While I agree with Vinay on the whole I think he makes certain classical mistakes, which is surprising given his extensive criticism of so many poorly conducted RCTs involving cancer drugs.
Take Invermectin as an example (and I've no idea whether it's useful or not for COVID). There are RCTs that claim it works (e.g. the Brazil trial) and others (e.g. the RECOVERY trial) that claim it doesn't. However, the UK RECOVERY TRIAL was highly flawed as it included patients up to 14 days from testing positive for COVID. Well under those circumstances of course the trial is going to be negative for Ivermectin as any antiviral really has to be given within 48 hours of the onset of symptoms. Further it is generally the case that any single drug is not useful for a viral illness. So if ohne is going to look at ivermectin or hydroxychloroquine in a trial the treatment arm should comprise the complete care regimen which includes azithromycin or doxycycline, prednisone, zinc, vitamin D, vitamin K2 etc...... Failure to do so in an RCT simply provides no useful information whatsoever.
Likewise, Vinay's comments on colonoscopies is probably flawed because one has to consider the individual and the overall status of the individual. e.g. Take an 85 yr old patient. If that patient has other issues (e.g. cardiovascular disease, etc...) then finding polyps and resecting those in a colonoscopy is unlikely to prolong OS as the patient will likely die from other causes before the colon cancer gets to him/her. however, if the patient is completely fit physically and medically, then a colonoscopy could easily prolong OS. But of course for an 85 yr old, that prolongation could be relatively small since very very few are likely to live beyond 100, let alone say 95. So the issue is far more complicated than Vinay portrays. Similarly if you have a fit 45 yr old where a polyp is found on a colonoscopy, then it is self-evident that resection will prevent the development of colon cancer from that polyp. But of course, continual follow-up is required since other polyps may develop.
Very well written, and I completely agree with your perspective. At the tender age of 75 I am still practicing medicine and I intend to keep doing so for the decades to come!
What VP says is “evidence” means *empiric* evidence ie from RCTs
But there is another model, whereby Bayesian logic is used for interpreting RCTs, and where prior knowledge can rightly be applied.
In this model, which is I argue the highest form of science, It comes down to pretest probability *and* the results of RCTs
Therefore, because the physics basis for masking is so strong, that is indeed incorporated into the interpretation of RCTs. In other words, our knowledge of physics is so strong, that when RCTs are inadequate, we can use physics to guide what is probably true. Therefore, while I agree that masking RCTs should be done, I don’t think it is anti-intellectual to opine that the best information we have is that masks can be useful during an unprecedented respiratory virus pandemic
And I have also explained why my assumption is that ivermectin is useless… I absolutely support its evaluation in an RCT, but I’m going to assume it is useless, unless there is strong evidence from RCTs to suggest otherwise
So, I think that VP ignores the important role of pretest probability in interpreting RCTs, and he is unjustified in putting down pathophysiologic reasoning and physics
Bayesian logic is rather low level math, something like using a hammer to fill a glass. In other words, it validates making logical leaps for people who have no actual empirically-based predictors to throw their speculations into a "model" which then validates their speculation. In other words, it doesn't test reality -- it tests the model in your head.
Whether or not that model actually applies to reality requires inference. Inference is what we do in real life when making decisions on the ground. It also is the basis of all superstition.
So, basically you're saying, you accept superstition (i.e., the mask inferences) for one reason ("because physics", which is actually a political argument, not a scientific one, because inference) and want to discard it for another (i.e., ivermectin).
Nope, you don't get to play preferences "because physics". The admission must be made that an inference is the opposite of "water tight" and that has to be considered a different class of methodology entirely to an RCT, which actually accounts for reality, rather that superstition, because it tests things that are actually measurable rather than using inference.
This is case and point why science cannot exist without philosophy. Otherwise it's just number games and fantasies, you know, Bayesian logic.
The number of people hanging onto "Masks must do something" despite MOUNTAINS of decent evidence that they do nothing and essentially NO evidence that they do anything with people in the real world is just astonishing. It is dressed up with "Bayesian this" or "stochastic that" but (and I love your "using a hammer to fill a glass" analogy) it is just flat out wrong.
When I was on psychiatry in medical school, we had a patient who was up before dawn every day, went to the window, and as we watched he lifted his hands and the sun rose synchronously. Every Bayesian analysis of the data says that his actions were 100% correlated with the sun rising. This is where so many of these "physics show that in conditions that have never and will never exist with real people in real places, masks might have done some particle reduction" recitations live. They just ignore all of the hundreds of studies that say that this does not apply in real people...which would be exactly the same as ignoring the fact that the sun rose each day after the patient was strapped to his bed.
I have tried to have conversations with these people, but their religious belief in doing whatever it takes to prove that masks work is insuperable. Sad.
Vinay and I have our differences, but to his credit, he has come around from "masks could be bioplausible" to "clearly they do not work and the evidence is overwhelming". Anyone who will abandon their medical-intervention-as-religion approach when given evidence is a really, really good doctor. Kudos to him. This article is spot on.
Dr. K - I just had major abdominal surgery and I cannot tell you how glad I was that - literally this past Monday - the mask mandate in the system I had surgery in had been lifted. Nurses and docs cheerfully entered my room sans masks and we chatted about my successful outcome and progress, no masks, no fear. It almost felt good! 😉. Happy to say I’m home now and continuing my journey
Any chance you would do a debate with someone who doesn't think that observational and mannequin studies are useless? Is there any sober minded person out there making this case?
This goes to a deep metaphysical issue at the core of the way science is done currently. Replicability does not guarantee agreement. That is a naive, basic bitch assumption. Anyone who does real science knows that each study will have different properties, even if you control everything possible.
Why? Because science happens in the real world, where there are actually non-finite sets of variables -- not some Platonic world of perfect forms, or the secular modern version of that: the Science as brought to you by political fantasies of utopia.
This is EBM poetry. Beautiful write up. Thank you doc.
Evidence based medicine is also ethical and justice-oriented.
https://youtu.be/5-K3obvnKYQ
While I agree with Vinay on the whole I think he makes certain classical mistakes, which is surprising given his extensive criticism of so many poorly conducted RCTs involving cancer drugs.
Take Invermectin as an example (and I've no idea whether it's useful or not for COVID). There are RCTs that claim it works (e.g. the Brazil trial) and others (e.g. the RECOVERY trial) that claim it doesn't. However, the UK RECOVERY TRIAL was highly flawed as it included patients up to 14 days from testing positive for COVID. Well under those circumstances of course the trial is going to be negative for Ivermectin as any antiviral really has to be given within 48 hours of the onset of symptoms. Further it is generally the case that any single drug is not useful for a viral illness. So if ohne is going to look at ivermectin or hydroxychloroquine in a trial the treatment arm should comprise the complete care regimen which includes azithromycin or doxycycline, prednisone, zinc, vitamin D, vitamin K2 etc...... Failure to do so in an RCT simply provides no useful information whatsoever.
Likewise, Vinay's comments on colonoscopies is probably flawed because one has to consider the individual and the overall status of the individual. e.g. Take an 85 yr old patient. If that patient has other issues (e.g. cardiovascular disease, etc...) then finding polyps and resecting those in a colonoscopy is unlikely to prolong OS as the patient will likely die from other causes before the colon cancer gets to him/her. however, if the patient is completely fit physically and medically, then a colonoscopy could easily prolong OS. But of course for an 85 yr old, that prolongation could be relatively small since very very few are likely to live beyond 100, let alone say 95. So the issue is far more complicated than Vinay portrays. Similarly if you have a fit 45 yr old where a polyp is found on a colonoscopy, then it is self-evident that resection will prevent the development of colon cancer from that polyp. But of course, continual follow-up is required since other polyps may develop.
Very well written, and I completely agree with your perspective. At the tender age of 75 I am still practicing medicine and I intend to keep doing so for the decades to come!
I have one such colleague. Here is his retort:
I agree, but only to a point.
What VP says is “evidence” means *empiric* evidence ie from RCTs
But there is another model, whereby Bayesian logic is used for interpreting RCTs, and where prior knowledge can rightly be applied.
In this model, which is I argue the highest form of science, It comes down to pretest probability *and* the results of RCTs
Therefore, because the physics basis for masking is so strong, that is indeed incorporated into the interpretation of RCTs. In other words, our knowledge of physics is so strong, that when RCTs are inadequate, we can use physics to guide what is probably true. Therefore, while I agree that masking RCTs should be done, I don’t think it is anti-intellectual to opine that the best information we have is that masks can be useful during an unprecedented respiratory virus pandemic
And I have also explained why my assumption is that ivermectin is useless… I absolutely support its evaluation in an RCT, but I’m going to assume it is useless, unless there is strong evidence from RCTs to suggest otherwise
So, I think that VP ignores the important role of pretest probability in interpreting RCTs, and he is unjustified in putting down pathophysiologic reasoning and physics
Bayesian logic is rather low level math, something like using a hammer to fill a glass. In other words, it validates making logical leaps for people who have no actual empirically-based predictors to throw their speculations into a "model" which then validates their speculation. In other words, it doesn't test reality -- it tests the model in your head.
Whether or not that model actually applies to reality requires inference. Inference is what we do in real life when making decisions on the ground. It also is the basis of all superstition.
So, basically you're saying, you accept superstition (i.e., the mask inferences) for one reason ("because physics", which is actually a political argument, not a scientific one, because inference) and want to discard it for another (i.e., ivermectin).
Nope, you don't get to play preferences "because physics". The admission must be made that an inference is the opposite of "water tight" and that has to be considered a different class of methodology entirely to an RCT, which actually accounts for reality, rather that superstition, because it tests things that are actually measurable rather than using inference.
This is case and point why science cannot exist without philosophy. Otherwise it's just number games and fantasies, you know, Bayesian logic.
The number of people hanging onto "Masks must do something" despite MOUNTAINS of decent evidence that they do nothing and essentially NO evidence that they do anything with people in the real world is just astonishing. It is dressed up with "Bayesian this" or "stochastic that" but (and I love your "using a hammer to fill a glass" analogy) it is just flat out wrong.
When I was on psychiatry in medical school, we had a patient who was up before dawn every day, went to the window, and as we watched he lifted his hands and the sun rose synchronously. Every Bayesian analysis of the data says that his actions were 100% correlated with the sun rising. This is where so many of these "physics show that in conditions that have never and will never exist with real people in real places, masks might have done some particle reduction" recitations live. They just ignore all of the hundreds of studies that say that this does not apply in real people...which would be exactly the same as ignoring the fact that the sun rose each day after the patient was strapped to his bed.
I have tried to have conversations with these people, but their religious belief in doing whatever it takes to prove that masks work is insuperable. Sad.
Vinay and I have our differences, but to his credit, he has come around from "masks could be bioplausible" to "clearly they do not work and the evidence is overwhelming". Anyone who will abandon their medical-intervention-as-religion approach when given evidence is a really, really good doctor. Kudos to him. This article is spot on.
Dr. K - I just had major abdominal surgery and I cannot tell you how glad I was that - literally this past Monday - the mask mandate in the system I had surgery in had been lifted. Nurses and docs cheerfully entered my room sans masks and we chatted about my successful outcome and progress, no masks, no fear. It almost felt good! 😉. Happy to say I’m home now and continuing my journey
Any chance you would do a debate with someone who doesn't think that observational and mannequin studies are useless? Is there any sober minded person out there making this case?
This goes to a deep metaphysical issue at the core of the way science is done currently. Replicability does not guarantee agreement. That is a naive, basic bitch assumption. Anyone who does real science knows that each study will have different properties, even if you control everything possible.
Why? Because science happens in the real world, where there are actually non-finite sets of variables -- not some Platonic world of perfect forms, or the secular modern version of that: the Science as brought to you by political fantasies of utopia.