[philipn]

It was not blinded. It was open-label and the outcomes were subjective (ICU admission). The doctors involved with the trial knew who got what and may have biased their actions based on that. Given the subjective outcome and small number of participants, this is particularly important. The trial would be slightly underpowered even if it were blinded.

Other studies on Vitamin D are retrospective cohort / observational studies which are heavily biased with possible confounders with respect to Vitamin D.

My personal opinion is that Vitamin D may help in COVID-19 but this trial does not 'confirm' that. Someone should run a similar trial with more participants and/or a fully blinded trial / a trial with more outcomes (biomarkers, etc).

[himinlomax]

There may be some subjectivity at play alright when deciding if borderline patients go to ICU or not, and that certainly lowers confidence in the numbers, but the effect size is quite large.

What would be interesting would be a follow up to see if patients have suffered lasting damages as has been reported; that could be done blind if the data is collected by imaging (for say heart damage) and analyzed by a different group. Though I have no idea how common those damages are.

[lhl]

While it's important to acknowledge the limitations of the pilot RCT, I think calling the outcomes as "subjective" goes too far - besides ICU admission, patients were tracked until discharge or death - a pretty hard outcome, to say the least.

The ICU admission procedure is also discussed: "The patients were admitted to the ICU by applying the rigorous protocol of the Reina J Sofia University Hospital (see supplementary material). Several fundamental aspects were considered when evaluating admission to the ICU: Presence of comorbidities, either individually or quantified in the modified age Charlson Comorbidity Index; Barthel's Index for functional assessment. It establishes the level of dependence of a patient according to his or her needs and clinical criteria: CURB-65 and SOFA scale and ATS/IDSA criteria [27]. A multidisciplinary Selection Committee was created, made up of intensivists,pulmonologists, internists and members of the ethics committee who decided on admission to the ICU."

WRT to bias, the description of the study is a bit confusing to me as it is described as "open label" (treatment known to the doctors and the patients) but also "double masked" which should hide the appearance of the treatment to the patient, investigator, or medical personnel.

The study describes the masking as: "The list generated was accessible randomization only to nonmasked specialists in the study in an attempt to minimize observation bias. The patients' data were recorded in the hospital's electronic medical record, with blind access by the technical data collectors and the statistician who carried out the study."

This description still leaves me confused, so hopefully that can get clarified (since treatment was oral, should be simple to mask w/ placebo), but in any case, the results are strong enough (and in concordance not only with the prior suggestive retrospective studies on Vitamin D and COVID, but also many mechanistic and RCT studies on Vitamin D's effects on respiratory illnesses and immune function) that hopefully a more rigorous, larger scale followup is being done somewhere. (Some other things about the study that I noticed is that patients didn't have Vitamin D status collected on intake, and as mentioned in the paper, obesity, BMI, and other metabolic markers weren't measured either.)