Nonspecific Vaccine Effects Journal Club no. 11
Charlotte Str?m
MD PhD Journalist Author. Owner at SharPen, Medicine in Media. Get your medical stories told
?? I don’t want to see, I can’t see – hence it (the evidence) is not there
For this issue of the Nonspecific Vaccine Effects Journal Club we will dig into a PhD thesis investigating the nonspecific vaccine effects of the BCG (Bacille-Calmette-Guerin) vaccine.
The PhD is truly remarkable. It contains three (not one, not two, but a complete set of 3!!) randomised controlled trials (RCTs). That is an amazing achievement and really hard work – because nothing compares to the laborious and long hours that have to be put into doing clinical trials.
Good job on all that hard work ?? ??
Effects of BCG vaccination on the immune system and health of adults in Denmark: Exploring non-specific effects of BCG
The thesis is interesting because it embarks on three (not one, not two, but a complete set of 3!!) RCTs based on the hypothesis that the BCG vaccine presumably has nonspecific effects. Two trials aimed to demonstrate nonspecific protection against Covid infection, and one trial aimed to demonstrate improved response to the influenza vaccination, i.e. nonspecific effects of the BCG vaccine.
Why is this interesting? It is interesting in a puzzling or even disturbing way that the researchers behind these trials managed to raise funding for three (not one, not two, but a complete set of 3!!) RCTs at a point in time with an abundance of published trials stressing that there is no shred of evidence to support the existence of nonspecific effects of the BCG vaccine.
Section 2.3 of the thesis justifies chasing after the NSE in three (not one, not two, but a complete set of 3!!) RCTs – based on observational studies which we know from JC no. 9 and 10 to be prone to bias and residual confounding, small underpowered studies, and a deliberate misinterpretation of data: (“italics” reflect quotes from the thesis)
“Randomised clinical trials (RCTs) conducted in Guinea-Bissau, where low birth-weight infants were randomised to BCG at birth or delayed at 6 weeks (local standard procedure at that time), showed reductions in child mortality of 38% (17-54%) in infants and of 16% (0-29%) by 12 months age.”
But hey – this is not true, but a misreporting of Clin Infect Dis An Off Publ Infect Dis Soc Am. 2017;65(7):1183. What really happened in this trial was outlined in detail in NSE Vacc Journal Club no. 3 . The NSE magical trick was applied to the data: Three negative trials were in an untransparent way meta-analyzed and magically made the negative trial results vanish in thin air. ?? ?? This dubious method is like a kinder egg with three null-studies --> Negative + negative + negative = positive results
Moreover, it is puzzling how the large scale RCTs investigating NSE of BCG get very little attention. The Danish Calmette trial (Arch Dis Child. 2017;102(3):224 and J Pediatric Infect Dis Soc.) almost appears to be positive study, when in fact it was a true null study:
“In Danish children, there was no effect of neonatal BCG vaccination on hospitalisation rate within 15 months of life or infectious disease hospitalisations overall. However, there was a positive effect in children born to BCG vaccinated mothers in the same range as was seen in African children.”
Take a closer look at the NSE Vacc Journal Club no. 7 which assessed these two publications and clearly demonstrated no nonspecific effect of BCG in 4262 Danish infants and a suspiciously large number of statistical tests to yield a singled out and most likely random significant secondary outcome – reporting it as if this was immensely interesting. What was really interesting from the Dansh Calmette Trial was that there was ZERO nonspecific vaccine effects from the BCG vaccine.
And hey – how about nonexisting NSE from BCG vaccination in 1272 Australian neonates (J Infect Dis.?2021 Oct 13;224(7):1115-1127 – that study is not even mentioned.
I think it is a bit early – already in the introduction section to give in: ?? I don’t want to see, I can’t see – hence it (the evidence) is not there.
Anyway, despite an overwhelming amount of data proving otherwise the researchers embarked on three (not one, not two, but a complete set of 3!!) RCTs to prove a hypothesis that no researcher has ever managed to replicate in the primary analysis of a sufficiently powered RCT. Can you imagine the large number of study participants that had to stand up for this… ?
What is even more remarkable is that this thesis reports three (not one, not two, but a complete set of 3!!) RCTs that failed completely to demonstrate a nonspecific vaccine effect in any of the primary outcomes.
?If it was not a tragic waste of research resources and an unethical misuse of 3.170 study subjects’ time and energy – it is almost hilarious.
Let’s dive in. The table below is copy-pasted from the thesis, the red box was inserted by me, and it gives an excellent overview of the three trials.
Study 1 – was already assessed in JC no. 5 , hence we need not linger for a long time on this study – just highlight that there was
?? ?? ??
·???????? No nonspecific effect of BCG on absenteeism; RR 1.23 (0.98-1.53)
·???????? No nonspecific effect of BCG on COVID-19; HR 1.31 (0.83-2.06)
·???????? No nonspecific effect of BCG on hospitalisation; HR 0.84 (0.42-1.66)
Bummer ??
Conclusion: The first RCT of three RCTs in this thesis was a true null study with no nonspecific effect of the BCG vaccine whatsoever.
Study 2 was a randomised placebo controlled, single-blinded trial, where 1.676 senior citizens were randomized 1:1 to BCG and placebo. The objective of the RCT was to reduce the risk of acute infection and to reduce the risk of COVID-19, hospitalisation, and selfreported respiratory illness among senior citizens. The results are indisputable stated in the table above:
?? ?? ??
?·?????? No nonspecific effect of BCG on acute infections; HR 0.89 (0.78- 1.02)
·???????? No nonspecific effect of BCG on verified COVID-19; HR 0.97 (0.75-1.26)
·???????? No nonspecific effect of BCG on all cause hospitalisation; HR 1.10 (0.80-1.50)
·???????? In fact BCG was associated with more respiratory symptoms; HR 1.21 (1.10-1.33)
?
Bummer again??
领英推荐
Conclusion: The second of three RCTs in this thesis was a true null study with no nonspecific effect of the BCG vaccine whatsoever.
The third study was a randomised placebo controlled, single-blinded trial with nested immunological study with the objective
“To improve serological response to influenza vaccination and to improve the resistance towards infections among senior citizens. To study induction of innate immune training.”
The “new black in NSE” among True Believers is enlightening the world with an endless series of papers suggesting immunological explanations to the nonspecific vaccine effects.
Let’s be clear crystal clear ??on one thing: It is really no surprise or breaking news that the immune system reacts to a vaccine and may do so with up- and downregulations of an abundance of cytokines. Why wouldn’t it? ?? Afterall the immune system was designed to detect, defend, and protect the body from pathogens, such as a vaccine. But who says that the immunological changes are nonspecific at all…?
And quite frankly it seems a bit off track to spend so much effort chasing after an immunological explanation on effects that simply cannot manifest clinically. And that points to the notorious Achilles’ heel ?? of NSE True Believers, who have an amazing – but surely no longer surprising – hard time proving NSE clinically! ??
Hence, the immunological explorations seem to be nothing but derailing the focus from the lack of clinical evidence.
Study 3:
273 senior citizens were randomised 1:1:1:1 to BCG > influenza vaccine, BCG+influenza vaccine, influenza vaccine >BCG, or influenza vaccine only (control). The in-vivo results of the study were:
?? ?? ??
·???????? No nonspecific effect of BCG on the incidence of self-reported infection
·???????? No nonspecific effect of BCG on influenza antibody titre four weeks after vaccination
Bummer again ?? – and again!
Conclusion: On top of the mountain of evidence that BCG has no nonspecific effects the third of three (not one, not two, but a complete set of 3!!) RCTs in this thesis now corroborate exactly that.
I wonder what is so hard to understand…?? This time it took 3.170 study subjects in three different trials to teach the researchers what was already known, had they cared to read the literature with skepticism – and not through the glasses of True Believers ??
Now we could leave it at that if it wasn’t for the overall interpretation of the thesis that include the following phrase:
"Overall, the results seem compatible with the interpretation that BCG is most likely to be effective in preventing infectious diseases in older or multimorbid populations, suggesting there is most to gain in people with weakened immune systems”
? No, they don’t! That is not at all what the data show ?? That is what clouded judgement looks like ????? - because the results de facto bury the hypothesis on nonspecific vaccine effects. ??
Alas, it seems to be very difficult – a constant struggle even ?? – to see what is in front of one’s nose: That there are no nonspecific vaccine effects of the BCG vaccine. With an amazing lack of contemplation it was further suggested in the thesis to run even more trials – despite the fact that three (not one, not two, but a complete set of 3!!) RCTs have just refuted the hypothesis:
“It seems indicated to conduct long-term follow-up of the randomised cohorts from the pandemic period with these potential benefits in mind. Future studies on NSEs of BCG should focus on elderly and/or multimorbid populations while carefully monitoring safety, and assess overall morbidity and mortality as well as incidence and severity of infection. Follow-up over several years would be preferable.”
For crying out loud, ?? leave the senior citizens on Funen alone! ?? Once again this is what clouded judgement looks like ????? - and what "potential benefits" - need I remind the reader here that three (not one, not two, but a complete set of 3!!) RCTs showed no nonspecific benefits. Not even potentially.
The really clever thing would be to cut off the funding ? ??to the continuous investigation of this dubious hypothesis. Alternatively, we’ll find ourselves a couple of years down the road ??? assessing yet another PhD thesis with one, two, or even three new RCTs investigating NSE. Although I don’t gamble ?? and hardly ever bet on anything?? I’ll probably make an exemption on this, as the odds are really good ?? for this upcoming scenario:
There will be one, two, and perhaps even three additional null studies on nonexisting nonspecific vaccine effects.
This concludes issue no. 11 of #NSEvaccJournalClub.
Stay tuned for more
For previous issues of the NSEvacc Journal Club:
Consultant: Drug Development, Training, Quality Management, Process Improvements. Grandfather x 3.5!
1 个月Once again I have to praise you for biting on this issue like a bulldog. I am truly disappointed on the colleagues that are just ignoring science on this and chooses to interpret data so that it serves their biased view on effects of vaccines. Vaccines do what they are designed to do ie stimulating the specific immune system to fight off infections or sensitivities. Well done Charlotte.