ABSTRACT
Introduction: PREPARE is a pragmatic clusterrandomized crossover trial that compares the effectiveness of two common pre-operative antiseptic skin solutions to reduce the risk of surgical site infection after orthopedic fracture surgery. The trial compares 2% chlorhexidine in 70% isopropyl alcohol (ChloraPrep™) versus 0.7% iodine povacrylex in 74% isopropyl alcohol (DuraPrep™), and recruiting sites alternate study solutions every 2 months. Before the US national response to the COVID-19 pandemic, all PREPARE trial clinical sites obtained informed consent in person at the hospitals or fracture clinics. However, after 13 March 2020, the COVID-19 restrictions limited inperson consenting at some hospitals. Affected clinical sites were encouraged to transition to telephone consent, which was already included as a consent option in the PREPARE protocol. We aimed to determine how COVID-19 restrictions impacted the number of enrolling clinical sites and participant enrollment in the PREPARE trial. Methods: Prior to implementing telephone consent, clinical sites had to determine local logistics and obtain institutional review board approval for telephone consent scripts and procedures from the central or local institutional review boards. We descriptively evaluated the number of clinical sites that switched to telephone consent, the number of clinical sites that had to pause enrollment, and the length of the enrollment pauses. We evaluated monthly enrollment at the following time periods: (1) prior to the COVID-19 restrictions (1 July 2019 to 13 March 2020), (2) immediately after the COVID-19 restrictions in place (March, April, and May 2020), and (3) from 1 June 2020 to 30 November 2020. Results are stratified by open and closed fractures and are summarized using descriptive statistics. Results: At the time of the pandemic, 13 clinical sites were participating in the PREPARE trial. Eleven (84.6%) clinical sites paused enrollment due to COVID- 19 restrictions. The median length of enrollment pause was 44 days (range = 7-92 days;interquartile range = 54 days). By 16 June 2020, all clinical sites resumed enrollment. The average monthly enrollment before the COVID-19 restrictions was 198 closed fracture participants (SD = 22, range = 161-227) and 41 open fracture participants (SD = 16, range = 22-60). The enrollment rate was the lowest in April 2020, when 47 closed fracture participants and nine open fracture participants were enrolled. By June 2020, enrollment began increasing. From 1 June 2020 to 30 November 2020, the average monthly enrollment rate was 183 closed fracture participants (SD = 30, range = 129-206) and 44 open fracture participants (SD = 12, range = 24-61), which was close to pre-COVID enrollment. Monthly enrollment between 2019 and 2020 was similar, except for the months of March to May 2020 for closed fracture enrollment (p = 0.001) and March and April 2020 for open fracture enrollment (p = 0.04) cohorts. Conclusion: By pre-emptively including telephone consent in the PREPARE protocol, clinical sites were quickly and ethically adapting their procedures for obtaining informed consent via telephone. Although multiple sites paused enrollment, the enrollment pause was brief and had minimal impact on enrollment. A highly pragmatic design allowed for minimal interruptions to enrollment during the pandemic.