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 tests until one is not rejected. It then stops, so that no subsequent hypotheses are eligible for rejection. This procedure strongly controls the familywise error rate (FWE), that is to say, the probability that any true hypotheses are rejected. This paper describes a simple generalization of this approach in which the null hypotheses are partially ordered. It is convenient to display the partial ordering in a directed acyclic graph (DAG). We consider sequentially rejective procedures based on the partial ordering, in which a hypothesis is tested only when all preceding hypotheses have been tested and rejected. In general such procedures do not control the FWE, but it is shown that when certain intersection hypotheses are added, strong control of the FWE is obtained. The purpose of the method is to construct inference strategies for confirmatory clinical trials that better reflect the trial objectives.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Edwards D,Madsen Jdoi
10.1002/sim.2905subject
Has Abstractpub_date
2007-12-10 00:00:00pages
5116-24issue
28eissn
0277-6715issn
1097-0258journal_volume
26pub_type
杂志文章abstract::Biological drug products are therapeutic moieties manufactured by a living system or organisms. These are important life-saving drug products for patients with unmet medical needs. Because of expensive cost, only a few patients have access to life-saving biological products. Most of the early biological products will ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5565
更新日期:2013-02-10 00:00:00
abstract::The mutation and natural selection phenomenon can and often does cause the failure of antimicrobial, herbicidal, pesticide and cancer treatments selection pressures. This phenomenon operates in a mathematically predictable behavior, which when understood leads to approaches to reduce and prevent the failure of the use...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6307
更新日期:2014-12-20 00:00:00
abstract::Existing methods for power analysis for longitudinal study designs are limited in that they do not adequately address random missing data patterns. Although the pattern of missing data can be assessed during data analysis, it is unknown during the design phase of a study. The random nature of the missing data pattern ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2773
更新日期:2007-07-10 00:00:00
abstract::Statistical tests have been proposed for determining whether incident cases of adverse health effects are 'clustered' together. Several procedures, termed 'focused', specifically analyse disease surveillance data around pre-specified putative sources of environmental hazard. Little has been done to compare the perform...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780142103
更新日期:1995-11-15 00:00:00
abstract::The analysis of multivariate time-to-event (TTE) data can become complicated due to the presence of clustering, leading to dependence between multiple event times. For a long time, (conditional) frailty models and (marginal) copula models have been used to analyze clustered TTE data. In this article, we propose a gene...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8506
更新日期:2020-05-30 00:00:00
abstract::Diseases can be interconnected. In the recent years, there has been a surge of multidisease studies. Among them, HDN (human disease network) analysis takes a system perspective, examines the interconnections among diseases along with their individual properties, and has demonstrated great potential. Most of the existi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8472
更新日期:2020-04-30 00:00:00
abstract::A frequent objective in medical research is the investigation of differences in patient survival between several experimental treatments and one standard treatment. In order to assess these differences statistically, we have to apply adjustments for multiple comparisons to prevent an increased number of false-positive...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4403
更新日期:2012-01-13 00:00:00
abstract::Teaching statistics to medical students is a challenging and often unrewarding task. However, few would argue the need for statistics in the medical school curriculum. In recent years, there has been a growing call for teaching only statistical concepts in medical schools. We strongly oppose this opinion and offer an ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2906
更新日期:2007-10-15 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::This paper discusses the benefits and limitations of adaptive sample size re-estimation for phase 3 confirmatory clinical trials. Comparisons are made with more traditional fixed sample and group sequential designs. It is seen that the real benefit of the adaptive approach arises through the ability to invest sample s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4102
更新日期:2011-12-10 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::Within the rich literature on generalized linear models, substantial efforts have been devoted to models for categorical responses that are either completely ordered or completely unordered. Few studies have focused on the analysis of partially ordered outcomes, which arise in practically every area of study, includin...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4318
更新日期:2012-01-13 00:00:00
abstract::The identification of new adverse drug reactions is often tricky. For a given case, the relationship between drug exposure and symptom occurrence is usually questionable. It could be investigated statistically from a series of drug-event association cases with an independence test between the two variables. Analysing ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780100621
更新日期:1991-06-01 00:00:00
abstract::The relative importance of prognostic factors in regression can be measured either by standardized regression coefficients or by percentages of explained variation in a dependent variable. One advantage of using explained variation is the direct comparability of qualitative prognostic factors with others, or of groups...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780122413
更新日期:1993-12-30 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::Increasing numbers of economic evaluations are conducted alongside randomised controlled trials. Such studies include factorial trials, which randomise patients to different levels of two or more factors and can therefore evaluate the effect of multiple treatments alone and in combination. Factorial trials can provide...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7322
更新日期:2017-08-15 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::We describe rank-based approaches to assess principal stratification treatment effects in studies where the outcome of interest is only well-defined in a subgroup selected after randomization. Our methods are sensitivity analyses, in that estimands are identified by fixing a parameter and then we investigate the sensi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5849
更新日期:2013-11-20 00:00:00
abstract::Multiple imputation by chained equations is a flexible and practical approach to handling missing data. We describe the principles of the method and show how to impute categorical and quantitative variables, including skewed variables. We give guidance on how to specify the imputation model and how many imputations ar...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4067
更新日期:2011-02-20 00:00:00
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 a medical study we are often interested in graphically displaying the relationship between continuous variables and clinical events indicating disease progression. Often, it is reasonable to make the minimal assumption that the risk of progression is an arbitrary monotone function of the continuous variable. Someti...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1561
更新日期:2003-10-30 00:00:00
abstract::We consider the problem of identifying subgroups of participants in a clinical trial that have enhanced treatment effect. Recursive partitioning methods that recursively partition the covariate space based on some measure of between groups treatment effect difference are popular for such subgroup identification. The m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8214
更新日期:2019-09-20 00:00:00
abstract::In randomised trials, continuous endpoints are often measured with some degree of error. This study explores the impact of ignoring measurement error and proposes methods to improve statistical inference in the presence of measurement error. Three main types of measurement error in continuous endpoints are considered:...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8359
更新日期:2019-11-30 00:00:00
abstract::Relative survival is used to estimate patient survival excluding causes of death not related to the disease of interest. Rather than using cause of death information from death certificates, which is often poorly recorded, relative survival compares the observed survival to that expected in a matched group from the ge...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2399
更新日期:2005-12-30 00:00:00
abstract::Virtually all clinical trials collect multiple endpoints that are usually correlated. Many methods have been proposed to control the family-wise type I error rate (FWER), but these methods often disregard the correlation among the endpoints, such as the commonly used Bonferroni correction, Holm procedure, Wiens' Bonfe...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4434
更新日期:2012-02-20 00:00:00
abstract::This paper discusses and compares several estimators of mean rate of change in unbalanced longitudinal data based on a model with randomly distributed regression coefficients across individuals. The estimators are unweighted and weighted means of these coefficients. The paper also evaluates commonly used variance esti...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780060509
更新日期:1987-07-01 00:00:00
abstract::Two important qualities of controlled clinical trials are that they reduce dependence on historical standards for evaluating therapy and separate the effect of treatment from the confounding influence of time. Whatever the theory of the clinical trial, however, time has not easily been banished from the analysis of me...
journal_title:Statistics in medicine
pub_type: 杂志文章,评审
doi:10.1002/sim.4780081106
更新日期:1989-11-01 00:00:00
abstract::We examine different methods to pool binary outcomes used both in parallel and cross-over trials. Odds ratio (OR) estimators obtained from joint conditional probabilities in cross-over trials, such as the Mantel-Haenszel and Peto methods, are compared to an OR estimator using marginal results of cross-over trials. Whe...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1206
更新日期:2002-08-15 00:00:00
abstract::A relationship between baseline risk and treatment effect is increasingly investigated as a possible explanation of between-study heterogeneity in clinical trial meta-analysis. An approach that is still often applied in the medical literature is to plot the estimated treatment effects against the estimated measures of...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/1097-0258(20001230)19:24<3497::aid-sim830>
更新日期:2000-12-30 00:00:00
abstract::A method is presented which allows us to adapt the sample size as well as the number and time points of interim analyses to the treatment difference observed at an interim look during the course of a clinical trial with censored survival time as the endpoint. The method allows the inclusion of data inspections during ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1136
更新日期:2001-12-30 00:00:00