ABSTRACT
Rationale The ACTIV 4B (OWS/NHLBI supported) clinical trial addresses the use of anti-platelet and anticoagulant agents in symptomatic COVID-19 positive non-hospitalized patients with regards to safety and prevention of macro- and micro-thrombotic events using a composite outcome (symptomatic DVT/PE, arterial thromboembolism, MI, CVA, hospitalization for CV/pulmonary events, mortality). Concerns regarding SARS-CoV- 2 transmission risk to research staff and overburdened institutional environments create challenges for standard event monitoring. In addition, safety or outcome events often occur at other institutions rather than the enrollment site. Therefore, research methodology was adapted to effectively evaluate and categorize safety events using a remote low touch approach. Methods Trial over can be found at NCT04498273. Potential adverse events identified through patient electronic data capture survey or call center assessments are handled remotely by central clinical study staff. If an event is identified as a possible endpoint or SAE by the central study staff the electronic data collection (EDC) system notifies the central medical monitoring team, and the enrolling site coordinator if patient enrolled from an acute care setting, that additional source documents are necessary. The medical coordinator works with the site coordinator, or will reach out independently to treating institutions to obtain necessary source documents. Based on a review of clinical data from the EDC and all available source documents, final arbitration of seriousness, relatedness and expectedness is be made by the study's Medical Monitor, and appropriate study entities (NIH, FDA, IRB, study leadership, pharmaceutical co.) are notified.Results The process as described has been successfully and effectively implemented in >50 patients with anticipation of 7000 patient eventual enrollment. Events have been captured, source documentation has been procured and events have been reported as per established protocol processes. Conclusion We have effectively implemented a medical safety event monitoring methodology in a “low touch” study design to assess events in the complex COVID-19 outpatient space. Elements of our system can be effectively replicated in other COVID and non-COVID clinical trials. .