Abstract:
:In many studies, a K degree of freedom large sample chi2 test is used to assess the effect of treatment on a multivariate response, such as an omnibus T2-like test of a difference between two treatment groups in any of K repeated measures. Alternately, a K df chi2 test may be used to test the equality of K+1 groups in a single outcome measure. Jennison and Turnbull (Biometrika 1991; 78: 133-141) describe group sequential chi2 and F-tests for normal errors linear models, and Proschan, Follmann and Geller (Statist. Med. 1994; 13: 1441-1452) describe group sequential tests for K+1 group comparisons. These methods apply to sequences of statistics that can be characterized as having an independent increments variance-covariance structure, thus simplifying the computation of the sequential variance-covariance matrix and the resulting sequential test boundaries. However, many commonly used statistics do not share this structure, including a Liang-Zeger (Biometrika 1986; 73: 13-22) GEE longitudinal analysis with an independence working correlation structure and a Wei-Lachin (J. Amer. Statist. Assoc. 1984; 79: 653-661) multivariate Wilcoxon rank test, among others. For such analyses, this paper describes the computation of group sequential boundaries for the interim analysis of emerging results using K df tests that are expressed as quadratic forms in a statistics vector that is distributed as multivariate normal, at least asymptotically. We derive the elements of the covariance matrix of multiple successive K df chi2 statistics based on established theorems on the distribution of quadratic forms. This covariance matrix is estimated by augmenting the data from the successive interim analyses into a single analysis from which the component sequential tests and their variance-covariance matrix can then be extracted. Boundary values for the sequential statistics can then be computed using the method of Slud and Wei (J. Amer. Statist. Assoc. 1982; 77: 862-868) or using the alpha-spending function of Lan and DeMets (Biometrika 1983; 70: 659-663) with a surrogate measure of information. An example is presented using the analysis of repeated cholesterol measurements in a clinical trial.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Lachin JM,Greenhouse SW,Bautista OMdoi
10.1002/sim.1637subject
Has Abstractpub_date
2003-11-15 00:00:00pages
3357-68issue
21eissn
0277-6715issn
1097-0258journal_volume
22pub_type
杂志文章abstract::A stochastic approximation EM algorithm (SAEM) is described for exploratory factor analysis of dichotomous or ordinal variables. The factor structure is obtained from sufficient statistics that are updated during iterations with the Robbins-Monro procedure. Two large-scale simulations are reported that compare accurac...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8217
更新日期:2019-09-20 00:00:00
abstract::If the sample size for a t-test is calculated on the basis of a prior estimate of the variance then the power of the test at the treatment difference of interest is not robust to misspecification of the variance. We propose a t-test for a two-treatment comparison based on Stein's two-stage test which involves the use ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19990715)18:13<1575::aid-s
更新日期:1999-07-15 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::Risk prediction models play an important role in prevention and treatment of several diseases. Models that are in clinical use are often refined and improved. In many instances, the most efficient way to improve a successful model is to identify subgroups for which there is a specific biological rationale for improvem...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6077
更新日期:2014-05-20 00:00:00
abstract::For massive survival data, we propose a subsampling algorithm to efficiently approximate the estimates of regression parameters in the additive hazards model. We establish consistency and asymptotic normality of the subsample-based estimator given the full data. The optimal subsampling probabilities are obtained via m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8783
更新日期:2021-01-30 00:00:00
abstract::It has been increasingly common to analyze simultaneously repeated measures and time to failure data. In this paper we propose a joint model when the repeated measures are semi-continuous, characterized by the presence of a large portion of zero values, as well as right skewness of non zero (positive) values. Examples...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3497
更新日期:2009-03-15 00:00:00
abstract::In drug-drug interaction (DDI) research, a two drug interaction is usually predicted by individual drug pharmacokinetics (PK). Although subject-specific drug concentration data from clinical PK studies on inhibitor/inducer or substrate's PK are not usually published, sample mean plasma drug concentrations and their st...
journal_title:Statistics in medicine
pub_type: 杂志文章,meta分析
doi:10.1002/sim.2837
更新日期:2007-09-10 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::The percentile-finding experimental design known variously as 'forced-choice fixed-staircase', 'geometric up-and-down' or 'k-in-a-row' (KR) was introduced by Wetherill four decades ago. To date, KR has been by far the most widely used up-and-down (U&D) design for estimating non-median percentiles; it is implemented mo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3590
更新日期:2009-06-15 00:00:00
abstract::Statisticians have long argued that randomized controlled trials should be sufficiently large to achieve their purpose, and for common diseases with major public health implications this has brought many benefits. However, there are many instances where it is unrealistic to expect clinicians to provide the information...
journal_title:Statistics in medicine
pub_type: 杂志文章,评审
doi:10.1002/sim.4780140204
更新日期:1995-01-30 00:00:00
abstract::A statistical definition of surrogate endpoints as well as validation criteria was first presented by Prentice. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs pointed to inadequacies of these criteria and suggested a new definition of surrogacy based on (i) t...
journal_title:Statistics in medicine
pub_type: 评论,杂志文章
doi:10.1002/sim.923
更新日期:2001-10-30 00:00:00
abstract::This paper describes compliance with the completion of a quality of life questionnaire in the Breast Cancer Prevention Trial, a large multi-centre randomized trial that is studying the efficacy of Tamoxifen in preventing breast cancer. In the first 4875 women enrolled in the control arm of the study, there was a very ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19980315/15)17:5/7<613::ai
更新日期:1998-03-15 00:00:00
abstract::Methods for dealing with tied event times in the Cox proportional hazards model are well developed. Also, the partial likelihood provides a natural way to handle covariates that change over time. However, ties between event times and the times that discrete time-varying covariates change have not been systematically s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5683
更新日期:2013-06-30 00:00:00
abstract::This paper considers the problem of selecting a set of regressors when the response variable is distributed according to a specified parametric model and observations are censored. Under a Bayesian perspective, the most widely used tools are Bayes factors (BFs), which are undefined when improper priors are used. In or...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6249
更新日期:2014-11-20 00:00:00
abstract::For many HIV-infected patients, use of antiretroviral therapy (ART) results in a sustained suppression of plasma viral load to undetectable levels. However, due to lack of antigenic stimulation, this may also result in a gradual loss of cell-mediated immune (CMI) responses that help control HIV infection. In concept, ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2555
更新日期:2007-02-10 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::We develop parametric maximum likelihood methods to adjust for treatment changes during follow-up in order to assess the causal effect of treatment in clinical trials with time-to-event outcomes. The accelerated failure time model of Robins and Tsiatis relates each observed event time to the underlying event time that...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1618
更新日期:2004-02-28 00:00:00
abstract::In clinical trials, treatment comparisons are often performed by models that incorporate important prognostic factors. Since these models require complete covariate information on all patients, statisticians frequently resort to complete case analysis or to omission of an important covariate. A probability imputation ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780090707
更新日期:1990-07-01 00:00:00
abstract::The mixed effect models for repeated measures (MMRM) analysis is sometimes used as a primary analysis in longitudinal randomized clinical trials. The SE for the treatment effect in the MMRM analysis is usually estimated by assuming the orthogonality of the fixed effect and variance-covariance parameters, which is the ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8474
更新日期:2020-04-30 00:00:00
abstract::Confounding factors are commonly encountered in observational studies. Several confounder-adjusted tests to compare survival between differently exposed subjects were proposed. However, only few studies have compared their performances regarding type I error rates, and no study exists evaluating their type II error ra...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6777
更新日期:2016-03-30 00:00:00
abstract::Multivariate outcomes measured longitudinally over time are common in medicine, public health, psychology and sociology. The typical (saturated) longitudinal multivariate regression model has a separate set of regression coefficients for each outcome. However, multivariate outcomes are often quite similar and many out...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3589
更新日期:2009-06-15 00:00:00
abstract::We extend the method proposed in a recent work by the Authors for trial-level general surrogate evaluation to allow combinations of biomarkers and provide a procedure for finding the "best" combination of biomarkers based on the absolute prediction error summary of surrogate quality. We use a nonparametric Bayesian mo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7996
更新日期:2019-03-30 00:00:00
abstract::Various aspects of portfolio management and project prioritization within the pharmaceutical industry are examined. It is shown that the cost and probability architecture of a project is a crucial aspect of its value. An appropriate simple tool for ranking projects is the Pearson index. Various difficulties are consid...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19961230)15:24<2689::AID-S
更新日期:1996-12-30 00:00:00
abstract::This paper reviews methods for mapping geographical variation in disease incidence and mortality. Recent results in Bayesian hierarchical modelling of relative risk are discussed. Two approaches to relative risk estimation, along with the related computational procedures, are described and compared. The first is an em...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780110802
更新日期:1992-06-15 00:00:00
abstract::Methods for multiple informants help to estimate the marginal effect of each multiple source predictor and formally compare the strength of their association with an outcome. We extend multiple informant methods to the case of hierarchical data structures to account for within cluster correlation. We apply the propose...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5967
更新日期:2014-02-20 00:00:00
abstract::The explanation of heterogeneity plays an important role in meta-analysis. The random effects meta-regression model allows the inclusion of trial-specific covariates which may explain a part of the heterogeneity. We examine the commonly used tests on the parameters in the random effects meta-regression with one covari...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1482
更新日期:2003-09-15 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::Methodology for the meta-analysis of individual patient data with survival end-points is proposed. Motivated by questions about the reliance on hazard ratios as summary measures of treatment effects, a parametric approach is considered and percentile ratios are introduced as an alternative to hazard ratios. The genera...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4086
更新日期:2010-12-20 00:00:00
abstract::We applied a two-stage random effects model to pulmonary function data from 31 sarcoidosis patients to illustrate its usefulness in analysing unbalanced longitudinal data. For the first stage, repeated measurements of percentage of predicted forced vital capacity (FVC%) from an individual were modelled as a function o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780080206
更新日期:1989-02-01 00:00:00
abstract::This paper investigates the impact on area life tables of the specification of unobserved frailty. Frailty specification may affect both the regression effects of area and individual level covariates, and lead to changes in the value of summary mortality parameters, such as life expectancy. The paper also investigates...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780141703
更新日期:1995-09-15 00:00:00