Evaluation of Risk Prediction with Hierarchical Data: Dependency Adjusted Confidence Intervals for the AUC.

The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods.

Association of Incident Cardiovascular Disease With Time Course and Cumulative Exposure to Multiple Risk Factors.

Background: The quantitative relationship of incident cardiovascular disease (CVD) to lifetime cumulative risk factor exposure is not well understood.

Objectives: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we examined the quantitative associations of cumulative exposure over time to multiple, simultaneously operating risk factors with CVD incidence and the incidence of its components.

Methods: Regression models were developed quantifying the influence of the time course and severity of multiple CVD risk factors, operating simultaneously, on risk of incident CVD.

Estimation and testing for clustered interval-censored bivariate survival data with application using the semi-parametric version of the Clayton-Oakes model.

The Kaplan-Meier estimator is ubiquitously used to estimate survival probabilities for time-to-event data. It is nonparametric, and thus does not require specification of a survival distribution, but it does assume that the risk set at any time t consists of independent observations. This assumption does not hold for data from paired organ systems such as occur in ophthalmology (eyes) or otolaryngology (ears), or for other types of clustered data.

Semiparametric predictive inference for failure data using first-hitting-time threshold regression.

The progression of disease for an individual can be described mathematically as a stochastic process. The individual experiences a failure event when the disease path first reaches or crosses a critical disease level. This happening defines a failure event and a first hitting time or time-to-event, both of which are important in medical contexts.

Accounting for delayed entry into observational studies and clinical trials: length-biased sampling and restricted mean survival time.

Individuals in many observational studies and clinical trials for chronic diseases are enrolled well after onset or diagnosis of their disease. Times to events of interest after enrollment are therefore residual or left-truncated event times. Individuals entering the studies have disease that has advanced to varying extents.

Group sequential design for randomized trials using "first hitting time" model.

Group sequential design (GSD) has become a popular choice in recent clinical trials as it improves trial efficiency by providing options for early termination. The implementation of traditional tests for survival analysis (eg, the log-rank test and the Cox proportional hazard (PH) model) in the GSD setting has been widely discussed. The PH assumption is required for conventional (sequential) design, it is, however, often violated in practice.

Variable Selection in Threshold Regression Model with Applications to HIV Drug Adherence Data.

The threshold regression model is an effective alternative to the Cox proportional hazards regression model when the proportional hazards assumption is not met. This paper considers variable selection for threshold regression. This model has separate regression functions for the initial health status and the speed of degradation in health.

Drug overdose mortality is associated with employment status and occupation in the National Longitudinal Mortality Study.

Background: Since 1999, over 702,000 people in the US have died of a drug overdose, and the drug overdose death rate has increased from 6.2 to 21.8 per 100,000.

Order-restricted inference for clustered ROC data with application to fingerprint matching accuracy.

Receiver operating characteristic (ROC) curve is commonly used to evaluate and compare the accuracy of classification methods or markers. Estimating ROC curves has been an important problem in various fields including biometric recognition and diagnostic medicine. In real applications, classification markers are often developed under two or more ordered conditions, such that a natural stochastic ordering exists among the observations.

Two-sample test for correlated data under outcome-dependent sampling with an application to self-reported weight loss data.

Standard methods for two-sample tests such as the t-test and Wilcoxon rank sum test may lead to incorrect type I errors when applied to longitudinal or clustered data. Recent alternatives of two-sample tests for clustered data often require certain assumptions on the correlation structure and/or noninformative cluster size. In this paper, based on a novel pseudolikelihood for correlated data, we propose a score test without knowledge of the correlation structure or assuming data missingness at random.

Reproductive and Hormonal Factors in Relation to Lung Cancer Among Nepali Women.

Of the 1.8 million global incident lung cancer cases estimated in 2012, approximately 60% occurred in less developed regions. Prior studies suggest sex differences in lung cancer risk and a potential role for reproductive and hormonal factors in lung cancer among women.

RNASeqDesign: A framework for RNA-Seq genome-wide power calculation and study design issues.

Massively parallel sequencing (a.k.a.

Generational trends and patterns in readmission within a statewide cohort of clients receiving heroin use disorder treatment in Maryland, 2007-2013.

The recent rise in opioid-related overdose deaths stresses the importance of understanding how heroin use disorders persist and what interventions are best suited for treating these illnesses. Trends show that there are diverse pathways leading to heroin use disorder that span multiple generations, but little is known about how different generations utilize and respond to treatment. This study provides insight into treatment utilization for young, middle-aged, and older adults by examination of an unusually rich longitudinal dataset of substance use disorder clients in Maryland who were treated for heroin use.

Using threshold regression to analyze survival data from complex surveys: With application to mortality linked NHANES III Phase II genetic data.

The Cox proportional hazards (PH) model is a common statistical technique used for analyzing time-to-event data. The assumption of PH, however, is not always appropriate in real applications. In cases where the assumption is not tenable, threshold regression (TR) and other survival methods, which do not require the PH assumption, are available and widely used.

Isoflavone pharmacokinetics and metabolism after consumption of a standardized soy and soy-almond bread in men with asymptomatic prostate cancer.

Epidemiologic associations suggest that populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, crossover trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy bread (SB) and soy-almond bread (SAB).

Acceptability and performance of the menstrual cup in South Africa: a randomized crossover trial comparing the menstrual cup to tampons or sanitary pads.

Background: In low-income settings, many women and girls face activity restrictions during menses, owing to lack of affordable menstrual products. The menstrual cup (MC) is a nonabsorbent reusable cup that collects menstrual blood. We assessed the acceptability and performance of the MPower® MC compared to pads or tampons among women in a low-resource setting.

Assessing discrimination of risk prediction rules in a clustered data setting.

The AUC (area under ROC curve) is a commonly used metric to assess discrimination of risk prediction rules; however, standard errors of AUC are usually based on the Mann-Whitney U test that assumes independence of sampling units. For ophthalmologic applications, it is desirable to assess risk prediction rules based on eye-specific outcome variables which are generally highly, but not perfectly correlated in fellow eyes [e.g.

Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer.

Background: Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy.

Joint analysis of current status and marker data: an extension of a bivariate threshold model.

This paper considers joint analysis of current status and marker data using a threshold model based on first hitting times. A failure time is defined as the time at which a subject's latent health status process first decreases to zero. We extend the bivariate Wiener process model in Whitmore et al.

Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory.

Subcortical dopamine D2 receptor (DRD2) signaling is implicated in cognitive processes and brain disorders, but the effect of DRD2 variants remains ambiguous. We measured allelic mRNA expression in postmortem human striatum and prefrontal cortex and then performed single nucleotide polymorphism (SNP) scans of the DRD2 locus. A previously uncharacterized promoter SNP (rs12364283) located in a conserved suppressor region was associated with enhanced DRD2 expression, whereas previously studied DRD2 variants failed to affect expression.

A nonparametric test for observational non-normally distributed ophthalmic data with eye-specific exposures and outcomes.

Purpose: To extend the Wilcoxon rank sum test to the analysis of clustered observational data with a binary exposure variable where not all cluster members (or subunits) have the same exposure status, as in ophthalmologic data where fellow eyes may differ in exposure status.

Methods: The Wilcoxon rank sum test statistic (Wc) is defined as the sum of ranks of all exposed subunits over all clusters. The large sample distribution of Wc is derived based on a two-stage permutation distribution approach which maintains the clustering structure of the exposure distribution in the original data.

Extension of the rank sum test for clustered data: two-group comparisons with group membership defined at the subunit level.

The Wilcoxon rank sum test is widely used for two-group comparisons for nonnormal data. An assumption of this test is independence of sampling units both between and within groups. In ophthalmology, data are often collected on two eyes of an individual, which are highly correlated.

The Wilcoxon signed rank test for paired comparisons of clustered data.

The Wilcoxon signed rank test is a frequently used nonparametric test for paired data (e.g., consisting of pre- and posttreatment measurements) based on independent units of analysis.

Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors.

Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Most reports suggest that BMD is highest in African-Americans, lowest in Asians, and intermediate in Caucasians, yet Asians have lower fracture rates than Caucasians. To assess the contributions of anthropometric and lifestyle characteristics to ethnic differences in BMD, we assessed lumbar spine and femoral neck BMD by dual-energy x-ray absorptiometry in 2277 (for the lumbar spine) and 2330 (for the femoral neck) premenopausal or early perimenopausal women (mean age, 46.

Ethnic variation in bone turnover in pre- and early perimenopausal women: effects of anthropometric and lifestyle factors.

Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Little is known, however, about ethnic variation in bone turnover. We measured serum osteocalcin (OC) and urinary N-telopeptide of type I collagen (NTX) levels in 2313 pre- or early perimenopausal women who were Caucasian (n = 1140), African-American (n = 651), Chinese (n = 247), or Japanese (n = 275) and were participating in the Study of Women's Health Across the Nation.