Clinical Trial Drug Safety Assessment for Studies and Submissions Impacted by COVID-19

TL;DR

This paper offers guidance on adapting clinical trial safety data analysis and reporting methods in response to COVID-19 disruptions, emphasizing modifications for safety assessments, data interpretation, and laboratory measurements.

Contribution

It provides specific recommendations for modifying safety analysis procedures in clinical trials affected by COVID-19, building on existing FDA/PHUSE guidelines.

Findings

Safety analyses can largely remain unchanged for controlled data.

Uncontrolled data summaries require cautious interpretation.

Special safety considerations are needed for COVID-19 related events.

Abstract

In this paper, we provide guidance on how standard safety analyses and reporting of clinical trial safety data may need to be modified, given the potential impact of the COVID-19 pandemic. The impact could include missed visits, alternative methods for assessments (such as virtual visits), alternative locations for assessments (such as local labs), and study drug interruptions. We focus on safety planning for Phase 2-4 clinical trials and integrated summaries for submissions. Starting from the recommended safety analyses proposed in white papers and a workshop, created as part of an FDA/PHUSE collaboration (PHUSE 2013, 2015, 2017, 2019), we assess what modifications might be needed. Impact from COVID-19 will likely affect treatment arms equally, so analyses of adverse events from controlled data can, to a large extent, remain unchanged. However, interpretation of summaries from uncontrolled data (summaries that include open-label extension data) will require even more caution than usual. Special consideration will be needed for safety topics of interest, especially events expected to have a higher incidence due to a COVID-19 infection or due to quarantine or travel restrictions (e.g., depression). Analyses of laboratory measurements may need to be modified to account for the combination of measurements from local and central laboratories.