Abstract:
:The Response Evaluation Criteria in Solid Tumors are used as standard guidelines for the clinical evaluation of cancer treatments. The assessment is based on the anatomical tumor burden: change in size of target lesions and evolution of nontarget lesions (NTL). Despite unquestionable advantages of this standard tool, Response Evaluation Criteria in Solid Tumors are subject to some limitations such as categorization of continuous tumor size or negligence of its longitudinal trajectory. In particular, it is of interest to capture its nonlinear shape and model it simultaneously with recurrent progressions of NTL and overall survival. We propose a multivariate nonlinear mechanistic joint frailty model for longitudinal data, recurrent events, and a terminal event. In the model, the tumor size trajectory is described using an ordinary differential equation that accounts for the natural growth and treatment-induced decline. We perform a simulation study to validate the method and apply the model to a phase III clinical trial in colorectal cancer. In the results of the analysis, we determine on which component, tumor size, NTL, or death the treatment acts mostly and perform dynamic predictions of death. We compare the model with other models that consider parametric functions or splines for the tumor size trajectory in terms of goodness of fit and predictive accuracy.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Król A,Tournigand C,Michiels S,Rondeau Vdoi
10.1002/sim.7640subject
Has Abstractpub_date
2018-06-15 00:00:00pages
2148-2161issue
13eissn
0277-6715issn
1097-0258journal_volume
37pub_type
杂志文章abstract::We study the group bridge and the adaptive group bridge penalties for competing risks quantile regression with group variables. While the group bridge consistently identifies nonzero group variables, the adaptive group bridge consistently selects variables not only at group level but also at within-group level. We all...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7619
更新日期:2018-04-30 00:00:00
abstract::Comparative studies of the accuracy of diagnostic procedures often use a paired design to gain in efficiency. Standard methods for analysing data from paired designs require complete observations. In many studies, however, one of the test results may be missing for some patients. In this paper, we propose a simple cor...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章
doi:10.1002/(SICI)1097-0258(19960815)15:15<1687::AID-S
更新日期:1996-08-15 00:00:00
abstract::When sample size is recalculated using unblinded interim data, use of the usual t-test at the end of a study may lead to an elevated type I error rate. This paper describes a numerical quadrature investigation to calculate the true probability of rejection as a function of the time of the recalculation, the magnitude ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19991230)18:24<3481::aid-s
更新日期:1999-12-30 00:00:00
abstract::The receiver operating characteristic (ROC) curve is a popular technique with applications, for example, investigating an accuracy of a biomarker to delineate between disease and non-disease groups. A common measure of accuracy of a given diagnostic marker is the area under the ROC curve (AUC). In contrast with the AU...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6863
更新日期:2016-06-15 00:00:00
abstract::In many epidemiological studies it is common to resort to regression models relating incidence of a disease and its risk factors. The main goal of this paper is to consider inference on such models with error-prone observations and variances of the measurement errors changing across observations. We suppose that the o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3343
更新日期:2008-11-10 00:00:00
abstract::In a typical bioequivalence trial, summary measures of the plasma concentration versus time profile are used to compare two formulations of a drug product. Commonly used measures include area under the curve (AUC), maximum plasma concentration (C(max)) and time to maximum concentration (T(max)). Equivalence of these s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/1097-0258(20001030)19:20<2855::aid-sim550>
更新日期:2000-10-30 00:00:00
abstract::Orthogonal polynomial scores (OPS) is a simple, biologically meaningful approach to characterize longitudinal data in phase I and II clinical pharmacology trials. It describes average, linear, quadratic and higher order polynomial characteristics of each subject's response over time with use of composite scores comput...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780120703
更新日期:1993-04-15 00:00:00
abstract::The use of data from multiple studies or centers for the validation of a clinical test or a multivariable prediction model allows researchers to investigate the test's/model's performance in multiple settings and populations. Recently, meta-analytic techniques have been proposed to summarize discrimination and calibra...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7653
更新日期:2018-05-30 00:00:00
abstract::Appropriate quantification of added usefulness offered by new markers included in risk prediction algorithms is a problem of active research and debate. Standard methods, including statistical significance and c statistic are useful but not sufficient. Net reclassification improvement (NRI) offers a simple intuitive w...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4085
更新日期:2011-01-15 00:00:00
abstract::A model is developed to estimate the effect of covariate imbalance on the size of a test of treatment efficacy in randomized clinical trials comparing two treatments when dispersion parameters are known. It is concluded that tests of homogeneity on the covariates should not be performed, that covariate imbalance is ju...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780080410
更新日期:1989-04-01 00:00:00
abstract::Clinical prediction models (CPMs) can inform decision making about treatment initiation, which requires predicted risks assuming no treatment is given. However, this is challenging since CPMs are usually derived using data sets where patients received treatment, often initiated postbaseline as "treatment drop-ins." Th...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7913
更新日期:2018-12-10 00:00:00
abstract::For robust detection performance, traditional control chart monitoring for biosurveillance is based on input data free of trends, day-of-week effects, and other systematic behaviour. Time series forecasting methods may be used to remove this behaviour by subtracting forecasts from observations to form residuals for al...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2835
更新日期:2007-09-30 00:00:00
abstract::The Rvachev-Baroyan-Longini model is a space-time predictive model of the spread of influenza epidemics. It has been applied to 128 cities of the USSR, and more recently, to forecasting the spread of the pandemic of 1968-1969 throughout 52 large cities. It is a deterministic, mass-action, space and time continuous mod...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780071107
更新日期:1988-11-01 00:00:00
abstract::Many extensions of survival models based on the Cox proportional hazards approach have been proposed to handle clustered or multiple event data. Of particular note are five Cox-based models for recurrent event data: Andersen and Gill (AG); Wei, Lin and Weissfeld (WLW); Prentice, Williams and Peterson, total time (PWP-...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/(sici)1097-0258(20000115)19:1<13::aid-sim2
更新日期:2000-01-15 00:00:00
abstract::We present an approach for inference on contrasts of clinically meaningful functionals of a survivor distribution (e.g., restricted mean, quantiles) that can avoid strong parametric or semiparametric assumptions on the underlying structure of the data. In this multistage approach, we first use an adaptive predictive m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4505
更新日期:2012-07-20 00:00:00
abstract::When asking 'what is known' about a drug or therapy or program at any time, both researchers and practitioners often confront more than a single study. Facing a variety of findings, where conflicts may outweigh agreement, how can a reviewer constructively approach the task? In this discussion, I will outline some ques...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780060304
更新日期:1987-04-01 00:00:00
abstract::In conventional survival analysis there is an underlying assumption that all study subjects are susceptible to the event. In general, this assumption does not adequately hold when investigating the time to an event other than death. Owing to genetic and/or environmental etiology, study subjects may not be susceptible ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5845
更新日期:2013-10-30 00:00:00
abstract::Exploring the possible reasons for heterogeneity between studies is an important aspect of conducting a meta-analysis. This paper compares a number of methods which can be used to investigate whether a particular covariate, with a value defined for each study in the meta-analysis, explains any heterogeneity. The main ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19991030)18:20<2693::aid-s
更新日期:1999-10-30 00:00:00
abstract::Data monitoring committees (DMCs) have become an increasingly common component of randomized clinical trials in recent years. As experience has accumulated, and more individuals and organizations have become involved in such activities, a variety of approaches to the operation of such committees has inevitably arisen....
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.730
更新日期:2001-09-15 00:00:00
abstract::New combination regimens evaluated in phase II cancer clinical trials often show promising results compared to the standard therapy for a disease system. Selection of patients with a better prognosis can be a prominent factor for this optimism. For most disease systems, prognostic variables that are related to the out...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.706
更新日期:2001-03-30 00:00:00
abstract::We propose a goodness-of-fit test statistic for linear regression with heterogeneous variance, which is asymptotically chi-square if the given model is correct. The test statistic is computed as a quadratic form of observed minus predicted responses. We apply the method to a linear regression for an ordinal categorica...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780130205
更新日期:1994-01-30 00:00:00
abstract::In the pharmaceutical industry, an assay method is considered validated if the accuracy and precision for an assay meet some acceptable limits. This paper discusses the assessment of assay precision in terms of the estimation of total variability of an assay from a one-way random effects model which is often considere...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780101006
更新日期:1991-10-01 00:00:00
abstract::This paper presents a statistical analysis of treatment effects in 24-hour ambulatory blood pressure recordings. The statistical models account for circadian rhythms, subject effects, and the effects of treatment with drugs or relaxation therapy. In view of the heterogeneity of the subjects, we fit a separate linear m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780070608
更新日期:1988-06-01 00:00:00
abstract::A new, intuitive method has recently been proposed to explore treatment-covariate interactions in survival data arising from two treatment arms of a clinical trial. The method is based on constructing overlapping subpopulations of patients with respect to one (or more) covariates of interest and in observing the patte...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3524
更新日期:2009-04-15 00:00:00
abstract::Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is therefore highly dynami...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4393
更新日期:2012-02-28 00:00:00
abstract::Suppression of premature ventricular contractions (PVCs) is one of the goals of antiarrhythmic therapy. In a clinical trial, however, it may be difficult to distinguish antiarrhythmic drug effect from spontaneous variation in PVCs. We propose the application of linear regression to PVC histories to ascertain drug effe...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章
doi:10.1002/sim.4780020305
更新日期:1983-07-01 00:00:00
abstract::Among many other uses, positron emission tomography (PET) can be used in studies to estimate the density of a neuroreceptor at each location throughout the brain by measuring the concentration of a radiotracer over time and modeling its kinetics. There are a variety of kinetic models in common usage and these typicall...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3510
更新日期:2009-03-15 00:00:00
abstract::We propose a new weighted hurdle regression method for modeling count data, with particular interest in modeling cardiovascular events in patients on dialysis. Cardiovascular disease remains one of the leading causes of hospitalization and death in this population. Our aim is to jointly model the relationship/associat...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6232
更新日期:2014-11-10 00:00:00
abstract::Combinatorial drugs have been widely applied in disease treatment, especially chemotherapy for cancer, due to its improved efficacy and reduced toxicity compared with individual drugs. The study of combinatorial drugs requires efficient experimental designs and proper follow-up statistical modeling techniques. Linear ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7971
更新日期:2019-01-30 00:00:00
abstract::Dependence between observations on a dichotomous variable renders invalid the usual chi-square tests of independence and inflates the variances of parameter estimates. Such a situation occurs, for example, when subjects consist of members of the same family or with repeated observations on the same person. In this pap...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780060408
更新日期:1987-06-01 00:00:00