Clinical Trials Impacted by the COVID-19 Pandemic: Adaptive Designs to the Rescue?

Area of Science:

• Biostatistics
• Clinical Trial Design
• Epidemiology

Background:

• The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent COVID-19 pandemic have disrupted numerous ongoing clinical trials.
• Non-COVID-19 clinical trials face unprecedented challenges due to the global health crisis, necessitating innovative solutions.

Purpose of the Study:

• To address the challenges posed by the COVID-19 pandemic to ongoing clinical trials in non-COVID-19 conditions.
• To illustrate potential solutions, including adaptive trial designs, for managing pandemic-related disruptions.

Main Methods:

• Exploration of adaptive design strategies, including blinded adaptations and Bayesian techniques.
• Development of approaches for trial resizing, early stopping, group-sequential designs, and sample size adjustments.
• Discussion of regulatory and operational considerations, such as Type I error rate control and data monitoring committees.

Main Results:

• Guidance provided on utilizing early read-outs and managing treatment effect heterogeneity.
• Methods for maintaining statistical integrity and adapting trials during the pandemic are detailed.
• A freely available R shiny app is presented to implement the discussed methods.

Conclusions:

• Adaptive trial designs offer viable solutions for clinical trials affected by the COVID-19 pandemic.
• Proactive planning and implementation of statistical methodologies are crucial for the successful continuation of non-COVID-19 research.
• The study provides practical tools and insights for statisticians, researchers, and regulatory bodies involved in clinical trials.