages 55-75, after which it decreased. …

Prognosis Of Stage Ii Colon Cancer By Non-Neoplastic Mucosa Gene Expresssion Profiling, Alain Barrier, Sandrine Dudoit, Et Al.

U.C. Berkeley Division of Biostatistics Working Paper Series

Aims. This study assessed the possibility to build a prognosis predictor, based on non-neoplastic mucosa microarray gene expression measures, in stage II colon cancer patients. Materials and Methods. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbor method was used for prognosis prediction using microarray gene expression measures. Leave-one-out cross-validation was used to select the number of neighbors and number of informative genes to include in the predictor. Based on this information, a prognosis predictor was proposed and its accuracy estimated by …

Colon Cancer Prognosis Prediction By Gene Expression Profiling, Alain Barrier, Sandrine Dudoit, Et Al.

U.C. Berkeley Division of Biostatistics Working Paper Series

Aims. This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in stage II and III colon cancer patients. Materials and Methods. Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (9 with a recurrence, 9 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbour method was used for prognosis prediction using T and NM gene expression measures. Six-fold cross-validation was applied to select the number of neighbours and the number of informative genes to include in the predictors. Based on this information, one T-based and one NM-based …

The Sensitivity And Specificity Of Markers For Event Times, Tianxi Cai, Margaret S. Pepe, Thomas Lumley, Yingye Zheng, Nancy Swords Jenny

Harvard University Biostatistics Working Paper Series

No abstract provided.

Bayesian Hierarchical Distributed Lag Models For Summer Ozone Exposure And Cardio-Respiratory Mortality, Yi Huang, Francesca Dominici, Michelle L. Bell

Johns Hopkins University, Dept. of Biostatistics Working Papers

In this paper, we develop Bayesian hierarchical distributed lag models for estimating associations between daily variations in summer ozone levels and daily variations in cardiovascular and respiratory (CVDRESP) mortality counts for 19 U.S. large cities included in the National Morbidity Mortality Air Pollution Study (NMMAPS) for the period 1987 - 1994.

At the first stage, we define a semi-parametric distributed lag Poisson regression model to estimate city-specific relative rates of CVDRESP associated with short-term exposure to summer ozone. At the second stage, we specify a class of distributions for the true city-specific relative rates to estimate an overall effect by …

Multiple Testing And Data Adaptive Regression: An Application To Hiv-1 Sequence Data, Merrill D. Birkner, Sandra E. Sinisi, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Analysis of viral strand sequence data and viral replication capacity could potentially lead to biological insights regarding the replication ability of HIV-1. Determining specific target codons on the viral strand will facilitate the manufacturing of target specific antiretrovirals. Various algorithmic and analysis techniques can be applied to this application. We propose using multiple testing to find codons which have significant univariate associations with replication capacity of the virus. We also propose using a data adaptive multiple regression algorithm to obtain multiple predictions of viral replication capacity based on an entire mutant/non-mutant sequence profile. The data set to which these techniques …

A Hypothesis Test For The End Of A Common Source Outbreak, Ron Brookmeyer, Xiaojun You

Johns Hopkins University, Dept. of Biostatistics Working Papers

The objective of this paper is to develop a hypothesis testing procedure to determine whether a common source outbreak has ended. We do not assume that the calendar date of exposure to the pathogen is known. We assume an underlying parametric model for the incubation period distribution of a 2-paramter exponential model with a guarantee time, although the parameters are not assumed to be known. The hypothesis testing procedure is based on the spacings between ordered calendar dates of disease onset of the cases. A simulation study was performed to evaluate the robustness of the methods to a lognormal model …

Effect Of Misreported Family History On Mendelian Mutation Prediction Models, Hormuzd A. Katki

Johns Hopkins University, Dept. of Biostatistics Working Papers

People with familial history of disease often consult with genetic counselors about their chance of carrying mutations that increase disease risk. To aid them, genetic counselors use Mendelian models that predict whether the person carries deleterious mutations based on their reported family history. Such models rely on accurate reporting of each member's diagnosis and age of diagnosis, but this information may be inaccurate. Commonly encountered errors in family history can significantly distort predictions, and thus can alter the clinical management of people undergoing counseling, screening, or genetic testing. We derive general results about the distortion in the carrier probability estimate …

Nonparametric And Semiparametric Inference For Models Of Tumor Size And Metastasis, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

There has been some recent work in the statistical literature for modelling the relationship between the size of primary cancers and the occurrences of metastases. While nonparametric methods have been proposed for estimation of the tumor size distribution at which metastatic transition occurs, their asymptotic properties have not been studied. In addition, no testing or regression methods are available so that potential confounders and prognostic factors can be adjusted for. We develop a unified approach to nonparametric and semiparametric analysis of modelling tumor size-metastasis data in this article. An equivalence between the models considered by previous authors with survival data …

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 …

Individual Prediction In Prostate Cancer Studies Using A Joint Longitudinal-Survival-Cure Model, Menggang Yu, Jeremy Taylor, Howard M. Sandler

The University of Michigan Department of Biostatistics Working Paper Series

For monitoring patients treated for prostate cancer, Prostate Specific Antigen (PSA) is measured periodically after they receive treatment. Increases in PSA are suggestive of recurrence of the cancer and are used in making decisions about possible new treatments. The data from studies of such patients typically consist of longitudinal PSA measurements, censored event times and baseline covariates. Methods for the combined analysis of both longitudinal and survival data have been developed in recent years, with the main emphasis being on modeling and estimation. We analyze data from a prostate cancer study that has been extended by adding a mixture structure …

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 …

Modeling The Incubation Period Of Anthrax, Ron Brookmeyer, Elizabeth Johnson, Sarah Barry

Johns Hopkins University, Dept. of Biostatistics Working Papers

Models of the incubation period of anthrax are important to public health planners because they can be used to predict the delay before outbreaks are detected, the size of an outbreak and the duration of time that persons should remain on antibiotics to prevent disease. The difficulty is that there is little direct data about the incubation period in humans. The objective of this paper is to develop and apply models for the incubation period of anthrax. Mechanistic models that account for the biology of spore clearance and germination are developed based on a competing risks formulation. The models predict …

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 …

Comparative Genomic Hybridization Array Analysis, Annette M. Molinaro, Mark J. Van Der Laan, Dan H. Moore

U.C. Berkeley Division of Biostatistics Working Paper Series

At the present time, there is increasing evidence that cancer may be regulated by the number of copies of genes in tumor cells. Through microarray technology it is now possible to measure the number of copies of thousands of genes and gene segments in samples of chromosomal DNA. Microarray comparative genomic hybridization (array CGH) provides the opportunity to both measure DNA sequence copy number gains and losses and map these aberrations to the genomic sequence. Gains can signify the over-expression of oncogenes, genes which stimulate cell growth and have become hyperactive, while losses can signify under-expression of tumor suppressor genes, …

Developing A Periodontal Screening Examination, Jeffrey R. Morgulis

Loma Linda University Electronic Theses, Dissertations & Projects

Periodontal disease is the primary cause of tooth loss in the adult, and therefore, early diagnosis of periodontal disease by the general practitioner is important in terms of prevention as well as treatment. The present study was designed to develop a periodontal screening examination which would fulfill the following requirements:

1. It should utilize precise and easily understood criteria.
2. It should take a short period of time.
3. It should enable the practitioner to accurately place patients into various disease categories.
4. It should enable the practitioner to easily and quickly relate these disease categories to treatment.

A "comprehensive" periodontal examination was performed …