Multiple testing procedures for adaptive enrichment designs: combining group sequential and reallocation approaches. 2016

Michael Rosenblum, and Tianchen Qian, and Yu Du, and Huitong Qiu, and Aaron Fisher
Department of Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA mrosen@jhu.edu.

Adaptive enrichment designs involve preplanned rules for modifying enrollment criteria based on accrued data in an ongoing trial. For example, enrollment of a subpopulation where there is sufficient evidence of treatment efficacy, futility, or harm could be stopped, while enrollment for the remaining subpopulations is continued. We propose a new class of multiple testing procedures tailored to adaptive enrichment designs. The procedures synthesize ideas from two general approaches. As in the modified group sequential approach, the procedures gain power by leveraging the covariance among statistics for different stages and different hypotheses. As in the alpha reallocation approach, the procedures lower rejection thresholds for the remaining null hypotheses after others have been rejected. The proposed procedures are proved to have power greater than or equal to several existing methods, and to strongly control the familywise Type I error rate when statistics are normally distributed. The methods are illustrated through simulations of a trial for a surgical intervention for stroke, involving two subpopulations.

UI MeSH Term Description Entries
D012107 Research Design A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. Experimental Design,Data Adjustment,Data Reporting,Design, Experimental,Designs, Experimental,Error Sources,Experimental Designs,Matched Groups,Methodology, Research,Problem Formulation,Research Methodology,Research Proposal,Research Strategy,Research Technics,Research Techniques,Scoring Methods,Adjustment, Data,Adjustments, Data,Data Adjustments,Design, Research,Designs, Research,Error Source,Formulation, Problem,Formulations, Problem,Group, Matched,Groups, Matched,Matched Group,Method, Scoring,Methods, Scoring,Problem Formulations,Proposal, Research,Proposals, Research,Reporting, Data,Research Designs,Research Proposals,Research Strategies,Research Technic,Research Technique,Scoring Method,Source, Error,Sources, Error,Strategies, Research,Strategy, Research,Technic, Research,Technics, Research,Technique, Research,Techniques, Research
D003627 Data Interpretation, Statistical Application of statistical procedures to analyze specific observed or assumed facts from a particular study. Data Analysis, Statistical,Data Interpretations, Statistical,Interpretation, Statistical Data,Statistical Data Analysis,Statistical Data Interpretation,Analyses, Statistical Data,Analysis, Statistical Data,Data Analyses, Statistical,Interpretations, Statistical Data,Statistical Data Analyses,Statistical Data Interpretations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068456 Clinical Studies as Topic Works about research studies that evaluate interventions or exposures on biomedical or health-related outcomes. The two main types of clinical studies are interventional studies (clinical trials) and observational studies.
D015233 Models, Statistical Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc. Probabilistic Models,Statistical Models,Two-Parameter Models,Model, Statistical,Models, Binomial,Models, Polynomial,Statistical Model,Binomial Model,Binomial Models,Model, Binomial,Model, Polynomial,Model, Probabilistic,Model, Two-Parameter,Models, Probabilistic,Models, Two-Parameter,Polynomial Model,Polynomial Models,Probabilistic Model,Two Parameter Models,Two-Parameter Model
D017063 Outcome Assessment, Health Care Research aimed at assessing the quality and effectiveness of health care as measured by the attainment of a specified end result or outcome. Measures include parameters such as improved health, lowered morbidity or mortality, and improvement of abnormal states (such as elevated blood pressure). Assessment, Outcome,Outcome Assessment,Outcome Assessment (Health Care),Outcomes Research,Assessment, Outcomes,Outcome Measures,Outcome Studies,Outcomes Assessment,Assessment, Outcome (Health Care),Assessments, Outcome,Assessments, Outcome (Health Care),Assessments, Outcomes,Measure, Outcome,Measures, Outcome,Outcome Assessments,Outcome Assessments (Health Care),Outcome Measure,Outcome Study,Outcomes Assessments,Research, Outcomes,Studies, Outcome,Study, Outcome

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