Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs
Thomas Burnett,Pavel Mozgunov,Philip Pallmann,Sofia S. Villar,Graham M. Wheeler,Thomas Jaki,Thomas Jaki +6 more
TLDR
The main features of adaptive designs and commonly used terminology are introduced, highlighting their utility and pitfalls, and their use is illustrated through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies.Abstract:
Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical, and efficient. These benefits are achieved while preserving the integrity and validity of the trial, through the pre-specification and proper adjustment for the possible alterations during the course of the trial. Despite much research in the statistical literature highlighting the potential advantages of adaptive designs over traditional fixed designs, the uptake of such methods in clinical research has been slow. One major reason for this is that different adaptations to trial designs, as well as their advantages and limitations, remain unfamiliar to large parts of the clinical community. The aim of this paper is to clarify where adaptive designs can be used to address specific questions of scientific interest; we introduce the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrate their use through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies.read more
Citations
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A new framework for developing and evaluating complex interventions: Update of Medical Research Council guidance
Kathryn Skivington,Lynsay Matthews,Sharon Anne Simpson,Peter Craig,Janis Baird,Jane M Blazeby,Kathleen A Boyd,Neil Craig,David P. French,Emma McIntosh,Mark Petticrew,Jo Rycroft-Malone,Martin White,Laurence Moore +13 more
TL;DR: JBl received funding from NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol and by the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures).
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Quantifying efficiency gains of innovative designs of two-arm vaccine trials for COVID-19 using an epidemic simulation model
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Point estimation for adaptive trial designs I: A methodological review
TL;DR: In this article , a comprehensive review of the methods to remove or reduce the potential bias in point estimation of treatment effects for adaptive clinical trial designs is presented, and a set of guidelines for trial statisticians is proposed.
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CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis.
TL;DR: The mechanistic target of rapamycin (mTOR) and wingless-related integration site (Wnt) signal transduction networks are evolutionarily conserved mammalian growth and cellular development networks as mentioned in this paper.
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Opportunity for efficiency in clinical development: An overview of adaptive clinical trial designs and innovative machine learning tools, with examples from the cardiovascular field.
TL;DR: The authors provide an overview of different types of adaptive designs in clinical trials and their applications to cardiovascular trials and highlight the increasing role of machine learning and use of metaheuristics to construct increasingly complex adaptive designs or to identify interesting features for improved predictions and classifications.
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