Mathematical analysis of Córdoba calcifediol trial suggests strong role for Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients
Jungreis et al.,
Mathematical analysis of Córdoba calcifediol trial suggests strong role for Vitamin D in reducing ICU..,
medRxiv, doi:10.1101/2020.11.08.20222638 (Preprint)
Analysis of Castillo et al. confirming efficacy of calcifediol treatment. Authors find that issues related to imperfect blinding and comorbidities can not explain the result found.
See
[compbio.mit.edu] for a response to issues raised on this analysis.
Jungreis et al., 12 Nov 2020, preprint, 2 authors.
Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.11.08.20222638; this version posted December 21, 2020. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Mathematical analysis of Córdoba calcifediol trial suggests strong role for
Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients
Irwin Jungreis1,2* and Manolis Kellis1,2
1
MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA
2
Broad Institute of MIT and Harvard, Cambridge, MA
*
Corresponding author: iljungr@csail.mit.edu
Abstract
A randomized controlled trial of calcifediol (25-hydroxyvitamin D3) as a treatment for hospitalized COVID-19
patients in Córdoba, Spain, found that the treatment was associated with reduced ICU admissions with very
large effect size and high statistical significance, but the study has had limited impact because it had only 76
patients and imperfect blinding, and did not measure vitamin D levels pre- and post-treatment or adjust for
several comorbidities. Here we reanalyze the reported results of the study using rigorous and well established
statistical techniques, and find that the randomization, large effect size, and high statistical significance
address many of these concerns. We show that random assignment of patients to treatment and control
groups is highly unlikely to distribute comorbidities or other prognostic indicators sufficiently unevenly to
account for the large effect size. We also show that imperfect blinding would need to have had an implausibly
large effect to account for the reported results. Finally, comparison with two additional randomized clinical trials
of vitamin D supplementation for COVID-19 in India and Brazil indicates that early intervention and rapid
absorption may be crucial for the observed benefits of vitamin D. We conclude that the Córdoba study provides
sufficient evidence to warrant immediate, well-designed pivotal clinical trials of early calcifediol administration
in a broader cohort of inpatients and outpatients with COVID-19.
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