From JWR on Yahoo: "There are two "facts" in th
Post# of 157631
(Total Views: 710)
Posted On: 05/17/2021 7:24:57 PM
From JWR on Yahoo:
"There are two "facts" in the FDA's statement on leronlimab that are incorrect and material:
1. For the CD10 trial, the announcement stated that "there was no observed effect of the drug on the study’s (CD10) primary endpoint or on any of the secondary endpoints." The NEWS2 score was a secondary endpoint on the trial and met stat sig for the entire population:
"In all treated patients, at the End of Treatment (or Day 14), patients in the leronlimab group were more than twice as likely to experience a beneficial improvement in NEWS2 scores compared to patients in placebo group (50% vs 20% p = 0.0223)."
NEWS2 is material to the study as it is also considered a gold standard for Covid progression and the most objective way to measure compared to symptom score.
2. For the CD12 trial, the FDA stated that the trial "also failed to find any effect of the drug on the primary study endpoint, with no difference seen in mortality...; or on any of the secondary endpoints." CD12 is a multi-arm study and the critical patient population is considered an arm of the study and not a subpopulation. The CD12 study had pre-established criteria for two population segments: severe and critical. For the CD12 study, mortality at 14 day was also a pre-established secondary endpoint. Therefore, for the critical arm the mortality benefit and a p-value of .023 is a valid secondary endpoint.
Note the SIMPLE trial for remdesivir established a 5 day treatment arm and a 10 day treatment arm. There were no required adjustments beyond a baseline adjustment (which adjusts for age distribution or other randomization issues) in the multi-arm Remdesivir study which led to its approval and set the standard for Covid studies going forward.
Treating the critical population as a post-hoc subpopulation is inaccurate and leads to a false perception of the CD12 results.
I appreciate the FDA's transparency but that includes an obligation to be objective and get the facts right. I am hoping they will do a correction."
"There are two "facts" in the FDA's statement on leronlimab that are incorrect and material:
1. For the CD10 trial, the announcement stated that "there was no observed effect of the drug on the study’s (CD10) primary endpoint or on any of the secondary endpoints." The NEWS2 score was a secondary endpoint on the trial and met stat sig for the entire population:
"In all treated patients, at the End of Treatment (or Day 14), patients in the leronlimab group were more than twice as likely to experience a beneficial improvement in NEWS2 scores compared to patients in placebo group (50% vs 20% p = 0.0223)."
NEWS2 is material to the study as it is also considered a gold standard for Covid progression and the most objective way to measure compared to symptom score.
2. For the CD12 trial, the FDA stated that the trial "also failed to find any effect of the drug on the primary study endpoint, with no difference seen in mortality...; or on any of the secondary endpoints." CD12 is a multi-arm study and the critical patient population is considered an arm of the study and not a subpopulation. The CD12 study had pre-established criteria for two population segments: severe and critical. For the CD12 study, mortality at 14 day was also a pre-established secondary endpoint. Therefore, for the critical arm the mortality benefit and a p-value of .023 is a valid secondary endpoint.
Note the SIMPLE trial for remdesivir established a 5 day treatment arm and a 10 day treatment arm. There were no required adjustments beyond a baseline adjustment (which adjusts for age distribution or other randomization issues) in the multi-arm Remdesivir study which led to its approval and set the standard for Covid studies going forward.
Treating the critical population as a post-hoc subpopulation is inaccurate and leads to a false perception of the CD12 results.
I appreciate the FDA's transparency but that includes an obligation to be objective and get the facts right. I am hoping they will do a correction."
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