4 ms·

The risk of round numbers and sharp thresholds in clinical practice

68 points by asplake 11mo ago

Terretta 11mo ago
This is helpful in any number of fields with metrics-driven responses.
avidiax 10mo ago
> paradoxical risk, where successful treatments unexpectedly lower the risk of higher-risk patients to below that of untreated lower-risk patients. This seems perhaps tautological whenever the treatment intensity is binary, and it's an effective treatment. Someone at the threshold that receives treatment would necessarily do better than someone at the threshold not receiving the treatment. It's a pretty good argument against any binary treatments, or at least to set the threshold low enough that improvement with treatment at the threshold is minimal.
- hyghjiyhu 10mo ago
  I have heard people gain weight intentionally to ensure they get these new weightloss drugs.
  - RobotToaster 10mo ago
    If you're close to the BMI cutoff for it, it makes sense.
uniqueuid 10mo ago
Reading this I could not help but think of compliance and treatment safety for self-managed dosing. It's evident, for example, that drugs such as Paracetamol (Tylenol for you Americans) should be dosed by body weight in children. To make life simpler for parents, they are given age and/or weight brackets, sometimes along with upper thresholds (e.g. mg/day). This of course means that lighter children are comparatively over-dosed and heavier children under-dosed compared to a median. The problem is - I think this works pretty well as a safeguard against dangerous over-dosing (i.e. liver toxicity etc.). Now how would we turn that advice into a gradual dosing recommendation? We can use mg/kg body weight as is done e.g. in antibiotics. But that carries the potentially fatal risk of miscalculation, and some parents might intentionally overdose over a wrong risk perception. What we would need is something like an exponential risk curve, indicating a "safe zone" and a "danger zone" while highlighting some critical threshold. This again would need to be age/weight-specific. Do we think parents would be deterred from giving a kid too high of a paracetamol dose? I'm not so sure, especially over time. So in the end, I think that in some cases (especially with self-administered dosing) round numbers and sharp thresholds may work well to mitigate fatal risks, even while increasing nonfatal risks.
- tgv 10mo ago
  First, many people are ... let's politely call it arithmetically challenged. They won't understand how to compute the amount and then obtain the correct dose. A chart or a table might have more success than a formula, no matter how simple the formula. Then again, the dangers of paracetamol overdose aren't high (and I would think it's less for children than for adults). It's typically only needed for a few days. Perhaps that's where the stress should go: stop as soon as you can.
  - MattJ100 10mo ago
    Depends what you call "high", but the risks are far higher than most other drugs relative to availability. "Paracetamol toxicity is one of the most common causes of poisoning worldwide." -- https://en.wikipedia.org/wiki/Paracetamol_poisoning#Epidemiology https://en.wikipedia.org/wiki/Paracetamol_poisoning#Epidemio...
    - RobotToaster 10mo ago
      I was once told by a doctor that if aspirin or paracetamol were invented today they probably wouldn't be approved, let alone sold over the counter.
  - uniqueuid 10mo ago
    Paracetamol is the most common cause of liver failure in the US. Its toxicity threshold is somewhere around 4g/day for an adult. I remember that my wife once bought an over the counter cold drug in Italy that had > 1g per pill. So we should be aware that it's very easy to overdose this particular drug. More info: https://www.ncbi.nlm.nih.gov/books/NBK441917/ https://www.ncbi.nlm.nih.gov/books/NBK441917/
    - wasabi991011 10mo ago
      > Its toxicity threshold is somewhere around 4g/day for an adult. I was surprised it was that low, but I think you misread/misremembered. From your link: > Toxicity is likely to develop in adults at: >12 g over a 24 hours, or 7.5 to 10 g in a single dose, or Doses 350mg/kg The 4g/day is the dosage threshold, but it seems they set it to 1/3 of the toxicity threshold.
bonsai_spool 10mo ago
This is an amazing paper (but I’m not a statistician, apologies if I am overstating its value). Note that the GitHub repository associated with the paper is 2 years old and that this journal is not very popular - it likely was sent to Nature or NEJM and not accepted, though I wonder why it wasn’t sent to Health Services Research. Here is the lab page of the author whose GitHub was used: https://adaptinfer.org/ https://adaptinfer.org/

68 points by asplake 11mo ago

This is helpful in any number of fields with metrics-driven responses.

> paradoxical risk, where successful treatments unexpectedly lower the risk of higher-risk patients to below that of untreated lower-risk patients. This seems perhaps tautological whenever the treatment intensity is binary, and it's an effective treatment. Someone at the threshold that receives treatment would necessarily do better than someone at the threshold not receiving the treatment. It's a pretty good argument against any binary treatments, or at least to set the threshold low enough that improvement with treatment at the threshold is minimal.

hyghjiyhu 10mo ago
I have heard people gain weight intentionally to ensure they get these new weightloss drugs.
- RobotToaster 10mo ago
  If you're close to the BMI cutoff for it, it makes sense.

uniqueuid 10mo ago

Reading this I could not help but think of compliance and treatment safety for self-managed dosing. It's evident, for example, that drugs such as Paracetamol (Tylenol for you Americans) should be dosed by body weight in children. To make life simpler for parents, they are given age and/or weight brackets, sometimes along with upper thresholds (e.g. mg/day). This of course means that lighter children are comparatively over-dosed and heavier children under-dosed compared to a median. The problem is - I think this works pretty well as a safeguard against dangerous over-dosing (i.e. liver toxicity etc.). Now how would we turn that advice into a gradual dosing recommendation? We can use mg/kg body weight as is done e.g. in antibiotics. But that carries the potentially fatal risk of miscalculation, and some parents might intentionally overdose over a wrong risk perception. What we would need is something like an exponential risk curve, indicating a "safe zone" and a "danger zone" while highlighting some critical threshold. This again would need to be age/weight-specific. Do we think parents would be deterred from giving a kid too high of a paracetamol dose? I'm not so sure, especially over time. So in the end, I think that in some cases (especially with self-administered dosing) round numbers and sharp thresholds may work well to mitigate fatal risks, even while increasing nonfatal risks.

tgv 10mo ago
First, many people are ... let's politely call it arithmetically challenged. They won't understand how to compute the amount and then obtain the correct dose. A chart or a table might have more success than a formula, no matter how simple the formula. Then again, the dangers of paracetamol overdose aren't high (and I would think it's less for children than for adults). It's typically only needed for a few days. Perhaps that's where the stress should go: stop as soon as you can.
- MattJ100 10mo ago
  Depends what you call "high", but the risks are far higher than most other drugs relative to availability. "Paracetamol toxicity is one of the most common causes of poisoning worldwide." -- https://en.wikipedia.org/wiki/Paracetamol_poisoning#Epidemiology https://en.wikipedia.org/wiki/Paracetamol_poisoning#Epidemio...
  - RobotToaster 10mo ago
    I was once told by a doctor that if aspirin or paracetamol were invented today they probably wouldn't be approved, let alone sold over the counter.
- uniqueuid 10mo ago
  Paracetamol is the most common cause of liver failure in the US. Its toxicity threshold is somewhere around 4g/day for an adult. I remember that my wife once bought an over the counter cold drug in Italy that had > 1g per pill. So we should be aware that it's very easy to overdose this particular drug. More info: https://www.ncbi.nlm.nih.gov/books/NBK441917/ https://www.ncbi.nlm.nih.gov/books/NBK441917/
  - wasabi991011 10mo ago
    > Its toxicity threshold is somewhere around 4g/day for an adult. I was surprised it was that low, but I think you misread/misremembered. From your link: > Toxicity is likely to develop in adults at: >12 g over a 24 hours, or 7.5 to 10 g in a single dose, or Doses 350mg/kg The 4g/day is the dosage threshold, but it seems they set it to 1/3 of the toxicity threshold.

bonsai_spool 10mo ago

This is an amazing paper (but I’m not a statistician, apologies if I am overstating its value). Note that the GitHub repository associated with the paper is 2 years old and that this journal is not very popular - it likely was sent to Nature or NEJM and not accepted, though I wonder why it wasn’t sent to Health Services Research. Here is the lab page of the author whose GitHub was used: https://adaptinfer.org/ https://adaptinfer.org/