6 ms·

It's an excellent point. Learning is not the same as science, and we need randomized trials to actually be sure of anything. Unfortunately, in the middle of a

It's an excellent point. Learning is not the same as science, and we need randomized trials to actually be sure of anything. Unfortunately, in the middle of a pandemic, that's not going to happen with enough speed to prevent a lot of people dying. The perfect can be the enemy of the good enough. We don't have to guess or learn about the mass of an electron; that's been well-established through great lab work. But not all decisions are like that. Many times the hardest decisions are those you make with incomplete and contradictory information ... and not making a decision is, in effect, making a decision. This is one of the things that's so interesting here. If it were simple yes/no, what's science and what's speculation, there wouldn't be much interesting learning or decision-making happening.

lonelappde 6y ago
RCT is not all of science. RCT is just one (very powerful) tool for making information quantifiable and for making decisions under uncertainty.
- raverbashing 6y ago
  This, exactly. The fixation on RCTs has kinda become "a meme" at this point. However it's lives on the line in some situations. Not everything can be double-blind. Not every experiment can be ethically done with a placebo (or done at all). Also the placebo effect is real but it is more pronounced in things like back pain or headaches, not so much in broken bones or aggressive viruses.
  - StavrosK 6y ago
    You don't need to have a placebo to do a controlled trial, you can just have a control arm of people you administer nothing to. How are you going to know if you have an improvement if you don't have something to compare your treatment to, though?
    - fhars 6y ago
      You need the placebo for the double blind RCT, which is still kind of the gold standard. But pronating patients is hard to do in a double blind fashion, so it is less of an issue here.
      - gus_massa 6y ago
        The double blind part is very difficult, but at least they can have a randomized control group [1]. It doesn't sound very difficult. Also, in most cases the control group get the "standard" treatment, because "do nothing" (taking literally the GP) is too bad. And you want to be sure that the new treatment is better than the "standard" treatment. [1] A real randomized control group, not an unrelated bunch of guys in another city of France.
      - bobosha 6y ago
        In some cases, the placebo is a currently approved treatment.
    - raverbashing 6y ago
      > How are you going to know if you have an improvement if you don't have something to compare your treatment to, though? Historical data? Past experiments? Sure, they might have biases, but the higher sample size of historical data can help with that. I think (specific) control groups make sense when you're talking about small effects or very specific cases (for example, the control group will undergo the standard treatment instead of the new treatment)
      - gus_massa 6y ago
        Historical data is useful as a rough guideline, but it is very difficult to use to make comparisons. For example: If there is a small Ebola outbreak in New York and you give the patients hydroxychloroquine and the death rate is 80%, is it good or bad?
gus_massa 6y ago
> Unfortunately, in the middle of a pandemic, that's not going to happen with enough speed to prevent a lot of people dying. How are you sure that this method is not worse than the ventilator method and will kill even more people during the pandemic? How many death did they get with this method? How many death would they had got with the ventilator method?
- wbl 6y ago
  Ventilators do lots of damage. If this gets the O2 up it's better since natural breathing doesn't break lung tissue.
- caymanjim 6y ago
  90% of people on ventilators die. It's hard to do much worse. And with numbers like that, I think it's perfectly ethical to try anything reasonable.
  - gus_massa 6y ago
    What is the original source of the 90%? Is it from this article: https://jamanetwork.com/journals/jama/fullarticle/2765184 https://jamanetwork.com/journals/jama/fullarticle/2765184 From the article: > The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. > As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. If you ignore the 831 patients that were still in the hospital, and consider only the 38 that survived and the 282 that died, you get 282/(282+38)=88%. It is a very short time. What are the odds for people that survive more than 4 days in the hospital? Did the team this post get the better results using the same accounting method? Did they apply this method only to the people that would need a ventilator or to more people because it is cheaper and easier to setup and maintain? (IIUC they used ventilator for the worse cases anyway.) > And with numbers like that, I think it's perfectly ethical to try anything reasonable. Do you want the best possible treatment to each patient, or you prefer that each doctor tries his/her pet theory in production?
- ineedasername 6y ago
achillesheels 6y ago
And unfortunately, there are doctors that will not make a move on an experimental therapy without it going through IRB approval, as I am learning with my own efforts at introducing a portable nebulizer biocidal therapy. Some will not take chances unless they see safety data first - they will let their patients and colleagues die first. As a former biomedical engineering researcher, this pandemic has been profoundly eye-opening in learning about the resistance to advancing the state of the art of medicine in the USA. (I’m not even speaking about the knee jerk reaction towards banning nebulizers in hospitals thanks to a flimsy NEJM letter last month reporting coronavirus aerosol contaminations.)
- _startingover 6y ago
  Yeah, the clinical culture isn’t really designed to handle a novel infectious disease. Of course patients are going to die.
- mmkhd 6y ago
  > they will let their patients and colleagues die first. No! They will definitively not let their patients and colleagues die firs! They will prevent you from killing them! You might believe in youRe therapy, but the vast amount if novel therapies will have (novel) adverse effects and you will haVe to supply the prove that your therapy will do less harm than doing the conventional thing. We have clinical trials to administer new therapies in a controlled and ethical way to cause the least harm. Just trying things will kill more people than it helps. The vast amount of new ideas do more harm than they help. Look at chloroquine and what a shit show it is, because everybody just tried it willy nilly. The side effect of harming Lupus patients who could not get their medicine alone caused tremendous unintended harm. And that wasn’t even harming because if administering a useless therapy with serious side effects. Move fast, fail fast and fail often aren great principles for developing software but they have no place in developing therapies. (I actually wanted to hurl swear words at you. But that helps nobody. It is true that medical research is overregulated and could be improved Bit there are reasons for that. Throwing all regulations away is just Trumpish behavior.)
  - achillesheels 6y ago

lonelappde 6y ago

RCT is not all of science. RCT is just one (very powerful) tool for making information quantifiable and for making decisions under uncertainty.

raverbashing 6y ago
This, exactly. The fixation on RCTs has kinda become "a meme" at this point. However it's lives on the line in some situations. Not everything can be double-blind. Not every experiment can be ethically done with a placebo (or done at all). Also the placebo effect is real but it is more pronounced in things like back pain or headaches, not so much in broken bones or aggressive viruses.
- StavrosK 6y ago
  You don't need to have a placebo to do a controlled trial, you can just have a control arm of people you administer nothing to. How are you going to know if you have an improvement if you don't have something to compare your treatment to, though?
  - fhars 6y ago
    You need the placebo for the double blind RCT, which is still kind of the gold standard. But pronating patients is hard to do in a double blind fashion, so it is less of an issue here.
    - gus_massa 6y ago
      The double blind part is very difficult, but at least they can have a randomized control group [1]. It doesn't sound very difficult. Also, in most cases the control group get the "standard" treatment, because "do nothing" (taking literally the GP) is too bad. And you want to be sure that the new treatment is better than the "standard" treatment. [1] A real randomized control group, not an unrelated bunch of guys in another city of France.
    - bobosha 6y ago
      In some cases, the placebo is a currently approved treatment.
  - raverbashing 6y ago
    > How are you going to know if you have an improvement if you don't have something to compare your treatment to, though? Historical data? Past experiments? Sure, they might have biases, but the higher sample size of historical data can help with that. I think (specific) control groups make sense when you're talking about small effects or very specific cases (for example, the control group will undergo the standard treatment instead of the new treatment)
    - gus_massa 6y ago
      Historical data is useful as a rough guideline, but it is very difficult to use to make comparisons. For example: If there is a small Ebola outbreak in New York and you give the patients hydroxychloroquine and the death rate is 80%, is it good or bad?

gus_massa 6y ago

> Unfortunately, in the middle of a pandemic, that's not going to happen with enough speed to prevent a lot of people dying. How are you sure that this method is not worse than the ventilator method and will kill even more people during the pandemic? How many death did they get with this method? How many death would they had got with the ventilator method?

wbl 6y ago
Ventilators do lots of damage. If this gets the O2 up it's better since natural breathing doesn't break lung tissue.
caymanjim 6y ago
90% of people on ventilators die. It's hard to do much worse. And with numbers like that, I think it's perfectly ethical to try anything reasonable.
- gus_massa 6y ago
  What is the original source of the 90%? Is it from this article: https://jamanetwork.com/journals/jama/fullarticle/2765184 https://jamanetwork.com/journals/jama/fullarticle/2765184 From the article: > The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. > As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. If you ignore the 831 patients that were still in the hospital, and consider only the 38 that survived and the 282 that died, you get 282/(282+38)=88%. It is a very short time. What are the odds for people that survive more than 4 days in the hospital? Did the team this post get the better results using the same accounting method? Did they apply this method only to the people that would need a ventilator or to more people because it is cheaper and easier to setup and maintain? (IIUC they used ventilator for the worse cases anyway.) > And with numbers like that, I think it's perfectly ethical to try anything reasonable. Do you want the best possible treatment to each patient, or you prefer that each doctor tries his/her pet theory in production?
ineedasername 6y ago

achillesheels 6y ago

And unfortunately, there are doctors that will not make a move on an experimental therapy without it going through IRB approval, as I am learning with my own efforts at introducing a portable nebulizer biocidal therapy. Some will not take chances unless they see safety data first - they will let their patients and colleagues die first. As a former biomedical engineering researcher, this pandemic has been profoundly eye-opening in learning about the resistance to advancing the state of the art of medicine in the USA. (I’m not even speaking about the knee jerk reaction towards banning nebulizers in hospitals thanks to a flimsy NEJM letter last month reporting coronavirus aerosol contaminations.)

_startingover 6y ago
Yeah, the clinical culture isn’t really designed to handle a novel infectious disease. Of course patients are going to die.
mmkhd 6y ago
> they will let their patients and colleagues die first. No! They will definitively not let their patients and colleagues die firs! They will prevent you from killing them! You might believe in youRe therapy, but the vast amount if novel therapies will have (novel) adverse effects and you will haVe to supply the prove that your therapy will do less harm than doing the conventional thing. We have clinical trials to administer new therapies in a controlled and ethical way to cause the least harm. Just trying things will kill more people than it helps. The vast amount of new ideas do more harm than they help. Look at chloroquine and what a shit show it is, because everybody just tried it willy nilly. The side effect of harming Lupus patients who could not get their medicine alone caused tremendous unintended harm. And that wasn’t even harming because if administering a useless therapy with serious side effects. Move fast, fail fast and fail often aren great principles for developing software but they have no place in developing therapies. (I actually wanted to hurl swear words at you. But that helps nobody. It is true that medical research is overregulated and could be improved Bit there are reasons for that. Throwing all regulations away is just Trumpish behavior.)
- achillesheels 6y ago