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
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.
Recently astonished watching a world expert describe how he had his staff load a bunch of cases into the algorithms in the ACC guidelines he worked on as lead author a few years ago
He said the best case scenario reveals a 70% success rate. This gave me hope that we can do better and so does your voice in the wilderness so to speak
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
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.
Recently astonished watching a world expert describe how he had his staff load a bunch of cases into the algorithms in the ACC guidelines he worked on as lead author a few years ago
He said the best case scenario reveals a 70% success rate. This gave me hope that we can do better and so does your voice in the wilderness so to speak