Having just yesterday got part two of my shingles vaccine I was doubly disappointed here. Apparently I am no less likely to get dementia and Dr Prasad won’t reveal the important bit. Is it good at preventing shingles? I had shingles about eight years ago and didn’t much enjoy it.
This was my feeble attempt at a joke. Clearly it failed, and probably deserved to. But he does sort of gesture at the question in the penultimate paragraph. But I agree. This was not a piece about shingles!
This commentary comes pretty close to declaring this study, or at least its claims, to be fraudulent, starting with another study that was clearly so. The nicest thing it says is that the claims are “magical”. What is closer to magical thinking is this commentary. Dr. Prasad substitutes his own words – better described as unfounded accusations - for the actual claims of the authors, no less their methods. Let’s look at the article’s “claims”, taken verbatim:
“The observed reduction of risk is clinically meaningful: if confirmed in clinical trials…”
“The biological mechanisms underlying these observations remain to be clarified experimentally.”
“Third, although our study is a natural experiment … it does not imply that associations are causal. Causality requires additional assumptions (outlined in the Methods alongside supporting evidence and discussion of remaining uncertainties).”
“Early divergence of Kaplan−Meier curves, while biologically plausible, can be a sign of unmeasured confounding..."
“…these findings, if confirmed in clinical trials and mechanistic studies, would have important implications for public health.”
In Methods, under “Assumptions for causal inference”:
“Although the above evidence supports exchangeability on observed dimensions, the influence of several unmeasured factors cannot be ruled out. … If they systematically differ between cohorts after matching, such unmeasured confounders may violate the exchangeability assumption.” They then include a variety of possibly important covariates that they could not measure, including particularly social determinants of health.
Every point raised by Dr. Prasad is discussed in the paper, some at considerable length in both the discussion and the methods. This includes the rapid divergence of the curves, whose explanation the authors concede is not evident, even though they did a variety of analyses, including 6 negative control outcomes, to explore obvious methodologic artifacts. The proposed explanations are framed as tentative; some speculative, some supported by cited evidence.
At the end of the day, the authors end up with the “claim” that the phenomenon is merely worth further exploration with stronger empirical designs (i.e. trials) and laboratory studies of mechanism. That’s it. Their claim is that the phenomenon deserves a closer and better look. Is that a universal “get out of inference free” card that protects against spurious claims? Only if the authors had not engaged in the serious methodologic efforts they did, which go unmentioned and unrebutted by Dr. Prasad.
I will add parenthetically that one of the more challenging aspects of such research is the TriNetX database itself, but that is an issue for another day. And if this turns out to be true, it's main value will be in mechanistic understanding, as the motivation to get this vaccine will always be to avoid shingles, not to improve heart health.
One could still legitimately take issue with the article's modest claims - i.e. that this hypothesis is worth further attention - and whether the many caveats are strong enough. But not using the hand-wavy, unidimensional arguments put forward by Dr. Prasad, not to mention his dismissive and almost contemptuous tone. Reasonable scientists can and will disagree as to how likely these data patterns are to represent causal relationships – which the authors do not claim and themselves may not agree on – but Dr. Prasad should engage with what the authors actually did and said, not a cartoon version. But that would take time and wouldn’t be as clickbaitable.
I would encourage every reader of this substack to read the actual paper to reflect not only on the strength of evidence provided by this study, but on the intellectual honesty of Dr. Prasad’s critique. And then decide which is more "magical".
There is only one shingles vaccine available in the US since 2021 -Shingrix which is recombinant. Before 2021 there was also a live, attenuated vaccine but it has not been available for years. The vaccine is quite effective, increasingly so as one ages which is unusual. But most people get some kind of side effect when they take it (not major except for very rare Guillain-Barré syndrome, but not pleasant either) and it takes two shots three to six months apart to actually be decently effective. But most would agree better than getting shingles in the final analysis.
Do you know the % of these shingle shots working? I’ve had 2 friends and my brother all get the shingles during covid. All 3 had the double shots. I’m hoping it was just coincidental and the % is high.
Shingrix in ZOE-50 and ZOE-70 produced 97.2% efficacy against zoster in adults 50 and older and 89.8% in those 70 and older, with about 91% efficacy against PHN (Post herpetic neuralgia...the really crummy part); the ZOE long-term follow-up cohort still showed roughly 79% to 82% efficacy at ten to eleven years post-vaccination.
thank you for this. Honest question, what does the 97% efficacy rate mean? percentage of people who dont get shingles compared to same age cohort who dont get the vaccine? i understand ARR, RRR and NNT but in this case im confused on how efficacy is defined. thank you again. ( Guillain Barre would be terrible.)
My observational, non-medical take is that “spiking” the immune system per COVID shots led to a rise in Shingles. A vaxxed and boosted 50 year old friend came down with Shingles. Her primary care doctor told her to quit the boosters. He was seeing a bunch of Shingles cases.
Having just yesterday got part two of my shingles vaccine I was doubly disappointed here. Apparently I am no less likely to get dementia and Dr Prasad won’t reveal the important bit. Is it good at preventing shingles? I had shingles about eight years ago and didn’t much enjoy it.
This was not a piece about shingles. You can research the studies on efficacy of the shot for shingles prevention.
This was my feeble attempt at a joke. Clearly it failed, and probably deserved to. But he does sort of gesture at the question in the penultimate paragraph. But I agree. This was not a piece about shingles!
This commentary comes pretty close to declaring this study, or at least its claims, to be fraudulent, starting with another study that was clearly so. The nicest thing it says is that the claims are “magical”. What is closer to magical thinking is this commentary. Dr. Prasad substitutes his own words – better described as unfounded accusations - for the actual claims of the authors, no less their methods. Let’s look at the article’s “claims”, taken verbatim:
“The observed reduction of risk is clinically meaningful: if confirmed in clinical trials…”
“The biological mechanisms underlying these observations remain to be clarified experimentally.”
“Third, although our study is a natural experiment … it does not imply that associations are causal. Causality requires additional assumptions (outlined in the Methods alongside supporting evidence and discussion of remaining uncertainties).”
“Early divergence of Kaplan−Meier curves, while biologically plausible, can be a sign of unmeasured confounding..."
“…these findings, if confirmed in clinical trials and mechanistic studies, would have important implications for public health.”
In Methods, under “Assumptions for causal inference”:
“Although the above evidence supports exchangeability on observed dimensions, the influence of several unmeasured factors cannot be ruled out. … If they systematically differ between cohorts after matching, such unmeasured confounders may violate the exchangeability assumption.” They then include a variety of possibly important covariates that they could not measure, including particularly social determinants of health.
Every point raised by Dr. Prasad is discussed in the paper, some at considerable length in both the discussion and the methods. This includes the rapid divergence of the curves, whose explanation the authors concede is not evident, even though they did a variety of analyses, including 6 negative control outcomes, to explore obvious methodologic artifacts. The proposed explanations are framed as tentative; some speculative, some supported by cited evidence.
At the end of the day, the authors end up with the “claim” that the phenomenon is merely worth further exploration with stronger empirical designs (i.e. trials) and laboratory studies of mechanism. That’s it. Their claim is that the phenomenon deserves a closer and better look. Is that a universal “get out of inference free” card that protects against spurious claims? Only if the authors had not engaged in the serious methodologic efforts they did, which go unmentioned and unrebutted by Dr. Prasad.
I will add parenthetically that one of the more challenging aspects of such research is the TriNetX database itself, but that is an issue for another day. And if this turns out to be true, it's main value will be in mechanistic understanding, as the motivation to get this vaccine will always be to avoid shingles, not to improve heart health.
One could still legitimately take issue with the article's modest claims - i.e. that this hypothesis is worth further attention - and whether the many caveats are strong enough. But not using the hand-wavy, unidimensional arguments put forward by Dr. Prasad, not to mention his dismissive and almost contemptuous tone. Reasonable scientists can and will disagree as to how likely these data patterns are to represent causal relationships – which the authors do not claim and themselves may not agree on – but Dr. Prasad should engage with what the authors actually did and said, not a cartoon version. But that would take time and wouldn’t be as clickbaitable.
I would encourage every reader of this substack to read the actual paper to reflect not only on the strength of evidence provided by this study, but on the intellectual honesty of Dr. Prasad’s critique. And then decide which is more "magical".
I would love an analysis on shingles…i think there are two types live and attenuated(?). 🙏
There is only one shingles vaccine available in the US since 2021 -Shingrix which is recombinant. Before 2021 there was also a live, attenuated vaccine but it has not been available for years. The vaccine is quite effective, increasingly so as one ages which is unusual. But most people get some kind of side effect when they take it (not major except for very rare Guillain-Barré syndrome, but not pleasant either) and it takes two shots three to six months apart to actually be decently effective. But most would agree better than getting shingles in the final analysis.
Do you know the % of these shingle shots working? I’ve had 2 friends and my brother all get the shingles during covid. All 3 had the double shots. I’m hoping it was just coincidental and the % is high.
Shingrix in ZOE-50 and ZOE-70 produced 97.2% efficacy against zoster in adults 50 and older and 89.8% in those 70 and older, with about 91% efficacy against PHN (Post herpetic neuralgia...the really crummy part); the ZOE long-term follow-up cohort still showed roughly 79% to 82% efficacy at ten to eleven years post-vaccination.
thank you for this. Honest question, what does the 97% efficacy rate mean? percentage of people who dont get shingles compared to same age cohort who dont get the vaccine? i understand ARR, RRR and NNT but in this case im confused on how efficacy is defined. thank you again. ( Guillain Barre would be terrible.)
My observational, non-medical take is that “spiking” the immune system per COVID shots led to a rise in Shingles. A vaxxed and boosted 50 year old friend came down with Shingles. Her primary care doctor told her to quit the boosters. He was seeing a bunch of Shingles cases.