Abstract
BACKGROUND: Disruptions to clinical trials conducted in the intensive care unit (ICU) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2; coronavirus disease 2019 [COVID-19]) pandemic included fewer new trials activated and more trials stopped. While a number of ongoing, non-COVID-19 clinical trials remained open to enrollment, the direct impact of the pandemic on ICUs instilled chaos in this already challenging environment. The numerous challenges need to be reported so investigators can proactively plan and manage these myriad challenges. Thus, the purpose of this study was to describe the impact of the COVID-19 pandemic on screening and accrual for a non-COVID-19 parent clinical trial enrolling critically ill ICU patients receiving mechanical ventilatory support. METHODS: A descriptive, retrospective design using quantitative data from detailed screening logs and qualitative observations with field notes from a parent clinical trial were used to address the objectives. The primary aims of the two-site parent clinical trial (n = 190) are to test the efficacy of self-administration of sedative therapy by mechanically ventilated ICU patients on anxiety and delirium occurrence. ICUs from two academic medical centers [names removed for blinding] plus a community hospital in Minnesota were screened daily for alert patients (Richmond Agitation Sedation Scale [RASS] - 2 to + 1), following commands, hemodynamically stable with sufficient hand grip strength to depress a push-button device. Screening data were summarized based on the primary reason patients were not enrolled (screen failures, declinations of consent). Descriptive statistics (frequencies, percentages), chi-square, and Fisher's Exact test were used to describe the data and to determine any differences among distributions of screening failures and recruitment declinations during the defined pre-pandemic (August 27, 2018-March 15, 2020, 2976 screened patients) and pandemic timeframes (March 16, 2020-February 28, 2022, 3912 screened patients). Qualitative data from varied sources such as screening logs, institutional email communications, staff field notes, and research team meeting minutes were summarized into themes. RESULTS: Despite significantly fewer screen failures due to hypotension, cognitive impairment/dementia, coma, or chemical paralysis with 938 additional patients on the screening log, more were accrued pre-pandemic (n = 55) than during the pandemic period (n = 45); declination reasons were non-significant. Pandemic burdens experienced by study personnel, ICU care providers, and patients/families were revealed that attributed to decreased accrual. CONCLUSIONS: While the parent clinical trial remained opened, cumulative factors adversely impacted the trial during the pandemic period with fewer patients accrued. The human toll of the pandemic on research staff, clinicians, and patients/family members demands that investigators be proactive in managing these challenges to conduct ICU clinical trials successfully, including careful oversight of human and financial resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT#02,819,141 Registered 29 June 2016.