This vitamin D/COVID-19 study has gone viral, because the results appear to be impressive and people love promoting vitamin D Unfortunately, the study itself is...problematic Some peer-review on twitter 1/nhttps://twitter.com/DavidDavisMP/status/1360647462197878791 …
-
-
4/n Firstly, the study type. People are talking about this as "randomized" because the authors use that word in the abstract But the authors didn't actually randomize patients!pic.twitter.com/e5BVM9cLgC
Show this thread -
5/n What the authors describe doing is, depending on how you read it, either a cluster-randomized trial with a sample size of 8, or a completely uncontrolled observational trial I think it's almost certainly the latter
Show this thread -
6/n Why? Well, a big clue is that this is what the authors got ethics approval to do. Another clue is that nowhere in the study is an actual method for randomization described!pic.twitter.com/8kG103qNlG
Show this thread -
7/n If the authors did indeed do a randomized trial on participants who consented only to a cohort study, it is a decidedly non-trivial issue Where I live, there would be firings, lawsuits, and potentially criminal proceedings
Show this thread -
8/n More likely, in my opinion, is that this is simply as the authors describe an observational cohort study of people in hospital who were either given calcifediol or not. They just use the word randomize incorrectly
Show this thread -
9/n But even then, there are massive issues For example, the PRIMARY ANALYSIS (60% mortality reduction) excludes ~20% of their total sample because of missing baseline data on vitamin D statuspic.twitter.com/jPDvuCHBrZ
Show this thread -
10/n And we get no information whatsoever on these missing people. Were they from the treated group? The control? Did they die, go to ICU etc? We have no idea!
Show this thread -
11/n Another issue is that there were 8 presumably quite different COVID-19 wards, but the authors basically ignore these differences. There is no discussion of the purpose of the wards, and no correction for it in the statistical model
Show this thread -
12/n Could the results be explained by different wards having different admissions protocols? Potentially, but we are given no information to make this assessment at all
Show this thread -
13/n This is even more troubling when you consider that the baseline vitamin D levels are different in the treated and control patients (for whom there was vit D information) So we know that the wards were different, but we don't know how much or whypic.twitter.com/Zr4TFceOOE
Show this thread -
14/n There's more. If this WAS indeed a cluster RCT (I'm skeptical), then the authors did the wrong analysis and the results are probably actually non-significant Excellent thread here:https://twitter.com/lycraolaoghaire/status/1360765704849481731?s=20 …
Show this thread -
15/n There are also numerous issues I haven't covered that
@fperrywilson does a great job dissecting here:https://twitter.com/fperrywilson/status/1360944814271979523?s=20 …Show this thread -
16/n There are other odd inconsistencies with the study. For example, they had 93 patients die and 110 ICU admissions That's a startlingly high ICU mortality rate, unless a majority of patients who died were not admitted to ICU
Show this thread -
17/n For some context, the average ICU mortality was about 30% in Spain at the time, which is still really high but not "almost 100%" highhttps://www.sciencedirect.com/science/article/abs/pii/S2341192920300986 …
Show this thread -
18/n The timelines are really weird. The study is reported as going for 91 days (1st March-31st May) but the K-M curves have 100 days for the treatment group. Probably a minor error, but still strangepic.twitter.com/SH9NKeiVgG
Show this thread -
19/n The K-M curves are also just bizarre. My guess is that they've confused the outcome death with the inverse for the second graph, but even then they really make little sense
Show this thread -
20/n Also, the study ran until May 31st. This magnificent, amazing, literally earth-shattering result (60% REDUCTION IN MORTALITY) took...8 months? And no news, barely any press, for a treatment that could save 60% of people with COVID-19?pic.twitter.com/UEwDfFLqB3
Show this thread -
21/n The study also wasn't pre-registered, which is an issue considering it started on March 1st 2020. When was the treatment protocol (HCQ+azithro and dexamethasone) decided on?pic.twitter.com/sRvMutWu9k
Show this thread -
22/n Also, how in the world did one relatively modest-sized hospital have 8 fully-dedicated COVID-19 wards open in Barcelona, at a time when Spain itself only had a handful of COVID-19 cases? Any Barcelonian followers who can elaborate?
Show this thread -
23/n The same author group wrote another paper on the same patient population in January. Why was there no mention of this trial, or the MASSIVE mortality reduction anywhere? None of this is necessarily disqualifying, it's just really odd!pic.twitter.com/n6J8ihD9S3
Show this thread -
24/n I should specify that none of this makes the study totally sketchy, it's just all really weird and they are things that the authors should have explained in the paper
Show this thread -
25/n Overall, what we have is a study that, if run as specified, was a non-randomized prospective cohort study that gives us very little/no new information on vitamin D for COVID-19
Show this thread -
26/n This doesn't mean that you shouldn't take vitamin D, it's relatively low-cost and the harm is mostly to your wallet, but the jury is still out whether it will have any benefit at all to COVID-19
Show this thread -
27/n Update: the authors have confirmed that this was not a randomized trial on PubPeer. They are still using the word "random" in a very confusing way, but what is described here is not an RCT by any descriptionpic.twitter.com/epHN075OA7
Show this thread -
28/n And I wrote a piece about this trial and COVID-19 and vitamin D in generalhttps://gidmk.medium.com/vitamin-d-and-covid-19-an-update-59fb2f9cceb5 …
Show this thread
End of conversation
New conversation -
Loading seems to be taking a while.
Twitter may be over capacity or experiencing a momentary hiccup. Try again or visit Twitter Status for more information.
)