Thread by @santiagokique

GBD propaganda arm, the Brownstone institute, has published an article claiming 1) the mRNA vax might be the 'wrong' vax for the population, 2) COVID vax dont reduce overall mortality and therefore governments shouldn't mandate COVID vax. Let's look at these claims. 🧵

First, let us look at the primary source of data for these claims, a preprint attempting to assess some signal of non-specific effects of the two major classes of COVID vaccines through a meta-analysis of industry-led vaccine RCTs. papers.ssrn.com/sol3/papers.cf…

F1 purports to show that while mRNA vaccines had no effect on overall mortality in these RCTs, adenovirus vaccines may have, and in particular this effect can be most heavily attributed to a reduction in CV mortality. Before diving into these, let's just review interpreting CIs

it is a common mistake to assume that bc CIs overlap = not significantly different, in fact CI overlap is simply inconclusive. The critical parameter is if the CI distribution of differences between the comparison distributions crosses 0 or not. Crosses 0 = not significant.

This common interpretive mistake is due to something called error propagation. Here's a good blog post on it from an NYU data science Phd student. towardsdatascience.com/why-overlappin…

What does that mean for our figure? Maybe there's a trend to lower mortality in adeno but with the underlying data in this analysis no conclusion can be drawn about overall mortality without additional analysis.

Indeed, if you look at the table with the mortality information for all of the adeno trials, the CIs for the relative risk of dying from any cause in the trial group vs placebo are huge...except for J&J.

In other words, the trend towards putatively decreased overall mortality in the meta-analysis from Adeno vaccines is likely almost entirely due to the J&J trial data. Also, if we look at f/u, pts in the Pfizer and Moderna trials were followed 2-2.5x as long as in J&J.

But CV mortality seems like a clear winner in the adeno group in spite of overall mortality figures! You might say. But if we look at the trial demographics in adeno vs mRNA most of the adeno trials have a much lower mean age and we know CV mortality scales with age. Moreover,

the differences in f/u time is still an issue. If you follow people for longer more people will die of more causes, by chance. If you look at one group followed over a longer period, vs another in a shorter period, you can't interpret mortality differences b/w those groups

This is complicated by the international nature of these trials. CV mortality is also dependent on the healthcare access an individual is able to get, which varies greatly between the countries in the study.

The authors of the preprint themselves acknowledge all of these limitations in their paper. They are not trying to be misleading. Rather, it's the GBD gang misapplying and misinterpreting their findings to serve their own ends, as they do time and time again with research.

You cannot conclude from this paper that mRNA vaccines *enhance* CV risk (you can't even conclude that adeno vaccines have any effect in either direction), but this is the way it is being misinterpreted online, the GBD authors know it, and they don't care to acknowledge it.

Returning to COVID, there's overwhelming evidence that vaccination reduces morbidity and mortality from COVID infection. Rehashing this massive body of evidence in this already long thread is not necessary. Everyone should be vaccinated against COVID-19.

It would be nice if everyone did go out and get vaccinated, boosted, but we've all already learned the painful lesson that without mandates this is probably an impossible task. Furthermore, a true universal COVID vaccine mandate has never and still does not exist.

Lastly, long covid remains an ignored topic from the GBD/infect everyone now (and again, and again ad infinitum) crowd. In other words, morbidity and not just mortality are important factors in determining whether or not an intervention is necessary.

This thread really focuses on the preprint, but there's additional reasons the Brownstone article is completely insane that are so dumb they would be exhausting to write about. Is it reasonable to hold vaccines to a standard of reducing overall mortality?

Reduction in overall mortality from a vaccine preventing an infectious disease depends on many other factors, including the prevalence of infections in the population at the time, and the particular subvariant in this case that is driving infections at a given time.

It depends on NPI use. Exposure risk of trial participants. The GBD folks implicitly assume these things to be meaningless, which is also too dumb to fathom in text.

https://twitter.com/santiagokique/status/1518643909945044992?s=20&t=kEsLtgcSgmDgJAxaPXQCDw

adding this here