Harmonizing heterogeneous endpoints in COVID-19 trials without loss of information - an essential step to facilitate decision making

Maja von Cube; Marlon Grodd; Martin Wolkewitz; Derek Hazard; Jerome Lambert

The WHO R&D Blueprint expert group (7) recommends to use a categorical endpoint ranging from full recovery to death. For example, based on this recommendation Cao et al. (8) chose their primary endpoint as the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. The seven-category ordinal scale of Cao et al. (8) consists of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death. Six of the registered clinical trials use such a categorical endpoint. The number of categories varies between six and eight states.