Nonsignificant trends in COVID-19 trials: Is there a significance?

Hundreds of clinical trials have been conducted on already available antiviral drugs or natural/herbal substances to repurpose for the treatment of COVID‐19, but with no conclusively consistent statistically significant positive results. Remdesvir, for example, is facing a confusing situation, after the two major large multinational studies SOLIDARITY and DisCoVeRy concluded that there are no significant survival benefits. In this viewpoint article, we claimed that the inconsistent time to initiate antiviral drugs during the course of COVID‐12 studies is the major contributing factor for this dilemma. We explained that patients already on mechanical ventilation at the study baseline are considered from a biologically different population than other severity groups. We provided a simple meta‐meta‐analysis to show how excluding them from statistical analysis could affect the statistical significance and conclusions.