Lessons Learned From Conducting Internet-Based Randomized Clinical Trials During a Global Pandemic

Abstract

As the severe acute respiratory syndrome coronavirus 2 pandemic evolved, it was apparent that well designed and rapidly conducted randomized clinical trials were urgently needed. However, traditional clinical trial design presented several challenges. Notably, disease prevalence initially varied by time and region, and the pockets of outbreaks evolved geographically over time. Coupled with an occupational hazard from in-person study visits, timely recruitment would prove difficult in a traditional in-person clinical trial. Thus, our team opted to launch nationwide internet-based clinical trials using patient-reported outcome measures. In total, 2795 participants were recruited using traditional and social media, with screening and enrollment performed via an online data capture system. Follow-up surveys and survey reminders were similarly managed through this online system with manual participant outreach in the event of missing data. In this report, we present a narrative of our experience running internet-based clinical trials and provide recommendations for the design of future clinical trials during a world pandemic.

Keywords: COVID-19; SARS-CoV-2; coronavirus; internet-based clinical trial; methodology.

Figure 1.

Progress timeline for all 3 studies (postexposure prophylaxis [PEP], preemptive treatment [PET], and pre-exposure prophylaxis [PrEP]). DMSB, Data and Safety Monitoring Board; FDA, US Food and Drug Administration; IND, investigational new drug; IRB, institutional review board.

Figure 2.

Comparison of the number of completed screening surveys versus completed enrollment by date of completion in 2020 for the postexposure prophylaxis/early treatment trial (A) and pre-exposure prophylaxis trial (B). Bars represent the total number of completed screening surveys each day, whereas the line represents the number of enrollments each day. Lettered markers have been placed at the date of external events that may have influenced recruitment. (A) Interview on ABC Good Morning America; (B) incorrect infographic regarding study protocol spread over WeChat social media platform; (C) interview on Dr. Oz television program; (D) Brazilian study demonstrating risk with high-dose hydroxychloroquine [12]; (E) VA study demonstrating no benefit from hydroxychloroquine in hospitalized coronavirus disease 2019 patients [13], (F) US Food and Drug Administration (FDA) warning issued regarding safety of hydroxychloroquine.

Figure 3.

Histogram presenting the distribution of times from participant enrollment to delivery of medication in hours for participants. Total US packages sent was 1255, with a median delivery time of 36 hours (interquartile range [IQR], 23.7 to 42.4 hours). Two thirds of participants enrolled outside of weekday daytime hours (875 of 1312). The first peak is those enrolling during weekday daytime hours. The second peak is those enrolling in the evening or night, being shipped the next day. The final peak is those enrolling after 3:00 pm on a Saturday or on a Sunday, being shipped on Monday, and receiving delivery on Tuesday morning. For the postexposure prophylaxis trial, the median time from highest risk exposure to starting study drug was 3 days (IQR, 2 to 4) days.