Vaccintrials safety illusion

Looking back on the introduction of the proven "Safe and Effective" MRNA vaccines, the "effective" aspect has disappointed: vaccination figures under COVID oversen are not reassuring and are at most unintentionally released. 80% of the deaths to COVID-19 during the Deltagolf was vaccinated¹See steig.nl: The big secret of the Deltagolf. More than 90% of the participants in the Long-Covid government project have been vaccinated²See What disease is the post-Covid report?, ook iets dat zou niet moeten kunnen na een trial die geen twijfel overliet aan effectiviteit. Maar het klinkt ook niet dat je zegt: “veilig” want als het niet effectief is tegen Covid, wat doet het dan wel? Het is immers geen zoutwateroplossing en de gestegen sterfte aan alle oorzaken en vele meldingen van bijwerkingen wekken ook geen vertrouwen. Dat zou echt niet zo moeten zijn na een trial die het sein “veilig” had opgeleverd. Pfizer heeft kennelijk een andere definitie van "veilig".

The basis of "safe" is becoming smaller

In the public discussion, it is assumed that the Pfizer trial³The Pfizer report: Summary Basis for Regulatory Action - COMIRNATY With over 43,000 participants provided sufficient evidence for the designation safe & effective.

Everyone who has viewed critical vaccinations studies has probably thought: "If a sample of 43,000 participants offers sufficient safety to inject the entire world population, why have mega studies done in the past with hundreds of thousands or even millions of test subjects?" The statistical knowledge that such an research design required existed in the 1950s and 1960s. Yet those investigations were not a little bigger: they were 40 times as large! And for some time we can finish it with a few tens of thousands. Why?

The larger, the more precise. The smaller, the more statistical uncertainty, which increases the possible insecurity.

Although 43,448 people were enrolled, the primary safety analysis on which the “safe” claim is based involved fewer participants because not everyone completed a full follow-up. The safety analysis involved 37,706 participants, which again makes you wonder how those 5,700 dropouts were selected. In any case, that results in an upper limit of ±10,000 additional deaths per 12 million vaccinated within 2 months. More precise is not possible. But a median follow-up duration of two months is also reported and this means that an unknown part of the group was followed for less than two months⁴“Safety was evaluated in 37,706 participants who received at least one dose of vaccine or placebo; 18,860 received BNT162b2 and 18,846 received placebo. At the time of the data cutoff, a median of two months of safety data was available for 18,860 vaccine recipients and 18,846 placebo recipients.”
— Polac Fp, et al. No, 2020. Dat levert een hogere bovengrens op die we niet precies kunnen berekenen omdat we de grootte van het uiteindelijke sample niet kennen. Dat zal dus kleiner zijn, en hoe kleiner het sample, hoe groter de onzekerheid. Daardoor gaat de statistische bovengrens verder omhoog en wordt "veilig" steeds minder veilig. Ik zal de grootte aangeven met <38.000.

The cut-off date chosen by Pfizer (November 14, 2020) determined how many participants had completed the two months. This therefore depends on the registration date of each participant and accurate registration thereof. Because individual data is not public, data integrity is only guaranteed by the manufacturer, who must be alert to possible 'sloppiness'. The fact that it is difficult to report imperfections is evident from how reports from an employee of the Pfizer trial, Brook Jackson, were handled.⁵ Interviews met Brook Jackson, die later in The BMJ (2021) the disorderly data collection and defective monitoring described)⁶Brook Jackson met video in The BMJ: https://www.bmj.com/content/375/bmj.n2635.

In the phase 3 security study of Pfizer (Sample <38,000), 21 people died in the Vaccing Group and 17 in the placebo group. 23% more death in the vaccinated group. Pfizer's conclusion was: no statistically significant difference in death, so the vaccine is "safe". For the argumentation theorists among us it is immediately as ready as a lump: absence of evidence is not proof of absence. Not only a statistical rule but a classic fallacy: the non sequuitur⁷Uitleg does not follow by chatgpt. But pharmaceutical companies don't think that way, so let's look in their own history to see whether that is a new insight. The study design (size) at Pfizer contrasts sharply with previous vaccine studies (move your mouse over the graph to zoom in):

If Pfizer can manage with approximately 44,000 participants (and < 38,000 in terms of safety), why were such numbers earlier than necessary? This could be related to a change in the meaning of the concept of 'safety'.

Waar denken we dat "veilig" voor staat?

Als je iemand met een visuele beperking helpt met "Het is veilig, u kunt oversteken" dan zeg je dat niet als je denkt dat er een kleine kans is dat hij wordt overreden. Dat zeg je pas als je zeker weet dat hij veilig de overkant zal bereiken. Als burger vaar je blind op farmaceuten. Maar die hebben andere standaarden.

In clinical practice, “safe” usually means: there is no significant difference from placebo in this study population, in the limited period of the trial. So that's the fallacy. In everyday speech, “safe” means something completely different, namely: no real risk of death or serious damage. But again it is unclear what “none real risk ”. That is not"no Risk ”. In which numbers should we think? Let's assume that a risk of 1 extra death per 10,000 punctures would still be considered acceptable (we will come back on risk categories later). It is the second safest category according to the official EMA/WHO classification. (Often:> 1/10, sometimes: 1/1,000-1/1,000, rarely: rarely: rarely: rarely: rarely: rarely: rarely: rarely: rarely: reld the ownership: 1,000, reld the ownership: reld the ownership: reld the ownership: reld the ownership: reld the ownership: reld the owner: reld the ownership: rarely: rarely: 1,000: rarely: 1,000: 1,000 and 1,000! 1/10,000-1/100,000.)

How big should a trial be?

We assume a hypothetical maximum risk: the additional chance of dying within two months (the duration of the trial!) after vaccination may not exceed 0.01% (1 in 10,000). For a population of 12 million vaccinated people (NL), this means a maximum of 1,200 deaths in two months - which you can also question, but we agreed to accept this as being 'safe'. It should also be weighed against the severity of the disease. What is also missing is the age aspect. All ages are tarred with the same brush, which raises ethical questions and can lead to statistical distortions.

Om uit te sluiten dat het risico groter is dan 0,01%,, zijn meer dan 1 miljoen proefpersonen nodig. (zie kopje Veldwerk, onderaan). Wil je daarbij een likelihood ratio van 100% bereiken dan worden het vele, vele miljoenen. Dat heeft dus geen zin meer als 'trial', dat is "uitrollen en zien wat er gebeurt".
However, Pfizer worked with < 38,000 test subjects. This means that you cannot statistically notice a small difference such as 1:10,000. In fact, with such small numbers you can only rule out that no more than approximately 10,000 to 12,000 deaths would occur in the first two months among 12 million vaccinated people.

This means that the Pfizer safety trial indicates that the total mortality in the population can remain the same by half due to the vaccinations, because that is what the numbers come down to. Everything in between is therefore declared acceptable (because 'safe').

Moreover, it is important that this calculation only applies to the duration of the trial: two months. We now know that side effects and deaths sometimes only become manifesto after 3–4 months (± 100 days) and possibly later. But also the suspected height of that risk of death would not have been observed in this underpowered study⁸Observational estimates appear to indicate a risk of 0.02% for the baseline series. That would be 2400 deaths for two months. That falls well within the insensitivity range of this design..

The ethical dimension

Medications are given to sick people. A small extra risk can be acceptable there, because the patient runs a high risk without treatment.
Vaccines, on the other hand, are given to healthy people, to children. That makes the balance fundamentally different. Can you let a healthy (younger) individual risk of death to prevent deaths elsewhere (in the elderly)? That is not a purely scientific, but above all an ethical and possibly culture -related question. And that is why perhaps a political one for a referendum.

"Mogen burgers gevaarlijke injecties nemen vanwege angsten, wat ook wel 'informed consent' wordt genoemd?"

Age dependence

Like many other disorders, COVID mortality is strong age-related. The percentage aboutmortality per age group is comparable across all age groups. The trials did not even remotely have the power to prove safety and effectiveness per age group separately. Results for an “average subject” were simply generalized to all ages. That might still be justifiable if the goal had been herd immunity. It goes without saying that the whole argument of herd immunity did not apply to an injection anyway. An intervention that did not reduce infections and was usually administered at the wrong time because it was effective for such a short time (what a panic football, if you put it all together again.)

Semantic and framing

The words themselves have suddenly evolved:

• "Vaccine" stood for an innocent first encounter with a pathogen, so that the body builds up immunity without any risk. With mRNA and vector vaccines, it has become a medicinal intervention because immunity is so temporary that the drug should preferably be administered a few weeks before infection - an impossible timing, as the 'boosters' have proven. The distribution through the body is also very different. Traditionally, the further away from the injection site, the weaker. mRNA vaccines are micro-submarines that can travel anywhere in the body and only release their active cargo upon arrival in a cell.
• “Trial” once stood for long-term, large-scale field studies (polio, BCG, hepatitis E, cholera). The Covid-19 trials were relatively small and short. Looking at the required power and the research carried out, they were mainly for the stage, shortcuts to approval. Meaningless data was interpreted as safe. The absence of evidence for excess mortality - the predictable outcome in these small samples - was framed as evidence to the contrary. This invites you to look at other vaccine studies because as we can see from the top 10 graph, almost all studies are numerically below the Pfizer trial discussed here. They only reach 11th place and much lower.

Conclusion

• Pfizer’s Trial did not proved that the vaccine safe was in the everyday sense of that word. It only proved that there was no significant difference in mortality over a limited period of time, compared to placebo. But absence of evidence is not evidence of absence.
• It was known in advance that this trial would not even remotely demonstrate that the safety of the vaccine would be at stake. The popularity of this range of sample sizes is understandable, from a pharmaceutical perspective. A lot has to happen if this is to produce a hard (significant) safety signal.
• To demonstrate true safety, much larger trials are needed — and that has been done historically. That's how it started. The claim “safe and effective” has become the result of framing and repetition, not of hard science.
• De cijfers zijn een harde grens: minder dan 12.000 doden in twee maanden na de prik, daar is de trial op gedimensioneerd. Dat is de uitspraak “veilig” ook. Minder dan 12.000 overlijdens in twee maanden is "veilig". Het zijn waarschijnlijk niet meer dan 2.000 vaccindoden per 2 maanden. Dat valt ruim binnen de marge. Tweeduizend.

Footnotes

• 1
  See steig.nl: The big secret of the Deltagolf
• 2
  See What disease is the post-Covid report?
• 3
  The Pfizer report: Summary Basis for Regulatory Action - COMIRNATY
• 4
  “Safety was evaluated in 37,706 participants who received at least one dose of vaccine or placebo; 18,860 received BNT162b2 and 18,846 received placebo. At the time of the data cutoff, a median of two months of safety data was available for 18,860 vaccine recipients and 18,846 placebo recipients.”
  — Polac Fp, et al. No, 2020
• 5
  Interviews met Brook Jackson
• 6
  Brook Jackson met video in The BMJ: https://www.bmj.com/content/375/bmj.n2635
• 7
  Uitleg does not follow by chatgpt
• 8
  Observational estimates appear to indicate a risk of 0.02% for the baseline series. That would be 2400 deaths for two months. That falls well within the insensitivity range of this design.