Subscribe to NRx Newsletter

CEO Update: Statement Regarding ZYESAMI™ Clinical Trial Inclusion Criteria and Endpoints

We have received questions about the data submitted to the US Food and Drug Administration (FDA) in support of our application for Emergency Use Authorization for ZYESAMI™ to treat patients suffering from Critical COVID-19 with respiratory failure. Since there seems to be some confusion about what the preprint says, I’m going to restate the science. 
ALL PATIENTS IN THE STUDY ARE INCLUDED in all top-level analyses of the primary endpoint. If you see n=196 that refers to all patients treated. Analysis of endpoints within subgroups only follows reports of endpoints for all patients, according to scientific best practice. That said, the original study protocol as approved by FDA specified that primary endpoints would be analyzed in a regression model that includes covariates that control for differences between the drug-treated and the placebo group at baseline. In this study, the randomization program implemented by the third-party CRO assigned more severe patients to the drug group than to the placebo group (see table 3 baseline characteristics). Remember, when you randomize patients, the computer is “flipping coins” and you should not expect that patients will always be matched in baseline characteristics. The regression analyses used were pre-agreed with FDA at the outset of the study and the manner in which covariates are used also follows published FDA guidance. The study initially planned to use the NIAID score as a measure of baseline severity, and the statistical analysis plan was modified prior to unblinding to use the type of ventilation as a measure of baseline severity instead, because it was a more objective measure. Readers are clearly free to interpret data as they choose. However, it’s important to understand the data in the first place. All patients and all hospitals, in the primary analysis, means exactly that. Nobody was excluded.