CD10 secondary outcomes include NEWS2, which NP already said should be significant improvement with LL compared to placebo on days 3, 7, and 14.
Per clinicaltrials, they also are using the WHO 7 point scale of respiratory and functional (health) status:
For the CD10 trial, they don't really define mild or moderate disease according to the WHO scale, but I would guess they would range from (5-6) for mild, and (3-4) for moderate. For severe, I think our trials would match severe with (3), and critical with (2-3).
Too bad they aren't looking at the change in WHO status, oh well.
I am currently reviewing a protocol to examine "proning" for mild-to-moderate hospitalized Covid subjects requiring supplemental oxygen, using WHO status as main outcome after 5 days. I thought it might be fun to play with statistics given the expected distribution of outcomes based on one institution's results thus far (all starting at score #4 on WHO scale):
(1) 1% - death
(2) 5% - intubated on mechanical ventillation or ECMO
(3) 14% -on non-invasive ventilation / HFNC: 14%
(4) 30% -stay in hospital on supplemental oxygen
(5) 10% -hospitalized, no supplemental oxygen
(6) and (7) - 40% - at home with or without limitations
So, 30% are expected to stay the same, 50% improve, and 20% get worse at day 5 in hospital after starting on supplemental oxygen. For moderate disease (WHO 4), only 40% are expected to go home at day 5. I assume it would be more for mild disease, say 50%?
The study used a Bayesian approach and estimated they would need to meet the "goal" of an additional 20% being discharged with 300 subjects (randomized 1:1 prone vs. supine). They plan to modify the number estimated to be needed in each arm after interim review of N=25 per arm.
I wonder what are the odds that LL improves WHO scale compared with placebo, and what statistics would be appropriate to use. Probably both groups will start off around 4.5 WHO scale, and placebo would be expected to go to say 5.2 after say 7 days. LL group would have to have a pretty high number go home to beat that. With 50% in placebo going home at a week say, we would need 75% or more go home I imagine in LL arm for statistical significance.
I guess it's impossible to handicap the odds. Based on significance hinted by NP for NEWS2 secondary outcomes, hopefully some of the other secondary outcomes like WHO Covid-19 health scale will "hit" too, but that one seems tougher. NEWS2 seems more sensitive to early mild changes compared to WHO score.
Lots of secondary endpoints, exploratory endpoints (with all the bloodwork), clinical parameters, and scenarios to evaluate!
I think the strongest evidence from mild-to-moderate will be reduction in SAEs and rapid improvement in some of the clinical symptom scores and vital parameters.
Looking forward to the reveal next week.
Per clinicaltrials, they also are using the WHO 7 point scale of respiratory and functional (health) status:
Quote:Change from baseline in the patient's health status on a 7-category ordinal scale [ Time Frame: Days 3, 7, and 14 ]
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities..
For the CD10 trial, they don't really define mild or moderate disease according to the WHO scale, but I would guess they would range from (5-6) for mild, and (3-4) for moderate. For severe, I think our trials would match severe with (3), and critical with (2-3).
Too bad they aren't looking at the change in WHO status, oh well.
I am currently reviewing a protocol to examine "proning" for mild-to-moderate hospitalized Covid subjects requiring supplemental oxygen, using WHO status as main outcome after 5 days. I thought it might be fun to play with statistics given the expected distribution of outcomes based on one institution's results thus far (all starting at score #4 on WHO scale):
(1) 1% - death
(2) 5% - intubated on mechanical ventillation or ECMO
(3) 14% -on non-invasive ventilation / HFNC: 14%
(4) 30% -stay in hospital on supplemental oxygen
(5) 10% -hospitalized, no supplemental oxygen
(6) and (7) - 40% - at home with or without limitations
So, 30% are expected to stay the same, 50% improve, and 20% get worse at day 5 in hospital after starting on supplemental oxygen. For moderate disease (WHO 4), only 40% are expected to go home at day 5. I assume it would be more for mild disease, say 50%?
The study used a Bayesian approach and estimated they would need to meet the "goal" of an additional 20% being discharged with 300 subjects (randomized 1:1 prone vs. supine). They plan to modify the number estimated to be needed in each arm after interim review of N=25 per arm.
I wonder what are the odds that LL improves WHO scale compared with placebo, and what statistics would be appropriate to use. Probably both groups will start off around 4.5 WHO scale, and placebo would be expected to go to say 5.2 after say 7 days. LL group would have to have a pretty high number go home to beat that. With 50% in placebo going home at a week say, we would need 75% or more go home I imagine in LL arm for statistical significance.
I guess it's impossible to handicap the odds. Based on significance hinted by NP for NEWS2 secondary outcomes, hopefully some of the other secondary outcomes like WHO Covid-19 health scale will "hit" too, but that one seems tougher. NEWS2 seems more sensitive to early mild changes compared to WHO score.
Lots of secondary endpoints, exploratory endpoints (with all the bloodwork), clinical parameters, and scenarios to evaluate!
I think the strongest evidence from mild-to-moderate will be reduction in SAEs and rapid improvement in some of the clinical symptom scores and vital parameters.
Looking forward to the reveal next week.
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