Using Randomization Tests to Address Disruptions in Clinical Trials

Authors

• Diane Uschner, The George Washington UniversityFollow
• Oleksandr Sverdlov, Novartis Pharmaceuticals Corporation
• Kerstine Carter, Boehringer Ingelheim GmbH
• Jonathan Chipman, University of Utah
• Olga Kuznetsova, Merck
• Jone Renteria, The George Washington University
• Adam Lane, Cincinnati Children's Hospital Medical Center
• Chris Barker, Inc
• Nancy Geller, National Heart, Lung, and Blood Institute (NHLBI)
• Michael Proschan, National Institute of Allergy and Infectious Diseases (NIAID)
• Martin Posch, MedUni Vienna
• Sergey Tarima, University of KentuckyFollow
• Frank Bretz, MedUni Vienna
• William F. Rosenberger, George Mason University

Abstract

Recent examples for unplanned external events are the global COVID-19 pandemic, the war in Ukraine, or most recently Hurricane Ian in Puerto Rico. Disruptions due to unplanned external events can lead to violation of assumptions in clinical trials. In certain situations, randomization tests can provide nonparametric inference that is robust to violation of the assumptions usually made in clinical trials. The ICH E9 (R1) Addendum on estimands and sensitivity analyses provides a guideline for aligning the trial objectives with strategies to address disruptions in clinical trials. In this article, we embed randomization tests within the estimand framework to allow for inference following disruptions in clinical trials in a way that reflects recent literature. A stylized clinical trial is presented to illustrate the method, and a simulation study highlights situations when a randomization test that is conducted under the intention-to-treat principle can provide unbiased results.

Document Type

Article

Publication Date

1-1-2024

Notes/Citation Information

Publisher Copyright: © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

Digital Object Identifier (DOI)

10.1080/19466315.2023.2257894

Archival?

Archival

Repository Citation

Uschner, Diane; Sverdlov, Oleksandr; Carter, Kerstine; Chipman, Jonathan; Kuznetsova, Olga; Renteria, Jone; Lane, Adam; Barker, Chris; Geller, Nancy; Proschan, Michael; Posch, Martin; Tarima, Sergey; Bretz, Frank; and Rosenberger, William F., "Using Randomization Tests to Address Disruptions in Clinical Trials" (2024). Biostatistics Faculty Publications. 182.
https://uknowledge.uky.edu/biostatistics_facpub/182