Thank you for another interesting, thought provoking article. As a practicing orthopedicsurgeon for decades, I have been telling patients: “insurance companies are in business to make money. If they are certain they will get to keep more of the insurance money than they have to pay out that’s good business. If anything costs them more money than they’re taking in, they will not pay. They do their own actuary research and come up with a decision. The ideal client to the insurance company is one who pays his premium and then dies immediately. I really believe it’s all that simple. With the apparently rather nebulous benefits of these newer very expensive flu interventions it’s no surprise what their position is.
Perhaps I don't read critically enough but if, near the beginning of an article about flu, I read "vaccination remains beneficial: vaccinated patients consistently experience less severe illness" I expect that to be a general statement about vaccinees.
But when I click the link to examine that claim I discover that it refers to a paper describing _Influenza vaccination and cardiovascular events in patients with ischaemic heart disease and heart failure_. A much more circumscribed claim.
The author isn't wrong I suppose. Technically. It's not the way I would have written it.
The "vaccination remains beneficial" link is similarly technically correct.
Perhaps I'm being overly pedantic, but I was hoping the author was providing me with links to stronger evidence for universal flu vaccination than I belive there is.
I only read the abstract. But the study endpoints were time to symptom relief and “viral load”. No mention of reduced hospitalizations.
Pretty tough to make a policy pitch without any nod to cost effectiveness. And I imagine it’s pretty tough to come up with cost effectiveness when the study did not assess any endpoints where cost metrics could properly be applied. It’s nice to talk about the healthcare costs of influenza hospitalization but (based on abstract at least) there doesn’t seem to be any evidence this drug affects that metric in any meaningful way.
This article is an embarrassment. If Baloxavir is as good as Tamiflu than it is, as the British would say, NBG. Aren’t you guys aware of the work of Karl Henagan and Tom Jefferson debunking Tamiflu? Yes it’s settled science. It doesn’t do Jack and it causes a lot of side effects.
I think you guys should withdraw this or at least ask Dr. Jefferson for his erudite comments, I think you and your readers will be enlightened. (he also produce the study debunking masks.)
Tom Jefferson and Carl Heneghan have published extensive research on their Trust the Evidence Substack regarding influenza antivirals, their lack of efficacy, and the serious potential harms associated with the use of Tamiflu.
Due respect to Dr. Curtis and the SM crew, all touting baloxavir, I disagree. Deep dive of the data here (https://tinyurl.com/23efmekb), published today. Baloxavir is exactly as good as the failed Tamiflu. A careful read shows almost entirely placebo effect. Moreover, it does not prevent flu either—it reduces test positivity, not illness (https://tinyurl.com/54ywzrev). I'm a big fan of SM, but think maybe the reading on baloxavir was a touch superficial—let the debates begin. Fun!
If it looked like I was touting baloxavir then I need to sharpen up my communication skills. My comment was meant to show that the article was scientifically and clinically worthless. I thought the term "virological gibberish" might convey the disrespect I have for the scientific validity of the serologic and immunological surrogates that saturate the medical literature on the viral/antiviral question.
Oh lord, I owe you an apology. Please forgive, don't know how I messed up the names, but I actually meant to be referring to the written piece from today—which was authored by a Dr. Harry Oken. So sorry, I see you're spot on!
I saw your comment on the podcast yesterday, too. You didn't think our discussion there was fair? I don't use either of the flu meds much, but the weight of the data does seem to now show a little benefit with regard to symptoms, a slight benefit in transmission with balox, and (probably) some benefit in hospitalized patients. You don't buy any of that?
You guys are always fair when you’ve carefully examined the data. Could be wrong, apologies if so, but my guess is none of you deep dived either of the baloxavir trials. One relates to transmission and shows no reduction in clinical illnesses, but a handy and deceptive very small reduction in laboratory positive illnesses. The other is a silly and inappropriate hybrid of a dose-finding and a Phase III trial for efficacy. Ultimately, it shows biloxivir and Tamiflu are the same. Since Tamiflu's effects are provably placebo almost entirely, that makes biloxivir a failed drug. Check out my posts and podcasts for more granular detail. And thank you for responding, takes courage—totally understand the baggage.
I’ll add something that burns me a bit: if we turned the NI drugs into a universal maxim, it would mean a crushing and deeply dangerous flooding of (already, overburdened) ERs, clinics and others by people in the first hours of their minor viral illness. All of them seeking a drug that works about as well as an over-the-counter nasal spray, by harnessing a placebo effect, for nearly $200 a pop, but won’t be relevant to more than 90% of them.
Final point, for Dr. Cifu: Respectfully, I don’t buy any suggestion baloxavir benefits hospitalized or critical patients (who are all way past the first 48h of their illness when treated). Little to no chance, I’d venture. Bad observational data, wet with healthy user bias, should in theory offer at least coin-flip accuracy, but it turns out to be wrong overwhelmingly, probably because of wishful thinking and cognitive bias. I’m open to any RCT that proves me wrong, but for now there’s no biologic plausibility for baloxavir helping inpatients. (Excited about Tamiflu inpatient RCTs, apparently soon to wrap. Pinky bets anyone?).
Except it doesn't "quell the flu". If one accepts the virological gibberish, it reduces the time to relief of symptoms by one day or so. The "study"(funded by the manufacturers) is so full of surrogate measures of supposed viral and immunological numbers that it is almost unreadable. The primary endpoint of time to relief of symptoms is soft to say the least. My favorite example for a measurement of viral activity was "Log10TCID (Tissue Culture Infective Dose) per millimeter. That was reduced from 4.5 to 1.6. Whatever that means, it does sound impressive. The real giveaway was the admission that Tamiflu was less expensive and equally effective---or, actually equally ineffective. The proposal to turn the pharmacies or other "health care" agencies into dispensaries would be a fiscal disaster, but a bonanza for the pharmaceutical industry. It would, no doubt, follow the path of the "free" covid injections that were actually funded by the government through massive creation of fiat money by the Federal Reserve. This circuitous route by which inflation is created seems to be little understood by the general public.
There is good evidence that, like with the 2024-25, vaccine, this year’s mismatched vaccine may worsen your risk. The most widely circulating strain is H3N2.
“In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2.”
“This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in long term care institutions.”
“Reasons for the current gap between policy and evidence are unclear, but given the huge resources involved, a re-evaluation should be urgently undertaken.”
Trivalent vaccine did not provide any protection for hospitalization. “On the contrary, we found a threefold increased risk of hospitalization in subjects who did get the TIV vaccine.” https://pubmed.ncbi.nlm.nih.gov/22525386/
Last year’s study of working-aged adults showed that the vaccine was associated with a higher risk of influenza during the 2024-2025 respiratory viral season, “suggesting that the vaccine has not been effective in preventing influenza this season.”
A simple straightforward solution, if one overlooks silly problems like symptom onset-to-treatment delay, flawed RIDT testing (50-60% sensitivity), every urgent care becoming a dispensary logistics, and the fact that Baloxavir severe or life-threatening effects include:
Thank you for another interesting, thought provoking article. As a practicing orthopedicsurgeon for decades, I have been telling patients: “insurance companies are in business to make money. If they are certain they will get to keep more of the insurance money than they have to pay out that’s good business. If anything costs them more money than they’re taking in, they will not pay. They do their own actuary research and come up with a decision. The ideal client to the insurance company is one who pays his premium and then dies immediately. I really believe it’s all that simple. With the apparently rather nebulous benefits of these newer very expensive flu interventions it’s no surprise what their position is.
Perhaps I don't read critically enough but if, near the beginning of an article about flu, I read "vaccination remains beneficial: vaccinated patients consistently experience less severe illness" I expect that to be a general statement about vaccinees.
But when I click the link to examine that claim I discover that it refers to a paper describing _Influenza vaccination and cardiovascular events in patients with ischaemic heart disease and heart failure_. A much more circumscribed claim.
The author isn't wrong I suppose. Technically. It's not the way I would have written it.
The "vaccination remains beneficial" link is similarly technically correct.
Perhaps I'm being overly pedantic, but I was hoping the author was providing me with links to stronger evidence for universal flu vaccination than I belive there is.
Thanks for publishing this Adam.
What is the ICER for this proposal?
I only read the abstract. But the study endpoints were time to symptom relief and “viral load”. No mention of reduced hospitalizations.
Pretty tough to make a policy pitch without any nod to cost effectiveness. And I imagine it’s pretty tough to come up with cost effectiveness when the study did not assess any endpoints where cost metrics could properly be applied. It’s nice to talk about the healthcare costs of influenza hospitalization but (based on abstract at least) there doesn’t seem to be any evidence this drug affects that metric in any meaningful way.
This article is an embarrassment. If Baloxavir is as good as Tamiflu than it is, as the British would say, NBG. Aren’t you guys aware of the work of Karl Henagan and Tom Jefferson debunking Tamiflu? Yes it’s settled science. It doesn’t do Jack and it causes a lot of side effects.
I think you guys should withdraw this or at least ask Dr. Jefferson for his erudite comments, I think you and your readers will be enlightened. (he also produce the study debunking masks.)
Tom Jefferson and Carl Heneghan have published extensive research on their Trust the Evidence Substack regarding influenza antivirals, their lack of efficacy, and the serious potential harms associated with the use of Tamiflu.
Due respect to Dr. Curtis and the SM crew, all touting baloxavir, I disagree. Deep dive of the data here (https://tinyurl.com/23efmekb), published today. Baloxavir is exactly as good as the failed Tamiflu. A careful read shows almost entirely placebo effect. Moreover, it does not prevent flu either—it reduces test positivity, not illness (https://tinyurl.com/54ywzrev). I'm a big fan of SM, but think maybe the reading on baloxavir was a touch superficial—let the debates begin. Fun!
If it looked like I was touting baloxavir then I need to sharpen up my communication skills. My comment was meant to show that the article was scientifically and clinically worthless. I thought the term "virological gibberish" might convey the disrespect I have for the scientific validity of the serologic and immunological surrogates that saturate the medical literature on the viral/antiviral question.
Oh lord, I owe you an apology. Please forgive, don't know how I messed up the names, but I actually meant to be referring to the written piece from today—which was authored by a Dr. Harry Oken. So sorry, I see you're spot on!
I saw your comment on the podcast yesterday, too. You didn't think our discussion there was fair? I don't use either of the flu meds much, but the weight of the data does seem to now show a little benefit with regard to symptoms, a slight benefit in transmission with balox, and (probably) some benefit in hospitalized patients. You don't buy any of that?
Adam
You guys are always fair when you’ve carefully examined the data. Could be wrong, apologies if so, but my guess is none of you deep dived either of the baloxavir trials. One relates to transmission and shows no reduction in clinical illnesses, but a handy and deceptive very small reduction in laboratory positive illnesses. The other is a silly and inappropriate hybrid of a dose-finding and a Phase III trial for efficacy. Ultimately, it shows biloxivir and Tamiflu are the same. Since Tamiflu's effects are provably placebo almost entirely, that makes biloxivir a failed drug. Check out my posts and podcasts for more granular detail. And thank you for responding, takes courage—totally understand the baggage.
I’ll add something that burns me a bit: if we turned the NI drugs into a universal maxim, it would mean a crushing and deeply dangerous flooding of (already, overburdened) ERs, clinics and others by people in the first hours of their minor viral illness. All of them seeking a drug that works about as well as an over-the-counter nasal spray, by harnessing a placebo effect, for nearly $200 a pop, but won’t be relevant to more than 90% of them.
Final point, for Dr. Cifu: Respectfully, I don’t buy any suggestion baloxavir benefits hospitalized or critical patients (who are all way past the first 48h of their illness when treated). Little to no chance, I’d venture. Bad observational data, wet with healthy user bias, should in theory offer at least coin-flip accuracy, but it turns out to be wrong overwhelmingly, probably because of wishful thinking and cognitive bias. I’m open to any RCT that proves me wrong, but for now there’s no biologic plausibility for baloxavir helping inpatients. (Excited about Tamiflu inpatient RCTs, apparently soon to wrap. Pinky bets anyone?).
Except it doesn't "quell the flu". If one accepts the virological gibberish, it reduces the time to relief of symptoms by one day or so. The "study"(funded by the manufacturers) is so full of surrogate measures of supposed viral and immunological numbers that it is almost unreadable. The primary endpoint of time to relief of symptoms is soft to say the least. My favorite example for a measurement of viral activity was "Log10TCID (Tissue Culture Infective Dose) per millimeter. That was reduced from 4.5 to 1.6. Whatever that means, it does sound impressive. The real giveaway was the admission that Tamiflu was less expensive and equally effective---or, actually equally ineffective. The proposal to turn the pharmacies or other "health care" agencies into dispensaries would be a fiscal disaster, but a bonanza for the pharmaceutical industry. It would, no doubt, follow the path of the "free" covid injections that were actually funded by the government through massive creation of fiat money by the Federal Reserve. This circuitous route by which inflation is created seems to be little understood by the general public.
There is good evidence that, like with the 2024-25, vaccine, this year’s mismatched vaccine may worsen your risk. The most widely circulating strain is H3N2.
“In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2.”
https://pubmed.ncbi.nlm.nih.gov/28562111/
“The unexpected findings of lower effectiveness with repeated vaccination and no protection given household exposure require further study.” https://pmc.ncbi.nlm.nih.gov/articles/PMC3693492/
“This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in long term care institutions.”
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005187.pub5/full
“Reasons for the current gap between policy and evidence are unclear, but given the huge resources involved, a re-evaluation should be urgently undertaken.”
https://pmc.ncbi.nlm.nih.gov/articles/PMC1626345/
Trivalent vaccine did not provide any protection for hospitalization. “On the contrary, we found a threefold increased risk of hospitalization in subjects who did get the TIV vaccine.” https://pubmed.ncbi.nlm.nih.gov/22525386/
Last year’s study of working-aged adults showed that the vaccine was associated with a higher risk of influenza during the 2024-2025 respiratory viral season, “suggesting that the vaccine has not been effective in preventing influenza this season.”
https://www.medrxiv.org/content/10.1101/2025.01.30.25321421v3
There is no evidence of the oft repeated claim that mismatched vaccines “lessen severity.”
Thank you for taking the time and contributing this piece. Always important to hear/examine multiple sides to an issue.
Agree with “2 (or more) sides to most stories “ approach. SM remains a valuable resource.
A simple straightforward solution, if one overlooks silly problems like symptom onset-to-treatment delay, flawed RIDT testing (50-60% sensitivity), every urgent care becoming a dispensary logistics, and the fact that Baloxavir severe or life-threatening effects include:
-Anaphylaxis or severe allergic reactions
-Hepatic injury or failure
-Neuropsychiatric symptoms (hallucinations, delirium)
-Blood dyscrasias (neutropenia, thrombocytopenia)
-Severe skin reactions (SJS/TEN)
-Viral rebound due to resistance mutations