6 ms·

The intent of non-invasive tests like this are that you give them to everyone, at scale, frequently. And specifically tune them to minimize false negatives. W

by ethbr1 2y ago

The intent of non-invasive tests like this are that you give them to everyone, at scale, frequently. And specifically tune them to minimize false negatives. Worst case with a false positive? You're causing someone anxiety and giving them an extra scan. Best case? You just saved someone's life by detecting an aggressive cancer early enough to do something about it. At the end of the day aggressive, metastatic cancer is a time game. If the cancer is given time, it becomes progressively harder and harder to treat, and effective treatment options become tougher on the rest of the body, until finally there's nothing to be done. So anything that gains time is critical.

giantg2 2y ago
They generally aren't going to give them to everyone. They will give them to everyone within a certain group, such as age 30+ since the under 30 group is very low risk (unless family history, etc). Similar to how they don't test most kids and younger people for cholesterol - it's just not a significant problem for that age group.
- ethbr1 2y ago
  Traditionally, tests have been metered that way because of costs (expensive reagents, preparation, processing) or side effects (radiation from scans). But the actual relevant equation is {cost of testing} vs {cost of delayed treatment} If the cost of testing, in economic and health senses, decreases while the cost of delayed treatment holds constant, a different mass deployment optimal point is created. Thankfully broader proactive testing is also in insurance companies' financial interests, given the high costs of late stage cancer treatment.
- bluGill 2y ago
  Nearly everyone will reach 30 in their life, so it is safe to say we give them to everyone. It isn't a one and done test, cancer can form at any time in your life. To be useful we need to give this to everyone over 30 (40, 50....?) , on a regular schedule (yearly?). The article doesn't specify those details (or at least not before I hit the sign in wall)
- absolutelastone 2y ago
  I think these days they do recommend screening all children for cholesterol.
  - AlexErrant 2y ago
    Which is good because "ASCVD is a disease that begins in childhood; hence, primordial prevention is an important target for improving cardiovascular morbidity and mortality later in life." > Elevated LDL-C and triglyceride levels have a positive correlation with atherosclerotic lesion prevalence that persists from childhood through early adulthood... Follow-up data from the Young Finns cohort after 12 and 27 yr also demonstrated positive correlations between elevated childhood serum cholesterol and triglycerides to elevated levels in adulthood... Children from the i3C cohort with high and borderline-high total cholesterol have 1.5 to 2.13 times the risk of both fatal and nonfatal cardiovascular events in adulthood than children without. In addition, i3C children with high and borderline-high triglycerides have 1.69 to 2.47 times the risk than children with normal triglycerides. https://journals.lww.com/jcrjournal/fulltext/2022/11000/primordial_prevention_of_atherosclerotic.2.aspx https://journals.lww.com/jcrjournal/fulltext/2022/11000/prim...
- litoE 2y ago
  One way to test lots of patients where a) there's a low probability that an individual patient will have the disease and b) the test is expensive is to first mix some of the blood of each of N patients and do one test on the mix. If the batch tests negative then all patients are negative and you've only paid for one test. If the batch tests positive then you have to repeat the test on the remaining blood of each of the N patients to determine which were positive. Thus, with a high probability you only pay for 1 test, and with a low probability you have to pay for N+1 tests. The value of N is easily computed to minimize the overall cost, given the cost of each test and the percentage of patients that have the disease.
nsxwolf 2y ago
Worst case is the scan “sees something” which then puts them on a diagnostic anxiety roller coaster for the rest of their lives, “just to be safe”. When in the alternate universe they might not have gone another 60 years hardly ever seeing a doctor.
- smt88 2y ago
  No, the worst case is death. Overdiagnosis of cancer leads to overtreatment, which has a risk of harm.
  - modzu 2y ago
    how is information making that worse? you either have a scan that shows a blip and you can use that information to inform your decision making, or you have no scan and go on without any kind of decision making. i know which option id prefer
    - jghn 2y ago
      Because you can wind up in a situation where the "blip" would have otherwise led to nothing problematic, but the followup for the "blip" actually does cause harm. And at an individual level it's impossible to tell which category you're in.
    - daedrdev 2y ago
      Every medical procedure after a scan has danger. Biopsies kill people. Colonospies kill people. The rate is extremely low, but test enough people who aren't at risk to have the disease and you will actively harm them.
jghn 2y ago
> Worst case with a false positive? You're causing someone anxiety and giving them an extra scan. It is arguable that this as minor an issue as you make it out to be. There has been work to try to assess this (google "cancer overdiagnosis"). The counterargument to what you state is that a false positive can not only lead to stress & unnecessary/more invasive screening, but a treatment plan that's a net negative. For instance: if a cancer were detected and it'd wind up being a cancer that someone dies with instead of from, and the treatment causes worse outcome than the cancer itself, that's not good. The hard issue here is that these things need to be determined at a population scale, and one can always cherry pick personal anecdotes in either direction to tug at heartstrings. We seem to have found ourselves at a point where it's clear there's a balance that needs to be struck, but it's unclear what that balance is yet.
- mattmaroon 2y ago
  He did say that you tune them to minimize false negatives. I do find it interesting that in the early days of HIV testing even most people who got a "positive" result were in fact negative. The tests have since greatly improved and the number of people taking a test due to hysteria rather than likelihood of infection declined. But I can imagine a world in which we get very many forms of liquid biopsies like this every year, and false positives become a thing we understand and are used to.
  - Goronmon 2y ago
    He did say that you tune them to minimize false negatives. That's a bit hand-wavy for something that appears to be the core issue with "test early, test often", isn't it?
    - mattmaroon 2y ago
      Well, it would seem hand-wavy to whichever scientists are tasked with improving it I'm sure! There's probably a lot of work involved. But it's pretty standard for new tests. The first ones are never the most reliable. Obviously the rate of false positives and expense of follow-up testing determine whether it's overall a good idea, but it probably will start out with a positive ROI that becomes a highly positive ROI pretty fast. I mean, yes, some people are going to freak out no matter how many times their doctor tells them about false negatives before they get the test. But overall this will save a lot of lives and as the test improves, a lot of money too.
belmarca 2y ago
I'm sorry but that is a very naive and honestly wrong take. An "extra scan" is not just giving anxiety. It raises cancer rates. It can discover underlying relatively bening conditions which affect insurance coverage, for example. It can cause anxiety. It takes away resources "just to make sure". At the scale you are proposing, false positives are a massive issue that you simply cannot ignore. It is all but trivial.
- moooo99 2y ago
  This is it, I am not sure how people can be so dismissive about the risks of over diagnosis. However, usually there are studies done to carefully weigh the risks and benefits of testing likes this. I would expect tests like these to become the norm for screening at risk populations at some point (usually people beyond a certain age or people with family history).
smt88 2y ago
This is incredibly wrong. This whole thread is. Cancer testing is not benign. False-positive cancer diagnosis has a >0 mortality rate, because further testing and treatment is potentially fatal. Just a colonoscopy can be fatal, as can a biopsy that requires anesthesia. The medical world weighs these things against each other and determines when the data shows that the risk of mortality from testing is smaller than the risk of cancer.
- blackeyeblitzar 2y ago
  > The medical world weighs these things against each other and determines when the data shows that the risk of mortality from testing is smaller than the risk of cancer. Let the patient weigh the odds. Especially when they can afford retesting or may be otherwise in good health or whatever. Plus the test’s algorithms can be tuned to provide more or less false positives.
  - smt88 2y ago
    > Let the patient weigh the odds. Patients are uninformed and emotional. Part of a doctor's job is to make the best decision for the patient using the information they have. For example, if you tell people that daily aspirin reduces the risk of heart disease, you might get a 25yo with no heart issues starting to take it. But if you look at actual data, all-cause mortality increases for people who have no risk of heart disease if they take daily aspirin, because aspirin can cause fatal internal bleeding. That's the kind of thing doctors know and need to be firm about.
    - blackeyeblitzar 2y ago
      I disagree. Doctors are frequently incompetent, don’t spend enough time with patients to understand them deeply, and are not aware of the latest research or these nuances. But leaving that aside, this is about patient control. Doctors should not be gatekeepers for diagnostics. I don’t even want them to be a gatekeeper for many relatively safe prescriptions, which is clearly a way to increase medical costs.

by ethbr1 2y ago

giantg2 2y ago

They generally aren't going to give them to everyone. They will give them to everyone within a certain group, such as age 30+ since the under 30 group is very low risk (unless family history, etc). Similar to how they don't test most kids and younger people for cholesterol - it's just not a significant problem for that age group.

ethbr1 2y ago
Traditionally, tests have been metered that way because of costs (expensive reagents, preparation, processing) or side effects (radiation from scans). But the actual relevant equation is {cost of testing} vs {cost of delayed treatment} If the cost of testing, in economic and health senses, decreases while the cost of delayed treatment holds constant, a different mass deployment optimal point is created. Thankfully broader proactive testing is also in insurance companies' financial interests, given the high costs of late stage cancer treatment.
bluGill 2y ago
Nearly everyone will reach 30 in their life, so it is safe to say we give them to everyone. It isn't a one and done test, cancer can form at any time in your life. To be useful we need to give this to everyone over 30 (40, 50....?) , on a regular schedule (yearly?). The article doesn't specify those details (or at least not before I hit the sign in wall)
absolutelastone 2y ago
I think these days they do recommend screening all children for cholesterol.
- AlexErrant 2y ago
  Which is good because "ASCVD is a disease that begins in childhood; hence, primordial prevention is an important target for improving cardiovascular morbidity and mortality later in life." > Elevated LDL-C and triglyceride levels have a positive correlation with atherosclerotic lesion prevalence that persists from childhood through early adulthood... Follow-up data from the Young Finns cohort after 12 and 27 yr also demonstrated positive correlations between elevated childhood serum cholesterol and triglycerides to elevated levels in adulthood... Children from the i3C cohort with high and borderline-high total cholesterol have 1.5 to 2.13 times the risk of both fatal and nonfatal cardiovascular events in adulthood than children without. In addition, i3C children with high and borderline-high triglycerides have 1.69 to 2.47 times the risk than children with normal triglycerides. https://journals.lww.com/jcrjournal/fulltext/2022/11000/primordial_prevention_of_atherosclerotic.2.aspx https://journals.lww.com/jcrjournal/fulltext/2022/11000/prim...
litoE 2y ago
One way to test lots of patients where a) there's a low probability that an individual patient will have the disease and b) the test is expensive is to first mix some of the blood of each of N patients and do one test on the mix. If the batch tests negative then all patients are negative and you've only paid for one test. If the batch tests positive then you have to repeat the test on the remaining blood of each of the N patients to determine which were positive. Thus, with a high probability you only pay for 1 test, and with a low probability you have to pay for N+1 tests. The value of N is easily computed to minimize the overall cost, given the cost of each test and the percentage of patients that have the disease.

nsxwolf 2y ago

Worst case is the scan “sees something” which then puts them on a diagnostic anxiety roller coaster for the rest of their lives, “just to be safe”. When in the alternate universe they might not have gone another 60 years hardly ever seeing a doctor.

smt88 2y ago
No, the worst case is death. Overdiagnosis of cancer leads to overtreatment, which has a risk of harm.
- modzu 2y ago
  how is information making that worse? you either have a scan that shows a blip and you can use that information to inform your decision making, or you have no scan and go on without any kind of decision making. i know which option id prefer
  - jghn 2y ago
    Because you can wind up in a situation where the "blip" would have otherwise led to nothing problematic, but the followup for the "blip" actually does cause harm. And at an individual level it's impossible to tell which category you're in.
  - daedrdev 2y ago
    Every medical procedure after a scan has danger. Biopsies kill people. Colonospies kill people. The rate is extremely low, but test enough people who aren't at risk to have the disease and you will actively harm them.

jghn 2y ago

> Worst case with a false positive? You're causing someone anxiety and giving them an extra scan. It is arguable that this as minor an issue as you make it out to be. There has been work to try to assess this (google "cancer overdiagnosis"). The counterargument to what you state is that a false positive can not only lead to stress & unnecessary/more invasive screening, but a treatment plan that's a net negative. For instance: if a cancer were detected and it'd wind up being a cancer that someone dies with instead of from, and the treatment causes worse outcome than the cancer itself, that's not good. The hard issue here is that these things need to be determined at a population scale, and one can always cherry pick personal anecdotes in either direction to tug at heartstrings. We seem to have found ourselves at a point where it's clear there's a balance that needs to be struck, but it's unclear what that balance is yet.

mattmaroon 2y ago
He did say that you tune them to minimize false negatives. I do find it interesting that in the early days of HIV testing even most people who got a "positive" result were in fact negative. The tests have since greatly improved and the number of people taking a test due to hysteria rather than likelihood of infection declined. But I can imagine a world in which we get very many forms of liquid biopsies like this every year, and false positives become a thing we understand and are used to.
- Goronmon 2y ago
  He did say that you tune them to minimize false negatives. That's a bit hand-wavy for something that appears to be the core issue with "test early, test often", isn't it?
  - mattmaroon 2y ago
    Well, it would seem hand-wavy to whichever scientists are tasked with improving it I'm sure! There's probably a lot of work involved. But it's pretty standard for new tests. The first ones are never the most reliable. Obviously the rate of false positives and expense of follow-up testing determine whether it's overall a good idea, but it probably will start out with a positive ROI that becomes a highly positive ROI pretty fast. I mean, yes, some people are going to freak out no matter how many times their doctor tells them about false negatives before they get the test. But overall this will save a lot of lives and as the test improves, a lot of money too.

belmarca 2y ago

I'm sorry but that is a very naive and honestly wrong take. An "extra scan" is not just giving anxiety. It raises cancer rates. It can discover underlying relatively bening conditions which affect insurance coverage, for example. It can cause anxiety. It takes away resources "just to make sure". At the scale you are proposing, false positives are a massive issue that you simply cannot ignore. It is all but trivial.

moooo99 2y ago
This is it, I am not sure how people can be so dismissive about the risks of over diagnosis. However, usually there are studies done to carefully weigh the risks and benefits of testing likes this. I would expect tests like these to become the norm for screening at risk populations at some point (usually people beyond a certain age or people with family history).

smt88 2y ago

This is incredibly wrong. This whole thread is. Cancer testing is not benign. False-positive cancer diagnosis has a >0 mortality rate, because further testing and treatment is potentially fatal. Just a colonoscopy can be fatal, as can a biopsy that requires anesthesia. The medical world weighs these things against each other and determines when the data shows that the risk of mortality from testing is smaller than the risk of cancer.

blackeyeblitzar 2y ago
> The medical world weighs these things against each other and determines when the data shows that the risk of mortality from testing is smaller than the risk of cancer. Let the patient weigh the odds. Especially when they can afford retesting or may be otherwise in good health or whatever. Plus the test’s algorithms can be tuned to provide more or less false positives.
- smt88 2y ago
  > Let the patient weigh the odds. Patients are uninformed and emotional. Part of a doctor's job is to make the best decision for the patient using the information they have. For example, if you tell people that daily aspirin reduces the risk of heart disease, you might get a 25yo with no heart issues starting to take it. But if you look at actual data, all-cause mortality increases for people who have no risk of heart disease if they take daily aspirin, because aspirin can cause fatal internal bleeding. That's the kind of thing doctors know and need to be firm about.
  - blackeyeblitzar 2y ago
    I disagree. Doctors are frequently incompetent, don’t spend enough time with patients to understand them deeply, and are not aware of the latest research or these nuances. But leaving that aside, this is about patient control. Doctors should not be gatekeepers for diagnostics. I don’t even want them to be a gatekeeper for many relatively safe prescriptions, which is clearly a way to increase medical costs.