The real issue here is demanding that billions of humans take a vaccine WITHOUT solid, RCT level evidence of overall mortality benefit. It’s one thing to recommend vaccination without overall mortality evidence; it’s another thing to compel it.
It may be impossible to conduct this research now - but it wasn’t then. And that’s the scandal.
Sadly, experts (such as you are) never held regulators to account. So we’re forced to make due with inadequate RCTs that can’t answer the only question I care about: If I take this shot, will I live longer?
Again, RCTs should have been conducted to answer this definitely and unambiguously. Seems obvious.
What did the Pfizer study find? The vaccines did not prevent infection. Of the 171 patients that developed infections, 9 had been fully vaccinated. Of note, there were more patients with comorbid conditions in the placebo group than in the treated group. Approximately 800 people dropped out of the study. 400 did not receive the second dose. No explanation. Approximately 400 did not receive the entire vaccination schedule. No explanation. Many patients were unblinded throughout the study. With such a small efficacy signal, any unblinding would be grounds for invalidating the entire study.
You state that "confounding, poor randomization, or statistical noise far more likely led to the striking but utterly implausible findings of the Danish group than proper methodology."
If that were the case, you should be able to identify these problems. Instead, you just casually mention that they are likely and waive away all the data used in the study as useless. That's not science - that's dismissing science just because you don't like the result.
You can say this is unlikely and needs more evidence (incredible claims need extra credible proof), but you can't just dismiss it by saying there might be data problems that you don't bother to identify.
I worked as a frontline COVID-19 provider during the pandemic. I spent the last 25 years practicing acute care internal medicine. I also did influenza vaccine research prior to medical school. These Lancet findings actually don't surprise me at all.
Long before the pandemic, one of the things that bothered me about the CDC and WHO was their estimates of influenza mortality. 30,000-60,000/year? Why was I so seldom seeing any of those deaths? I wasn't seeing them because they weren't there. During the H1N1 epidemic of 2009, only ~13,000 deaths were reported. Yet I saw many. Weird, right? The following winter, there were no flu cases. However, the same excess wintertime mortality occurred. Yet, *the same relative survival benefit* to influenza vaccine administration.
The CDC's influenza death estimates are off by an order of magnitude. Check out the American Lung Association's tally of influenza deaths, sometime (taken from death certificates): a few *hundred*, to a few thousand per year. Wintertime deaths, meanwhile, are overwhelmingly due to more cardiovascular deaths, though also with excess (greater relative peak, but lower absolute numbers) deaths from *pneumonia* (non-flu) and chronic lung disease. Many of the excess deaths are triggered by viruses, no doubt. But not by flu- they all get tested for flu at admission after all!
Meanwhile, it has been shown that influenza vaccine recipients are less likely to get the common cold during the months after their vaccine administration. It is believed that *any* antigen unregulates T-cell numbers and responsiveness. I have strong reason to believe then that the statistical survival benefit from flu vaccines (or killed virus, or attenuated virus vaccines) is from something other than reducing flu deaths. Instead, they, like the Astra-Zeneca vaccine, reduce *illness*. Among frail elderly, even colds can kill.
So, neither absurd, nor implausible. But in fact, *likely*, especially in terms of *relative risk*. But *not so significant* in *absolute* terms to change policy. If Pfizer or Moderna offer an (updated) mRNA vaccine each fall, I will sign up. I will also get my annually updated non-mRNA influenza vaccine. I recommend everyone else do the same.
When I wrote this I had not yet realized that Substack is different than The Athletic, and sometimes comments are better than the original post, and I need to read all of them.
So - this is a thought-provoking line of thought, and some of it resonates with me (like WTF is up with the annual ballparking of flu deaths by the CDC, although I want to assume that covid will make this practice unacceptable and inexcusable going forward, as I suspect almost all sick admits will now get a flu/covid test).
(Unfortunately they did not report on all cause mortality, which gets my inner cynic going, but they might just not have been interested). On the one hand, it lends support to your theory, in that there was a drop in cardiovascular events of 36% among the vaccinated cohort, and a 26% drop in CV deaths among those vaccinated. However - these were pretty small #s, and it was entirely driven by those "with recent acute coronary syndrome." In fact, the CV death rate was actually *higher* in those without recent ACS who were vaccinated (which was not statistically significant and presumably noise.) But zero death or CV event benefit to so-called "stable outpatients."
Since "stable outpatients" comprise the vast majority of any of these covid vaccine trials, I find it beyond any reason that this group could see a 62% mortality benefit largely driven by better CV outcomes. It's also very hard to explain the utter lack of this benefit from the mRNA vaccines, given their similar-but-different approach to cellular production of closely related spike proteins to that of the adenovirus vector vaccines.
I would still be shocked if this difference in mortality were maintained in a massive head-to-head trial of these two types of vaccines. Absolutely shocked.
The most likely reason for the lower non-covid mortality from those who took the adenovirus vaccines is that those vaccines offer poorer protection against covid. Hence individuals who are in a very, very bad health overall will be much more likely to die from covid if they take an adenovirus vaccine. The mRNA vaccines protect the same group from covid deaths reasonably well, and therefore there will be a larger group of people very close to death among those who have taken the mRNA vaccine.
The real issue here is demanding that billions of humans take a vaccine WITHOUT solid, RCT level evidence of overall mortality benefit. It’s one thing to recommend vaccination without overall mortality evidence; it’s another thing to compel it.
It may be impossible to conduct this research now - but it wasn’t then. And that’s the scandal.
Sadly, experts (such as you are) never held regulators to account. So we’re forced to make due with inadequate RCTs that can’t answer the only question I care about: If I take this shot, will I live longer?
Again, RCTs should have been conducted to answer this definitely and unambiguously. Seems obvious.
Agreed?
More conservative people who tend to take less risks may have chosen a traditional vaccine like J&J rather than the new MRNA vaccines.
What did the Pfizer study find? The vaccines did not prevent infection. Of the 171 patients that developed infections, 9 had been fully vaccinated. Of note, there were more patients with comorbid conditions in the placebo group than in the treated group. Approximately 800 people dropped out of the study. 400 did not receive the second dose. No explanation. Approximately 400 did not receive the entire vaccination schedule. No explanation. Many patients were unblinded throughout the study. With such a small efficacy signal, any unblinding would be grounds for invalidating the entire study.
You state that "confounding, poor randomization, or statistical noise far more likely led to the striking but utterly implausible findings of the Danish group than proper methodology."
If that were the case, you should be able to identify these problems. Instead, you just casually mention that they are likely and waive away all the data used in the study as useless. That's not science - that's dismissing science just because you don't like the result.
You can say this is unlikely and needs more evidence (incredible claims need extra credible proof), but you can't just dismiss it by saying there might be data problems that you don't bother to identify.
I worked as a frontline COVID-19 provider during the pandemic. I spent the last 25 years practicing acute care internal medicine. I also did influenza vaccine research prior to medical school. These Lancet findings actually don't surprise me at all.
Long before the pandemic, one of the things that bothered me about the CDC and WHO was their estimates of influenza mortality. 30,000-60,000/year? Why was I so seldom seeing any of those deaths? I wasn't seeing them because they weren't there. During the H1N1 epidemic of 2009, only ~13,000 deaths were reported. Yet I saw many. Weird, right? The following winter, there were no flu cases. However, the same excess wintertime mortality occurred. Yet, *the same relative survival benefit* to influenza vaccine administration.
The CDC's influenza death estimates are off by an order of magnitude. Check out the American Lung Association's tally of influenza deaths, sometime (taken from death certificates): a few *hundred*, to a few thousand per year. Wintertime deaths, meanwhile, are overwhelmingly due to more cardiovascular deaths, though also with excess (greater relative peak, but lower absolute numbers) deaths from *pneumonia* (non-flu) and chronic lung disease. Many of the excess deaths are triggered by viruses, no doubt. But not by flu- they all get tested for flu at admission after all!
Meanwhile, it has been shown that influenza vaccine recipients are less likely to get the common cold during the months after their vaccine administration. It is believed that *any* antigen unregulates T-cell numbers and responsiveness. I have strong reason to believe then that the statistical survival benefit from flu vaccines (or killed virus, or attenuated virus vaccines) is from something other than reducing flu deaths. Instead, they, like the Astra-Zeneca vaccine, reduce *illness*. Among frail elderly, even colds can kill.
So, neither absurd, nor implausible. But in fact, *likely*, especially in terms of *relative risk*. But *not so significant* in *absolute* terms to change policy. If Pfizer or Moderna offer an (updated) mRNA vaccine each fall, I will sign up. I will also get my annually updated non-mRNA influenza vaccine. I recommend everyone else do the same.
When I wrote this I had not yet realized that Substack is different than The Athletic, and sometimes comments are better than the original post, and I need to read all of them.
So - this is a thought-provoking line of thought, and some of it resonates with me (like WTF is up with the annual ballparking of flu deaths by the CDC, although I want to assume that covid will make this practice unacceptable and inexcusable going forward, as I suspect almost all sick admits will now get a flu/covid test).
That said: the day before you posted this, a fairly ideal study came out to assess your proposition, namely a meta-analysis of cardiovascular deaths from actual flu shot RCTs -- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791733
(Unfortunately they did not report on all cause mortality, which gets my inner cynic going, but they might just not have been interested). On the one hand, it lends support to your theory, in that there was a drop in cardiovascular events of 36% among the vaccinated cohort, and a 26% drop in CV deaths among those vaccinated. However - these were pretty small #s, and it was entirely driven by those "with recent acute coronary syndrome." In fact, the CV death rate was actually *higher* in those without recent ACS who were vaccinated (which was not statistically significant and presumably noise.) But zero death or CV event benefit to so-called "stable outpatients."
Since "stable outpatients" comprise the vast majority of any of these covid vaccine trials, I find it beyond any reason that this group could see a 62% mortality benefit largely driven by better CV outcomes. It's also very hard to explain the utter lack of this benefit from the mRNA vaccines, given their similar-but-different approach to cellular production of closely related spike proteins to that of the adenovirus vector vaccines.
I would still be shocked if this difference in mortality were maintained in a massive head-to-head trial of these two types of vaccines. Absolutely shocked.
The most likely reason for the lower non-covid mortality from those who took the adenovirus vaccines is that those vaccines offer poorer protection against covid. Hence individuals who are in a very, very bad health overall will be much more likely to die from covid if they take an adenovirus vaccine. The mRNA vaccines protect the same group from covid deaths reasonably well, and therefore there will be a larger group of people very close to death among those who have taken the mRNA vaccine.