I wonder how the aspirin trials would look in regular people (I haven’t checked, are any of your randomized trials in normal people?). Mike Darwin on aspirin;
″...My point was that other NSAID drugs wreak more death and mayhem than Vioxx did every year, and yet thy are sold OTC and no one gives the truly incredibly morbidity and mortality a second thought. Any GP or ED doc will regurgitate countless stories of serious GI bleeding due to NSAIDS (and especially aspirin) on cue. Of course, they don’t mention all the hemorrhagic strokes caused by aspirin’s anti-platelet activity because they have no way to distinguish those from “regular strokes” and with so much of the population on aspirin that wouldn’t be easy.
Aspirin causes a truly gruesome and often fatal condition in children called Reye’s syndrome, and if it were any other drug than aspirin, it WOULD have been pulled from the market, Instead, a massive educational campaign was launched to teach parents not to give sick children aspirin – the rational thing to do! However, meanwhile (until the population was educated), children continued to be neurologically maimed and killed by Reye’s. I’ve dialyzed youngsters with multi-system organ failure from Reye’s and it is a wretched and heartbreaking illness with a poor outcome.”
Is this comment anything more than playing on peoples’ emotions and an appeal to authority? Who is Mike Darwin and why should I believe anything he says? Is he a doctor? Should I trust him because his last name is Darwin? Does he cite any statistics or make any claims that can be fact-checked in this quote? Is it proven that Aspirin CAUSES Reye’s syndrome, as the quote claims? I usually appreciate your input gwern, but with this comment I’ve lost respect for you.
Is this comment anything more than playing on peoples’ emotions and an appeal to authority?
Yes. It makes multiple easily falsifiable claims about aspirin, its effects, and history.
Who is Mike Darwin and why should I believe anything he says?...Should I trust him because his last name is Darwin?
2 seconds in google for ‘mike darwin’ would lead you straight to http://en.wikipedia.org/wiki/Mike_Darwin which explains who he is, what he has done, and his real name, for that matter.
Is it proven that Aspirin CAUSES Reye’s syndrome, as the quote claims?
These effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy. An estimated 10-20% of NSAID patients experience dyspepsia, and NSAID-associated upper gastrointestinal adverse events are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States, and represent 43% of drug-related emergency visits. Many of these events are avoidable; a review of physician visits and prescriptions estimated that unnecessary prescriptions for NSAIDs were written in 42% of visits.[5]
Did you spend even a minute trying to answer your questions before composing your rhetorical reply?
I usually appreciate your input gwern, but with this comment I’ve lost respect for you.
Good thing that, as far as I know, I don’t care about your opinion.
Actually I did google Mike Darwin, but that didn’t give me any reason to believe all of the claims he made. He’s the founder of some cryonics company that I’ve never heard of. How does that qualify him as an expert on aspirin? The Wikipedia page about him is also riddled with warnings, which make me skeptical of the other content I might find there.
I also googled aspirin and Reye’s syndrome. Apparently you did too, but didn’t read what popped up very carefully. Aspirin has been ASSOCIATED with Reye’s syndrome in EPIDEMIOLOGICAL studies. Epidemiological studies are not capable of proving causation.
I already know NSAIDs can increase the risk of having a GI bleed. You aren’t teaching me anything new. What is at question is whether the risks of taking aspirin outweigh the benefits.
In light of your comments and attitude, I plan to disregard your opinion as well from here on out.
Edit: I thought the Vioxx vs. NSAID death comparison sounded funny too, so I took a look at some of the numbers.
It is thought that Vioxx over 5 years caused between 88,000 to 140,000 serious cases of heart disease. Per year, that works out to 17,600 to 28,000.
Of those who developed heart disease, it is estimated that 30-40% died. That gives us 5,280 to 7,040 on the low end and 8,400 to 11,200 on the high end.
What about NSAIDs?
It is estimated there are about 60,000,000 NSAID users annually. 1-2% of people who take NSAIDs develop GI events, like a hemorrhage. That’s 600,000 to 1,200,000 people.
Estimates of deaths caused by NSAIDs are between 3,200 to 16,500 per year.
So we have, looking at Vioxx vs. NSAIDs:
5,280 to 11,200 deaths per year vs. 3,200 to 16,500 deaths per year
The low estimate puts NSAIDs ahead, the high estimate puts them below. They seem roughly comparable to me. When you take into account how widespread NSAID use is compared to Vioxx, I think you have a strong argument that NSAIDs are much safer than Vioxx.
At its peak, Vioxx was taken by about 20,000,000 Americans.
I also googled aspirin and Reye’s syndrome. Apparently you did too, but didn’t read what popped up very carefully. Aspirin has been ASSOCIATED with Reye’s syndrome in EPIDEMIOLOGICAL studies. Epidemiological studies are not capable of proving causation.
No, but you asked if there was evidence. Correlation doesn’t imply causation but it is Bayesian evidence for causation.
Yes, I see you did use the word “proven”. That does lesson the force of my comment but not by very much. I’m curious actually what you mean by proven outside a mathematical context. In this context, the correlation is extremely strong, and there’s no obvious alternate hypothesis. I’m not completely sure what you consider in this context to be an acceptable amount of evidence, but the medical consensus seems clear, and the links Gwern gave show that the correlation exists even when one tries to control for other variables.
I think he wants randomized controlled trials. Which of course no ethics board would ever approve because avoiding aspirin in kids is not that hard or expensive, and the cost of confirming it would be too high.
(“You want to test whether slamming your face into the wall causes pain, and doesn’t just correlate with it? Why on earth?”)
We have a plausible mechanism (confirmed by massive amounts of science) by which slamming your face into the wall causes pain; for the link between Aspirin and Reye’s syndrome there is no such plausible mechanism.
Well, at least in the drug world it is more convincing if you have a rational mechanism by which a drug could cause some effect.
A plausible alternative hypothesis is that children who get sick sometimes are developing Reye’s syndrome and take Aspirin. The problem with epidemiological studies is that it is IMPOSSIBLE to control for other variables. This is why randomized controlled trials are essential and give you a kind of information epidemiological studies never can.
My point is not that Aspirin doesn’t cause Reye’s syndrome, but that it is impossible to say one way or the other. Maybe it does, maybe it doesn’t. The data is unavailable and likely never will be. So if you are an honest person who values the truth, you can’t say that it does.
I wonder how the aspirin trials would look in regular people (I haven’t checked, are any of your randomized trials in normal people?). Mike Darwin on aspirin;
Is this comment anything more than playing on peoples’ emotions and an appeal to authority? Who is Mike Darwin and why should I believe anything he says? Is he a doctor? Should I trust him because his last name is Darwin? Does he cite any statistics or make any claims that can be fact-checked in this quote? Is it proven that Aspirin CAUSES Reye’s syndrome, as the quote claims? I usually appreciate your input gwern, but with this comment I’ve lost respect for you.
Yes. It makes multiple easily falsifiable claims about aspirin, its effects, and history.
2 seconds in google for ‘mike darwin’ would lead you straight to http://en.wikipedia.org/wiki/Mike_Darwin which explains who he is, what he has done, and his real name, for that matter.
2 seconds in Google for ‘aspirin reyes syndrome’:
http://en.wikipedia.org/wiki/Reye%27s_syndrome#Aspirin
http://www.mayoclinic.com/health/reyes-syndrome/DS00142
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1290500/
Had you spent 5 seconds googling his NSAID claim, you might have run into http://en.wikipedia.org/wiki/Non-steroidal_anti-inflammatory_drug#Adverse_effects which mentions:
Did you spend even a minute trying to answer your questions before composing your rhetorical reply?
Good thing that, as far as I know, I don’t care about your opinion.
Actually I did google Mike Darwin, but that didn’t give me any reason to believe all of the claims he made. He’s the founder of some cryonics company that I’ve never heard of. How does that qualify him as an expert on aspirin? The Wikipedia page about him is also riddled with warnings, which make me skeptical of the other content I might find there.
I also googled aspirin and Reye’s syndrome. Apparently you did too, but didn’t read what popped up very carefully. Aspirin has been ASSOCIATED with Reye’s syndrome in EPIDEMIOLOGICAL studies. Epidemiological studies are not capable of proving causation.
I already know NSAIDs can increase the risk of having a GI bleed. You aren’t teaching me anything new. What is at question is whether the risks of taking aspirin outweigh the benefits.
In light of your comments and attitude, I plan to disregard your opinion as well from here on out.
Edit: I thought the Vioxx vs. NSAID death comparison sounded funny too, so I took a look at some of the numbers.
It is thought that Vioxx over 5 years caused between 88,000 to 140,000 serious cases of heart disease. Per year, that works out to 17,600 to 28,000.
Of those who developed heart disease, it is estimated that 30-40% died. That gives us 5,280 to 7,040 on the low end and 8,400 to 11,200 on the high end.
What about NSAIDs?
It is estimated there are about 60,000,000 NSAID users annually. 1-2% of people who take NSAIDs develop GI events, like a hemorrhage. That’s 600,000 to 1,200,000 people.
Estimates of deaths caused by NSAIDs are between 3,200 to 16,500 per year.
So we have, looking at Vioxx vs. NSAIDs:
5,280 to 11,200 deaths per year vs. 3,200 to 16,500 deaths per year
The low estimate puts NSAIDs ahead, the high estimate puts them below. They seem roughly comparable to me. When you take into account how widespread NSAID use is compared to Vioxx, I think you have a strong argument that NSAIDs are much safer than Vioxx.
At its peak, Vioxx was taken by about 20,000,000 Americans.
No, but you asked if there was evidence. Correlation doesn’t imply causation but it is Bayesian evidence for causation.
I asked if it was proven that aspirin causes Reye’s syndrome. The correct answer is, “No, it is not.”
Yes, I see you did use the word “proven”. That does lesson the force of my comment but not by very much. I’m curious actually what you mean by proven outside a mathematical context. In this context, the correlation is extremely strong, and there’s no obvious alternate hypothesis. I’m not completely sure what you consider in this context to be an acceptable amount of evidence, but the medical consensus seems clear, and the links Gwern gave show that the correlation exists even when one tries to control for other variables.
I think he wants randomized controlled trials. Which of course no ethics board would ever approve because avoiding aspirin in kids is not that hard or expensive, and the cost of confirming it would be too high.
(“You want to test whether slamming your face into the wall causes pain, and doesn’t just correlate with it? Why on earth?”)
We have a plausible mechanism (confirmed by massive amounts of science) by which slamming your face into the wall causes pain; for the link between Aspirin and Reye’s syndrome there is no such plausible mechanism.
Well, at least in the drug world it is more convincing if you have a rational mechanism by which a drug could cause some effect.
A plausible alternative hypothesis is that children who get sick sometimes are developing Reye’s syndrome and take Aspirin. The problem with epidemiological studies is that it is IMPOSSIBLE to control for other variables. This is why randomized controlled trials are essential and give you a kind of information epidemiological studies never can.
My point is not that Aspirin doesn’t cause Reye’s syndrome, but that it is impossible to say one way or the other. Maybe it does, maybe it doesn’t. The data is unavailable and likely never will be. So if you are an honest person who values the truth, you can’t say that it does.