The specific story includes yet another failure of oseltamivir (Tamiflu) to provide benefit in the treatment of influenza. The larger story is why some therapies persist in the absence of any evidence of benefit. Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.
If there was something that we as physicians could actually do to treat influenza then oseltamivir would have disappeared a long time ago. Since there is nothing but we feel we have to do something, we prescribe oseltamivir.
On the other hand, the existence of oseltamivir, and thus the ability to do something, may reduce the rate of antibiotic prescriptions for influenza, so maybe it is useful after all.
Insightful article, Dr. Mandrola. It's disconcerting that despite compelling evidence of oseltamivir's lack of efficacy and associated adverse events, it continues to be employed in the treatment of influenza. I think you touched upon an important point about the drivers of such persistent use - optimism, ignorance of history, and to some extent, inertia. It's human nature to hope for a silver bullet solution and stick to long-held beliefs, even when faced with contrary evidence. This, however, doesn't excuse the need for us, as medical professionals, to critically appraise the therapies we employ and to update our practice in light of new evidence.
Another point worth considering is the role of the pharmaceutical industry in promoting and maintaining the status quo. After all, millions of doses of oseltamivir were stockpiled based on initial studies and recommendations, pointing to a potentially larger issue of industry influence on clinical guidelines and practices.
Finally, your discussion highlights the crucial importance of transparency and open data in clinical research. These can pave the way for better informed medical practices, potentially saving significant resources while ensuring patient safety. Thank you for initiating this discussion and I look forward to more insightful reads in the future
"Please feel free to disagree with me." Such a statement embodies the admirable mindset of an individual truly practicing the art of critical evidence appraisal. Continue your exceptional work, Dr. Mandrola. Your writings continue to inspire and enlighten us.
Why would you want to stop a flu or even prevent it? Unless you are at extreme risk for complications, the flu is nothing more than your body taking itself on a repair course. This is why things like Tamiflu and flu vaccines never work and never will.
Why can't big pharma science come up with a cure or prevention for a much simpler cold? This is the basic of presumed bodily indiscretions and yet big pharma has no drug to combat them or prevent them. So why would I trust a flu drug?
Did the meta analysis look at the timing of when the first dose was taken in the various trials? Since that is always mentioned as a critical part of this medication’s supposed effectiveness I’m surprised that wasn’t discussed. (I looked at the analysis and didn’t see mention of timing, but it’s possible I missed it.)
Second, getting relief 17 hours sooner from very unpleasant symptoms seems like a great treatment, still a worthwhile endpoint even though not as serious as reducing hospitalization. My question is what is the rate of adverse reactions (nausea etc,) and how does that compare to the incidence of 17-hour sooner symptom relief?
I find the conflict of interest btw “opinion leaders and guideline writers” to be increasingly distasteful, and the tenor of some of that work product to indeed be nefarious and outright tainted.
I also agree about the motivation of undue optimism and ignorance of history. These people are hidebound to repeat their mistakes, over and over again.
Rational, superstitious, superstitious that pretends to be rational?
I think the last of these three is the very worst.
I'm a broken record, but using 99.7% CI instead 95% CI would cure us of the BS fluff. It will also force medicine to really understand the mechanisms of treatment in the predictive way that chemists predict reactions and physicists predict motion and energy/particle transformations.
Gnostic scientism that is the problem.
I am also as comfortable being a "peasant". If you don't know in a rigorously scientific way, what would should ask is what would your Mom, Nonna, Busia do? (Basically, our mothers born before about 1945.) The soup or hot lemon water or burned toast or take a nap might be placebos or just distractions to let time pass but they are generally benign.
There are many many ways to improve upon the maternal instincts that have served humanity, but we have to really be scientific not just sort of scientific.
I recently, at a meeting heard a pharmaceutical representative make two statements. The first was that a fifth Covid wave was happening and the second was that Paxlovid was available.
A busy general practitioner overworked and burnt out, having ten to 15 minute consults and encouraged by patient pressure, will write a prescription usually in a vaccinated person, without any evidence except that delivered in person and glossy advertising from the rep. Advertising is powerful and patients who apply pressure and have no access to publications are easy targets as are their community doctors.
Once again what “studies show...” contradict the real life experience I see in my influenza patients, so I have to wonder about the study design. When prescribed within the first 48 hours of symptoms, Tamiflu very often brings swift, blessed relief from the fever, chills, and bone racking body aches. I suspect some patients are started on it too late for it to be effective, or the side effects are too intolerable to continue.
There is what an individual doctor "observes" anecdotally, and there is science based on hundreds of data points under controlled conditions. I prefer doctors who don't think they are smarter than the best research.
There’s plenty of evidence from patients and prescribers. Why would you believe something you read when your personal experience is exactly the opposite? Why would you discount objective reality over something “experts” tell you?
Treaters have excessive "faith" in their treatments. Patients are afraid of suffering/death and are ignorant of the treatments they are accepting. These two dynamics restrain most attempts to institute evidence-based (safe, effective) treatments. The expansion of the for-profit health system enables the suppression/ignoring of "negative" results like you review here. And so there we are!
Another likely reason Dr's write it is because patients want it. Patients/consumers have been told it works and now consider it "the standard of care." They become disgruntled when an apparently effective treatment is denied them. So, for the physician, it is easier to write it. Side effects are seemingly limited and, thus, so is the downside to prescribing it. As opposed to an unhappy patient, sick with the flu, who believes that their doctor isn't doing anything for them.
This is another deleterious result of the travesty of direct-to-consumer advertising.
One might wonder about strain specific effects... not familiar with the specific mechanism of action of Tamiflu.
I had a pretty remarkable personal anecdotal experience with it myself about 20 years ago... Had cough and fever for a week during Thanksgiving while working in an urgent care... 4 days in, the nurse said to me "You don't look good..." Did a influenza swab which was almost instantly positive. Called in an Rx to a local pharmacy and took first dose as I left the shift that night. One hour drive home... by the time I got home, I felt dramatically better... fever broke, sore throat and cough were breaking...
That all said, It has subconsciously colored my thinking about Tamiflu, but I always keep in mind that this was my one, personal anecdotal experience, and I generally try to defer to evidence like this when treating my own patients.
For motivation, what about lawsuits? Would a doctor be more liable to lose a wrongful-death lawsuit if someone died without being recommended Tamiflu than if they'd been given it?
Also, I think there's a factor on both doctor and patient sides to do something rather than wait-it-out. Makes the doctor feel like they're doing a job, and the patient also feels like they're being proactive. Personally, I understand the frustration - I went into the college med center 4 weeks after a nasty flu with a persistent cough and was told "just wait, it'll go away". Walked away feeling like that was a useless trip to the doctor. Now that I am older, as someone who is more cautious about medications, I get it. Healing going to take time. Though I do wish they'd recommended a humidifier and Vitamin C.
“Excess optimism, ignorance of history and laziness.”
Thank you for this - for so long I was blasting the “$ is THE motivator” part, and I still think it’s a pretty strong motivator, however, these other three are great pondering points once the $ part backseats.
Sadly history always repeats itself; optimism gets replaced with pessimism (at least with public health in my personal world), and laziness seems a big problem in healthcare as “mouse clicker medicine” took over with EMRs, order sets, and critical thinking became less.
If there was something that we as physicians could actually do to treat influenza then oseltamivir would have disappeared a long time ago. Since there is nothing but we feel we have to do something, we prescribe oseltamivir.
On the other hand, the existence of oseltamivir, and thus the ability to do something, may reduce the rate of antibiotic prescriptions for influenza, so maybe it is useful after all.
First alleviation of symptoms reduced by 17 hours. Though one might have a higher chance of nausea. But no reduction in hospitalizations.
Insightful article, Dr. Mandrola. It's disconcerting that despite compelling evidence of oseltamivir's lack of efficacy and associated adverse events, it continues to be employed in the treatment of influenza. I think you touched upon an important point about the drivers of such persistent use - optimism, ignorance of history, and to some extent, inertia. It's human nature to hope for a silver bullet solution and stick to long-held beliefs, even when faced with contrary evidence. This, however, doesn't excuse the need for us, as medical professionals, to critically appraise the therapies we employ and to update our practice in light of new evidence.
Another point worth considering is the role of the pharmaceutical industry in promoting and maintaining the status quo. After all, millions of doses of oseltamivir were stockpiled based on initial studies and recommendations, pointing to a potentially larger issue of industry influence on clinical guidelines and practices.
Finally, your discussion highlights the crucial importance of transparency and open data in clinical research. These can pave the way for better informed medical practices, potentially saving significant resources while ensuring patient safety. Thank you for initiating this discussion and I look forward to more insightful reads in the future
"Please feel free to disagree with me." Such a statement embodies the admirable mindset of an individual truly practicing the art of critical evidence appraisal. Continue your exceptional work, Dr. Mandrola. Your writings continue to inspire and enlighten us.
Why would you want to stop a flu or even prevent it? Unless you are at extreme risk for complications, the flu is nothing more than your body taking itself on a repair course. This is why things like Tamiflu and flu vaccines never work and never will.
Why can't big pharma science come up with a cure or prevention for a much simpler cold? This is the basic of presumed bodily indiscretions and yet big pharma has no drug to combat them or prevent them. So why would I trust a flu drug?
Did the meta analysis look at the timing of when the first dose was taken in the various trials? Since that is always mentioned as a critical part of this medication’s supposed effectiveness I’m surprised that wasn’t discussed. (I looked at the analysis and didn’t see mention of timing, but it’s possible I missed it.)
Second, getting relief 17 hours sooner from very unpleasant symptoms seems like a great treatment, still a worthwhile endpoint even though not as serious as reducing hospitalization. My question is what is the rate of adverse reactions (nausea etc,) and how does that compare to the incidence of 17-hour sooner symptom relief?
Yes the timing of the first dose is absolutely crucial.
I find the conflict of interest btw “opinion leaders and guideline writers” to be increasingly distasteful, and the tenor of some of that work product to indeed be nefarious and outright tainted.
I also agree about the motivation of undue optimism and ignorance of history. These people are hidebound to repeat their mistakes, over and over again.
How would we prioritize attributes of medicine?
Rational, superstitious, superstitious that pretends to be rational?
I think the last of these three is the very worst.
I'm a broken record, but using 99.7% CI instead 95% CI would cure us of the BS fluff. It will also force medicine to really understand the mechanisms of treatment in the predictive way that chemists predict reactions and physicists predict motion and energy/particle transformations.
Gnostic scientism that is the problem.
I am also as comfortable being a "peasant". If you don't know in a rigorously scientific way, what would should ask is what would your Mom, Nonna, Busia do? (Basically, our mothers born before about 1945.) The soup or hot lemon water or burned toast or take a nap might be placebos or just distractions to let time pass but they are generally benign.
There are many many ways to improve upon the maternal instincts that have served humanity, but we have to really be scientific not just sort of scientific.
I recently, at a meeting heard a pharmaceutical representative make two statements. The first was that a fifth Covid wave was happening and the second was that Paxlovid was available.
A busy general practitioner overworked and burnt out, having ten to 15 minute consults and encouraged by patient pressure, will write a prescription usually in a vaccinated person, without any evidence except that delivered in person and glossy advertising from the rep. Advertising is powerful and patients who apply pressure and have no access to publications are easy targets as are their community doctors.
Once again what “studies show...” contradict the real life experience I see in my influenza patients, so I have to wonder about the study design. When prescribed within the first 48 hours of symptoms, Tamiflu very often brings swift, blessed relief from the fever, chills, and bone racking body aches. I suspect some patients are started on it too late for it to be effective, or the side effects are too intolerable to continue.
There is what an individual doctor "observes" anecdotally, and there is science based on hundreds of data points under controlled conditions. I prefer doctors who don't think they are smarter than the best research.
The Covid fiasco taught me to trust observable facts over shady research.
The blessed relief you speak of typically comes within 2 or 3 days regardless of whether one takes Tamiflu. This is exactly why you have control arms.
Actually it's within hours if you start it early enough. I've prescribed many times, and if given on time works within a day.
Placebo effect.
Likely written by someone who doesn’t work in primary care, and has never prescribed Tamiflu.
Likely correct: Why would they prescribe something when there's no evidence it works?
There’s plenty of evidence from patients and prescribers. Why would you believe something you read when your personal experience is exactly the opposite? Why would you discount objective reality over something “experts” tell you?
Excellent writing! 👏
Treaters have excessive "faith" in their treatments. Patients are afraid of suffering/death and are ignorant of the treatments they are accepting. These two dynamics restrain most attempts to institute evidence-based (safe, effective) treatments. The expansion of the for-profit health system enables the suppression/ignoring of "negative" results like you review here. And so there we are!
Public health is political and institutional. Politicians and institutions have a hard time walking back recommendations.
Another likely reason Dr's write it is because patients want it. Patients/consumers have been told it works and now consider it "the standard of care." They become disgruntled when an apparently effective treatment is denied them. So, for the physician, it is easier to write it. Side effects are seemingly limited and, thus, so is the downside to prescribing it. As opposed to an unhappy patient, sick with the flu, who believes that their doctor isn't doing anything for them.
This is another deleterious result of the travesty of direct-to-consumer advertising.
One might wonder about strain specific effects... not familiar with the specific mechanism of action of Tamiflu.
I had a pretty remarkable personal anecdotal experience with it myself about 20 years ago... Had cough and fever for a week during Thanksgiving while working in an urgent care... 4 days in, the nurse said to me "You don't look good..." Did a influenza swab which was almost instantly positive. Called in an Rx to a local pharmacy and took first dose as I left the shift that night. One hour drive home... by the time I got home, I felt dramatically better... fever broke, sore throat and cough were breaking...
That all said, It has subconsciously colored my thinking about Tamiflu, but I always keep in mind that this was my one, personal anecdotal experience, and I generally try to defer to evidence like this when treating my own patients.
Lots of patients have had the same experience
For motivation, what about lawsuits? Would a doctor be more liable to lose a wrongful-death lawsuit if someone died without being recommended Tamiflu than if they'd been given it?
Also, I think there's a factor on both doctor and patient sides to do something rather than wait-it-out. Makes the doctor feel like they're doing a job, and the patient also feels like they're being proactive. Personally, I understand the frustration - I went into the college med center 4 weeks after a nasty flu with a persistent cough and was told "just wait, it'll go away". Walked away feeling like that was a useless trip to the doctor. Now that I am older, as someone who is more cautious about medications, I get it. Healing going to take time. Though I do wish they'd recommended a humidifier and Vitamin C.
“Excess optimism, ignorance of history and laziness.”
Thank you for this - for so long I was blasting the “$ is THE motivator” part, and I still think it’s a pretty strong motivator, however, these other three are great pondering points once the $ part backseats.
Sadly history always repeats itself; optimism gets replaced with pessimism (at least with public health in my personal world), and laziness seems a big problem in healthcare as “mouse clicker medicine” took over with EMRs, order sets, and critical thinking became less.