[HN Gopher] The risk of round numbers and sharp thresholds in cl...
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The risk of round numbers and sharp thresholds in clinical practice
Author : asplake
Score : 63 points
Date : 2025-11-22 08:51 UTC (7 days ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| Terretta wrote:
| This is helpful in any number of fields with metrics-driven
| responses.
| avidiax wrote:
| > 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 wrote:
| I have heard people gain weight intentionally to ensure they
| get these new weightloss drugs.
| RobotToaster wrote:
| If you're close to the BMI cutoff for it, it makes sense.
| uniqueuid wrote:
| 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 wrote:
| 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 wrote:
| 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/Parace
| tamol_poisoning#Epidemio...
| RobotToaster wrote:
| 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 wrote:
| 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/
| wasabi991011 wrote:
| > 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.
| connicpu wrote:
| Right, the 4g/day number is the amount that should be
| safe for any relatively healthy adult (minus whatever is
| making them take the medicine). I should hope it isn't
| too close to the number where you can cause permanent
| damage.
| add-sub-mul-div wrote:
| It's become fashionable to fearmonger about it lately,
| but I agree, it's safe to assume the makers wouldn't
| tolerate the liability that would come with a single
| extra dose above the given instructions causing that kind
| of harm.
| LorenPechtel wrote:
| Yeah, toxic at 2.5x therapeutic level. Crazy in an OTC.
| throwaway173738 wrote:
| Yeah I've noticed that a lot of cold/flu remedies that have
| potential for drug abuse have huge amounts of acetaminophen
| adddes such that if you took both the flu medication and
| some tylenol, or you took multiple medications you'd be
| risking killing your liver. I worry that this is
| intentional.
| lotsofpulp wrote:
| A simple google search resolves this issue:
|
| https://www.tylenol.com/safety-dosing/dosage-for-children-
| in...
|
| If people aren't capable of finding this information, or even
| calculating it, it's an education system/societal problem.
| dmd wrote:
| Oh, then let's just fix that then! Simple!
| matheusmoreira wrote:
| Depending on location doctors will frequently come into
| contact with people who are illiterate, as in unable to
| write down their own names on a piece of paper. They still
| need care and it cannot wait until society has been fixed.
| Mistletoe wrote:
| What you are implying would work great in a world that had
| prioritized education. We don't live in that world in
| America for sure unfortunately.
|
| > The statement is a popular anecdote from the 1980s,
| illustrating a widespread misunderstanding where many
| consumers thought that a 1/4 pound burger was larger than a
| 1/3 pound burger because the number "4" is larger than "3".
| This led to the failure of a new third-pound burger
| campaign by the fast-food chain A&W.
| bonsai_spool wrote:
| Acetaminophen/Tylenol/Paracetamol and many similar drugs are
| indeed dosed by weight in the hospital but as sibling comments
| say, this is likely too complex for parents.
|
| In the hospital, a formulary likely carries pills of different
| medication amounts, so a nurse can readily administer the
| correct dose - which a parent would struggle with.
| matheusmoreira wrote:
| > To make life simpler for parents, they are given age and/or
| weight brackets, sometimes along with upper thresholds (e.g.
| mg/day).
|
| In my country doctors calculate the exact dosages and write
| them down on the prescription.
| HL33tibCe7 wrote:
| You're severely overestimating the mental capacity of a large
| section of the population.
|
| In fact, almost the entire population after little sleep or on
| a bad day is likely to make mistakes while following your
| proposed scheme.
| rayiner wrote:
| https://www.awrestaurants.com/press/press-
| release/101921-aw-... ("In the 1980s, A&W tried to compete
| with the immensely popular McDonald's Quarter Pounder by
| offering a bigger, juicier 1/3 Pound Burger at the same
| price. Unfortunately, Americans aren't so great at math.
| Confused consumers wrongly assumed that 1/4 was bigger than
| 1/3 (You know, because 4 is bigger than 3) and the whole
| experiment went down in history as a huge marketing fail.").
| xyzzy_plugh wrote:
| Furthermore it's incredibly convenient to mentally cache
| volumes like "10mL for this one, 24mL for that one" for ~6-12
| months at a time.
| uniqueuid wrote:
| Sure, most of us stay in system 1 (heuristic) most of the
| time.
|
| But I think it's wrong to assume most people are incapable of
| serious, thorough thinking. Parents around the world
| correctly dose medication for their kids all the time, and
| they mostly do this completely fine.
|
| The key is that people are clever when they both can and want
| to, and some communication regarding drugs is not well-
| designed to alert them to want at the right time.
| HL33tibCe7 wrote:
| > But I think it's wrong to assume most people are
| incapable of serious, thorough thinking
|
| I never said otherwise. I said that many are incapable, not
| most
| wolfi1 wrote:
| interestingly enough the antidote to tylenol poisoning is ACC
| (Acetylcysteine), a drug many could have in their household
| nick__m wrote:
| the acronym is NAC for N-Acetyl-L-Cystenine (the L is
| implied). With ACC you could theoretically have S-acetyl-L-
| Cystenine and that not the antidote !
| o11c wrote:
| Let's suppose arithmetic is a solved problem and only consider
| manufacturing and distribution.
|
| The major barrier to self-managed dosing, even if you want to
| do it properly, is that there's a huge difference between one
| pill and two pills. And trying to cut pills in half (if even
| possible for a particular pill structure) often makes very
| uneven halves (which is a problem for day-to-day variation even
| if a consistent "10% more than half" dose would be fine).
|
| I have seen dose differences of ~10% to be ignored between
| brands or over time, so that's probably safe-ish to ignore
| (certainly much better than the current 50%-if-lucky-
| else-100%). But counting out 10 pills is certainly a pain;
| realistically, aiming for a 5-pill typical dose would be more
| reasonable.
|
| My impression from looking at OTC costs is that the bottle
| costs more than anything, so manufacturing probably isn't the
| bottleneck. A side-effect of the current "one pill" mindset, in
| conjunction with expiration dates, is that low-dose pills are
| generally not available in higher counts, but there's nothing
| fundamental about this.
|
| Are there any "delayed/gradual release" concerns that get worse
| for many small pills rather than one large one? If so, is it
| really more significant than the wrong-dose problem?
| bonsai_spool wrote:
| 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/
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