Physical Sciences and Mathematics Commons^™

A General Approach To Goodness Of Fit For U Processes, Debashis Ghosh, Youngjoo Cho

Debashis Ghosh

Goodness of fit procedures are essential tools for assessing model adequacy in statistics. In this work, we present a general theory and approach to goodness of fit techniques based on U-processes for the accelerated failure time (AFT) model. Many of the examples will focus on U-statistics of order 2. While many authors have proposed goodness of fit tests for U-statistics of order one, less has been developed for higher order U-statistics. In this paper, we propose goodness of fit tests for U-statistics of order 2 by using theoretical results from Nolan and Pollard (1987) and Nolan and Pollard (1988). We …

Hypothesis Testing For An Extended Cox Model With Time-Varying Coefficients, Takumi Saegusa, Chongzhi Di, Ying Qing Chen

Chongzhi Di

In many randomized clinical trials, the log-rank test has routinely been used to detect a treatment effect under the Cox proportional hazards model for censored time-to-event outcomes. However, it may lose power substantially when the proportional hazards assumption does not hold. There are approaches to testing the proportionality, such as the smoothing spline-based score test by Lin, Zhang and Davidian (2006). In this paper, we consider an extended Cox model assuming time-varying treatment effect. We then use smoothing splines to model the time-varying treatment effect, and we propose spline-based score tests for the overall treatment effect. Our proposed tests take …

Software For 'The Predictive Hazard Ratio For Biomarker Evaluation Studies', Debashis Ghosh

Debashis Ghosh

This is software to accompany the paper `The predictive hazard ratio for biomarker evaluation studies.' It is saved as a compressed ZIP folder.

The Predictive Hazard Ratio For Biomarker Evaluation Studies, Debashis Ghosh

Debashis Ghosh

There is tremendous scientific and medical interest in the use of biomarkers to better facilitate medical decision making. In this article, we present a simple framework for assessing the predictive ability of a biomarker. The methodology requires use of techniques from a subfield of survival analysis termed semicompeting risks; results are presented to make the article self-contained. A crucial parameter for evaluating is the predictive hazard ratio, which is different from the usual hazard ratio from Cox regression models for right-censored data. This quantity will be defined; its estimation, inference and adjustment for covariates will be discussed. Aspects of censoring …

A Causal Framework For Surrogate Endpoints With Semi-Competing Risks Data, Debashis Ghosh

Debashis Ghosh

In this note, we address the problem of surrogacy using a causal modelling framework that differs substantially from the potential outcomes model that pervades the biostatistical literature. The framework comes from econometrics and conceptualizes direct effects of the surrogate endpoint on the true endpoint. While this framework can incorporate the so-called semi-competing risks data structure, we also derive a fundamental non-identifiability result. Relationships to existing causal modelling frameworks are also discussed.

Communitywide Trends In The Use And Outcomes Associated With Beta-Blockers In Patients With Acute Myocardial Infarction: The Worcester Heart Attack Study, Helme Silvet, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Despite the benefits associated with beta-blocker therapy in patients with acute myocardial infarction (AMI), limited recent data are available describing the extent of use of this therapy and the associated hospital and long-term outcomes, particularly from the perspective of a population-based study. Data are also limited about the characteristics of patients with AMI who do not receive beta-blockers. This study examines more than 2 decades of trends in the use of beta-blockers in hospitalized patients with AMI. METHODS: Communitywide study of 10,374 patients hospitalized with confirmed AMI in all metropolitan Worcester hospitals during 12 annual periods between 1975 and …

Two-Decade-Long Trends (1975-1997) In The Incidence, Hospitalization, And Long-Term Death Rates Associated With Complete Heart Block Complicating Acute Myocardial Infarction: A Community-Wide Perspective, Frederick Spencer, Samer Jabbour, Darleen Lessard, Jorge Yarzebski, Shmuel Ravid, Virginia Zaleskas, Michael Hyder, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: The purpose of this community-wide study was to describe a >2-decade-long experience (1975-97) in the incidence and death rates associated with complete heart block (CHB) in patients with acute myocardial infarction (AMI). Limited population-based data exist describing recent, and changes with time therein, incidence and case-fatality rates associated with CHB complicating AMI.

METHODS: We conducted an observational study of 9082 metropolitan Worcester, Mass, residents (1990 census = 437,000) hospitalized with validated AMI in all greater Worcester hospitals during 11 1-year periods between 1975 and 1997.

RESULTS: Overall, CHB developed in 5.0% of patients with AMI. The incidence rates of …

Trends In Atrial Fibrillation Complicating Acute Myocardial Infarction, Jane Saczynski, David Mcmanus, Zheng Zhou, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) and this arrhythmia is associated with increased morbidity and mortality in patients with AMI. Limited information is available, however, about changing, and contemporary, trends in the incidence and death rates associated with AF complicating AMI. We examined the magnitude and impact of AF and the risk of stroke and hospital and long-term death rates in a population-based study of patients hospitalized with AMI. The study population consisted of 7,513 residents of the Worcester, Massachusetts, metropolitan area hospitalized with AMI at all greater Worcester medical centers during 9 biennial …

Twenty-Two Year (1975 To 1997) Trends In The Incidence, In-Hospital And Long-Term Case Fatality Rates From Initial Q-Wave And Non-Q-Wave Myocardial Infarction: A Multi-Hospital, Community-Wide Perspective, Mark Furman, Harold Dauerman, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

OBJECTIVES: The goal of this study was to examine long-term trends in the incidence, in-hospital and long-term mortality patterns in patients with an initial non-Q-wave myocardial infarction (NQWMI) as compared with those with an initial Q-wave myocardial infarction (QWMI). BACKGROUND: Limited data are available describing trends in the incidence and mortality from an initial QWMI and NQWMI from a multi-hospital community-wide perspective. METHODS: Our study was an observational study of 5,832 metropolitan Worcester, Massachusetts residents (1990 census = 437,000) hospitalized with validated initial acute MI in all greater Worcester hospitals during 11 annual periods between 1975 and 1997. RESULTS: The …

Recent And Temporal Trends (1975 To 1999) In The Treatment, Hospital, And Long-Term Outcomes Of Hispanic And Non-Hispanic White Patients Hospitalized With Acute Myocardial Infarction: A Population-Based Perspective, Jorge Yarzebski, Carmen Bujor, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Extremely limited population-based data are available describing recent and temporal trends in the characteristics, treatment, and outcomes of Hispanic and non-Hispanic white patients hospitalized with acute myocardial infarction (AMI).

METHODS: This was a community-based, observational study of 9649 greater Worcester residents hospitalized in all hospitals serving the Worcester, Massachusetts, metropolitan area in 12 one-year periods between 1975 and 1999. In the total study sample, 171 (2%) patients were Hispanic. Hispanic patients were matched with 395 non-Hispanic white patients on the basis of age, sex, and year of hospitalization.

RESULTS: Hispanics were more likely to present to greater Worcester hospitals …

A Communitywide Perspective Of Sex Differences And Temporal Trends In The Incidence And Survival Rates After Acute Myocardial Infarction And Out-Of-Hospital Deaths Caused By Coronary Heart Disease, Robert Goldberg, Edward Gorak, Jorge Yarzebski, David Hosmer, Priscilla Dalen, Joel Gore, Joseph Alpert, James Dalen

Jorge L. Yarzebski

BACKGROUND: The purpose of the study was to examine overall differences and temporal trends therein between men and women regarding the incidence rates, in-hospital and long-term survival after initial acute myocardial infarction (AMI), and out-of-hospital deaths caused by coronary disease.

METHODS AND RESULTS: This nonconcurrent prospective study was carried out in 16 teaching and community hospitals in Worcester, Mass., in six time periods between 1975 and 1988. A total of 3,148 patients hospitalized with validated initial AMI comprised the study sample. The age-adjusted incidence rates of initial AMI increased between 1975 and 1981 in the two sexes, with a marked …

Bleeding Complications In Patients With Anemia And Acute Myocardial Infarction, Harold Dauerman, Darleen Lessard, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

Anemia has recently been associated with increased mortality in patients who undergo percutaneous coronary intervention. The mechanisms associated with increased mortality among patients who have anemia have not been defined. We sought to determine whether patients who had anemia and acute myocardial infarction (AMI) might be at higher risk for bleeding or cardiogenic shock during acute hospitalization compared with patients who did not have anemia. This population-based study included 5,378 residents of the Worcester metropolitan area who were hospitalized with a diagnosis of AMI in five 1-year periods from 1995 to 2003. Patients were analyzed according to the presence or …

Meta-Analysis For Surrogacy: Accelerated Failure Time Models And Semicompeting Risks Modelling, Debashis Ghosh, Jeremy M. Taylor, Daniel J. Sargent

Debashis Ghosh

There has been great recent interest in the medical and statistical literature in the assessment and validation of surrogate endpoints as proxies for clinical endpoints in medical studies. More recently, authors have focused on using meta-analytical methods for quanti cation of surrogacy. In this article, we extend existing procedures for analysis based on the accelerated failure time model to this setting. An advantage of this approach relative to proportional hazards model is that it allows for analysis in the semi-competing risks setting, where we constrain the surrogate endpoint to occur before the true endpoint. A novel principal components procedure is …

Combining Multiple Models With Survival Data: The Phase Algorithm, Debashis Ghosh, Zheng Yuan

Debashis Ghosh

In many scientic studies, one common goal is to develop good prediction rules based on a set of available measurements. This paper proposes a model averaging methodology using proportional hazards regression models to construct new estimators of predicted survival probabilities. A screening step based on an adaptive searching algorithm is used to handle large numbers of covariates. The nite-sample properties of the proposed methodology is assessed using simulation studies. Application of the method to a cancer biomarker study is also given.

Semiparametric Analysis Of Recurrent Events: Artificial Censoring, Truncation, Pairwise Estimation And Inference, Debashis Ghosh

Debashis Ghosh

The analysis of recurrent failure time data from longitudinal studies can be complicated by the presence of dependent censoring. There has been a substantive literature that has developed based on an artificial censoring device. We explore in this article the connection between this class of methods with truncated data structures. In addition, a new procedure is developed for estimation and inference in a joint model for recurrent events and dependent censoring. Estimation proceeds using a mixed U-statistic based estimating function approach. New resampling-based methods for variance estimation and model checking are also described. The methods are illustrated by application to …

Composite Endpoint Analysis For Assessing Surrogacy With Censored Data, Debashis Ghosh

Debashis Ghosh

Background: There is great interest in the development of surrogate endpoints using new technologies in medical research. The promise of such endpoints is that they would allow for faster completion of clinical trials and would be potentially cost-effective.

Purpose: In determining surrogacy, it is important to distinguish the roles of surrogate from the true endpoint. The latter should be thought of as the gold standard. We discuss a framework in which the utility of a surrogate endpoint is based on whether or not as part of a composite endpoint, it yields treatment effects that associate with that on the true …

A Note On Empirical Likelihood Inference Of Residual Life Regression, Ying Qing Chen, Yichuan Zhao

Yichuan Zhao

Mean residual life function, or life expectancy, is an important function to characterize distribution of residual life. The proportional mean residual life model by Oakes and Dasu (1990) is a regression tool to study the association between life expectancy and its associated covariates. Although semiparametric inference procedures have been proposed in the literature, the accuracy of such procedures may be low when the censoring proportion is relatively large. In this paper, the semiparametric inference procedures are studied with an empirical likelihood ratio method. An empirical likelihood confidence region is constructed for the regression parameters. The proposed method is further compared …

Censored Data Regression In High-Dimension And Low-Sample Size Settings For Genomic Applications, Hongzhe Li

Hongzhe Li

New high-throughput technologies are generating various types of high-dimensional genomic and proteomic data and meta-data (e.g., networks and pathways) in order to obtain a systems-level understanding of various complex diseases such as human cancers and cardiovascular diseases. As the amount and complexity of the data increase and as the questions being addressed become more sophisticated, we face the great challenge of how to model such data in order to draw valid statistical and biological conclusions. One important problem in genomic research is to relate these high-throughput genomic data to various clinical outcomes, including possibly censored survival outcomes such as age …