Abstract:
:Non-linear mixed-effects models (NLMEMs) are used to improve information gathering from longitudinal studies and are applied to treatment evaluation in disease-evolution studies, such as human immunodeficiency virus (HIV) infection. The estimation of parameters and the statistical tests are critical issues in NLMEMs since the likelihood and the Fisher information matrix have no closed form. An alternative method to numerical integrations, in which convergence is slow, and to methods based on linearization, in which asymptotic convergence has not been proved, is the Stochastic Approximation Expectation-Maximization (SAEM) algorithm. For the Wald test and the likelihood ratio test, we propose estimating the Fisher information matrix by stochastic approximation and the likelihood by importance sampling. We evaluate these SAEM-based tests in a simulation study in the context of HIV viral load decrease after initiation of an antiretroviral treatment. The results from this simulation illustrate the theoretical convergence properties of SAEM. We also propose a method based on the SAEM algorithm to compute the minimum sample size required to perform a Wald test of a given power for a covariate effect in NLMEMs. Lastly, we illustrate these tests on the evaluation of the effect of ritonavir on the indinavir pharmacokinetics in HIV patients and compare the results with those obtained using the adaptative Gaussian quadrature method implemented in the SAS procedure NLMIXED.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Samson A,Lavielle M,Mentré Fdoi
10.1002/sim.2950subject
Has Abstractpub_date
2007-11-30 00:00:00pages
4860-75issue
27eissn
0277-6715issn
1097-0258journal_volume
26pub_type
杂志文章abstract::Identification of the latency period for the effect of a time-varying exposure is key when assessing many environmental, nutritional, and behavioral risk factors. A pre-specified exposure metric involving an unknown latency parameter is often used in the statistical model for the exposure-disease relationship. Likelih...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8038
更新日期:2019-03-30 00:00:00
abstract::Bioequivalence or interaction trials are commonly studied in crossover design and can be analysed by nonlinear mixed effects models as an alternative to noncompartmental approach. We propose an extension of the population Fisher information matrix in nonlinear mixed effects models to design crossover pharmacokinetic t...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4390
更新日期:2012-05-20 00:00:00
abstract::Correlated data are obtained in longitudinal epidemiological studies, where repeated measurements are taken on individuals or groups over time. Such longitudinal data are ideally analyzed using multilevel modeling approaches, which appropriately account for the correlations in repeated responses in the same individual...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5880
更新日期:2013-12-10 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::Meta-analysis is the methodology for combining findings from similar research studies asking the same question. When the question of interest involves multiple outcomes, multivariate meta-analysis is used to synthesize the outcomes simultaneously taking into account the correlation between the outcomes. Likelihood-bas...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4327
更新日期:2011-10-30 00:00:00
abstract::Interpretation of the Mantoux test for tuberculous infection can be complicated by cross-reactions caused by infection with non-specific mycobacteria. Thus, the distribution of positive indurations is a mixture of two distributions. To estimate tuberculous infection prevalence, the marginal distribution of indurations...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.745
更新日期:2001-04-15 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 a phase I clinical trial in cancer patients, the drug involved had one known main adverse effect, which also occurs spontaneously in cancer patients with a fairly high frequency. Experiments in rats have shown marked effects of the drug on tumour growth in high doses, but also dose-dependent toxicity. Consequently,...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780140909
更新日期:1995-05-15 00:00:00
abstract::Medical costs data with administratively censored observations often arise in cost-effectiveness studies of treatments for life-threatening diseases. Mean of medical costs incurred from the start of a treatment until death or a certain time point after the implementation of treatment is frequently of interest. In many...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1556
更新日期:2004-11-15 00:00:00
abstract::Many observational studies adopt what we call retrospective convenience sampling (RCS). With the sample size in each arm prespecified, RCS randomly selects subjects from the treatment-inclined subpopulation into the treatment arm and those from the control-inclined into the control arm. Samples in each arm are represe...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7808
更新日期:2018-05-20 00:00:00
abstract::Comparative calibration is the broad statistical methodology used to assess the calibration of a set of p instruments, each designed to measure the same characteristic, on a common group of individuals. Different from the usual calibration problem, the true underlying quantity measured is unobservable. Many authors ha...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19970830)16:16<1889::aid-s
更新日期:1997-08-30 00:00:00
abstract::The Cardiac Arrythmia Suppression Trial was stopped much earlier than planned. Statistical considerations played a very important role in the decision. Flexible group sequential testing was developed for the trial by implementing a Lan and DeMets procedure with use of the permutation test. We compute P-values from the...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1002/sim.4780090915
更新日期:1990-09-01 00:00:00
abstract::In many community-based studies on the incidence of dementia, a target population is screened and a subsample is clinically evaluated at baseline and follow-up. Incidence rates are affected by missed cases at both exams and this complicates the estimation of these rates. Recent work proposes a regression-based techniq...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000615/30)19:11/12<1577:
更新日期:2000-06-15 00:00:00
abstract::Testing the equality of 2 proportions for a control group versus a treatment group is a well-researched statistical problem. In some settings, there may be strong historical data that allow one to reliably expect that the control proportion is one, or nearly so. While one-sample tests or comparisons to historical cont...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7579
更新日期:2018-03-30 00:00:00
abstract::A Non-Parametric Maximum Likelihood approach to the estimation of relative risks in the context of disease mapping is discussed and a NPML approximation to conditional autoregressive models is proposed. NPML estimates have been compared to other proposed solutions (Maximum Likelihood via Monte Carlo Scoring, Hierarchi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/1097-0258(20000915/30)19:17/18<2539::aid-s
更新日期:2000-09-15 00:00:00
abstract::Funnel plots are widely used to visualize grouped data, for example, in institutional comparison. This paper extends the concept to a multi-level setting, displaying one level at a time, adjusted for the other levels, as well as for covariates at all levels. These level-adjusted funnel plots are based on a Markov chai...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5677
更新日期:2014-09-20 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::Kappa coefficients are measures of correlation between categorical variables often used as reliability or validity coefficients. We recapitulate development and definitions of the K (categories) by M (ratings) kappas (K x M), discuss what they are well- or ill-designed to do, and summarize where kappas now stand with ...
journal_title:Statistics in medicine
pub_type: 杂志文章,评审
doi:10.1002/sim.1180
更新日期:2002-07-30 00:00:00
abstract::Clinical studies that involve the recording of two or more distinct and well-defined events on each subject give rise to multiple event data. Treatment comparisons are usually reported in univariate analyses of time to first event or number of events observed. However, this approach may not uncover the 'full story' of...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1002/(sici)1097-0258(19970430)16:8<941::aid-sim
更新日期:1997-04-30 00:00:00
abstract::Service on the Data Monitoring Committee of the CPEP (Calcium for Pre-eclampsia Prevention) has led us to four conclusions about clinical trials which we should like to present to this gathering of biostatisticians for their reactions: (i) meta-analyses of the pertinent published trials of the same therapy should alwa...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19960630)15:12<1263::AID-S
更新日期:1996-06-30 00:00:00
abstract::The estimation of attributable risk in the presence of confounding and effect modification is studied in this paper. Different adjustment methods for the attributable risk are reviewed. The results of a stimulation study comparing these methods under the unrestricted multinomial sampling model are reported. From the s...
journal_title:Statistics in medicine
pub_type: 杂志文章,评审
doi:10.1002/sim.4780111606
更新日期:1992-12-01 00:00:00
abstract::The cost and efficiency of training clinical centre staff and of duplicate data entry in clinical trials is reviewed. Training is an essential component of quality assurance programmes and it is usually carried out at regular intervals in long-term clinical trials. Initial training of staff and regular retraining is i...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780090118
更新日期:1990-01-01 00:00:00
abstract::Much has been published on various aspects of data analysis and reporting from clinical trials within the biopharmaceutical environment. This ranges from regulatory guidelines on the format and content of registration dossiers to recommendations on data presentation and the statistical methodologies that are appropria...
journal_title:Statistics in medicine
pub_type: 杂志文章,评审
doi:10.1002/(sici)1097-0258(19980815/30)17:15/16<1829:
更新日期:1998-08-15 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::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::The principles and historical development of clinical trials are outlined briefly. Some issues that extend the basic philosophy first put forward by Sir Austin Bradford Hill 40 years ago and that will need consideration in the future application of clinical trials are discussed. ...
journal_title:Statistics in medicine
pub_type: 传,历史文章,杂志文章
doi:10.1002/sim.4780010414
更新日期:1982-10-01 00:00:00
abstract::Between-community variance or community-by-time variance is one of the key factors driving the cost of conducting group randomized trials, which are often very expensive. We investigated empirically whether between-community variance could be reduced by controlling individual- and/or community-level covariates and ide...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19990315)18:5<539::aid-sim
更新日期:1999-03-15 00:00:00
abstract::Ewell and Ibrahim derived the large sample distribution of the logrank statistic under general local alternatives. Their asymptotic results enable us to extend several group sequential designs which allow for early stopping in favour of the null hypothesis to the setting in which the cure rate model is appropriate. In...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/1097-0258(20001130)19:22<3023::aid-sim638>
更新日期:2000-11-30 00:00:00
abstract::Our objective is to develop a model to estimate the relative risk of disease in each area, Ai, i=1, ... , n, of a region and to identify areas of unusually high or low risk. We use a product partition model (PPM) in which we assume that the true relative risks can be partitioned into a number of components or sets of ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3253
更新日期:2008-08-30 00:00:00
abstract::A new exponentially weighted moving average (EWMA) control chart well suited for 'online' routine surveillance of medical procedures is introduced. The chart is based on inter-event counts for failures recorded when the failures occur. The method can be used for many types of hospital procedures and activities, such a...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2520
更新日期:2007-01-15 00:00:00