Abstract:
:Combining multiple markers can improve classification accuracy compared with using a single marker. In practice, covariates associated with markers or disease outcome can affect the performance of a biomarker or biomarker combination in the population. The covariate-adjusted receiver operating characteristic (ROC) curve has been proposed as a tool to tease out the covariate effect in the evaluation of a single marker; this curve characterizes the classification accuracy solely because of the marker of interest. However, research on the effect of covariates on the performance of marker combinations and on how to adjust for the covariate effect when combining markers is still lacking. In this article, we examine the effect of covariates on classification performance of linear marker combinations and propose to adjust for covariates in combining markers by maximizing the nonparametric estimate of the area under the covariate-adjusted ROC curve. The proposed method provides a way to estimate the best linear biomarker combination that is robust to risk model assumptions underlying alternative regression-model-based methods. The proposed estimator is shown to be consistent and asymptotically normally distributed. We conduct simulations to evaluate the performance of our estimator in cohort and case/control designs and compare several different weighting strategies during estimation with respect to efficiency. Our estimator is also compared with alternative regression-model-based estimators or estimators that maximize the empirical area under the ROC curve, with respect to bias and efficiency. We apply the proposed method to a biomarker study from an human immunodeficiency virus vaccine trial. Copyright © 2017 John Wiley & Sons, Ltd.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Kim S,Huang Ydoi
10.1002/sim.7274subject
Has Abstractpub_date
2017-07-10 00:00:00pages
2347-2362issue
15eissn
0277-6715issn
1097-0258journal_volume
36pub_type
杂志文章abstract::Regardless of whether a statistician believes in letting a data set speak for itself through nominal p-values or believes in strict alpha conservation, the interpretation of experiments which are negative for the primary endpoint but positive for secondary endpoints is the source of some angst. The purpose of this pap...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000330)19:6<767::aid-sim
更新日期:2000-03-30 00:00:00
abstract::Statistical methods for analyzing recurrent events have attracted significant attention. The majority of existing works consider situations in which subjects are observed over time periods and events of interest that occurred during the course of follow-up are recorded. In some applications, a subject may leave the st...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8042
更新日期:2019-04-15 00:00:00
abstract::Effective statistical help to biological and medical research demands thorough involvement of the statistician. The breadth of his activities can be illustrated by considering the questions he needs to discuss with his scientific colleagues in the course of planning a comparative experiment. The paper presents and com...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章
doi:10.1002/sim.4780010103
更新日期:1982-01-01 00:00:00
abstract::In this paper the following problem of clinical research is explored. Several potential new treatments are available for use against a certain disease. These are evaluated in a series of pilot studies which will constitute phase II clinical trials. The most promising will then be compared with a standard treatment in ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780050510
更新日期:1986-09-01 00:00:00
abstract::In natural history studies of chronic disease, it is of interest to understand the evolution of key variables that measure aspects of disease progression. This is particularly true for immunological variables among persons infected with the human immunodeficiency virus (HIV). The natural time scale for such studies is...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780131103
更新日期:1994-06-15 00:00:00
abstract::In applications such as medical statistics and genetics, we encounter situations where a large number of highly correlated predictors explain a response. For example, the response may be a disease indicator and the predictors may be treatment indicators or single nucleotide polymorphisms (SNPs). Constructing a good pr...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4014
更新日期:2010-10-30 00:00:00
abstract::A popular method to control multiplicity in confirmatory clinical trials is to use a so-called hierarchical, or fixed sequence, test procedure. This requires that the null hypotheses are ordered a priori, for example, in order of clinical importance. The procedure tests the hypotheses in this order using alpha-level t...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2905
更新日期:2007-12-10 00:00:00
abstract::Quantifying socioeconomic disparities and understanding the roots of inequalities are growing topics in cancer research. However, socioeconomic differences are challenging to investigate mainly due to the lack of accurate data at individual-level, while aggregate indicators are only partially informative. We implement...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8392
更新日期:2020-01-15 00:00:00
abstract::We consider the analysis of serial biomarkers to screen and monitor individuals in a given population for onset of a specific disease of interest. The biomarker readings are subject to error. We survey some of the existing literature and concentrate on two recently proposed models. The first is a fully Bayesian hierar...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000229)19:4<617::aid-sim
更新日期:2000-02-29 00:00:00
abstract::Incomplete and unbalanced multivariate data often arise in longitudinal studies due to missing or unequally-timed repeated measurements and/or the presence of time-varying covariates. A general approach to analysing such data is through maximum likelihood analysis using a linear model for the expected responses, and s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780070132
更新日期:1988-01-01 00:00:00
abstract::In monitoring a clinical trial or other observational study with a survival endpoint, sometimes the numbers of patients entering and dying at each time point are presented, but the connections between them are kept confidential. Hence, the exact time to failure or censoring for each individual is missing. We refer to ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2819
更新日期:2007-08-30 00:00:00
abstract::This paper gives a standard error for Cohen's Kappa, conditional on the margins of the observed r x r table. An explicit formula is given for the 2 x 2 table, and a procedure for the more general situation. A parsimonious log-linear model is suggested for the general case and an approximate confidence interval for kap...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780100512
更新日期:1991-05-01 00:00:00
abstract::Hypothesis testing, in which the null hypothesis specifies no difference between treatment groups, is an important tool in the assessment of new medical interventions. For randomized clinical trials, permutation tests that reflect the actual randomization are design-based analyses for such hypotheses. This means that ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000530)19:10<1319::aid-s
更新日期:2000-05-30 00:00:00
abstract::Pooling biospecimens prior to performing lab assays can help reduce lab costs, preserve specimens, and reduce information loss when subject to a limit of detection. Because many biomarkers measured in epidemiological studies are positive and right-skewed, proper analysis of pooled specimens requires special methods. I...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6496
更新日期:2015-07-30 00:00:00
abstract::Identification of key factors associated with the risk of developing cardiovascular disease and quantification of this risk using multivariable prediction algorithms are among the major advances made in preventive cardiology and cardiovascular epidemiology in the 20th century. The ongoing discovery of new risk markers...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2929
更新日期:2008-01-30 00:00:00
abstract::We suggest measures to quantify the degrees of necessity and of sufficiency of prognostic factors for dichotomous and for survival outcomes. A cause, represented by certain values of prognostic factors, is considered necessary for an event if, without the cause, the event cannot develop. It is considered sufficient fo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8331
更新日期:2019-10-15 00:00:00
abstract::Cancer patients, chronic kidney disease patients, and subjects infected with HIV are routinely monitored over time using biomarkers that represent key health status indicators. Furthermore, biomarkers are frequently used to guide initiation of new treatments or to inform changes in intervention strategies. Since key m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7675
更新日期:2018-08-15 00:00:00
abstract::We present methods for binomial regression when the outcome is determined using the results of a single diagnostic test with imperfect sensitivity and specificity. We present our model, illustrate it with the analysis of real data, and provide an example of WinBUGS program code for performing such an analysis. Conditi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1656
更新日期:2004-04-15 00:00:00
abstract::Phase II studies in oncology are frequently conducted as two-stage single-arm trials with a binary endpoint indicating tumor response. As a common feature of these designs, the sample sizes of the two stages and the decision rules for the interim and the final analysis have to be pre-specified and adhered to strictly ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6479
更新日期:2015-06-15 00:00:00
abstract::Antimicrobial resistance has become one of the main public health burdens of the last decades, and monitoring the development and spread of non-wild-type isolates has therefore gained increased interest. Monitoring is performed based on the minimum inhibitory concentration (MIC) values, which are collected through the...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5939
更新日期:2014-01-30 00:00:00
abstract::In lifetime data, like cancer studies, there may be long term survivors, which lead to heavy censoring at the end of the follow-up period. Since a standard survival model is not appropriate to handle these data, a cure model is needed. In the literature, covariate hypothesis tests for cure models are limited to parame...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8530
更新日期:2020-07-30 00:00:00
abstract::We consider the problem of identifying a subgroup of patients who may have an enhanced treatment effect in a randomized clinical trial, and it is desirable that the subgroup be defined by a limited number of covariates. For this problem, the development of a standard, pre-determined strategy may help to avoid the well...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4322
更新日期:2011-10-30 00:00:00
abstract::In this paper, we define a modified version τ(b) of Kendall's tau to measure the association in a pair (X,Y) of random variables subject to fixed left censoring due to known lower detection limits. We provide a nonparametric estimator of τ(b) and investigate its asymptotic properties. We then assume an Archimedean cop...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4319
更新日期:2011-11-20 00:00:00
abstract::Correlated response data arise often in biomedical studies. The generalized estimation equation (GEE) approach is widely used in regression analysis for such data. However, there are few methods available to check the adequacy of regression models in GEE. In this paper, a graphical method is proposed based on Cook and...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.889
更新日期:2001-10-15 00:00:00
abstract::Longitudinal biomarker data are often collected in studies, providing important information regarding the probability of an outcome of interest occurring at a future time. With many new and evolving technologies for biomarker discovery, the number of biomarker measurements available for analysis of disease progression...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8687
更新日期:2020-11-20 00:00:00
abstract::For patients who were previously treated for prostate cancer, salvage hormone therapy is frequently given when the longitudinal marker prostate-specific antigen begins to rise during follow-up. Because the treatment is given by indication, estimating the effect of the hormone therapy is challenging. In a previous pape...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5890
更新日期:2014-01-30 00:00:00
abstract::In a longitudinal study of workers in seven Norwegian aluminium plants, the time to development of asthmatic symptoms could only be determined to lie in the interval between two consecutive health examinations. In a previous paper we analysed the data by survival techniques for interval censored data. In the present p...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780131708
更新日期:1994-09-15 00:00:00
abstract::Clustered grouped survival data arise naturally in clinical medicine and biological research. For example, in a randomized clinical trial, the variable of interest is the time to occurrence of a certain event with or without a new treatment and the data are collected from possibly correlated subjects from independent ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1323
更新日期:2003-06-30 00:00:00
abstract::Laboratory determinations on children aged 6 to 10 years obtained over a 5-year period are analysed by a method described in detail for differentiating between children from exposed and control areas of Seveso, Italy. In the analysis, stratification is employed to distinguish the separate days of laboratory measuremen...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780020221
更新日期:1983-04-01 00:00:00
abstract::It has been well known that ignoring measurement error may result in substantially biased estimates in many contexts including linear and nonlinear regressions. For survival data with measurement error in covariates there has been extensive discussion in the literature with the focus being on the Cox proportional haza...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2892
更新日期:2007-11-20 00:00:00