The emergence of Coronavirus Disease 2019 (COVID-19) caused by the novel SARS-CoV-2 virus in Wuhan, China in December 2019, raised many challenges to clinical research. Even now, investigators, industry sponsors, and institutional review boards/ethical committees (IRB/EC) struggle to maintain the safety of trial participants and researchers, while promoting the continuity of ongoing clinical studies. COVID-19 has spread to more than 215 countries, infected more than 8 million people, and caused close to 500,000 deaths globally as of this submission. The United States is caring for the largest number of cases, currently at 2 million, with over 25,000 deaths. Without a proven vaccine or treatment, the mortality rate in the United States is projected to be as high as 135,000-140,000 by August 2020. By comparison, the H1N1 influenza pandemic of 2009 infected 60.8 million individuals and resulted in 12,469 deaths in over 12 months in the United States (Centers for Disease Control and Prevention, CDC, estimation). In general, it is estimated that a person infected with COVID-19 can infect others while an individual with the H1N1 influenza virus infected and those with the seasonal influenza infected about Clearly, the transmission and mortality rates are what makes COVID-19 a global concern and a source of disquietude.
Adapting clinical trials for COVID-19
The conduct of clinical studies changed soon after the U.S. Department of Health & Human Services (HHS) issued a COVID-19 Public Health Emergency on January 31, 2020. The FDA, investigators, industry sponsors, and IRBs/ECs, among others, were required to act quickly to assess the status of ongoing studies and restructure research processes accordingly. Unanticipated deviations to protocols became unavoidable, as subjects were unable to attend study visits due to travel restrictions, clinic closures, and quarantine requirements. Elective surgeries and protocol-specified procedures were postponed to diminish environmental contamination and to preserve limited personal protective equipment (PPE). Research staff were instructed to work remotely and study enrollment was only allowed for trials required for a participant’s health (e.g., oncology treatment protocol). Other challenges included possible interruptions in the supply of investigational product and other clinical trial shipments. The “stay-at-home orders” issued by various governmental authorities appropriately emphasized the safety of subjects, but negatively impacted recruitment and enrollment into clinical studies and affected data collection.
The acceleration of clinical research
The pandemic has also stimulated new clinical research as investigators desperately search for ways to learn about the virus and its impact, characterize the patient populations affected, and test the efficacy of candidate interventions. In the United States alone, there are 17,500 clinical trials reporting a status of currently recruiting new subjects that are possibly affected by the COVID-19 pandemic. Additionally, the Food and Drug Administration (FDA) accelerated their processes for evaluating requests for investigational new drug (IND) applications with the creation of the Coronavirus Treatment Acceleration Program (CTAP). Oversight organizations altered their standard operating procedures and provided guidance to reduce the regulatory burden imposed by the pandemic on investigators. The FDA also issued a guidance document in March 2020 (updated April 16, 2020) to assist stakeholders in clinical research with the purpose of acknowledging protocol deviations and to provide recommendations to protect the safety of subjects and maintain the integrity of the clinical trials.