Let me look at the situation strictly from the standpoint of our trial.
If a patient gets discharged from hospital, then they have effectively met the primary endpoint of the trial. There is no question of going back on that one simply because they later got worse. They have the value 1 or 2 (red below) in the 8-point scale. (3 in bold black is also part of the PE)
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities and/or requiring home oxygen
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, requiring supplemental oxygen
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Death
Among the secondary endpoints we have:
Proportion of patients clinically recovered [ Time Frame: At days 14, 28, 42, and 60 ]
Ordinal Scale of 1, 2 or 3
All-cause mortality [ Time Frame: At days 14, 28, 42, and 60 ]
All-cause mortality
Proportion of patients discharged alive [ Time Frame: At days 14, 28, 42, and 60 ]
Ordinal Scale 1 or 2
Clinical Status [ Time Frame: Days 14, 28, 42, and 60 ]
Ordinal Scale
Duration of invasive mechanical ventilation or ECMO [ Time Frame: 28 days ]
Days
Length of hospital stay [ Time Frame: 28 days ]
Days
Length of ICU stay [ Time Frame: 28 days ]
Days
In all the bold SE, we have either met or have a superior outcome if the patient was discharged early.
It is only in all-cause mortality and Clinical status that the evaluations continue potentially well after treatment period, and the situation you envision can actually hurt our trial results. For instance, patient is discharged Day 11, disease relapses and they worsen by Day 28 and possibly die Day 31. Here that patient gives us a bad score in later-days Clinical status and all-cause mortality even though they were not given LL on Day 14 and after. Yes, that would be unfair to us since perhaps more doses of LL would have avoided such result.
However that is why it makes sense to keep these as Secondary Endpoints. It is a worst case scenario but in order for it to happen, that same patient has already given us a positive outcome for all the other endpoints (Bold black) including our PE. So, for the trial, I think this is deemed a sensible trade-off, a compromise we have to make that will not hurt us in the long run - with goal being showing LL succeeds in PE and some SE at least.
