In an opinion article that reviews the ways clinical research was interpreted and applied incorrectly during the pandemic, authors write: “One common thread in the foibles associated with the use of hydroxychloroquine, corticosteroids, and [COVID-19 convalescent plasma (CCP)] was the failure to consider biological plausibility in clinical decision making. Although it could be argued that the pathogenesis of COVID-19 was not fully understood in the first year of the pandemic, it was known that a related virus, SARS-CoV-1, rapidly transitioned from a viral to an inflammatory phase of disease and that most patients died due to the latter. For hydroxychloroquine, biological plausibility was clung to because of in vitro data, although efficacy was disproved in vivo; for corticosteroids, biological plausibility was not sufficiently considered based on their known mechanism of action and their use in non–critically ill patients, in whom trial data showed they were not effective; and for CCP, biological plausibility was not considered in the design of [randomized controlled trials] of hospitalized patients based on its known mechanism of antiviral action—namely, antiviral activity and historical evidence of clinical efficacy.
“Clinical research amid the pandemic underscores the need for clinicians conducting trials to consider biological plausibility in study design and interpretation. Even during a pandemic, physicians should consider the complex interplay between the scientific underpinnings of the relevant disease and clinical outcomes. This could refine clinical practice and avoid missteps in the future, which would be a positive legacy from the COVID-19 pandemic.”