Mathematical analysis of Córdoba calcifediol trial suggests strong role for Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients

  1. Irwin Jungreis
  2. Manolis Kellis

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

A randomized controlled trial of calcifediol (25-hydroxyvitamin D 3 ) 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.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.11.08.20222638: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04366908RecruitingPrevention and Treatment With Calcifediol of COVID-19 Induce…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.11.08.20222638 on medRxiv