Journal ArticleDOI
Tutorial on statistical considerations on subgroup analysis in confirmatory clinical trials.
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TLDR
This tutorial considers issues related to subgroup analyses and their impact on the interpretation of findings of completed trials that met their main objectives and provides guidance on the design and analysis of clinical trials that account for the expected heterogeneity of treatment effects across subgroups.Abstract:
Clinical trials target patients who are expected to benefit from a new treatment under investigation. However, the magnitude of the treatment benefit, if it exists, often depends on the patient baseline characteristics. It is therefore important to investigate the consistency of the treatment effect across subgroups to ensure a proper interpretation of positive study findings in the overall population. Such assessments can provide guidance on how the treatment should be used. However, great care has to be taken when interpreting consistency results. An observed heterogeneity in treatment effect across subgroups can arise because of chance alone, whereas true heterogeneity may be difficult to detect by standard statistical tests because of their low power. This tutorial considers issues related to subgroup analyses and their impact on the interpretation of findings of completed trials that met their main objectives. In addition, we provide guidance on the design and analysis of clinical trials that account for the expected heterogeneity of treatment effects across subgroups by establishing treatment benefit in a pre-defined targeted subgroup and/or the overall population. Copyright © 2016 John Wiley & Sons, Ltd.read more
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Optimized adaptive enrichment designs
Thomas Ondra,Sebastian Jobjörnsson,Robert A. Beckman,Carl-Fredrik Burman,Carl-Fredrik Burman,Franz König,Nigel Stallard,Martin Posch +7 more
TL;DR: This work optimize frequentist single- and adaptive two-stage trial designs for the development of targeted therapies, where in addition to an overall population, a pre-defined subgroup is investigated and shows that partial enrichment designs can substantially improve the expected utilities.
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Multiplicity considerations in subgroup analysis
TL;DR: Key considerations in confirmatory subgroup analysis based on one or more pre-specified patient populations are reviewed, including a survey of multiplicity adjustment methods recommended in multi-population phase III clinical trials.
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Design and estimation in clinical trials with subpopulation selection.
TL;DR: This work discusses a class of designs that allow selection of a predefined subgroup and investigates the precision and accuracy of the maximum likelihood estimator at the end of the study via simulations, finding that the required sample size is chiefly determined by the subgroup prevalence.
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Home visits for uncontrolled asthma among low-income adults with patient portal access
Andrea J. Apter,A. Russell Localio,Knashawn H Morales,Xiaoyan Han,Luzmercy Perez,Alyssa N. Mullen,Marisa Rogers,Heather Klusaritz,John T. Howell,Maryori Canales,Tyra Bryant-Stephens +10 more
TL;DR: Home visits with emphasis on self-management education might be necessary to facilitate patient-clinician communication and to improve outcomes for asthma, for low-income adults with uncontrolled asthma.
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Propensity Score Weighting for Causal Subgroup Analysis
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TL;DR: The CAPRIE trial as discussed by the authors evaluated the relative efficacy of clopidogrel and aspirin in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed.
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Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer
Rafael G. Amado,Michael S. Wolf,Marc Peeters,Eric Van Cutsem,Salvatore Siena,Daniel J. Freeman,Todd Juan,Robert Sikorski,Sid Suggs,Robert Radinsky,Scott D. Patterson,David D. Chang +11 more
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