Protocol deviations resulting from COVID-19
NASH, COVID-19-related drug kit delays
EMERGENCY
The study was conducted between December 2019 and December 2021 at 79 sites in the United States during the height of the COVID-19 pandemic. On 27 March 2020, Madrigal, the sponsor, issued an administrative letter (following the Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency Guidance for Industry, Investigators and IRBs issued by the US Food and Drug Administration on 25 March 2020) to sites with information on the following topics:Documentation of protocol deviations with attribution to COVID-19 when applicable;Flexibility for screening and enrollment windows, study visit windows and study procedures and collection of laboratory results at study visits in situations in which patient access was unsafe or restricted due to COVID-19, including allowing telehealth phone visits;Delivery of investigational medicinal product to patients who could not come to the investigative site for a study visit;Guidance on investigative site monitoring, focusing on a remote site monitoring plan; andChanges in informed consent to implement a more flexible approach to clinical studies.Largely due to COVID-19-related drug kit delays in the DB arms, 86–88% of DB patients missed study visits (inclusive of visits where no study drug was provided) and the average number of missed monthly visits in the DB arms was 2–3 over the 52-week treatment period. Only 19% of OL non-cirrhotic (NC) patients with NASH had missed study visits.