Keep in mind that they made an active effort not to use the actual receipt of Zostavax in their analyses. At no point in their analysis do they separate groups based on actual vaccine receipt. Both in the case of dementia and in the case of zoster, they note a reduction in the overall incidence based on the magnitude of the regression discontinuity, and then divide by the fractional overall uptake of the vaccine to multiply the "scaled" effect to account for the incomplete uptake.
As I wrote before, this leads to the counter-intuitive result that the lower the vaccine uptake, the higher the scaled effect becomes. If something else caused the effect - chance or an unsuspected outside influence - this technique would not only fail to find that, but would be utterly insensitive to it.
This isn't classical epidemiology at all, so ARR and RRR aren't meaningful in the usual sense. This is handwaving algebra dressed in fancy doctor clothes and pretending to belong at the party.
I haven't had the shingles vaccine, but I'm recovering. I have had pretty severe neuritis and chronic pain after the infection. At the age of 77, I have no sign of dementia (knock on wood). I may get the shingles vaccine, but I must wait a year for it to be effective.
Well I will have to read things more carefully so I can win a t-shirt! Personally, preventing shingles was enough motivation for me to get Shingrex. I got it "early" because I know so many people who got shingles in their 30s and 40s. If it reduces my risk of dementia a little then that is just a bonus.
Interesting, although isn’t it the case that often prevention of the infection itself is of a lower efficacy than second order effects ? Eg VE against infection vs VE against hospitalizations/death for a number of different vaccines? Given that the shingles vaccine is very likely producing a second order effect (or in better terms a “Non Specific Effect” as described by Christine Stabell Benn and her work) it wouldn’t seem like a strong dispute that the effect could be higher than infection prevention.
As for the disparate findings between sexes, this is also a very well documented finding for Non specific effects of vaccines, again demonstrated by Stabell et al and her work. Females are found to have a much larger NSEs across multiple vaccines, so it again doesn’t seem like a strong rebuttal of the findings
I think you were correct the first time to focus on ARR. Isn't the bottom line number needed to treat? Which equals 1/ARR. With the numbers published, you would need to treat 43 patients to prevent 1 case of shingles but only 29 to prevent 1 case of dementia. And if you know there are 1 million new cases of shingles each year and 10 million new cases of dementia it seems to facility bringing clarity to issues of both bio-plausibility and efficacy. Focusing on RRR seems to miss something at best or be misleading at worst.
Also a quick note that not *everyone* over 50 should receive the Shingles vaccine. Some of us have had Shingles prior to age 50 and thus would not need the vaccine.
With regard to the recommendation to take the shingles vaccine, it appears that in the NEJM article, the incidence of post-herpetic neuralgia in those over 70 was 0.01% in the vaccine group vs 0.09% in the placebo group over 3.8 yrs. That's an NNT of 1,250. Pretty slim benefit.
The numbers for shingles itself are somewhat better, but there you're preventing a nuisance, not a lot-term morbidity.
Not sure why Dr. Cifu is so enthusiastic about pt's over 50 all taking the shingles vaccine, "full stop."
Thank you. My training is in law, so things like sussing out the important distinctions in risk reduction in medical research depend on the clear and honest explanations of those in that field. I really appreciate your highlighting the importance of the 2 measures in a context that I might have otherwise missed it, though I could have recited a "definitional statement." What you do matters.
Heehee, I am not intelligent-enough to win a t-shirt but I promise you that I learn a LOT from these posts. I am a "sensible patient" with issues that I address often of course with my doctors. Some are holistic, some need to move on... I want to work with my doctors to make my quality of life best it can be. They always laugh when I tell them that is the most I want, I know that they are not able to do the impossible. I am blessed, for the most part, but I know that my role in my own health matters. Love this story as the subject of medications being used for various things that it was not designed to do and how amazing these discoveries are. If I loved someone whose dementia slowed because of that... wow! I take one med for gastroparesis that works but it is not legal for that... I don't know why it may have saved my life.
https://www.statnews.com/2025/01/07/alzheimers-disease-research-link-between-herpes-virus-head-trauma-dementia/ This describes another herpes virus (hominis type 1) that can cause dementia.
Keep in mind that they made an active effort not to use the actual receipt of Zostavax in their analyses. At no point in their analysis do they separate groups based on actual vaccine receipt. Both in the case of dementia and in the case of zoster, they note a reduction in the overall incidence based on the magnitude of the regression discontinuity, and then divide by the fractional overall uptake of the vaccine to multiply the "scaled" effect to account for the incomplete uptake.
As I wrote before, this leads to the counter-intuitive result that the lower the vaccine uptake, the higher the scaled effect becomes. If something else caused the effect - chance or an unsuspected outside influence - this technique would not only fail to find that, but would be utterly insensitive to it.
This isn't classical epidemiology at all, so ARR and RRR aren't meaningful in the usual sense. This is handwaving algebra dressed in fancy doctor clothes and pretending to belong at the party.
I haven't had the shingles vaccine, but I'm recovering. I have had pretty severe neuritis and chronic pain after the infection. At the age of 77, I have no sign of dementia (knock on wood). I may get the shingles vaccine, but I must wait a year for it to be effective.
Well I will have to read things more carefully so I can win a t-shirt! Personally, preventing shingles was enough motivation for me to get Shingrex. I got it "early" because I know so many people who got shingles in their 30s and 40s. If it reduces my risk of dementia a little then that is just a bonus.
Interesting, although isn’t it the case that often prevention of the infection itself is of a lower efficacy than second order effects ? Eg VE against infection vs VE against hospitalizations/death for a number of different vaccines? Given that the shingles vaccine is very likely producing a second order effect (or in better terms a “Non Specific Effect” as described by Christine Stabell Benn and her work) it wouldn’t seem like a strong dispute that the effect could be higher than infection prevention.
As for the disparate findings between sexes, this is also a very well documented finding for Non specific effects of vaccines, again demonstrated by Stabell et al and her work. Females are found to have a much larger NSEs across multiple vaccines, so it again doesn’t seem like a strong rebuttal of the findings
I think you were correct the first time to focus on ARR. Isn't the bottom line number needed to treat? Which equals 1/ARR. With the numbers published, you would need to treat 43 patients to prevent 1 case of shingles but only 29 to prevent 1 case of dementia. And if you know there are 1 million new cases of shingles each year and 10 million new cases of dementia it seems to facility bringing clarity to issues of both bio-plausibility and efficacy. Focusing on RRR seems to miss something at best or be misleading at worst.
Dr Cifu, your attitude is that of a true scientist. I, who have been a researcher throughout my career, appreciate this. Congratulations
Well of course, however I agree with you that the finding is telling.
Also a quick note that not *everyone* over 50 should receive the Shingles vaccine. Some of us have had Shingles prior to age 50 and thus would not need the vaccine.
Actually, still recommended.
and with no good RCT data to support that rec as far as I am aware
With regard to the recommendation to take the shingles vaccine, it appears that in the NEJM article, the incidence of post-herpetic neuralgia in those over 70 was 0.01% in the vaccine group vs 0.09% in the placebo group over 3.8 yrs. That's an NNT of 1,250. Pretty slim benefit.
The numbers for shingles itself are somewhat better, but there you're preventing a nuisance, not a lot-term morbidity.
Not sure why Dr. Cifu is so enthusiastic about pt's over 50 all taking the shingles vaccine, "full stop."
Thank you. My training is in law, so things like sussing out the important distinctions in risk reduction in medical research depend on the clear and honest explanations of those in that field. I really appreciate your highlighting the importance of the 2 measures in a context that I might have otherwise missed it, though I could have recited a "definitional statement." What you do matters.
Heehee, I am not intelligent-enough to win a t-shirt but I promise you that I learn a LOT from these posts. I am a "sensible patient" with issues that I address often of course with my doctors. Some are holistic, some need to move on... I want to work with my doctors to make my quality of life best it can be. They always laugh when I tell them that is the most I want, I know that they are not able to do the impossible. I am blessed, for the most part, but I know that my role in my own health matters. Love this story as the subject of medications being used for various things that it was not designed to do and how amazing these discoveries are. If I loved someone whose dementia slowed because of that... wow! I take one med for gastroparesis that works but it is not legal for that... I don't know why it may have saved my life.