Abstract:
:This paper investigates the design and analysis of dose-finding trials with two agents. The set of doses for each agent is fixed in advance. The goal of the trial is to find the set of dose combinations with probability of toxicity closest to a pre-specified value. For each of the two agents we assume that the probability of toxicity of an agent is non-decreasing with dose when the dose of the other agent is fixed. Using this assumption we construct a new non-parametric design that operates on a two-dimensional grid of all possible dose combinations. A bivariate isotonic regression estimator of the maximum tolerated combinations is described. We conclude that the new design and the bivariate isotonic estimator are superior to the procedure where several independent dose-finding trials are run.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Ivanova A,Wang Kdoi
10.1002/sim.1796subject
Has Abstractpub_date
2004-06-30 00:00:00pages
1861-70issue
12eissn
0277-6715issn
1097-0258journal_volume
23pub_type
杂志文章abstract::In observational studies with censored data, exposure-outcome associations are commonly measured with adjusted hazard ratios from multivariable Cox proportional hazards models. The difference in restricted mean survival times (RMSTs) up to a pre-specified time point is an alternative measure that offers a clinically m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8206
更新日期:2019-09-10 00:00:00
abstract::In this paper, an approach to estimating the cumulative mean function for history process with time dependent covariates and right censored time-to-event variable is developed using the combined technique of joint modeling and inverse probability weighting method. The consistency of proposed estimator is derived. Theo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6998
更新日期:2016-11-10 00:00:00
abstract::In the field of cluster detection, a weighted normal model-based scan statistic was recently developed to analyze regional continuous data and to evaluate the clustering pattern of pre-defined cells (such as state, county, tract, school, hospital) that include many individuals. The continuous measures of interest are,...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3990
更新日期:2010-10-15 00:00:00
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::This paper concerns using modified weighted Schoenfeld residuals to test the proportionality of subdistribution hazards for the Fine-Gray model, similar to the tests proposed by Grambsch and Therneau for independently censored data. We develop a score test for the time-varying coefficients based on the modified Schoen...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5815
更新日期:2013-09-30 00:00:00
abstract::Clinical trials often assess efficacy by comparing treatments on the basis of two or more event-time outcomes. In the case of cancer clinical trials, progression-free survival (PFS), which is the minimum of the time from randomization to progression or to death, summarizes the comparison of treatments on the hazards f...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6096
更新日期:2014-05-30 00:00:00
abstract::The use of classification and regression tree (CART) methodology is explored for the diagnosis of patients complaining of anterior chest pain. The results are compared with those previously obtained using correspondence analysis and independent Bayes classification. The technique is shown to be of potential value for ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19970415)16:7<717::aid-sim
更新日期:1997-04-15 00:00:00
abstract::The additional time to complete a three-period two-treatment (3P2T) cross-over trial may cause a greater number of patient dropouts than with a two-period trial. This paper develops maximum likelihood (ML), single imputation and multiple imputation missing data analysis methods for the 3P2T cross-over designs. We use ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19960130)15:2<127::AID-SIM
更新日期:1996-01-30 00:00:00
abstract::Predicting an individual's risk of experiencing a future clinical outcome is a statistical task with important consequences for both practicing clinicians and public health experts. Modern observational databases such as electronic health records provide an alternative to the longitudinal cohort studies traditionally ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6526
更新日期:2015-09-20 00:00:00
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) cur...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7274
更新日期:2017-07-10 00:00:00
abstract::Pearson's chi-squared, the likelihood-ratio, and Fisher-Freeman-Halton's test statistics are often used to test the association of unordered r x c tables. Asymptotical, exact conditional, or exact conditional with mid-p adjustment methods are commonly used to compute the p-value. We have compared test power and signif...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2839
更新日期:2007-10-15 00:00:00
abstract::Researchers in clinical science and bioinformatics frequently aim to learn which of a set of candidate biomarkers is important in determining a given outcome, and to rank the contributions of the candidates accordingly. This article introduces a new approach to research questions of this type, based on targeted maximu...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3414
更新日期:2009-01-15 00:00:00
abstract::Multistate models are increasingly being used to model complex disease profiles. By modelling transitions between disease states, accounting for competing events at each transition, we can gain a much richer understanding of patient trajectories and how risk factors impact over the entire disease pathway. In this arti...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7448
更新日期:2017-12-20 00:00:00
abstract::Exposure to a carcinogen is likely to be reflected by temporal clustering of cancer cases among the community members. Detection of such clustering is a complicated task in general and more so in a small workplace community with low turnover rate. In this study we applied the CUSCORE test and the q-interval statistic ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1534
更新日期:2003-10-15 00:00:00
abstract::Testing involving the intra-class kappa coefficient is commonly performed in order to assess agreement involving categorical ratings. A number of procedures have been proposed, which make use of the limiting null distribution as the sample size goes to infinity in order to compute the observed significance. As with ma...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6135
更新日期:2014-07-30 00:00:00
abstract::Meta-analysis has generally been accepted as a fundamental tool for combining effect estimates from several studies. For binary studies with rare events, the Peto odds ratio (POR) method has become the relative effect estimator of choice. However, the POR leads to biased estimates for the OR when treatment effects are...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6301
更新日期:2014-12-10 00:00:00
abstract::Assessment of quality of life is becoming standard in clinical trials. A popular method for measuring quality of life is with instruments which utilize multiple-item subscales, in which each item is scored on a Likert scale. Most statistical methods for the analysis of quality of life data in clinical trials do not ex...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19991115)18:21<2917::aid-s
更新日期:1999-11-15 00:00:00
abstract::Knee replacement is the most commonly used surgical treatment for knee arthritis. It has been reported that knee replacement rates vary across both regions and counties. This paper used data from Medicare patients to develop explanations for the variation. One problem with our data is that we do not have patient level...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19960915)15:17<1875::AID-S
更新日期:1996-09-15 00:00:00
abstract::A method has been developed for simultaneously comparing the usefulness of many treatments of established value for symptomatic medical conditions. Medical assessment of outcome is not employed. Instead patients are required to assess treatments prescribed during the course of ordinary general practice rather than und...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/sim.4780040104
更新日期:1985-01-01 00:00:00
abstract::In the analysis of survival data, there are often competing events that preclude an event of interest from occurring. Regression analysis with competing risks is typically undertaken using a cause-specific proportional hazards model. However, modern alternative methods exist for the analysis of the subdistribution haz...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4123
更新日期:2011-03-15 00:00:00
abstract::Prognostic models are used in medicine for investigating patient outcome in relation to patient and disease characteristics. Such models do not always work well in practice, so it is widely recommended that they need to be validated. The idea of validating a prognostic model is generally taken to mean establishing tha...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000229)19:4<453::aid-sim
更新日期:2000-02-29 00:00:00
abstract::Often in randomized clinical trials and observational studies in occupational and environmental health, a non-negative continuously distributed response variable denoting some metabolites of environmental toxicants is measured in treatment and control groups. When observations occur in both unexposed and exposed subje...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3170
更新日期:2008-06-15 00:00:00
abstract::Longitudinal studies are commonly used to study processes of change. Because data are collected over time, missing data are pervasive in longitudinal studies, and complete ascertainment of all variables is rare. In this paper a new imputation strategy for completing longitudinal data sets is proposed. The proposed met...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.740
更新日期:2001-09-15 00:00:00
abstract::Using both simulated and real datasets, we compared two approaches for estimating absolute risk from nested case-control (NCC) data and demonstrated the feasibility of using the NCC design for estimating absolute risk. In contrast to previously published results, we successfully demonstrated not only that data from a ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7143
更新日期:2017-02-10 00:00:00
abstract::Outcomes research often requires estimating the impact of a binary treatment on a binary outcome in a non-randomized setting, such as the effect of taking a drug on mortality. The data often come from self-selected samples, leading to a spurious correlation between the treatment and outcome when standard binary depend...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2226
更新日期:2006-02-15 00:00:00
abstract::We obtained maximum likelihood estimates (MLEs) of the proportion cured pi c and mean log survival time mu t for a sample of 4355 patients with intraocular melanoma whose survival times subsequent to treatment were assumed to follow a log-normal distribution. Following stratification by tumour size, MLEs of pi c and m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780090814
更新日期:1990-08-01 00:00:00
abstract::We consider Cox proportional hazards regression when the covariate vector includes error-prone discrete covariates along with error-free covariates, which may be discrete or continuous. The misclassification in the discrete error-prone covariates is allowed to be of any specified form. Building on the work of Nakamura...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3159
更新日期:2008-05-20 00:00:00
abstract::Small but important therapeutic effects of new treatments can be most efficiently detected through the study of large randomized prospective series of patients. Such large scale clinical trials are nowadays commonplace. The alternative is years of polemic and debate surrounding several trials each too small to detect ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780010105
更新日期:1982-01-01 00:00:00
abstract::Spatial scan statistics are widely used for count data to detect geographical disease clusters of high or low incidence, mortality or prevalence and to evaluate their statistical significance. Some data are ordinal or continuous in nature, however, so that it is necessary to dichotomize the data to use a traditional s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2607
更新日期:2007-03-30 00:00:00
abstract::Estimation and group comparison of survival curves are two very common issues in survival analysis. In practice, the Kaplan-Meier estimates of survival functions may be biased due to unbalanced distribution of confounders. Here we develop an adjusted Kaplan-Meier estimator (AKME) to reduce confounding effects using in...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2174
更新日期:2005-10-30 00:00:00