Barriers, Solutions, and Opportunities for Adapting Critical Care Clinical Trials in the COVID-19 Pandemic
Authors: Cook Deborah , Taneja Shipra , Krewulak Karla , Zytaruk Nicole , Menon Kusum , Fowler Rob , Lamontagne François , Kho Michelle E. , Rochwerg Bram , Masse Marie-Hélène , Lauzier François , O’Hearn Katie , Adhikari Neill K. J. , Burns Karen E. A. , Bosma Karen J. , English Shane , McNally Dayre , Turgeon Alexis F. , Brochard Laurent , Parker Melissa , Clayton Lucy , Rishu Asgar , Tuttle Angie , Daneman Nick , Fergusson Dean , McIntyre Lauralyn , Kelly Laurel , Orr Sherrie , Austin Peggy , Mulligan Sorcha , Fiest Kirsten ,   Canadian Critical Care Trials Group and Canadian Clinical Research Network
Published: July 2024

Importance

The COVID-19 pandemic created unprecedented challenges for clinical trials worldwide, threatening premature closure and trial integrity. Every phase of research operations was affected, often requiring modifications to protocol design and implementation.

Objectives

To identify the barriers, solutions, and opportunities associated with continuing critical care trials that were interrupted during the pandemic, and to generate suggestions for future trials.

Design, Setting, and Participants

This mixed-methods study performed an explanatory sequential analysis involving a self-administered electronic survey and focus groups of principal investigators (PIs) and project coordinators (PCs) conducting adult and pediatric individual-patient randomized trials of the Canadian Critical Care Trials Group during the COVID-19 pandemic. Eligible trials were actively enrolling patients on March 11, 2020. Data were analyzed between September 2023 and January 2024.

Main Outcomes and Measures

Importance ratings of barriers to trial conduct and completion, solutions employed, opportunities arising, and suggested strategies for future trials. Quantitative data examining barriers were analyzed using descriptive statistics. Data addressing solutions, opportunities, and suggestions were analyzed by qualitative content analysis. Integration involved triangulation of data sources and perspectives about 13 trials, synthesized by an interprofessional team incorporating reflexivity and member-checking.

Results

A total of 13 trials run by 29 PIs and PCs (100% participation rate) were included. The highest-rated barriers (on a 5-point scale) to ongoing conduct during the pandemic were decisions to pause all clinical research (mean [SD] score, 4.7 [0.8]), focus on COVID-19 studies (mean [SD] score, 4.6 [0.8]), and restricted family presence in hospitals (mean [SD] score, 4.1 [0.8]). Suggestions to enable trial progress and completion included providing scientific leadership, implementing technology for communication and data management, facilitating the informed consent process, adapting the protocol as necessary, fostering site engagement, initiating new sites, streamlining ethics and contract review, and designing nested studies. The pandemic necessitated new funding opportunities to sustain trial enrollment. It increased public awareness of critical illness and the importance of randomized trial evidence.

Conclusions and Relevance

While underscoring the vital role of research in society and drawing the scientific community together with a common purpose, the pandemic signaled the need for innovation to ensure the rigor and completion of ongoing trials. Lessons learned to optimize research procedures will help to ensure a vibrant clinical trials enterprise in the future.