Here's an explanation I read for Hep B & flu recommendations:
"Universal vaccination recommendations work better than targeted vaccinations because of convenience and education. The U.S. used to have targeted Hep B vaccine recommendations, but uptake was poor. After a universal recommendation, there was a big decline in disease, and many lives (and livers) were saved. The same thing happened with the flu vaccine; universal recommendations increased uptake among high-risk groups."
Herd immunity is good reason for universal recommendations even when risk is low, but this is entirely different logic. I'm guessing that this argument is also behind the nirsevimab and yearly Covid recommendations.
I find it problematic on principle, but also think, despite the success she notes, that this is ultimately increasing mistrust of vaccines in general.
Not that it's much better, but Beyfortus is $500/dose, not $1300. You can tell there is obvious price inflation since it costs the same for the 0.5mg as the 1mg dose. If they were making any sort of only reasonable profit, twice as much medicine should theoretically cost twice as much money. If $500 is enough money for 1mg, why isn't $250 enough for 0.5mg?
Thank you for writing this! I am a pediatrician and have been reading these studies and ranting about the issues you discuss here since the product first came out in fall 2023. I’ve felt pretty alone in my concerns about this unfortunately.
The conversation in the comments is very good, and I’d like to add a few thoughts.
Even among people interested in the topic enough to comment on your post, there’s confusion about the difference between vaccine in the usual sense and monoclonal antibody. The antibody product does not engage with the immune system and is completely gone in 5 months, for better or worse. There have been serious safety concerns about actual RSV vaccines in children, including a recent trial of mRNA based RSV vaccine that was halted this month. The monoclonal antibody would likely have fewer safety issues (though I agree we should be paying more attention to them than we are). I believe it was called a vaccine during the regulatory process to allow coverage for children on Medicaid through the Vaccines for Children program. I think there may be liability advantages for the manufacturer when it’s called a vaccine too, but am not sure about that.
The wholesale cost per dose in the US is actually about $500, but your points about the excessive cost are still valid. Synagis (the previous monoclonal Ab product used only for high risk infants) is quite a bit more expensive. It was close to $2000/dose and had to be given monthly during the viral season, often 5 doses total. A long acting product given only once to high risk infants is definitely more cost effective for those children as well as less burdensome, so this product does have a role for certain babies. The massive cost of giving this product universally to healthy infants is not justified in my opinion however.
The presentation of data in these studies is skewed to favor the drug, which is expected with the significant conflicts of interest. The term “very severe RSV” is an example. This is defined as a child in the hospital requiring supplemental O2, which is almost the only reason a child would be admitted to hospital with RSV. That’s an outcome worth trying to avoid, but presenting essentially any admission as “very severe” is a slanted use of terminology meant to influence a less informed reader of the studies.
Informed consent for this product in the office is time consuming because of the nuanced issues. It would be easier and faster to just say “do you want to keep your baby out of the hospital with RSV? I’ve got a shot for that”. I go over the pros and cons in a way that makes sense for the particular family, tend to end up apologizing for the ambivalent discussion and telling them that the baby almost certainly will be fine no matter what they decide. Parents typically say “that’s OK, doctor, we’re glad you’re telling the truth”, but it can be hard for parents to decide what to do. Of course, it’s their job to make important decisions about their baby’s health, and my job to help them with that. But sound recommendations from the regulatory agencies that we support as taxpayers is a reasonable expectation for complicated topics like this. They’ve let us down on that front and a lot of families are coming to realize that.
I think we should also be talking about the unique ethical issues in universal recommendation of a temporary and expensive pharmaceutical product to prevent an inevitable and routine childhood illness. I know of no other medication with those characteristics. It’s a little different from usual vaccine ethics I think.
Thanks again for tackling this topic. I agree with your choice to opt out of this product for your healthy baby. I’m also so grateful to Sensible Medicine for providing a forum for these discussions.
I could add that, in the process of making individual evidence-based decisions, when we have clinically significant efficacy (OR for the primary outcome of benefit) and safety (OR for the primary adverse effect) demonstrated by sufficiently valid evidence, the decision should not be driven primarily by efficacy. Instead, it should be based on the balance of benefit and risk for the specific patient. This is determined by estimating the baseline risk of outcomes in our patient and adjusting the patient’s NNT accordingly.
For example, suppose my healthy patient, given their background, has an estimated risk of hospitalization due to RSV of 0.1%. In the European Drysdale et al study, in healthy infants ≤12 months of age. RSV hospitalizations were significantly reduced by 83.3%.
What would be the NNT for my patient if I administer Nirsevimab?
Answer: Adjust the efficacy from the study (83%) based on my patient’s baseline risk (0.1% or 1 in 1,000) of experiencing an RSV hospitalization. This gives the Absolute Risk Reduction (ARR) for my patient= 0,083
Then, calculate the NNT by taking the inverse: 100/0,083=1.204,819 1204 that is NNT adjusted to my patient’s risk).
Is it justifiable for the mother or father that it would be necessary to administer the medication to 1204 patients like mine to prevent one hospitalization due to or associated with RSV?
This product is a modified monoclonal antibody. Modified to remain in the body appx.5-9 month I believe. Dr. Helene Banoun has a very detailed paper regarding concerns about this product. The other factor that may cause more serious illness in infants is that these viruses do not take turns to infect. You may find 2,3 or4 four different respiratory viruses affecting the child at the same time(rhinno virus, influenza, parainfluenza, entero virus) which may exacerbate the illness. And of course these products are , without proper investigation, ending up on the children's vaccine list, and thus, no liability issues for those who produce them. I believe pediatricians need intense courses in immunology and immunopathology before they should even consider recommending these products.
Here kids are offered it in the 1st RSV season of their lifes. I have seen many kids with it hospitalized in the 1st season. But more in the 2nd, where they do not get it. Is there any study about the 2nd season?
There was a follow up study that specifically looked to confirm that taking this product is the first season did not worsen outcomes in the second season (and it didn't).
Clear summary of the relevant trials. Pertinent list of objections and identifying of weaknesses in the methodology (both inclusions and choice of endpoints).
And even with those limitations, only a tiny absolute risk reduction in soft endpoints.
It is insanity to suggest that “every infant” needs this. Premature, low birthweight, unable to breastfeed? Maybe. But again without a trial in those cohorts.
That’s before we begin to consider the cost effectiveness of such a policy. I suspect this would come out to a very inefficient use of health care dollars.
Yet another example of the gatekeepers and policy makers failing to exercise their fiduciary duties.
Thank you for this informative piece. Can you explain, for the lay Sensible Medicine reader like me, why "medically attended RSV" is an inferior outcome to study than "all-cause LRTI hospitalizations?" Are you hypothesizing that in some scenario, getting the RSV shot increases the chance of succumbing to a different LRTI? (I'm sure this will be obvious as soon as you explain it!)
Medically attended RSV would include any visit to the pediatrician or to urgent care. RSV LRTI hospitalizations would be any hospitalization for a lower respiratory tract illness that includes a confirmed RSV diagnosis. Then any cause LRTI hospitalization would be from any respiratory illness. Medically attended RSV seems weak because parents may have different criteria for taking their child to the doctor for a cold or flu like illness and not all of these will reach the level of concern for a parent to add this extra shot for their child. All cause may be better than RSV alone because if there was a chance that this antibody worsened or didn't affect all cause LRTI hospitalizations then does it really matter? A parent won't care that their child wasn't hospitalized specifically for RSV... just that they weren't hospitalized at all. That's my understanding but happy to get a different perspective.
Thank you for including breastfeeding! It absolutely matters if baby is breastfeeding (on demand) & at home. I have watched it with my own eyes-baby is sniffly & nurses, clears up within 30 minutes. An hour or so later snot returns, baby nurses, it clears up. The amazing effects of breastfeeding on health still make me exclaim. This is also why I don’t rush to wean my kiddos-to me it’s worth it for the extra immune benefits.
Do remember - Synagis (an older, less expensive monoclonal antibody for RSV prophylaxis) has shown significant benefit for newborns and babies up to at least a year old with significant RSV morbidity & mortality risk factors (e.g. premature birth, congenital cardiovascular diseases).
This essay would support the decisions I was making to deny health plan coverage for this prophylactic when recommended for healthy term babies over 3 months of age. I retired from my job as Medical Director of a TPA shortly after this product went on the market. At that time I did not believe the likely benefits justified the very high costs. It seems I was correct…
Here is a short and simple synopsis our group has published of all the latest evidence for this treatment https://cfpclearn.ca/tfp361/ . We have also done a podcast on this topic at https://therapeuticseducation.org - the podcast was free (for 3 months) when it came out but now behind a subscription paywall.
Thank you for this! I am 55, and no longer have young children. NONE of my 4 children were hospitalized for RSV or other illness as babies. I did not use daycare and breastfed. It seems like parents are just taking pediatrician blanket recommendations without exploring or asking any questions at all. This drug is also being perceived as a vaccination; I'm not sure if that is how it is presented to parents.
Christine, I am a decade older, did not use daycare and breastfed as well; none of our 4 were ever hospitalized for anything either. When did this all become a “thing”? I had one late winter baby, the rest were early spring, summer & fall. I remember the Hib vaccine, but RSV is relatively new? My RN daughter has 5 young children—ever since covid we have been discussing all the vaccines—she finally pushed back against them with her 5th [born 5/23] and declined the HepB in hospital, and is on an amended schedule for the others. She had been boondoggled by big pharma/pediatricians before then.
I am 54 and my youngest is 11yrs , at home births with no thingymajigs, breastfeeding on demand, but crucially no industrial medicine care pre birth which seems to determine the sophistry used.
When you go through illness with someone ,the trajectory of the illness is held and monitored and visible.
By using pharmaceuticals you are not saving the child distress but you are *saving* the mother's commercial viability & getting a momentum for drug usage that outweighs it's cons list.
This is great for new Mums especially, and unusually she questioned why breastfeeding was not a variable 🥳
Here's an explanation I read for Hep B & flu recommendations:
"Universal vaccination recommendations work better than targeted vaccinations because of convenience and education. The U.S. used to have targeted Hep B vaccine recommendations, but uptake was poor. After a universal recommendation, there was a big decline in disease, and many lives (and livers) were saved. The same thing happened with the flu vaccine; universal recommendations increased uptake among high-risk groups."
Herd immunity is good reason for universal recommendations even when risk is low, but this is entirely different logic. I'm guessing that this argument is also behind the nirsevimab and yearly Covid recommendations.
I find it problematic on principle, but also think, despite the success she notes, that this is ultimately increasing mistrust of vaccines in general.
Not that it's much better, but Beyfortus is $500/dose, not $1300. You can tell there is obvious price inflation since it costs the same for the 0.5mg as the 1mg dose. If they were making any sort of only reasonable profit, twice as much medicine should theoretically cost twice as much money. If $500 is enough money for 1mg, why isn't $250 enough for 0.5mg?
More likely the purpose of the drug is to line the coffers of the manufacturers of said drug.
Thank you for writing this! I am a pediatrician and have been reading these studies and ranting about the issues you discuss here since the product first came out in fall 2023. I’ve felt pretty alone in my concerns about this unfortunately.
The conversation in the comments is very good, and I’d like to add a few thoughts.
Even among people interested in the topic enough to comment on your post, there’s confusion about the difference between vaccine in the usual sense and monoclonal antibody. The antibody product does not engage with the immune system and is completely gone in 5 months, for better or worse. There have been serious safety concerns about actual RSV vaccines in children, including a recent trial of mRNA based RSV vaccine that was halted this month. The monoclonal antibody would likely have fewer safety issues (though I agree we should be paying more attention to them than we are). I believe it was called a vaccine during the regulatory process to allow coverage for children on Medicaid through the Vaccines for Children program. I think there may be liability advantages for the manufacturer when it’s called a vaccine too, but am not sure about that.
The wholesale cost per dose in the US is actually about $500, but your points about the excessive cost are still valid. Synagis (the previous monoclonal Ab product used only for high risk infants) is quite a bit more expensive. It was close to $2000/dose and had to be given monthly during the viral season, often 5 doses total. A long acting product given only once to high risk infants is definitely more cost effective for those children as well as less burdensome, so this product does have a role for certain babies. The massive cost of giving this product universally to healthy infants is not justified in my opinion however.
The presentation of data in these studies is skewed to favor the drug, which is expected with the significant conflicts of interest. The term “very severe RSV” is an example. This is defined as a child in the hospital requiring supplemental O2, which is almost the only reason a child would be admitted to hospital with RSV. That’s an outcome worth trying to avoid, but presenting essentially any admission as “very severe” is a slanted use of terminology meant to influence a less informed reader of the studies.
Informed consent for this product in the office is time consuming because of the nuanced issues. It would be easier and faster to just say “do you want to keep your baby out of the hospital with RSV? I’ve got a shot for that”. I go over the pros and cons in a way that makes sense for the particular family, tend to end up apologizing for the ambivalent discussion and telling them that the baby almost certainly will be fine no matter what they decide. Parents typically say “that’s OK, doctor, we’re glad you’re telling the truth”, but it can be hard for parents to decide what to do. Of course, it’s their job to make important decisions about their baby’s health, and my job to help them with that. But sound recommendations from the regulatory agencies that we support as taxpayers is a reasonable expectation for complicated topics like this. They’ve let us down on that front and a lot of families are coming to realize that.
I think we should also be talking about the unique ethical issues in universal recommendation of a temporary and expensive pharmaceutical product to prevent an inevitable and routine childhood illness. I know of no other medication with those characteristics. It’s a little different from usual vaccine ethics I think.
Thanks again for tackling this topic. I agree with your choice to opt out of this product for your healthy baby. I’m also so grateful to Sensible Medicine for providing a forum for these discussions.
Excellent analysis Dharini, congratulations.
I could add that, in the process of making individual evidence-based decisions, when we have clinically significant efficacy (OR for the primary outcome of benefit) and safety (OR for the primary adverse effect) demonstrated by sufficiently valid evidence, the decision should not be driven primarily by efficacy. Instead, it should be based on the balance of benefit and risk for the specific patient. This is determined by estimating the baseline risk of outcomes in our patient and adjusting the patient’s NNT accordingly.
For example, suppose my healthy patient, given their background, has an estimated risk of hospitalization due to RSV of 0.1%. In the European Drysdale et al study, in healthy infants ≤12 months of age. RSV hospitalizations were significantly reduced by 83.3%.
What would be the NNT for my patient if I administer Nirsevimab?
Answer: Adjust the efficacy from the study (83%) based on my patient’s baseline risk (0.1% or 1 in 1,000) of experiencing an RSV hospitalization. This gives the Absolute Risk Reduction (ARR) for my patient= 0,083
Then, calculate the NNT by taking the inverse: 100/0,083=1.204,819 1204 that is NNT adjusted to my patient’s risk).
Is it justifiable for the mother or father that it would be necessary to administer the medication to 1204 patients like mine to prevent one hospitalization due to or associated with RSV?
This product is a modified monoclonal antibody. Modified to remain in the body appx.5-9 month I believe. Dr. Helene Banoun has a very detailed paper regarding concerns about this product. The other factor that may cause more serious illness in infants is that these viruses do not take turns to infect. You may find 2,3 or4 four different respiratory viruses affecting the child at the same time(rhinno virus, influenza, parainfluenza, entero virus) which may exacerbate the illness. And of course these products are , without proper investigation, ending up on the children's vaccine list, and thus, no liability issues for those who produce them. I believe pediatricians need intense courses in immunology and immunopathology before they should even consider recommending these products.
Here kids are offered it in the 1st RSV season of their lifes. I have seen many kids with it hospitalized in the 1st season. But more in the 2nd, where they do not get it. Is there any study about the 2nd season?
There was a follow up study that specifically looked to confirm that taking this product is the first season did not worsen outcomes in the second season (and it didn't).
https://academic.oup.com/jpids/article/13/2/144/7534315
Thanks!
This deserves more than 1 like.
Clear summary of the relevant trials. Pertinent list of objections and identifying of weaknesses in the methodology (both inclusions and choice of endpoints).
And even with those limitations, only a tiny absolute risk reduction in soft endpoints.
It is insanity to suggest that “every infant” needs this. Premature, low birthweight, unable to breastfeed? Maybe. But again without a trial in those cohorts.
That’s before we begin to consider the cost effectiveness of such a policy. I suspect this would come out to a very inefficient use of health care dollars.
Yet another example of the gatekeepers and policy makers failing to exercise their fiduciary duties.
Thank you for this informative piece. Can you explain, for the lay Sensible Medicine reader like me, why "medically attended RSV" is an inferior outcome to study than "all-cause LRTI hospitalizations?" Are you hypothesizing that in some scenario, getting the RSV shot increases the chance of succumbing to a different LRTI? (I'm sure this will be obvious as soon as you explain it!)
Medically attended RSV would include any visit to the pediatrician or to urgent care. RSV LRTI hospitalizations would be any hospitalization for a lower respiratory tract illness that includes a confirmed RSV diagnosis. Then any cause LRTI hospitalization would be from any respiratory illness. Medically attended RSV seems weak because parents may have different criteria for taking their child to the doctor for a cold or flu like illness and not all of these will reach the level of concern for a parent to add this extra shot for their child. All cause may be better than RSV alone because if there was a chance that this antibody worsened or didn't affect all cause LRTI hospitalizations then does it really matter? A parent won't care that their child wasn't hospitalized specifically for RSV... just that they weren't hospitalized at all. That's my understanding but happy to get a different perspective.
See also the FAERS Deaths
https://geoffpain.substack.com/p/deaths-from-rsv-jabs-synagis-palivizumab
Thank you for including breastfeeding! It absolutely matters if baby is breastfeeding (on demand) & at home. I have watched it with my own eyes-baby is sniffly & nurses, clears up within 30 minutes. An hour or so later snot returns, baby nurses, it clears up. The amazing effects of breastfeeding on health still make me exclaim. This is also why I don’t rush to wean my kiddos-to me it’s worth it for the extra immune benefits.
Do remember - Synagis (an older, less expensive monoclonal antibody for RSV prophylaxis) has shown significant benefit for newborns and babies up to at least a year old with significant RSV morbidity & mortality risk factors (e.g. premature birth, congenital cardiovascular diseases).
This essay would support the decisions I was making to deny health plan coverage for this prophylactic when recommended for healthy term babies over 3 months of age. I retired from my job as Medical Director of a TPA shortly after this product went on the market. At that time I did not believe the likely benefits justified the very high costs. It seems I was correct…
Here is a short and simple synopsis our group has published of all the latest evidence for this treatment https://cfpclearn.ca/tfp361/ . We have also done a podcast on this topic at https://therapeuticseducation.org - the podcast was free (for 3 months) when it came out but now behind a subscription paywall.
Thank you for this! I am 55, and no longer have young children. NONE of my 4 children were hospitalized for RSV or other illness as babies. I did not use daycare and breastfed. It seems like parents are just taking pediatrician blanket recommendations without exploring or asking any questions at all. This drug is also being perceived as a vaccination; I'm not sure if that is how it is presented to parents.
Christine, I am a decade older, did not use daycare and breastfed as well; none of our 4 were ever hospitalized for anything either. When did this all become a “thing”? I had one late winter baby, the rest were early spring, summer & fall. I remember the Hib vaccine, but RSV is relatively new? My RN daughter has 5 young children—ever since covid we have been discussing all the vaccines—she finally pushed back against them with her 5th [born 5/23] and declined the HepB in hospital, and is on an amended schedule for the others. She had been boondoggled by big pharma/pediatricians before then.
Yay Elizabeth🏵
I am 54 and my youngest is 11yrs , at home births with no thingymajigs, breastfeeding on demand, but crucially no industrial medicine care pre birth which seems to determine the sophistry used.
When you go through illness with someone ,the trajectory of the illness is held and monitored and visible.
By using pharmaceuticals you are not saving the child distress but you are *saving* the mother's commercial viability & getting a momentum for drug usage that outweighs it's cons list.
We cannot place blame on the patient or parent for following what their doctors are recommending.