Who benefits most from remdesivir? A comparison of subgroup identification methods

Music City Center 

The Adaptive COVID-19 Treatment Trial found that remdesivir hastened recovery times compared to placebo for adults hospitalized with COVID-19. Subgroup analysis by baseline ordinal score (OS), defined by oxygen therapy use, found that people receiving supplemental oxygen at enrollment benefitted most from remdesivir. A post-hoc analysis developed the "ACTT risk score", combining OS, ANC, ALC, and platelets. The ACTT risk score better predicts disease outcomes than OS alone, and the highest ACTT risk quartile benefitted most from remdesivir. In contrast, we find that the 4C mortality score (a broadly validated COVID-19 mortality risk score) is more prognostic than the ACTT risk score but did not identify a subgroup benefitting most. We also applied SIDES, an algorithm explicitly focused on defining subgroups benefitting most from treatment. SIDES found a larger remdesivir benefit for people enrolling within 15 days from symptom onset, consistent with other work, and for those enrolling with both low hemoglobin and high blood pressure- a novel finding. We compare subgroup identification performance of SIDES to prognostic score-based approaches in simulation.

subgroup

SIDES

prognostic score

individualized medicine 

Biopharmaceutical Section