And a false positive screening result is not innocuous: it incurs costs in a variety of different ways, including human health.
If you're otherwise healthy and would have a 1/1,000,000 chance of having the disease before the test, and then you test positive with a test that is 99% accurate, you are ~100x more likely to have the disease than before - but that's still only 1/10,000 - not at all 99% likely, even though the test was "99% accurate"
That said, I think with this knowledge the test still confers helpful information. I might decide to spend $1000 on an additional diagnostic, even knowing that I'm still very likely to be negative. Depends on how wealthy I am, and how serious the disease is, and what the treatments for it are.
The problem is that diagnostics aren't necessarily risk-free. For example, there's a non-zero risk of death while getting a colonoscopy, to the point that false positives from unnecessary testing can increase all-cause mortality for patients.
Turns out, I needed to go to the bathroom frequently during the day which was an annoyance but I never had anything close to an "accident" nor did I feel any strong urge to evacuate at night. So the whole experience turned out to be a huge nothing-burger and I had a few polyps that got sniped that weren't cancerous - so now I have peace of mind that I didn't have before.
Late 20's Hispanic lady shows up in the ER with what they think is probably food poisoning. But they do a CT. Which shows changes in her liver which probably is a fatty liver. But they do a biopsy just in case. Biopsy results in a bleed which requires a transfusion and 4 days in the hospital. Biopsy result, fatty liver.
Surprisingly few ER docs anywhere in the world have even a rudimentary understanding of the risks of CT scanning patients. There's a lot of information around about this, but my own first hand (anecdotal) experience is that I've had ER docs try to convince me that it's basically the same as an X-Ray and act like I'm a crazy person when I explain that it's orders of magnitude higher and cumulative over a lifetime. On one hand, it's not their job to care about your long term health - they need to rule out an emergency and get you out the door as quickly as possible - but it's very concerning.
It's a bit like how general practitioners aren't taught about nutrition at all, so give out really poor advice for heart disease patients (the leading cause of mortality in Western economies).
https://en.wikipedia.org/wiki/Linear_no-threshold_model
Edit: For comparison, a chest X-ray is around 0.1mSv, a chest CT at 6.1mSv, so a factor of 61 between (https://www.radiologyinfo.org/en/info/safety-xray ). Compared to natural exposure (usually 1 to 3mSv/a) however, a chest CT isn't that bad at 2 to 3 years natural dose, 2 polar flights or 1 year of living at higher altitude or Ramsar (https://aerb.gov.in/images/PDF/image/34086353.pdf ). Acute one-time dose damage has been shown above 100mSv, below that there is no damage shown, only statistical extrapolations.
So I'd say that the risk of using a CT right away should be lower than the risk of overlooking a bleed or a clot in an emergency, where time is of the essence and the dance of "let's do an X-ray first..." might kill more patients than the cancers caused by those CTs.
Yeah, but what's the alternative when you have a stroke? They need to understand it's type and the mistake here is likely to be fatal since they require opposite treatments.
The trial followed 25,000 adults from the US and Canada over a year, with nearly one in 100 getting a positive result. For 62% of these cases, cancer was later confirmed.
(It also had a false negative rate of 1%:)
The test correctly ruled out cancer in over 99% of those who tested negative.
Based on your quoted sections, we can infer:
1. About 250 people got a positive result ("nearly one in 100")
2. Of those 250 people, 155 (62%) actually had cancer, 95 did not.
3. About 24,750 people got a negative test result.
4. Assuming a false negative rate of 1% (the quote says "over 99%") it means of those 24,750 people, about 248 actually did have cancer, while about 24,502 did not.
When you write it out like that (and I know I'm making some rounding assumptions on the numbers), it means the test missed the majority of people who had cancer while subjecting over 1/3 of those who tested positive to fear and further expense.
This is a bizarre thing to say in response to... a clear statement of the positive and negative predictive value. PPV is 62% and NPV is "over 99%".
Your calculations don't appear to have any connection to your criticism. You're trying to back into sensitivity ("the test missed the majority of people who had cancer") from reported PPV and NPV, while complaining that sensitivity is misleading and honest reporting would have stated the PPV and NPV.
Nope, there is another important thing that matters: some of the cancers tested are really hard to detect early by other means, and very lethal when discovered late.
I would not be surprised if out of the 155 people who got detected early, about 50 lives were saved that would otherwise be lost.
That is quite a difference in the real world. Even if the statistics stays the same, the health consequences are very different when you test for something banal vs. for pancreatic cancer.
Let's say you do have a positive test for pancreatic cancer. Overall 5 year survival rate 12%, but other than with other cancers, people continue to die after that. Basically, it is almost a death sentence if it is a true positive. Early detection will increase your odds a bit, and prolong your remaining expected lifetime, but even stage 1 pancreatic cancer, only 17% survive to 10 years. Let's say you are one of the 99% of false positives, because everyone gets tested in this hypothetical scenario. Let's say imaging and biopsy looks clean. No symptoms (which you typically don't have until stage 3 with pancreatic cancer, where it is far too late anyways). With the aforementioned odds, what would you do?
Panic? Certainly, given that if it is a real positive, you might as well order your headstone.
Panic more? Maybe people with those news will change their behaviour and engage in risky activities, get depressed, or attempt suicide (https://jamanetwork.com/journals/jamanetworkopen/fullarticle... ). All of which will kill some of those people.
Get surgery to remove your pancreas? Well, just the anesthesia as a 0.1% chance of killing you, the surgery might kill 0.3% in total. No pancreas means you will instantly have diabetes, which cuts your life expectancy by 20 years.
Start chemotherapy? Chemo is very dangerous, and there is no chemo mixture known to be effective against pancreatic cancer, usually you just go with the aggressive stuff. It is hard to come by numbers as to how many healthy people a round of chemo would kill, but in cancer patients, it seems that at least 2% and up to a quarter die in the 4 weeks following chemotherapy (https://www.nature.com/articles/s41408-023-00956-x ). And chemotherapy itself has a risk of causing cancers later on.
Start radiation therapy? Well, you don't have a solid tumor to irradiate, so that is not an option anyways. But if done, it would increase your cancer risk as well as damage the irradiated organ (in that case probably your pancreas).
So in all, from 100 positive tests you have 99 false positives in this scenario. If just one of those 99 false positives dies of any of the aforementioned causes, the test has already killed more people than the cancer ever would have. Even if no doctor would do surgery, chemotherapy or radiation treatment on those hypothetical false positives, the psychological effects are still there and maybe already too deadly.
So it is a very complex calculation to decide whether a test is harmful or good. Especially in extreme types of cancer.
Take those 99% false positives. If you just remove the pancreas from everyone, you remove 20 years of lifetime through severe diabetes. In terms of lost life expectancy, you killed up to 25 people. Surgery complications might kill one more. In all, totally not worth it, because even if you manage to save everyone of those 1% true positives, you still killed more than 20 (statistical) people.
And the detection rate might be increased by more testing. But it needs to be a whole lot more, and it won't help. Usually pancreatic cancer is detected in stage 3 or 4, when it becomes symptomatic, 5 year survival rate below 10% (let's make it 5% for easier maths). The progression from stage 1 to stage 3 takes less than a year if untreated. So you would need to test everyone every 6 months to get detections into the stage 1 and stage 2 cases, that are more treatable. Let's assume you get everyone down to stage 1, with a survival rate of roughly 50% at 5 years, 15% at 10 years. We get a miracle cure developed after 10 years where everyone who is treated survives. So basically we get those 15% 10-year-survivors all to survive to their normal life expectancy (minus 20 because no more pancreas). Averaging they get an extra 10 years each.
Pancreatic cancer is diagnosed in 0.025% of the population each year. In the US at 300Mio., thats 750k in 10 years. With our theoretical miracle cure after 10 years for 15%, that is a gain of 1.125Mio years lifetime. A 1 hour time needed for testing per each of 300Mio people twice a year for 10 years already wastes 685k years of lifetime, so half the gain already. That calculation is already in "not worth it" territory if the waiting time for the blood-draw appointment is increased. That calculation is already off if you calculate the additional strain on the healthcare system, and the additional deaths that will cause.
This alone is a disqualifier for your scenario. A test with 99 per cent of false positives will not be widely used, if at all. (And the original Galleri test that the article was about is nowhere near to that value, and it is not intended to be used in low-risk populations anyway.)
I am all for wargaming situations, but come up with some realistic parameters, not "Luxembourg decided to invade and conquer the USA" scenarios.
You are arguing for testing everyone there. If you cannot detect them by other means, you need to test for them this way. And do it for everyone. You have already set up the unrealistic wargaming scenario. You picked pancreatic cancer as your example where you do have to test every 6 months at least, because if you do it more rarely, the disease progression is so fast that testing is useless. There are no specific risk groups for pancreatic cancer beyond a slight risk increase by "the usual all-cancer risk factors". Nothing to pick a test group by.
And a 99% overall false positive rate is easy to achieve, lot's of tests that are in use have this property if you just test everyone very frequently. Each instance of testing has an inherent risk of being a false positive, and if you repeat that for each person, their personal false-positive risk of course goes up with it. All tests that are used frequently have an asymptotic 100% false positive rate.
Are you mistaking me for someone else? I never said or even implied that.
"And a 99% overall false positive rate is easy to achieve,"
Not in the real world, any such experiment will be shut down long before the asymptotic behavior kicks in. Real healthcare does not have unlimited resources to play such games. That is why I don't want to wargame them, it is "Luxembourg attacks the US scenario".
"There are no specific risk groups for pancreatic cancer"
This is just incorrect, people with chronic pancreatitis have massively increased risk of developing pancreatic cancer (16x IIRC). There also seems to be a hereditary factor.
Czech healthcare system, in fact, has a limited pancreatic cancer screening program since 2024, for people who were identified as high-risk.
https://www.cgs-cls.cz/screening/program-vyhledavani-rakovin...
Why probably?
I don't see where this "probably" comes from; it could well be the other way round. It is a new technology and its weak and strong points / applications may differ significantly from what we currently use.
Say that you are hunting the elusive snipe, one bird in a million. With standard techniques, you will have a lot of false positives.
But if you learn that the elusive snipe gives off a weird radio signal that other birds don't, your hunt will be a lot shorter.
Same with relatively rare cancers. If you can detect some very specific molecule or structure, your test will be quite reliable anyway. That is why I don't get your use of "probably". Unless you are really familiar with the underlying biochemistry, the probabilities cannot be guessed.
There is absolutely no reason why tests for rare diseases should have high false positive rates. In many other diseases, they don't. For example (although the underlying technology differs), Down syndrome is rare, but its detection barely has any false positives. You can test the entire pregnant population for Downs reliably, and many countries already do that.
https://www.cgs-cls.cz/screening/program-vyhledavani-rakovin...
For such programs, a blood test would be a huge boon and they could even expand the coverage a bit.
https://thennt.com/thennt-explained/
Also why I don't bother with PSA tests until I start getting symptoms: https://thennt.com/nnt/psa-test-to-screen-for-prostate-cance...
Reading the article, I'm still not sure about the accuracy, and don't have the time to carefully parse the whole article. I see at least the following statements (there may be more):
The trial followed 25,000 adults from the US and Canada over a year, with nearly one in 100 getting a positive result. For 62% of these cases, cancer was later confirmed.
and
The test correctly ruled out cancer in over 99% of those who tested negative.
Running the test using multiple different labs helps eliminate contamination and handling errors but most false positives are due to genetics and long term environmental factors.
Also, these tests are a grand a pop if I'm reading it directly (which I may not be)
Edit: There is in fact another comment on this thread of someone doing exactly this: https://news.ycombinator.com/item?id=45652535
To answer your question directly I don't have strong feelings about it. I would prefer if they were freely accessible, other than maybe things like antibiotics that have clear externalities.
I'm okay with insurance companies saying they won't pay for them unless a doctor writes a script, but to gate keep relatively harmless drugs the way we do isn't my favorite policy. There are many times I would love to get a drug but don't want to talk to a doctor about it. This is one of the reasons companies like KHealth exist - they're just rent seeking on a silly system. You can get anything you want, you just have to jump through hoops, but all those hoops just make doctors richer and health care cost more.
They're "trained to understand this type of stuff" in the sense that it will get a mention in medical school. Overwhelmingly, they aren't "trained to understand this type of stuff" in the sense that if you pose them a simple problem of this type, they'll be able to calculate the answers.
> Next, suppose I told you that most doctors get the same wrong answer on this problem – usually, only around 15% of doctors get it right. (“Really? 15%? Is that a real number, or an urban legend based on an Internet poll?” It’s a real number. See Casscells, Schoenberger, and Grayboys 1978; Eddy 1982; Gigerenzer and Hoffrage 1995; and many other studies. It’s a surprising result which is easy to replicate, so it’s been extensively replicated.)