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Vitamin D study #67 of 96
1/22 Late treatment study
Nogués et al., SSRN, doi:10.2139/ssrn.3771318 (Preprint)
Calcifediol Treatment and COVID-19-Related Outcomes
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Cluster RCT with 930 hospitalized patients, 550 treated with calcifediol, showing significantly lower ICU admission and death with treatment. Note that the randomization in this trial is by ward. Authors report that patients were allocated to empty beds available at admission time regardless of patient conditions, and that staff in all wards followed the same protocol.
Note that this preprint was censored by the Lancet. The Lancet reportedly requested a review from a Twitter user that posted negative comments [1]. The review provides useful feedback for the authors to improve the reporting of the cluster nature of the RCT, and to explain the delay in registration, however it is highly unusual to censor a preprint in this way. Authors have responded to the issues raied here: [2]

Nogués et al., 1/22/2021, Cluster Randomized Controlled Trial, Spain, Europe, preprint, 15 authors, dosage calcifediol 0.5mg day 1, 0.27mg day 4, 0.27mg day 8, 0.27mg day 16, 0.27mg day 31.
risk of death, 64.0% lower, RR 0.36, p = 0.001, treatment 36 of 551 (6.5%), control 57 of 379 (15.0%), adjusted per study.
risk of ICU admission, 82.0% lower, RR 0.18, p < 0.001, treatment 30 of 551 (5.4%), control 80 of 379 (21.1%), adjusted per study.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. For an individual study the most serious outcome may have a smaller number of events and lower statistical signficance, however this provides the strongest evidence for the most serious outcomes when combining the results of many trials.
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