hckrnws

https://europepmc.org/article/MED/39937880

Sadly, the group lists funding sources as: National Cancer Institute: P30CA069533 National Cancer Institute: P30CA069533

So the group's activities likely on pause, and with a good likelihood of closure due to the lack of NIH indirects from the current administration.

What is the correct amount of indirect for NIH grants? I'm not informed enough to have an opinion on this, but based on seeing the luxurious facilities and high administrative staffing levels at many research universities it seems like there might be some fat we could cut? I've read claims by other prominent researchers that this change is a net positive since it will free up funding for more actual research. So, I don't know who to believe?

Well just last year there were front-page stories on this website about the ballooning number of bureaucrats/admin staff at US universities. I think there was a flurry of articles since the proportion of admin staff had just exceeded faculty/students, or something similar. I'm with you though, I don't know who to believe, from the outside looking in. But some of the stuff that's been cut is only taking us back 5 years and it's hard for me to get worked up over that. What would really help with all these cuts is some historical perspective. Has 60% overhead been the norm for 50 years, 20 years, 5 years?

Gut response to this is twofold. First 'luxurious' sounds wasteful, but I guess that's the intent of the word. I suspect it's a trivial component of total funding, but is the most visible to non-science types.

Second, 'read claims' but not citing them sounds a lot like the hand-wavey 'People are saying ...'

Noted medical researcher and oncologist Dr. Vinay Prasad appears to be one of those people. I don't know whether his statements are accurate but he seems pretty knowledgeable about the system.

https://www.sensible-med.com/p/cutting-nih-indirects-is-sens...

Ah Dr. Vinay Prasad, a big fan of Robert Kennedy Jr.

He also compared the vaccine mandate to the Third Reich.

A very nuanced and balanced individual.

Do you have a substantive comment on that article or are you going to stick with low-effort, ad hominem snark?

metadata on Prasad is important data - if he cannot get basic COVID epidemiology science correct, and if he has a history of promoting a controversial agenda, it is telling gauge of how reliable the information he presents.

A quick look through his post: he cites overhead from several universities as "luxurious" but doesn't really go in to the specifics of why/how NIH and the institutions negotiated this amount. A lot of what he's complaining about seems more like his personal beef with university bureaucracy, which he tries to tie to indirects, but I think it smacks of someone who didn't bother to pay attention to the "people" part of the institutions he works for vs. the technical part of his work (see related post on linux kernel maintainer politics https://news.ycombinator.com/item?id=43037699)

He is wrong about private foundations with their no-overhead/15-20% cap. These grants are routinely rejected by university contracting; or if accepted, it doesn't really count to justifying a faculty's salary (and hence their future career at the institution) as bean counters do not consider the overhead enough to keep the department in the red/lights on when operating overhead costs are considered. The general gist I got when reviewing foundation grant opportunities were "that's nice, haha, but do this on your own time and not department time".

FWIW LunaSea's response is almost identical to what I'd drafted, but then deleted.

caycep's given a much more comprehensive response around the logistics & finances, as well as why someone's recent and objectively alarming public statements can (obviously) be used to assess their credibility and impartiality.

If this is the one & only person you can cite as a follow-up of your "So I don't know who to believe?", then my doubts remain.

I would be surprised if much of that funding went to constructing those fancy buildings - donors who want their name over the door like to do that. Keeping the lights on, air heated/conditioned, stockrooms stocked, etc don't come cheap. Let's also remember that the government doesn't _just_ get all the research output from that grant money, they get a pipeline of researchers (and undergraduates) that feed industry (plus world class research facilities that can do more research, beyond what the government directly funds). And that's a large part of what has made the US so economically successful, and such a desirable place for people to learn and work.

(Also professors and post docs in many areas can make a lot more in industry, so let's not knock them too much if a university wants to look at least a little attractive to them)

I've worked in higher ed for 26 years with nearly a decade each at two large research universities (1 public, 1 private). Indirects fund administrative (compliance, legal, HR, etc) overhead, facilities (bricks, mortar, plumbing, HVAC, etc.) and all the other stuff that a research lab needs to function and comply with the terms of their grant funding.

I'm sorry but there's no luxurious facilities being funded with research grant indirects. You've been misled or are mistaken.

Yes - I mean in the private sector, hiring an employee is what, 1.4-1.6x salary cost? NIH indirects mirror that.

Fair enough. So what is the optimal percentage for indirects? Did the NIH previously have it too low, too high, or exactly right? Is there some way to quantify this?

We likely aren’t going to be able to find a local or global optimum. But whatever it is one thing is for sure; a bunch of ill informed decision makers with no experience or expertise on the matter who come in and make sweeping changes are far more likely to cause great harm than good.

Can someone build an agent that identifies groups that will have to stop activities and then match them with groups outside the US?

This could potentially help to sustain their work if the other groups/labs agree to take over.

Good idea. If the American voter/taxpayer (by proxy) isn’t willing to pay for it, let’s find ways to find people who are

Genuinely curious: why downvote this idea?

Please remember this next time there's an election.

HN crowd remembering it is not enough. The problem in the U.S. is that the electorate is divided into two camps: the educated and the uneducated. The uneducated camp votes without a deep understanding of important issues, and they can easily be influenced using "culture wars" topics such as DEI and trans kids. Consider that 53% of Americans approve of the administration’s performance so far—why is that? How can we effectively explain things to that 53%? That’s the challenge.

"stupid people like trump and dont understand policy and are easily influenced. smart people(like me) like kamala and know whats best for everyone, how can we explain this to them"

hackernews is just reddit in slow motion

This is such surface level and frankly lazy dismissal of a stance or political view that a huge swath of people hold. It's like your "education" didn't really prepare you for the fact that other smart or educated people could come to different conclusions, so you use backwards logic to assign a label of uneducated to them just because they came to different conclusions. The arrogance of it is astonishing.

It is a fact that there is a difference in level of education. See: https://www.pbs.org/newshour/politics/trump-overwhelmingly-l...

The numbers are undisputable. City voters (who tend to be better educated) overwhelmingly vote one way versus rural voters. We can discuss the reasons for it, but if you don't even agree that this is a fact then I don't know how to discuss it.

Or a different take (because we didn't really do the "numbers" and removed all variables and angles to this):

- Right-leaning individuals are more likely to want to live in rural areas. Arguably to be left alone by leftist policies. So there is an element of filtering. Additionally, perhaps rural-living individuals are simply less-likely to go to higher education.

- People with more education have spent more time being indoctrinated by left-wing education. Let's be honest, schooling is heavily biased towards the left, especially higher-education.

- Maybe left-leaning individuals are more likely to send their kids for higher education and degrees.

- And the opposite of above. As an example, because I lean "right", I'm less likely to send my kids to an American indoctrination camp to get a degree. You could laugh and judge and claim disbelief, but this is very real and I'm serious. I've literally had smart, well thinking friends from school turn into zombies spouting left-wing talking points after moving to an American college. And not "smart" left-leaning talking points, they're arguably brain-washed and not even using their intelligence to reason their left-leaning views with me.

- People with more education are more likely to have been pressured by peer-groups to vote left. See: Cancel culture and intimidation on campuses against right-leaning individuals/speakers. And the opposite of that, left-leaning individuals are pushed out of rural areas due to pressure or push back from locals.

- People in urban centers are more likely to be exposed to political ads, campaigns, and things like "DEI" re-education programs in workplaces.

- Rural areas are less likely to have or fund arguably weird teaching policies to children at a young age. E.g. the whole drag-queen story hour stuff that the right is upset about.

- Left-leaning policies and programs are more likely to get funding by NGOs.

So you want to argue numbers, let's argue them. But don't pretend like there aren't any variables that drive those numbers other than "oh uneducated (implying stupid) people vote right" which if you are honest, was exactly the angle you were going for as a dog-whistle to other "educated" or "left-leaning" readers.

> As an example, because I lean "right", I'm less likely to send my kids to an American indoctrination camp to get a degree. You could laugh and judge and claim disbelief, but this is very real and I'm serious. I've literally had smart, well thinking friends from school turn into zombies spouting left-wing talking points after moving to an American college. And not "smart" left-leaning talking points, they're arguably brain-washed and not even using their intelligence to reason their left-leaning views with me.

Another way of putting this would be “I’ve seen people go off and get exposed to new ideas, and when they came back they no longer agreed with me.” But that doesn’t mean we should block access to learning.

I'm very cognizant of that, and I would understand it if they came back and reasoned or debated with me. But I promise you, the stuff I got back from some of these individuals was pure talking points and they were downright hostile and aggressive to even entertaining the idea of a debate on certain topics. It was eerie, and I love spirited debate and hot topics; they make in-person conversation lively as long as everyone stays civil.

On the other hand, your use of descriptors such as “American indoctrination camps” and “zombies spouting left-wing talking points” does not make it seem like you’re particularly open or receptive to “spirited debate”. These are not “civil” terms used by someone who is seriously interested in having his or her ideas challenged.

From my perspective, it sounds like your friends were exposed to ideas that would have been previously unavailable to them, and having had their horizons expanded, came to modify their views on certain things they had been effectively taught as dogma until that point. Then, when they came back and tried to communicate those newfound viewpoints, they were dismissed as brainwashed zombies who weren’t using their intelligence. I certainly would not consider it worth my time to argue with someone who believes me to be indoctrinated beyond hope and dismisses my intellectual capability simply because he or she disagrees with me.

To summarize your argument, the rural-urban political divide is driven by self-selection and environmental factors, where right-leaning individuals deliberately choose rural areas to avoid left-wing influences, while urban areas reinforce left-wing views through higher education, workplace policies, and cultural pressure.

This is a novel argument, one that I have not seen discussed a lot. If this is the truth then great.

But I am worried that it is not true. I am worried that what is really happening is that Billionaires are taking advantage of less educated voters by convincing them to vote against their self interests. They do so by shifting their focus to the "values and cultural issues" of the moment. In the past, it was gay marriage and abortion; today, it's trans kids and DEI. Once these issues dominate the conversation, little attention is paid to the real priorities and actions of these billionaires: Cuts to funds that research cancer (the topic of this thread), cuts to Medicaid, food stamps and other welfare programs, cuts to education, cuts to development assistance to the poorest in the world and so on, all to fund tax cuts for the wealthy.

If you're interested in this angle here's a book I can recommend: https://www.amazon.com/Whats-Matter-Kansas-Conservatives-Ame...

If your fear was true, the solution would be simple: the democrats could focus on important issues instead of pushing these (from my point of view, ridiculous and dangerous) cultural issues. Yet they push them vehemently, which caused this response. Why do you think they do that?

The current democratic leadership is dumb, in my opinion, because they allow attention to be diverted. They should shift towards the center on the "values and cultural issues" in order to neutralize the conservative advantage, then they will be able to do things that the middleclass (and lower) cares about, such as healthcare and health research, education, consumer protections and so on, and make the Billionaires pay their fair share of taxes.

I am afraid that is not what they learned :/ from what I can tell, they think Kamala ran too far to the right (whatever that means) and lost her base. It seems to me that these values are more important to them than we would rationally think possible.

To come back to the previous topic: n=1, but I moved out of a city to escape the bullshit and find some common-sense. I have a master's degree and my wife is an MD. We are not the only ones in our circle that deliberatly moved into a rural area :)

How happy are you with the NIH cuts, US withdrawal from Climate Agreement, vaccine sceptic being made secretary of health, US alienating Europe, proposed ethnic cleansing of Gaza, etc.? Maybe you have to deal with fewer trans kids, DEI and other such bullshit, but when you look at the big picture was it worth the trade off?

I believe in subsidiarity. If we cannot maintain strong families and raise children well, larger issues will become unsolvable in the future. Focusing on larger-scale issues at the expense of the most basic health of society is a recipe for long-term disaster.

Which means are justified to solve climate change and achieve world peace? And if we sacrifice everything our society is built on to reach those ends, where does that leave us?

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Can you help us understand why you support cuts to NIH and cancer research?

I can't help you with your reading comprehension. Where did I make any such statement?

I am merely pointing out that hysterically calling ~50% of the population stupid, uneducated etc, while feeling smugly superior to them, was not a winning strategy in 2016 or 2024, and proponents of said strategy seem unable to learn from repeated failures.

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You're doing great, keep it up!

This and so much more.

79% accuracy. Useless

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It's a pity that even discussing policy/objectives/outcomes is fraught with danger here. Partisan sniping obviously doesn't belong, but we now live in a world where vaccines, energy production and efficiency of use, climate science et al, are all "politicized".

For those wielding power, that's a feature, not a bug.

> we now live in a world where vaccines, energy production and efficiency of use, climate science et al, are all "politicized".

Oh, you speak from my heart. I wish these were not partisan and weren't coded for allegiances. Some things we should just be able to agree on, much like water being wet.

Every time the Culture War escalates to cover another important topic I groan.

Aw come on - the money is obviously much better spent on some armored Cybertrucks.

I've known > 10 people who have died from this cancer. It is my #1 fear (cancer wise). My best friend died 3 months to the day after being diagnosed. It is both a blessing and a curse how quickly this kills you. The day before he found out we went on a long walk. Within a couple of weeks we'd walk around the block, then just sit in his living room and talk for hours. The bad times lasted about 1 week and the last 2-3 days he was not really there.

I really hope this test becomes a reality and is OTC and not too expensive.

Just lost my father to pancreatic cancer as well a couple weeks ago. They caught it very early with a CT scan, performed a significant surgery followed by radiation and chemo. The chemo nearly killed him. Had a couple ok months after chemo, but then it spread and the last couple weeks were awful. Even catching this stupid cancer really early often isn't enough - I hate it.

just a hunch, but if you can detect it via CT or MRI isn't it already too late? I guess these blood tests can detect it even earlier an then the prognosis could be significally better

Not necessarily but that's the idea. Tumors will start shedding cells into the bloodstream as they start forming. These types of tests are able to identify tumor cells in a blood draw.

It's good that people are focusing on detecting such things early but unfortunately the management of any cancer basically falls into two categories - burn it or remove it. Burning maybe done via radiation, chemo etc. And treating liquid malignancies is even difficult.

I lost my absolutely fit and fine father last year to AML. I couldn't do jack shit about it and have this lingering feeling of how archiac the whole medical science - especially the drug discovery is.

No one in medical field is interested to cure any disease. All want to manage it so that pharma can get as many "subscribers" as possible to keep that money flowing in.

And such novel tests is just another mechanism to enroll new subscribers early in the journey to earn money for some more months. That's all.

> No one in medical field is interested to cure any disease. All want to manage it so that pharma can get as many "subscribers" as possible to keep that money flowing in.

I can assure you this is absolutely, 100% false. *Maybe* at the highest, corporate levels. I've never been privy to that level of discourse. I have however spent a lot of time working with the boots on the ground. Never have I come across a single one who intentionally avoided "a cure".

> No one in medical field is interested to cure any disease. All want to manage it so that pharma can get as many "subscribers" as possible to keep that money flowing in.

Care to support such outrageous claims with actual evidence or?

I was going to ask about this number, because it seems high enough to be statistically improbable, but back-of-the-envelope arithmetic says otherwise: there are about 10 cases of pancreatic cancer per 100,000 people per year [1], so let's say each person has a 1 in 10,000 chance of a diagnosis each year. If you know somebody for 50 years, there's a 1 in 200 chance they receive a diagnosis in that time, so you'd expect to need to know 2000 people to eventually know 10 diagnosed people. 2000 is a lot, but "knowing" a person is a pretty loose term, and pancreatic cancer has a miserably high death rate within 5 years, so it's unfortunately plausible.

[1] https://seer.cancer.gov/statfacts/html/pancreas.html

The number of people you know who have or die of cancer grows exponentially with age once you are an adult.

In 20s-early 30s, maybe 0 if your parents/uncles/aunts are lucky. You can be completely oblivious to it if your older relatives manage to escape it.

By 40 you start hearing about friends having it pretty routinely. We seem to have hit a one close friend per year pace at the moment.

Every time I talk to my 70+ parents, they are telling me about a funeral they've been to recently, often caused by either cancer or heart disease.

if you take the 1/200 chance over 50 years, here is the percent chance you know 10 diagnoses depending on your number of friends/acquaintances

50 people: 8.36149e-12 %

500 people: 0.026%

1000 people 3.1%

2000 people: 50%

This is people I know or my family knows. My mother knows 4-5 people. I've had 2 coworkers die of it. I've had 1 in-law die of it. It's crazy how fast the numbers add up.

Keep in mind that there could be clusters of cases related to environmental contamination so it's very possible that some people know more people who get a particular form of cancer.

My best friend died of pancreatic cancer at 41. By the time he received the diagnosis, it was too late. The cancer had metastasized so extensively that the surgeons could do nothing when they attempted to operate. What began as mild lower back pain led to a slow and agonizing death in just a few months.

That's exactly what happened to my friend's father. He had been complaining about lower back pain for many months and going to physio for it. During a family re-union during Christmas, he had to be hospitalized and got diagnosed with stage 4 pancreatic cancer. One week later, he died.

How generic these symptoms are! I always wonder if medical science has really attempted to study these diseases to understand their unique symptoms.

I lost my dad at age 62 last year to AML. His generic symptom was weakness.

I signed in just to upvote this. I've lost friends and relatives to this. I couldn't agree more that I fear this cancer more than any other- because it is so untreatable by the time it's caught. An inexpensive test would be incredibly helpful towards improving the survivability.

I'm so sorry for your loss. Could you share how old they were ? I'm relatively young, but the fear of getting some form of cancer is on my mind lately. And the timing of it always seems to be so cruel.

He was 76 and in really good health. Worked out regularly. Ate well.

Aspiring pancreatic cancer survivor here. This is excellent news. Part of the reason this is such a deadly form of cancer is that there are often no symptoms until it's far too late. I know that there is a blood marker - CA19 - can indicate issues with the pancreas. I don't know if this blood test is related to that or anything, but any advancements on this disease are great and sorely needed.

This is different and the study says it performs better than CA19

> The nanosensor correctly identified healthy individuals 98% of the time,

Since pancreatic cancer would have to be detected before any symptoms occur for this to be useful, the test would have to be applied to everyone. The incidence of PC is 1 per 10,000 per year. If the test is applied once per year, then for every true positive result there would be 200 false positives (actually worse, since it only detects PC 3/4 of the time.)

If you can cheaply test everyone, and narrow down the number of people requiring more expensive testing, you can potentially, at scale, detect and limit negative health outcomes. There is both an economic and societal benefit to testing and treating people.

If the more expensive testing is at all invasive (for example, biopsies) or still has false positives (benign tumors, say) then it could end up being a net negative. This effect has bedeviled screening for other cancers, like breast and prostate cancers.

Sure but the current state of affairs is clearly not optimal from an individual patients perspective. You notice this as you hit 40, 50 years old.

I know multiple "woops we don't screen often/early/proactively for that" cancer deaths in mid 30s to mid 50s.

I even know a few "wow good thing you had that CT scan for xyz, we just found some unrelated Stage 2 cancer elsewhere" people.

I know ZERO "oops false positive, we killed you with an invasive procedure" deaths. I know they happen, just clear to me its less often than the above.

From now on we should probably make all medical decisions treatment decisions based upon your steveBK's personal experiences.

Maybe you are young and/or lucky, but you'll find over time an increasingly disconcerting amount of friends&family dying preventable/otherwise treatable (with screening) deaths from cancer.

Note I said "from an individuals perspective". It is possible for the system to be optimized from a cost/benefit system level perspective without it providing the best possible outcome for each individual. Given that its run by the government & for-profit insurance, this is probably the case.

I think it is a bit hard to argue that the US medical system in general is perfect, and beyond reproach. Let alone the gaps in our pro-active cancer screening. Places like South Korea and China do far more, with less.

Can you please let me know which part of my reply made you think I was arguing that the US medical system is perfect?

Most of these symptom-less-until-you-are-dead cancers are very very slow moving and mostly hit above certain ages.

It's all in tuning the population & frequency.

You could test those aged 30+ or 40+ every 5, maybe even every 10 years.

I understand the recommendation for breast cancer screening is that women should stop doing it above age (I think) 70, even though the incidence of BC continues to increase with age, due to declining benefit/risk.

Correct a lot of stuff can stop being screened for because of incidence of disease, how slowly it moves, expected remaining lifespan, and ability of elderly to endure whatever treatment they would receive anyway.

Here is the link to the actual paper.

https://www.science.org/doi/10.1126/scitranslmed.adq3110

There seems to be a ton of benefits to doing all kinds of blood work - from vitamin deficiencies, hormonal changes, cancer signs, etc. Our system is very reactionary in that we order all these tests AFTER we get sick.

Why is there not a more proactive approach to getting bloodwork done with as many tests as possible? We should see this type of service like going to the dentist.

Seems like a good industry to disrupt.

You have to be careful with screening tests.

Say that this test has a false positive 1 in 1000 times. If you test 100,000 people, you'll get 100 positives that need invasive further testing and followup, and 5 real pancreatic cancer cases.

Society will pay for 100,000 tests, and 105 cases of followup. You may cause lasting harm to some of those 105 people. And then it's not clear if you can improve the survival of the 5 pancreatic cancer cases much. They'll live longer after diagnosis (because you diagnosed earlier) but not necessarily longer overall.

(One other screening effect: You'll find more "real cancer" that is so slow growing that it may have always remained subclinical before the more sensitive testing; And the most serious cancers, you won't find so much sooner, because they grow so much in the interval between tests.)

You would need to take into account how aggressive a given cancer is and our ability to treat it.

For instance, prostate cancer blood screening often led to radical treatments that are no longer thought to be worth it for most people.

> most prostate cancer grows so slowly, if it grows at all, that other illnesses are likely to prove lethal first

https://www.nytimes.com/2023/05/08/health/prostate-cancer-sc...

In the case of pancreatic cancer, it is much more aggressive and you need to catch it early.

> In the case of pancreatic cancer, it is much more aggressive and you need to catch it early.

It's not clear that the cancers that you would find early with a more sensitive test are those more aggressive cancers.

The pancreatic cancers we find with our current detection (generally after becoming symptomatic) are typically quite aggressive. But are they all the cancers? Likewise, if the cancer is aggressive, it can grow quite a bit between screening intervals and not be found all that early.

(Part of why we think that "finding cancer early" is such a benefit is that because the smaller/earlier cancers we find are less aggressive than the cancers that we first find when they're huge and spread. There is definitely an effect from earlier detection but our estimate of it has been confused by this effect.)

As we've increased cancer screening, we've found that survival rates have gone up, as have survival times after detection... but unfortunately we've often also found that the screening doesn't always reduce the number of people dying of that cancer at a certain age. Instead, you find more cancers, and you find them earlier so more people live to 5 years, even if you've changed nothing. Cancer treatment has gotten better, but most of the benefits we have expected from better cancer screening have not materialized.

Finding pancreatic cancer early sounds good. And it may be able to reduce mortality from pancreatic cancer, but it's not a sure thing.

My grandfather (a doctor) always used to say this. There’s also an aggressive fast growing kind of prostate cancer, but treatment basically does nothing for survival rates (or at least that was the case decades ago when he was practicing.)

So his advice was, don’t look, don’t treat. Either you have the slow one and treatment is harmful, or you have the fast one and you’re going to die soon anyway.

Your grandfather's take has become increasingly accepted for prostate cancer. There is more of a watch and see attitude to make sure that the patient doesn't have a rare case of aggressive growth.

As you mentioned, the outcomes aren't significantly different, regardless of how you treat it.

From the article linked above:

> Researchers followed more than 1,600 men with localized prostate cancer who, from 1999 to 2009, received what they called active monitoring, a prostatectomy or radiation with hormone therapy.

Over an exceptionally long follow-up averaging 15 years, fewer than 3 percent of the men, whose average age at diagnosis was 62, had died of prostate cancer. The differences between the three treatment groups were not statistically significant.

The irony is he died of prostate cancer. He ignored his own advice and treated it. It did not change the outcome or buy him much time, if any.

You can just run test multiple times to eradicate this possibility or you can confirm it with another method.

> You can just run test multiple times to eradicate this possibility

The measurements are not independent and the quality of the measurement is not improved by this.

> you can confirm it with another method.

Yes. And usually the other method is invasive and expensive and bears some risk.

And then you get results like the blood test saying "very likely cancer" and the biopsy saying "uh, probably not?" that you need to decide what to do with.

I'm confused. If this blood test gave a false positive that wasn't due to an anomaly in the blood itself, then why can't we assume that the likelihood of getting a false positive twice is lower than getting it once?

> I'm confused. If this blood test gave a false positive that wasn't due to an anomaly in the blood itself,

That's the errant part. A small amount of the false positives will be because of lab issues. The rest will be because this patient is different in some way, but not all of them are cancer. Medicine doesn't have very many perfectly specific tests.

So you have a patient who has some weird enzymes around because they're genetically different, for example, and they always pop positive on this particular test. Or has an unusual diet that causes some other non-tested-for-enzyme level to be high enough to set off this sensor. Or whatever.

In this case, the specificity is 98%, so this false positive rate is about 2%.

There was a seminar given to the breast cancer society by an epidemiologist years who who presented them with a scenario:

Prevalence of breast cancer: 1%

Sensitivity (percent of people who have the disease test positive): 90%

Specificity (percent of people without the disease test negative): 91%

And asked, "How many people who test positive have the disease?" (i.e., positive predictive value)

It's only 1/11. I think only 20% got it right (in a 4 answer multiple choice question)

Yah, I'm well familiar with the base rate fallacy and I still catch myself screwing it up. It's so unintuitive. I use mental math a lot to counter my intuition.

If sensitivity is high and the base rate is low, you can approximate it with .01 / (1-.91).

Or, mental math assuming 10,000 people is not unreasonable for your case (100 with disease, 90 true positives; 9900 * 9/100 false positives.. divide everything by 9 to make it easier, 10 true positives and 99 false positives, or 10/109 or say "9%".

For people surprised by this argument, the phenomenon he's invoking here has a name: the Bayesian Base Rate Fallacy.

Can't you just run the test again instead of doing a full follow up? 1/1000 * 1/1000 = 1/1,000,000

You only get that probability if the test results are completely uncorrelated, chances are, they're not.

I'd assume the chances of getting a second false positive if you already got one are much higher.

You are assuming that those false positive rates are fixed, but they aren't. The "positive" criteria are done by an analysis exactly as sophisticated as a human scanning a list of numbers. The process is a joke and it needs to be improved by more data and better analysis, not this nonsensical "don't test people because they might be positive" argument.

No, I'm assuming there's a tradeoff between sensitivity (spotting cancers) and specificity (having your positive results actually be cancer).

ANOVA to pick variables and then reasonably selecting thresholds is a fine process that avoids overfit.

The big problem is, biology is messy and measuring lots of people to find correct thresholds is really expensive and time consuming. It's not really a technological problem, though technology has helped a little.

> You may cause lasting harm to some of those 105 people.

Could you elaborate on this?

you will do surgery on some of the 105 people. Some of them might die from complications, infections, etc or at least have lasting damage. Since several of the 5 people will not be any better off with treatment it's entirely possible that the screening produces palpably worse outcome.

The earlier you screen, the worse this is, since the ratio of false positives vs true positives gets higher and higher, for example 1000 vs 5 or 10000 vs 5.

It's also psychologically harmful to have the positive test hanging over your head. I'm nearing the age where doctors start harassing about colonoscopies. You can do an at-home test instead of the full procedure, and it has a very good chance of ruling out the need for a colonoscopy. But it also has a high false positive rate; there's a decent chance that you'll end up in a state of "need a colonoscopy, also a colon cancer screener flagged you". I'm dreading the colonoscopy prep, but I'm not doing the at-home thing.

I've had colonoscopies twice. Was just half a day of inconvenience if you schedule it for the morning.

The scope, right? Not the at-home test? The only thing about the scope that bugs me is the prep.

I've been scoped twice and the prep sucks. It's shitting your ass out for half a day. On the positive side, getting sedated isn't half bad and you get the day off work.

And if you aren’t a fan of being sedated (I’ve never been, and I’d prefer to keep it that way), you can opt to do it without sedation. Had a colonoscopy and an upper endoscopy the same day, no sedation. A little uncomfy, but not painful. If you can push yourself through hard weight training sets, or run a 50k, or anything else that entails a bit of discomfort, a colonoscopy is no biggy.

I'm another one who's had two colonoscopies. Try to schedule it for the morning so that most of the fasting time will be while you're asleep. The prep is not a lot of fun, but it's only about half a day and it's very much not as bad as gastroenteritis or anything else that'll give you a good bout of diarrhoea.

For example you might do surgery on people who wouldn’t benefit.

How come nobody seems uses this kind of math when it came to COVID prophylactics? Or did they?

Then let's take those things into account when calculating what tests to do. Surely, though, we can do better as a society than solving this with "no preemptive testing except for extreme risks".

There's a ton of research and regulatory oversight in this area, and the choices made generally make sense. You can safely assume that the testing recommendations are 3-5 years behind the research, though.

The US Preventive Services Task Force (USPSTF) is the body doing that meta-analysis and writing recommendations. The recommendations are for general patients (high-risk patients should be identified and guided by their doctors), and are based on how much the screening/prevention will extend or improve patients' lives. The USPSTF explicitly does not consider monetary cost.

https://www.uspreventiveservicestaskforce.org/uspstf/recomme...

We do, it's not as if we aren't doing any testing. I've been getting a yearly prostatic antigen test for several years now.

The recommendations tend to take these into account, and then you and your doctor adjust.

Sometimes politics gets into it, like with the recent changes to breast cancer recommendations, but, overall, it works well for many people.

> Surely, though, we can do better as a society

We haven't even solved the most basic shit like shelter, food, education, &c for millions of people in the west, as a society we're faaaaaaaaar from universal yearly full health checkups. As an individual feel free to get private checks, they'll gladly take your money

The fact that there are huge costs in the USA to even periodic medical checkups has severely impacted longevity in the USA to the point it ranks close to Cuba in longevity. Those with a health plan are close to the highest ranked nations. The poor without a plan at all are around ~4-5 less long lived. There is a nice rabbit hole in this data. https://www.google.com/search?q=longevity+charts&rlz=1C1CHZN...

This has a huge GDP cost in the USA, that needs to be addressed. The causes are big pharma/hospo/AMA/insuro/lobbyo.... One wonders why the AMA is there? - they limit the numbers of doctors trained in Universities/training hospitals to forestall price competition among doctors by various means. Dentists do the same.

There is no proven health benefit to periodic medical checkups for healthy adults. At the population level it's a waste of resources. But certain preventive screening services are covered at no cost to the patient because they've been shown to be effective through high quality research studies.

https://www.healthcare.gov/coverage/preventive-care-benefits...

fixed annual, I agree, but symptom/test based assessments are useful

Cost of a yearly checkup should be "taken care of", because Obamacare mandated free annual checkups, as long as you don't accidentally trigger any other billing codes while you're there. But, regardless of cost, there's a shortage of providers, so it's hard to schedule the checkup. And there's still a lot of uninsured people out there.

> Society will pay for 100,000 tests

For better or worse, under the American healthcare system, the patient pays for those tests, sometimes covered by insurance. If the tests are paid for out of pocket by the patient, is there still such issue?

The economic argument doesn't change whether it's a private cost or purely a social cost (private costs are included in social costs, since private expenditures are part of society's expenditures).

I think the issue is exactly the same no matter who pays.

To reframe it from the individual patient's perspective, when you take a test simply for the sake of screening, there is the chance you'll learn something true that helps you, and the chance you will learn something false that hurts you

I was the tech lead at a YC company doing exactly this (Spot Health, W22) until a little while ago. There's a ton of very hopeful things happening in the industry behind the scenes. Insurance via employee benefit schemes is the lever to drive this into people's lives.

The industry refers to this as gap closure - care gaps are instances of a patient not receiving care when they should have. For example, not getting treatment for stage 1 cancer because you didn't have a checkup is a care gap.

Insurance companies are very incentivised to close care gaps because it results in cheaper premiums. Incentives between health insurance and patients are often not aligned (as we've seen in the news recently), but this is one case where they are radically incentivised to offer additional diagnostics if it results in fewer costly payouts for severe illnesses that come later.

In the medium term, the cost of full genome sequencing is quietly experiencing a 10x decrease in cost. Within a decade, I expect it to be the norm that all people are fully genetically sequenced and for the correlations enabled by that dataset to have made the value of being sequenced 10x. So probably a 100x increase or so in the value of genome sequencing over the next few years.

(Also, before anyone says it, yes 23&Me should feel very very ashamed for the deanonymised patient record data breaches they've experienced. The whole industry needs a slap in the face when it comes to privacy)

I guess after ~30 years past grad school in the software industry, having had high hopes for the internet and everything back in the 90s, I'm way too cynical.

This won't be used to "close the care gap", unless they can charge more $$ for the additional checkups than they'll expect to have to give out in care as a result.

And they'll drop anyone suspected of needing too much care in the future based on their genome, even if they aren't sick. Pre-existing conditions times 100 (you know they'll be re-instated by the current administration soon enough).

e.g. 17% of the people with that gene had cancer, and you have it, so raise your rates 151%. Oh wait, 37% of the people with this other gene had dementia - you're no longer covered.

Eventually, they'll only accept those people with a genomic lifetime 90% profit profile. That's the way this sort of thing works in the "real" world.

GINA prohibits health insurance companies from denying coverage or setting premiums based on member genetics.

Despite how much we know in medicine we still know too little. Bloodwork will give you a snapshot of that persons blood chemistry. It’s still up to the doctor and lab to put together what that composition means. In other words, if there is too much iron in the blood there could be x number of reasons for that. Most might be benign, and a small handful could be life threatening.

(Not a doctor just surrounded by them)

I believe the answer is the false discovery rate - https://en.wikipedia.org/wiki/False_discovery_rate

Theranos tried the "move fast and test blood" approach. Maybe one of the existing testing companies can find a more balanced approach in the current environment.

Theranos’ specific claim was that they could do existing tests with way less blood and way less cost. One of the ways they kept their fraud under wraps was to simply do the tests the old way behind the scenes.

So, blood tests in general were not the controversial part of Theranos.

As others have pointed out, the obstacles to large scale prophylactic blood testing are false positives, and general resistance of health insurers to fund anything not strictly reacting to disease or injury.

Widespread pre-emptive testing was not what Theranos tried. Defrauding investors that the technology existed for widespread, inexpensive pre-emptive testing even at small scale is what Theranos tried.

There is almost certainly gold in them hills if you dig deep enough and survey systematically enough, but Theranos started with precise coordinates, claiming they'd "found it", and demanded investors for a mine, while privately they were thinking "If we don't find it on the surface, who cares, we got paid, this is how VC works".

Theranos’s issue was that their tests simply didn’t work. It was more “move fast and pretend to test blood”.

It probably all comes down to cost. I remember reading studies about widespread melanoma screening and they were writing things that basically amounted to: "overall it adds ~0.5 day of life expectancy to the average Joe, based on costs &co it's worth it if you consider 1 year of human life worth $30k"

I find that doctors are very resistant to ordering blood tests. I often get responses saying it isn’t necessary or whatever. I feel patients should be entitled to whatever diagnostics they demand. I don’t know why doctors are even needed to get that done. Other than the scam of insurance coverage of course.

For me (eu) the dentist is pricy but these tests are included in public and private; i can ask my doctor any time and i get them, including for markers. Dentist costs, I do it every 6 months, but most people i know maybe once every few years.

The issue is that too much tests could also lead to false negatives and all the impacts that follow, especially on the patient's mind.

I just order them myself every year at LabCorp. https://www.ondemand.labcorp.com/products

I definitely prefer doing the testing myself instead of begging the doctor to order things.

About the only time I go to doctors is to beg for antibiotics- which they often refuse to give me. They say, "oh, it's probably a virus." Okay, but all of the virus tests I can find came back negative. I have a CBC showing elevated WBC. Coughing up yellow-green slime. Can you order a sputum culture for me? "no, come back if you are still sick after 10 days". Great, $200 and 30 minutes in the waiting room getting exposed to other sickos for nothing, miss another week of work. The gatekeeping of medical care infuriates me. I have plenty of money, let me use it to get better faster.

At this point you just order the same antibiotics off of Amazon for your "fish" and self administer?

I mean, you’re supposed to get a yearly checkup. They do blood work.

Yes but that blood work checks things like cholesterol and vitamin deficiencies. They aren't checking for these types of markers that point toward cancers. They may notice something is out of whack that may lead to more specific testing but I think the overall question is why aren't we just checking for everything more frequently with these blood draws?

I had to explicitly ask for Vit D and Iron/Ferritin to be added to the default bunch of tests on my decennial check-up as I was constantly tired. They eventually found out I had iron-deficient anaemia caused by undiagnosed Coeliac disease.

It's very important to advocate for yourself at the doctor.

My wife went to the doctor many times complaining about fatigue. Response: "Oh, you're unemployed, you must be just bored...".

We moved, new doctor, new yearly checkup, and one attentive doctor noticed something on her. 6 months and a whole battery of tests later she got a diagnosis of EDS. A genetic disease that causes issues with connective tissue.

She was always tired because her muscles were compensating in places where people who have normal connective tissue can rely on this tissue as a stabilizer.

I'm very glad that you were able to get your diagnosis.

The amount of blood drawn isn't enough to run all of these tests at once. They would need to multiple blood draws for tests that in most cases will end up being unnecessary.

I had a wide panel at one point after a statistically unlikely health event.

It was something like 300ml of blood spread over ~40 vials. They tried to charge me $7500.

It did lead to a diagnosis.

It's unnecessary until it finds something. My doctor is pretty thorough and I will give 3 vials with my yearly physical bloodwork. I get a pretty comprehensive set of results but my grandfather died of pancreatic cancer and I'd love for this to be included in that testing.

It's complicated - for screening to be done, the mortality reduction must outweigh the overtreatment and overdiagnosis risks.

Depends on the country you live in. There are countries that don't do them with similar health results as countries that do them.

There is a stereotype that Dutch doctors will prescribe paracetamol for anything because they are really defensive with medication and doctor visits and the result is generally the same as countries that do check ups.

Yes, but insurance does not cover large amounts of screening tests. Last year my A1C check was not covered. In North Carolina my wife's vitamin D test is not covered by her primary or gyno for routine checks.

Public service announcement: There are already blood tests for detecting pancreatic cancer and other cancers on the market, and more coming, depending on where you live. So get tested, if this is something you are worried about.

I believe the only commercially available one in the US is Grail's Galleri (https://www.galleri.com).

More info on this category of tests: https://www.cancer.org/cancer/screening/multi-cancer-early-d...

There are many tests in the pipeline -- although the technology is there, the regulatory and evidence process is slow. (Data relating to detecting cancer early, by its nature, takes a long time and a lot of people to prove out.)

The Galleri website says:

>Assumes screening is available for all prostate, breast, cervical, and colorectal cancer cases and 43% of lung cancer cases (based on the estimated proportion of lung cancers that occur in screen-eligible individuals older than 40 years).

Doesn't list pancreatic.

EDIT: never mind, I found a more complete list.

https://www.galleri.com/what-is-galleri/types-of-cancer-dete...

If Grail's Galleri is that great, why isn't it part of an annual checkup?

It's expensive, accuracy isn't very high, and no one has done the studies to demonstrate that it actually improves subject outcomes. By its very nature that type of research takes a long time because the investigators have to wait years to detect a difference in subject survival rates or other significant endpoints.

There's a huge amount of funding going into the liquid biopsy space so things will improve. But don't expect rapid changes in clinical practice.

Annual might not be any good. I knew a guy who had a history of colon cancer in his family. He got checked annually from his mid 30s on. At 46, a few months after a clear checkup, he visited his doctor who sent him for another check, and bam: he had cancer.

NHS is evaluating it now in a trial. https://www.nhs-galleri.org

An update on that trial: https://www.bmj.com/content/386/bmj.q1706

It doesn't look great.

Absolutely right! This test is hyped. It has abysmally low sensitivity of 16% to detect stage I cancers and overall 44% for cancers of other stages. It is extremely poor sensitivity for any detection test.

Sounds great.

> The Galleri test is available by prescription only.

But JFC I can't stand being required to get permission from one of those glorified bureaucrats just to collect data on my own body.

If you're feeling like your doctor/PCP is a gatekeeper, get a new one, seriously. Maybe I've been lucky, but my doctors have always written scripts for anything I ask for, assuming there's some validity to my need, and (though I've never tried) we're not talking about controlled substances.

Diagnostic test... they may not know what to do with the results, but I doubt you'll get pushback for a script. Insurance may give you a hard time, however, so assume you're going out of pocket.

> If you're feeling like your doctor/PCP is a gatekeeper, get a new one, seriously.

The problem is that even if they open the gate upon approach, they are still keeping it. It’s not about being denied, it’s about being required to ask permission.

There are online services that will pretty much rubber stamp your prescription for the test. AgelessRx and Function Health are two.

So for a test like this, do you just give it to everyone without symptoms?

For a very high mortality cancer is it even useful to test after you have reason to test?

I read about these tests and breakthroughs that involve general predictions and test, but I'm pretty sure when I go into the doctor I'm not screened proactively for all that much.

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.

> 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.

The existing downsides of a might-be-cancer hit on a test are real, for now - a statistically significant number of people with a breast cancer diagnosis end up killing themselves out of despair or doing radical surgery "to be sure", which detracts from the social benefit of mammograms. But there's no indication that they would persist if false positives were more common because proactive testing was more common. There would be a pipeline of followup testing and risk evaluation, which would be normalized by how common it was and how nonlethal diagnostic hits would become.

It would become "Oh, yeah, my cousin got a hit, but followup biopsy said it was a mutation that doesn't metastasize. Guess we'll see next week." rather than "My great-grandmother died of breast cancer, my mother died of breast cancer, my friend's aunt died of breast cancer, this feels like a death sentence", which is the information people who receive hits on their mammogram testing are acculturated with now.

Again, this is a well studied topic. Anyone claiming they've identified the one true answer isn't someone who should be believed. The topic is complex, at best. But these are not hypothetical situations. There are data to support the point to which you're countering.

You are correct that there exists a world where the problem is minimized and at that point obviously the math changes. But we're not there yet.

The argument is over whether we should seek to get there.

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.

Whether one should bias to allow more false positives or false negatives depends on the next steps after a false positive vs the risks after a false negative.

False positive: more costly scans

False negative: untreatable terminal illness

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?

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.

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.

The emphasis there is on "further treatment". The test itself is broadly benign (except the general risks associated with phlebotomy and any risk of psychological harm).

The issue is that doctors often over-react to adverse results due to the risk of being sued if it did turn out to be a true positive.

I have two examples of this. One was during a routine blood test I had a liver enzyme flag up, which was then further investigated non-invasively with ultrasound and it was determined that I might either have moderately developed NAFLD (non-alcoholic fatty liver disease, I'm obese) or very early stage NASH (non-alcoholic steatohepatitis) associated fibrosis. The doctor wanted to perform a liver biopsy to confirm which is obviously an invasive procedure with a 1%-ish risk of complications.

My response was to ask how the treatment would differ between diagnoses, and he said in either case the treatment would be the same: lifestyle change. He agreed that from a risk perspective the biopsy was just inviting additional risk for no benefit, but that policy is to recommend the test and if I refuse it I'll need to sign an indemnification document saying I was refusing further diagnostics against medical advice. A few years go by, I've made efforts to improve my lifestyle, lost weight, and now my liver tests are all normal proving it was just NAFLD after all.

In another case, I had a suspicious finding in an eye test which (long story short) led to me getting two head CT scans which showed no problems. In hindsight, I think a double dose of brain radiation over a common minor finding with no other symptoms was a crazy over-reaction and I would have refused if I had all the facts, but it could have been a life threatening situation in some ridiculously tiny percentage of cases so it was all rush rush and I didn't have time to weigh it up.

Often the correct thing to do may be a combination of further non-invasive testing, repeating the test (possibly after a period of time), and "watchful waiting". Doctors often don't feel comfortable with the level of personal risk that could expose them to, and for good reason. That is the issue, not the test.

> The issue is that doctors often over-react to adverse results due to the risk of being sued if it did turn out to be a true positive.

Do you think a patient is going to receive a false positive and accept a response from a doctor of, "Oh, might be a false positive. Let's ignore it and not do any more risky testing."?

That scenario makes no sense from either perspective. If you get a positive, you do more testing (or skip to treatment).

Your examples are well-taken and I understand them, but they don't apply to cancer. When you detect cancer with any test, you immediately do something risky: either a further test that involves risk, or treatment that involves a lot of risk.

I didn’t say we do nothing, it’s just the next step doesn’t have to be invasive testing.

Obviously the particulars are going to come down to the specific test, but you could be looking at a set of MRIs, repeated a few weeks apart to determine, firstly if it is a false positive, and secondly, how aggressive it seems to be.

In other cases it might be just repeating the test periodically and watching out for other symptoms. We do this with cervical screenings for example, since it’s quite a slow moving disease, where a low grade result will just result in you being put on a more frequent testing pathway.

It has been suggested that we should move to a similar protocol with prostate testing too, where a high PSA shouldn’t result in any immediate action unless there are other symptoms, but rather the test should be repeated periodically to monitor how the numbers are changing.

Now, that’s not to say you should do all tests. The test could still be pointless (i.e. there are no actions one can take in response to the result either way) or ,more commonly, simply not cost effective. However I fundamentally do not agree that more information itself is harmful, it’s just our response to it that’s lacking and that should be improved.

> Do you think a patient is going to receive a false positive and accept a response from a doctor of, "Oh, might be a false positive. Let's ignore it and not do any more risky testing."?

I mean, it depends on the test; a reasonable answer could be this is likely a false positive and confirmation tests have risks, here are some symptoms to look out for, and we'll test on a regular basis and see if anything changes. That's not appropriate for all positive results from screenings, but it is for some.

I feel like you're missing the point. Yes, false positives have risks. But if blood tests (or in the case of bowel cancer, fecal tests like cologuard) are effective, we can replace more invasive screening options with them. People have historically been encouraged to get colonoscopies once they reach a certain age because, for the general population, the risks of cancer are higher than the risks associated with a colonoscopy above the age of 50. Developing less invasive tests lets us lower that age, catching more cancers, while at the same time making screening safer for people already in the recommended screening window.

Also, pancreatic cancer, which is what the original article is about, has no alternate form of screening. Most people only find out they have it once it's already symptomatic, which is usually stage 3 or 4

> But if blood tests (or in the case of bowel cancer, fecal tests like cologuard) are effective, we can replace more invasive screening options with them.

That is not what I'm arguing against. People in this thread are talking about testing earlier and more often because we have these new tests, not "just" replacing existing tests.

The math is very unlikely to work out that we should do that.

Howso? Existing solutions vs more widely deployed and frequent blood+fecal tests followed up by existing solutions in the case of a potential positive?

I'd argue that you are the one missing the point.

These things are already taken into account via population scale statistics. In most cases, it's at best debatable whether more or less screening leads to an overall better outcome across the entire population aggregate. The argument against more screening is that it can (and the claim is it does) lead to overall worse outcomes in aggregate. For any individual case however, the story may be totally different.

What we need are better mechanisms to bin positive results to steer people towards a finer grained course of action. That'd change the math to be more of an overall net benefit.

> 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.

> 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.

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.

> Doctors should not be gatekeepers for diagnostics.

Doctors mostly aren't gatekeepers for risk-free diagnostics, like a blood test for a vitamin deficiency. Insurance companies are.

But for risky tests, doctors have a duty to "do no harm" and can't/shouldn't order something that they know causes an increase in all-cause mortality for their patients.

The concept is the same with antibiotics or anything else a patient might ask for without knowing the risks.

> Doctors mostly aren't gatekeepers for risk-free diagnostics

That's not entirely true. There are more than a few diagnostics in the US that the FDA explicitly discouraged companies from offering without physician referral. E.g. whole genome sequencing several years ago

Whole-genome sequencing leads to unnecessary treatment, like mastectomies. It’s not risk-free.

Whole-genome sequencing gives me more information about my health than I had before. Being ignorant is not risk free.

the obvious answer is additional testing to reduce the likelihood of a false positive -- if additional tests are invasive those tests can be weighed on the balance of risk just the same. i think the real problem is cost, we cant afford/manage to do that correctly currently, which is exactly what improved non invasive tests could enable and disrupt this reactionary approach forever

> if additional tests are invasive those tests can be weighed on the balance of risk just the same

So let's say you have an extremely safe test. Let's use the "mail your poop to a lab" test for colon cancer as an example.

If that test (regardless of its accuracy) comes back with a positive, you're going to do one of two things: A) order a colonoscopy, perhaps with biopsy, to confirm the presence of a malignant tumor; B) start treatment immediately (if you trust the initial test enough).

So that brings you back to square one: you shouldn't do the test, regardless of the safety, if the math works out to make it riskier (due to false positives and unnecessary tests/treatment).

i think i agree about "if the math works out" -- but thats the hard question isnt it? isnt the accuracy of the poop test significant? if 2 or 3 poop tests increase our confidence in the result it changes the risk:benefit calculation for the colonoscopy or treatment. thats an easy win. but even if it did not, is the result from the (preventative) poop test less valid data than a patient complaining of pain? so generally speaking i agree we dont want to enable a path to risky procedures based on dubious evidence, but i think overall we are presently operating with a dearth of information (waiting for symptoms) and the math itself improves by having more proactive testing (information) in the first place

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.

No, the worst case is death. Overdiagnosis of cancer leads to overtreatment, which has a risk of harm.

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

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.

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.

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.

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.

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.

I think these days they do recommend screening all children for cholesterol.

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/prim...

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)

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.

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).

Depends, colon cancer, breast cancer, prostrate cancer, etc. are pretty commonly tested/screened for in certain age groups and that definitely saves lives.

My aunt died of pancreatic cancer last year. It's a pretty common and aggressive form of cancer. She only had a few months from diagnosis to the grave. By the time she got diagnosed, there was nothing that they could do except provide pain relief.

My dad got lucky to get his detected relatively early (they happened to be doing an unrelated test and "saw something", but that just meant two years of chemo and all those side effects before he died. If they hadn't found it when they did it would have been 1 year of side effect free life followed by 6 months of pain for something untreatable - in short overall a better end of life though he would have lost 6 months. If they had found it 6 months sooner though odds are it would have been treated and he would still be with us.

If we don't detect more people early and try to cure them, it will never be solved. The more people that get detected early, the better chance everyone has of surviving, especially those in the future.

AFAIU, with pancreatic cancer usually by the time you have symptoms you are already stage 4 and uncurable. So I'm assuming the intent is to test non-symptomatic people.

That's what I was assuming as well. But then that leads to my other question, do we really regularly screen people this proactively for much at all?

In the US, asymptomatic people 50+ are routinely screened for colon cancer with a much more expensive and invasive process. A cheap blood test for another major killer seems pretty reasonable to add in.

Are we still doing colonoscopies on "everybody", or are we pivoting to the mail-in stool sample tests? FWIW, my health plan sent my wife and I the mail-in kits last year.

There is still debate on that. Colonoscopies are expensive and invasive, but they are the "gold standard". A colonoscopy is every 10 years, the mail in sample is every 3 (check with your doctor to see what is right for you). The mail in sample is not as sensitive as well - I used to know someone who died of colon cancer 1 year after a negative mail in sample, a colonoscopy would have saved her life. If the mail in sample finds anything they send you to a colonoscopy anyway (but you get to the front of the waiting list) to fix the problem.

For people at low risk the mail in sample is likely good enough, and since a colonoscopy has other risks (including kill you) may even be on balance be better for those. However anyone with a higher risk should get colonoscopies. Where the line between low and high risk is though is very much up for debate.

The above is general discussion. For medical advice talk to your doctor - who will know the right questions to ask to figure out what is right for you.

How do the "mail-in" samples compare against the Amazon "take a dab of stool and mix it in this bottle and look for a color change" test kits?

Depends. there are several different tests. Many are testing a for more things. I'm pretty sure the person I knew above who died a year latter had a basic test and we don't know if the better ones would have caught hers in time.

How long prior to that mail-in test was her previous colonoscopy?

There's a long list of stuff people are supposed to be screened for. Many people die of stuff that has high survival rates when caught early.

Pap tests, mammograms, prostate exams, are other examples for cancer.

Don’t forget about skin cancers. Screening for it is easily among the least invasive and least uncomfortable screening procedures for any kind of cancer, yet many people miss the opportunity for an early diagnosis

Measuring your blood pressure is an example of proactive screening.

I assume we will start screening for things like cancer when the test will be as simple / cheap as measuring your blood pressure.

Isn't this fundamentally a statistical issue? With a test sensitivity of 99%, meaning a 1% false positive rate, administering it universally to individuals would generate a significant number of false positives. This influx could overwhelm the system, potentially limiting access for those who genuinely require medical attention.

That's what I'm wondering too. Even if 1%, if the follow up is very expensive, the initial test might be cheap but overall cost might be very expensive / prohibitive.

So you are arguing we should just let people die?

This is a cancer that is typically detected only after it advances far enough that you will be dead in 6 months (not treatment possible). If we could detect it 2 years sooner it would be treatable and most people could life for many more years. Sure the total cost of a positive will be much higher - between whatever tests to verify it isn't a false positive, and all the treatment it will be a lot more money. However by spending that money many people will live a lot longer.

Maybe you don't like any old people, but I often wish I could show my dad my latest project. This test could have saved his life if we had it 15 years ago.

Technically we just "let people die" all the time.

We could spend more money on road safety (or say, reduce the speed limit to 10 mph) but we don't because the costs are too high.

Now, given the relatively common but almost universally fatal nature of pancreatic cancer, any sort of moderately effective screening is probably worth doing, but the argument that if we don't then some people will die isn't very strong.

That is a very differnt problem.

If you test enough people, you can reach a point where given you have a positive test, there is say a 90% chance it's a false positive. Taking further action can potentially harm you. Given the danger of further testing, and that many time people see no benefit from treatment, its is completely possible on average it can make die more often to get tested.

Only sometimes. A generalization like that is false. Until we have more data we won't know how the risks play out .

Screening recommendations are based on statistical arguments that take false positives (plus the risk of the test itself) into account and calculate whether more people would be helped than harmed.

If the test is cheap, you could run it 2 or 3 times. Then the false positive rate would be pretty low and you could proceed with more intense treatments/diagnostics.

That assumes that what causes the false positive is some kind of analytical noise in the test. The bigger concern is biological noise that would persist if you tested the patient again.

It might still be useful to know you have weird protease activity that isn’t cancer derived, but the more of these tests we do, the more likely it is that for every person, there’ll be at least one non-cancer oddity that looks like cancer signal for at least some test.

Isn't this problem fixed by just doing another blood test?

I thought that's how HIV rapid testing works.

Sensitivity is the false negative rate.

Although it is the opposite of what the doctors want, I would prefer a less sensitive but highly specific test.

If I had 80% sensitivity I'd miss out on 20% of cancers, but if I could match that with a 99.9% specificity I'd have very few false positives.

I hope this type of test can tune that direction.

> The nanosensor correctly identified healthy individuals 98% of the time, and identified people with pancreatic cancer with 73% accuracy.

ctrl+f specificity

Apparently, the current US administration has learned from the antiquated Bell Lab, its many large companies' research division, and inability for small biz to do independent research.

They're going back to DARPA model of smaller and much numerous grants approach which tends to be more responsive to real world needs.

Theorectical realm, like Livermore Lab or Idaho DoE, might take a backseat or they could just do many more smaller grants but with very specific real-world needs.

So, your first grant had better be (at least a micro-)success or it will be a long time before another grant comes along.

Is this the test offered by https://www.functionhealth.com/? I know they have an early cancer blood screening as a part of their tests.

Has anyone tried function? I'm curious how legit it is.

My parents got it for me. A lot of dark pattern upselling on the website you can't correct there but relatively painless to correct that on the phone. All the labwork seems to be done via CLIA labs in the standard way, they grab as many vials of blood as you'd expect and the numbers for one test were close to the ones from a test my doctor ran. Lots of hogwash interpretation in addition.

So: they're predatory but play by the rules.

I have wondered about it as well. I worry that I'll get a few results that are slightly outside of normal range and then sit around wondering if I'm dying, which seems like more stress than it's worth.

i have, feel it's reasonably priced, and i've been pleased with what i've gotten for the money. i wanted it for exactly the reason of "don't wait until after you've got a serious problem".

How come we’re always talking about new and amazing tests, but I never am able to actually get these test at the doctor?

Cheap for whom?

And it the part I can read without subscription it says simple test not cheap. Did they mention they price further down.

there's a number of new testing companies popping up (like superpower.com) that I recently used which make it easy to get these tests. doctors don't like ordering them because then they become medically responsible for the results.

Cue the doctors and industry saying "too many tests are bad for you"

Elizabeth Holmes: I was too early!

Speaking of the banality of evil in another thread, Elizabeth Holmes really just made a poorly timed stock pick. Lying and stuff, that’s a constant amongst that type, so let’s factor that out.

She might have been right all along though, weird.

There is an enormous gulf between what Theranos was doing and these sorts of tests. For starters, one was just making crap up. The other actually has some potential merit.

Her notion of frequent and cheap diagnostics was correct. But the main difference with their solution was being able to just do a finger prick, which was maybe a nice idea but definitely did not work. And their claims, knowing it didn’t work, were fraudulent and harmed thousands of people who got bad test results.

Steven P. Jobs.

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Thats for the summary. This is huge if proven true. The problem with many of the cancer tests historically is their high false positive rate.

Isn't this still too high of a false positive rate to be useful? IIUC, if you give this to 100,000 people, it will give you 2,000 false positive results. But only 13.5 new pancreatic cancer cases occur per 100,000 adults in the U.S. each year [0]. So if you took this test annually, a positive result still means a less than 1% chance you have cancer?

[0]: https://seer.cancer.gov/statfacts/html/pancreas.html

edit: although that NCI data doesn't make sense to me. If only 13.5 new cases appear per 100K, how can that accumulate to lifetime diagnosis rate of 1.7%? 100000 * 0.017 = 1700; 1700 / 13.5 = ~126 years to accumulate a 1.7% chance of diagnosis.

I wonder what the follow up test is like / cost. If it is highly accurate, but you end up doing expensive follow up tests for 2,000 people ... that has to factor into the overall "cost" of such screening right?

You wouldn't just screen the entire population with this test. You'd give it to the high risk factor subpopulations where the rate is way higher than 13.5 / 100K: older people, tobacco users, etc.

Makes sense, thanks.