Chain Procedures: A Class of Flexible Closed Testing Procedures With Clinical Trial Applications

Millen, Brian A.; Dmitrienko, Alex

doi:10.1198/sbr.2010.09014

Cited by 40 publications

(65 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, when selecting a criterion to be used in sample size calculations, it is important to ensure that it is consistent with the trial's clinical objectives. As pointed out in several publications (see, for example, Millen and Dmitrienko, 2011), a potential limitation of the disjunctive and related success criteria is that they are symmetric in the sense that the null hypotheses are treated as being interchangeable. However, clinical objectives and associated null hypotheses are not interchangeable in multiple settings.…”

Section: Power Calculations In Clinical Trials With Multiple Objectivesmentioning

confidence: 99%

“…These general goals can be accomplished within the Clinical Scenario Evaluation (CSE) framework (Benda et al, 2010;Friede et al, 2010). Conceptually similar approaches to quantitative evaluation of multiple analysis strategies were also proposed in Dmitrienko et al (2011a) and Millen and Dmitrienko (2011).…”

Section: Clinical Scenario Evaluation Approachmentioning

confidence: 99%

“…A more flexible approach is supported by the class of nonparametric (Bonferroni-based) chain procedures Millen and Dmitrienko, 2011) that enable complex decision trees. Each chain procedure is uniquely defined by two sets of procedure parameters, initial hypothesis weights and initial transition parameters, defined as follows:…”

Section: Single-family Multiplicity Problemsmentioning

confidence: 99%

“…When the joint distribution is fully specified, a parametric version of the chain procedures can be constructed (Millen and Dmitrienko, 2011). The class of parametric chain procedures includes as special cases the single-step Dunnett, step-down Dunnett and parametric fallback procedures (Huque and Alosh, 2008).…”

Section: Single-family Multiplicity Problemsmentioning

confidence: 99%

“…Over the past decades, a variety of powerful MTPs have been developed and many of them have found applications in clinical trials. This includes, for example, the Holm, Hochberg and Hommel procedures, as well as other methods that allow the sponsor to specify the relative importance of different objectives, e.g., the fixed-sequence, fallback and chain procedures (Wiens, 2003;Wiens and Dmitrienko, 2005;Millen and Dmitrienko, 2011) and gatekeeping procedures Dmitrienko, D'Agostino and Huque, 2013). To provide an example of a successful application of a powerful MTP in confirmatory Phase III settings, Hommel-based gatekeeping procedures were used in the lurasidone clinical trials in patients with schizophrenia (Meltzer et al, 2011;Nasrallah et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Power Calculations in Clinical Trials With Complex Clinical Objectives

Dmitrienko

Paux

Brechenmacher

2015

Journal of the Japanese Society of Computational Statistics

Self Cite

View full text Add to dashboard Cite

Over the past decade, a variety of powerful multiple testing procedures have been developed for the analysis of clinical trials with multiple clinical objectives based, for example, on several endpoints, dose-placebo comparisons and patient subgroups. Sample size and power calculations in these complex settings are not straightforward and, in general, simulation-based methods are used. In this paper, we provide an overview of power evaluation approaches in the context of clinical trials with multiple objectives and illustrate the key principles using case studies commonly seen in the development of new therapies.

show abstract

Section: Power Calculations In Clinical Trials With Multiple Objectivesmentioning

confidence: 99%

Section: Clinical Scenario Evaluation Approachmentioning

confidence: 99%

Section: Single-family Multiplicity Problemsmentioning

confidence: 99%

Section: Single-family Multiplicity Problemsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Power Calculations in Clinical Trials With Complex Clinical Objectives

Dmitrienko

Paux

Brechenmacher

2015

Journal of the Japanese Society of Computational Statistics

Self Cite

View full text Add to dashboard Cite

show abstract

Graphical approaches for multiple comparison procedures using weighted Bonferroni, Simes, or parametric tests

et al. 2011

View full text Add to dashboard Cite

The confirmatory analysis of pre-specified multiple hypotheses has become common in pivotal clinical trials. In the recent past multiple test procedures have been developed that reflect the relative importance of different study objectives, such as fixed sequence, fallback, and gatekeeping procedures. In addition, graphical approaches have been proposed that facilitate the visualization and communication of Bonferroni-based closed test procedures for common multiple test problems, such as comparing several treatments with a control, assessing the benefit of a new drug for more than one endpoint, combined non-inferiority and superiority testing, or testing a treatment at different dose levels in an overall and a subpopulation. In this paper, we focus on extended graphical approaches by dissociating the underlying weighting strategy from the employed test procedure. This allows one to first derive suitable weighting strategies that reflect the given study objectives and subsequently apply appropriate test procedures, such as weighted Bonferroni tests, weighted parametric tests accounting for the correlation between the test statistics, or weighted Simes tests. We illustrate the extended graphical approaches with several examples. In addition, we describe briefly the gMCP package in R, which implements some of the methods described in this paper.

show abstract

Development of gatekeeping strategies in confirmatory clinical trials

et al. 2011

Self Cite

View full text Add to dashboard Cite

This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial-specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus.

show abstract

Chain Procedures: A Class of Flexible Closed Testing Procedures With Clinical Trial Applications

Cited by 40 publications

References 15 publications

Power Calculations in Clinical Trials With Complex Clinical Objectives

Power Calculations in Clinical Trials With Complex Clinical Objectives

Graphical approaches for multiple comparison procedures using weighted Bonferroni, Simes, or parametric tests

Development of gatekeeping strategies in confirmatory clinical trials

Contact Info

Product

Resources

About