Analyses of pandemic effects
Despite the onset of the pandemic in March, 2020, all clinical sites were able to continue entering infants in the screening log. However, only one site was permitted to continue any other clinical research activity during the peak pandemic epochs, including parent interactions and approaching for consent. The data coordinating center (DCC) tracks the number of infants who become eligible, are approached for consent, and who are consented and enrolled. The DCC also captures available information as to why an eligible patient could not be approached (e.g.: staff or family not available) or the apparent reason for parental refusal of consent (e.g.: study procedures too burdensome, or parent does not want to participate in research). For purposes of this analysis, we defined five study epochs to be representative of the sequential periods of pandemic-related effects, beginning December 31, 2018 and ending July 22, 2022. The pre-COVID epoch (12/31/18-3/5/20) represents the baseline screening and enrollment activity from initial enrollment until pandemic onset. The COVID-1 epoch (3/6/20- 7/31/20) includes the lockdown period when clinical sites severely restricted or suspended all clinical research activity except for screening, and the COVID-2 epoch (8/1/20- 3/5/21) reflects the beginning recovery in clinical research activity. The Post-COVID-1 epoch (3/6/21- 11/11/21) represents continuing recovery from the peak adverse pandemic effects, and Post-COVID-2 (11/12/21- 7/22/22) represents our final observed epoch of continuing recovery in study conduct.During the peak pandemic epoch and beginning recovery, several site-specific actions were approved by multiple site IRBs to improve consent rates. These included approval for telemedicine-based or REDCap-based consents, and approval for early consent for subjects potentially eligible for enrollment but not yet satisfying all criteria required for enrollment and for randomization.