4 ms·

> They don't [get evidence of efficacy], though. They need a control group. This is false. Control groups, preferably in double-blind studies, are an essential

> They don't [get evidence of efficacy], though. They need a control group. This is false. Control groups, preferably in double-blind studies, are an essential part of best practices. However, the bar for what constitutes evidence is much lower than that. Evidence is any fact that makes a relevant conclusion more or less likely. Evidence need not be conclusive in and of itself. Over time, the cumulative effects of less-strong evidence can form the basis for a reasonable inductive conclusion. Sorry to be trite, but as an example, a person can have evidence that their romantic partner loves them without the use of an identical twin. Insisting on gold standard medical evidence before allowing someone to undergo life-saving treatment—when the preponderance of the evidence that does exist supports that treatment—is, to be blunt, the very definition of depraved heart murder. It demonstrates a wanton disregard toward human life in the face of the known likelihood that it will result in some number of deaths. More broadly, however, it is an extremely poor policy, in that this meme both weakens society's critical thinking generally and—among those who see through the elitist charade—significantly weakens the respect of those scientists who make the claim.

deleted 3y ago
[deleted]
A_D_E_P_T 3y ago
> Control groups, preferably in double-blind studies, are an essential part of best practices. I wouldn't go that far. I think that a paradigm built upon a broader evidence base -- e.g. with far more extensive postmarketing surveillance of drugs -- would be more ethical, of more benefit to society, and ultimately more effective. Double-blinded studies can miss, can be confounded by placebo effects, can easily be confounded by crooked researchers, and are frequently just plain unethical from first principles. I don't think that they should be considered "essential."
- random78965 3y ago
  I think all your criticisms of randomized controlled trials (apart from the ethical one) apply to your suggested approach, no? RCTs are the gold standard for demonstrating efficacy precisely because of the controls. I agree that they're not going to give you enough info about potential side-effects - a thorough monitoring program is definitely necessary for that. But without RCTs, showing that a drug works would be much harder. How would you weed out the snake oil?
  - A_D_E_P_T 3y ago
    RCTs were not required and were rarely performed prior to 1962, and yet that period from roughly 1940 to 1960 is still today widely known as "the Golden Age of drug development." How did they know, back then, that new drugs work? Simple: They have sufficiently powerful (in a statistical sense) effects in a patient population. Very powerful effects require a very small population -- this applies to ALL drugs that are curative -- whereas moderate effects would require a large population. Reasonably sized safety trials and extensive postmarketing surveillance are entirely sufficient. > How would you weed out the snake oil? The current paradigm is "better 10,000 people die of neglect than 1 person die of snake oil or quackery." I'm okay with a little bit of snake oil if it means that more drugs are being introduced more quickly, and I trust practitioners and patients to, more often than not, determine the therapeutic regimens that are right for them.
    - youainti 3y ago
      Those were also small molecule drugs which are relatively simple to produce compared to modern large molecule drugs (biologics such as modern insulin, mrna vaccines, humira, many cancer drugs, etc.)
      - AstralStorm 3y ago
        You might be surprised that the modern processes for true biologicals like peptides and mRNA are actually simpler than the chemical processes for classic drugs. E.g. solid state peptide synthesis. Once you can make a 10 peptide one, you can make a 1000 unit one in an identical way with more iteration. Compare that to establishing a bespoke chemical process for each drug, or messing with purification of natural biologicals, or fusing antibodies to protein or peptides to grow inside a whole cell. They should be actually cheap. They aren't because new. Humira is quite a bit harder to manufacture cleanly than a peptide or mRNA, and still harder than a plain solid state synthesized and folded protein. It requires a lot of post translational modification, which means cellular machinery, which means a whole bacterial cell you now have to grow, feed and remove from the product.
    - 3y ago

deleted 3y ago

[deleted]

A_D_E_P_T 3y ago

> Control groups, preferably in double-blind studies, are an essential part of best practices. I wouldn't go that far. I think that a paradigm built upon a broader evidence base -- e.g. with far more extensive postmarketing surveillance of drugs -- would be more ethical, of more benefit to society, and ultimately more effective. Double-blinded studies can miss, can be confounded by placebo effects, can easily be confounded by crooked researchers, and are frequently just plain unethical from first principles. I don't think that they should be considered "essential."

random78965 3y ago
I think all your criticisms of randomized controlled trials (apart from the ethical one) apply to your suggested approach, no? RCTs are the gold standard for demonstrating efficacy precisely because of the controls. I agree that they're not going to give you enough info about potential side-effects - a thorough monitoring program is definitely necessary for that. But without RCTs, showing that a drug works would be much harder. How would you weed out the snake oil?
- A_D_E_P_T 3y ago
  RCTs were not required and were rarely performed prior to 1962, and yet that period from roughly 1940 to 1960 is still today widely known as "the Golden Age of drug development." How did they know, back then, that new drugs work? Simple: They have sufficiently powerful (in a statistical sense) effects in a patient population. Very powerful effects require a very small population -- this applies to ALL drugs that are curative -- whereas moderate effects would require a large population. Reasonably sized safety trials and extensive postmarketing surveillance are entirely sufficient. > How would you weed out the snake oil? The current paradigm is "better 10,000 people die of neglect than 1 person die of snake oil or quackery." I'm okay with a little bit of snake oil if it means that more drugs are being introduced more quickly, and I trust practitioners and patients to, more often than not, determine the therapeutic regimens that are right for them.
  - youainti 3y ago
    Those were also small molecule drugs which are relatively simple to produce compared to modern large molecule drugs (biologics such as modern insulin, mrna vaccines, humira, many cancer drugs, etc.)
    - AstralStorm 3y ago
      You might be surprised that the modern processes for true biologicals like peptides and mRNA are actually simpler than the chemical processes for classic drugs. E.g. solid state peptide synthesis. Once you can make a 10 peptide one, you can make a 1000 unit one in an identical way with more iteration. Compare that to establishing a bespoke chemical process for each drug, or messing with purification of natural biologicals, or fusing antibodies to protein or peptides to grow inside a whole cell. They should be actually cheap. They aren't because new. Humira is quite a bit harder to manufacture cleanly than a peptide or mRNA, and still harder than a plain solid state synthesized and folded protein. It requires a lot of post translational modification, which means cellular machinery, which means a whole bacterial cell you now have to grow, feed and remove from the product.
  - 3y ago