Terrific article that exhibits all of the thoughtfulness that we have come to expect from Dr. Foy and the other principal authors on Sensible Medicine.
I really appreciate Dr. Foy’s “rules for applying clinical trial results to patient care”. He puts the “art” of medicine to task and wisely cautions against blind implementation of guidelines.
This strikes me as a nearly perfect article: so congratulations. It’s simple and straightforward and it captures a very serious problem that we were routinely discount, the difference between internal validity and external validity.
I go on rounds and Residents refer to “goal directed management” of heat failure with almost no real appreciation of just how far away our patients lie from those in the trials
Most approved drugs fail to maintain external validity because clinicians are guilty of (1) the more is better bias (2) the do something new bias, and (3) the (many) clinicians are suckers dynamic. These factors are leavened when drug companies use DTC advertising to convince consumers of the wonders of their drug, and get these consumers to put pressure on their doctors. The last might not apply with a generically available med such as spironolactone.
And then comes pharmacogenetics. How do we know that the pt is or is not sensitive to the specific drug based on their inherited metabolic pathways? How many know whether it is a “ drug “ or a “ pro-drug “ that is being prescribed ( clopidogrel vs prasugrel )? 85 y/o female with depression noticed no improvement in symptoms nor intolerance at max dose of commonly used SSRI. Per her genetic testing, done for other reasons, she would’ve needed double the maximum dose for it to increase the effectiveness of same. But, can you imagine what the pharmacist would have thought when the prescription was issued, and what the insurance review letter would have looked like ? And then there’s OBRA guidelines …. Individualized therapy is paramount and like the article states, if the pt wouldn’t have been included in the trial, proceed with caution. “ The patient died in electrolyte balance “
Importantly relevant to virtually all daily meds. Most statin trials, for instance, used run-out phases in which 20-40% dropped out, yet virtually no one is carefully monitored for their first months on a statin. This is why side effects and intolerance are often up to TEN times higher in real world experience than in trials, making guidelines and published AE rates deeply misleading. Thank you again, beautifully explained.
I think that external validity is a vital consideration and along w/ ARR, NNT should be a priority in shared decision making ( and even “paternalistic” recommendations ).
Fantastic, precise, and concise article with specific actionable recommendations. Bravo.
Terrific article that exhibits all of the thoughtfulness that we have come to expect from Dr. Foy and the other principal authors on Sensible Medicine.
We hit the jackpot with all of the authors on this substack.
I really appreciate Dr. Foy’s “rules for applying clinical trial results to patient care”. He puts the “art” of medicine to task and wisely cautions against blind implementation of guidelines.
This strikes me as a nearly perfect article: so congratulations. It’s simple and straightforward and it captures a very serious problem that we were routinely discount, the difference between internal validity and external validity.
I go on rounds and Residents refer to “goal directed management” of heat failure with almost no real appreciation of just how far away our patients lie from those in the trials
It’s 4 drugs for everyone, all day, every day….just as the guideline writers (and their funding sources) hoped.
Thankfully, we have writers like those on SM who encourage skepticism.
Thank you for this important summary exemplifying internal and external validity. I look forward to my nursing students reading it.
If the system is proven flawed and the path we are on is treacherous and misguided, then, always remember that leadership is a choice not a position.
Most approved drugs fail to maintain external validity because clinicians are guilty of (1) the more is better bias (2) the do something new bias, and (3) the (many) clinicians are suckers dynamic. These factors are leavened when drug companies use DTC advertising to convince consumers of the wonders of their drug, and get these consumers to put pressure on their doctors. The last might not apply with a generically available med such as spironolactone.
And then comes pharmacogenetics. How do we know that the pt is or is not sensitive to the specific drug based on their inherited metabolic pathways? How many know whether it is a “ drug “ or a “ pro-drug “ that is being prescribed ( clopidogrel vs prasugrel )? 85 y/o female with depression noticed no improvement in symptoms nor intolerance at max dose of commonly used SSRI. Per her genetic testing, done for other reasons, she would’ve needed double the maximum dose for it to increase the effectiveness of same. But, can you imagine what the pharmacist would have thought when the prescription was issued, and what the insurance review letter would have looked like ? And then there’s OBRA guidelines …. Individualized therapy is paramount and like the article states, if the pt wouldn’t have been included in the trial, proceed with caution. “ The patient died in electrolyte balance “
Beautifully direct, Dr. Foy, thank you.
Importantly relevant to virtually all daily meds. Most statin trials, for instance, used run-out phases in which 20-40% dropped out, yet virtually no one is carefully monitored for their first months on a statin. This is why side effects and intolerance are often up to TEN times higher in real world experience than in trials, making guidelines and published AE rates deeply misleading. Thank you again, beautifully explained.
I think that external validity is a vital consideration and along w/ ARR, NNT should be a priority in shared decision making ( and even “paternalistic” recommendations ).