key: cord-0735617-xs148ce8
authors: Duffett, M.; Cook, D. J.; Strong, G.; Lee, J. H.; Kho, M. E.
title: The effect of COVID-19 on critical care research: A prospective longitudinal multinational survey
date: 2020-10-23
journal: nan
DOI: 10.1101/2020.10.21.20216945
sha: 555653d960ba2d1834c1f8304bfb7c7238986cfe
doc_id: 735617
cord_uid: xs148ce8

Importance: The COVID-19 pandemic has increased the need for high-quality evidence in critical care, while also increasing the barriers to conducting the research needed to produce such evidence. Objective: To determine the effect of the first wave of the COVID-19 pandemic on critical care clinical research. Design: Monthly electronic survey (March - August 2020). Setting: Adult or pediatric intensive care units (ICUs) from any country participating in at least one research study before the COVID-19 pandemic. Participants: We recruited one researcher or research coordinator per center, identified via established research networks. Intervention(s): None Main Outcome(s) and Measure(s): Primary: Suspending recruitment in clinical research; Secondary: impact of specific factors on research conduct (5-point scales from no effect to very large effect). We assessed the association between research continuity and month, presence of hospitalized patients with COVID-19, and population (pediatric vs. adult ICU) using mixed-effects logistic regression. Results: 126 centers (56% pediatric) from 23 countries participated. 95 (75%) of centers suspended recruitment in at least some studies and 37 (29%) suspended recruitment in all studies on at least one month. The proportion of centers reporting recruitment in all studies increased over time (OR per month 1.3, 95% CI 1.1 to 1.5, p = 0.007), controlling for hospitalized patients with COVID-19 and type of ICU (pediatric vs. other). The five factors most frequently identified as having a large or very large effect on clinical research were: local prioritization of COVID-19 specific research (68, 54%), infection control policies limiting access to patients with COVID-19 (61, 49%), infection control policies limiting access to the ICU (52, 41.6%), increased workload of clinical staff (38, 30%), and safety concerns of research staff (36, 29%). Conclusions and Relevance: Decisions to pause or pursue clinical research varied across centers. Research activity increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles to safely sustain research during this and future pandemic waves are urgently needed.

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The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint 3 COVID-19. Guiding principles to safely sustain research during this and future pandemic waves are urgently needed.

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

We conducted a monthly online survey administered from March 8 to August 24, 2020, approaching representatives from adult and pediatric ICUs if they were enrolling patients in at least one clinical research study before the WHO declaration of the pandemic on March 11, 2020.

We recruited sites through research networks (Canadian Critical Care Trials Group, Pediatric Acute Lung Injury and Sepsis Investigators, Australia and New Zealand Intensive Care Society Clinical Trials Group, Pediatric Acute and Critical Care Medicine Asian Network), and Twitter.

After, Research Ethics Board (REB) approval we sent monthly surveys to one investigator or research coordinator at each site with up to two reminders to non-respondents each month. We included 33 items that captured site demographics, presence of patients with COVID-19 in the hospital and the ICU, characteristics of any clinical research studies underway or stopped, and perceived barriers to research conduct. The survey instrument was in English. No incentive was provided. Survey completion implied informed consent.

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint For analysis, children's hospitals housed within larger hospitals and each site of multi-site hospitals were considered separate centers. For centers with multiple ICUs, each was considered separately or as one center, per local self-report. We retained all complete and partial surveys, using the number responses to that question as the denominator. We reported data as median (interquartile range [IQR]) or count (percentage). We used Chi-square tests to compare the characteristics of centers continuing recruitment in all studies versus those that did not. We used mixed effects logistic regression to examine the association between time (months since the start of the pandemic) and research continuity, controlling for center type (exclusively pediatric vs other) and the presence of patients with COVID-19 in that hospital on that month. We report odds ratios (OR) with their corresponding 95% confidence intervals (CI) and used p <0.05 as the criterion for statistical significance. We used R version 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria) to perform the analysis. 

In this monthly survey of 123 centers in 23 countries we observed that decisions to suspend recruitment in clinical research during the first wave of the pandemic varied across centers and decreased over time, despite the presence of hospitalized patients with COVID-19. These substantial effects, even in countries such as Canada and Australia that were not overwhelmed, both likely underestimate the true effect on research activity globally. Despite fewer children with COVID-19 admitted to hospital and even fewer admitted to ICUs, PICUs reported being just as likely to experience clinical research disruptions as adult ICUs. One potential explanation for this is the need for surge capacity planning that required pediatric ICUs to admit adult patients with COVID-19 ( Figure 3 ). 1,2 This is particularly evident in the early period of our survey (March -May 2020).

Amidst the challenges to conducting research during the pandemic, several much-needed large multi-center RCTs of therapies for COVID-19 have been launched and completed. [3] [4] [5] Learning from these studies, investigators around the world can adapt research logistics to best suit the local context to ensure timely continuation and completion of pertinent clinical research studies. 6, 7 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 23, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint

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Critical Illness in Patients With COVID-19: Mounting an Effective Clinical and Research Response

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020.10.21.20216945 doi: medRxiv preprint