@article{4b8e075631cc40cd96e6cb52eac8015a,
title = "Efficient Adaptive Designs for Clinical Trials of Interventions for COVID-19",
abstract = "The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial{\textquoteright}s scientific validity or integrity. In this article, we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.",
keywords = "Adaptive trial, Group sequential design, Multi-arm multi-stage, Pandemic research, Platform trial, SARS-CoV-2",
author = "Nigel Stallard and Lisa Hampson and Norbert Benda and Werner Brannath and Thomas Burnett and Tim Friede and Kimani, {Peter K.} and Franz Koenig and Johannes Krisam and Pavel Mozgunov and Martin Posch and James Wason and Gernot Wassmer and John Whitehead and Williamson, {S. Faye} and Sarah Zohar and Thomas Jaki",
note = "Funding Information: This article was initiated by the Adaptive Designs and Multiple Testing Procedures Joint Working Group of the Austro-Swiss (ROeS) and the German (IBS-DR) Regions of the International Biometric Society, chaired by Rene Schmidt and Lisa Hampson, and with support from Werner Brannath and Andreas Faldum. J. Wason received funding from UK Medical Research Council (MC_UU_00002/6 and MR/N028171/1). T. Jaki received funding from UK Medical Research Council (MC_UU_00002/14). This report is independent research arising in part from Prof Jaki{\textquoteright}s Senior Research Fellowship (NIHR-SRF-2015-08-001) supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care (DHCS), or the Federal Institute for Drugs and Medical Devices (BfArM). Martin Posch and Franz Koenig (Medical University of Vienna) are members of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 853966. This Joint Undertaking receives support from the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme and EFPIA. We are grateful to an associate editor and three anonymous referees for their helpful comments that have improved the article. Funding Information: Martin Posch reports grants from Novartis Pharma AG, grants from Mediconomics GmbH, grants from Merck KGaA, grants from Abbott Laboratories, grants from Almirall, outside the submitted work. He is also a member of the IMI Project Consortium EU-PEARL. Publisher Copyright: {\textcopyright} 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2020",
month = oct,
day = "1",
doi = "10.1080/19466315.2020.1790415",
language = "English",
volume = "12",
pages = "483--497",
journal = "Statistics in Biopharmaceutical Research",
issn = "1946-6315",
publisher = "Taylor and Francis Ltd.",
number = "4",
}