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Gates, Bezos invest in cancer blood test (quadrangleonline.com)
111 points by ourmandave on Jan 12, 2016 | hide | past | web | favorite | 35 comments

Serum nucleic acid sampling to screen for malignancies has a few problems. One issue is that it runs into the realities of Bayes theorem.

You may want to consider what happened to Pathway Genomics. Their screening test claiming to detect 10 cancers in healthy people drew the ire of the U.S. Food and Drug Administration past year, which sent the company a letter saying:

"We have [...] examined published literature and have not found any published evidence that this test or any similar test has been clinically validated as a screening tool for early detection of cancer in high risk individuals," the letter states.

... We have reviewed the information presented on your website in the white paper, entitled “Liquid Biopsy for the Detection and Monitoring of Cancer: Analysis of 96 Hotspot Mutations via Plasma Derived Circulating Tumor DNA,” dated September 2015. It is unclear how the literature that you cited, addressing the presence of circulating tumor DNA (ctDNA) in already-diagnosed patients, is adequate to support the expansive claims of screening for early cancer detection using ctDNA in undiagnosed patients for up to 10 different cancers with the CancerInterceptTM Detect...

We believe you are offering a high risk test that has not received adequate clinical validation and may harm the public health.."

For the full letter from the FDA, see http://www.fda.gov/downloads/MedicalDevices/ResourcesforYou/... ( it is a pdf )

According to the Warning Letter, Pathway never registered with the FDA, never received clearance, and never performed any (reported) clinical trials. The key sentence from the letter is:

"We have conducted a review of our files and have been unable to identify any Food and Drug Administration (FDA) records reflecting the approval, clearance, or listing of these devices."

They were seeking to fly under the radar as a "lab-derived test" or LDT, using an FDA loophole that the FDA is increasingly seeking to close (also see Theranos). The "we've reviewed the literature" part is just the FDA's attempt to dig into what's been published to see if they can find ANY support for their marketing claims — even if there were volumes of papers on their method, they still would have been sent the warning letter (which is a Very Serious thing to get from the FDA).

The issue wasn't that "this test is too risky for us" it's that they were 100% out of compliance. If you sell a medical device, it must be classified for risk and at the very least registered with the FDA. In the case of a cancer diagnostic, there is zero chance it would be a Class I (lowest) device, so they (at least) would have needed "clearance" requiring a submission of something called a 510(k) documenting tests they've done on their product, audits of suppliers, etc. etc. In addition to the 510(k) submission itself, they would need documented evidence of having put in place a "quality management system" that puts standard operating procedures around 100% of product development from cradle to grave. This is why health tech/biotech companies need to raise so much money, as this is a lot of overhead.

If their test were classified as Class III (highest risk), they would need "approval" rather than "clearance," the bar for which is even higher (although this is primarily limited to ingestibles/implantables). Just the FDA submission itself costs something like a quarter million dollars.

GRAIL, on the other hand, is raising a huge amount of money partially because they know how much it costs to run proper trials and earn a clearance or approval. It's apples and oranges to compare the two.

Some example of Class III devices from Wikipedia :

> Examples of Class III devices that currently require a premarket notification include implantable pacemaker, pulse generators, HIV diagnostic tests, automated external defibrillators, and endosseous implants.[19]

I don't see how an cancer test can not be less than Class III. A misdiagnosis is potentially lethal.

A CBC (complete blood count) test is a class I...

There are also major medical training systems, for technicians and pathologists, who perform and interpret them.

The devices are class 2. Putting a QBC Star in every primary care clinic improves the quality of care delivered across the board and they are designed toward sensitivity: an automated counter has to have a low threshold for abnormal, which then kicks it to a human for review.

And the techs are trained to kick anything that looks like a blast to a pathologist. And it's not a one-time, in the school house tid-bit of education: every time they do a manual diff, they can't get from their cell counts to the signature block without acknowledging they need to show blasts to a pathologist.

> Serum nucleic acid sampling to screen for malignancies has a few problems. One issue is that it runs into the realities of Bayes theorem.

Which is that the occurrence of a genuine positive result is so rare that the false positives vastly outnumber the real positives unless your test is amazingly good.

And this is a bad thing when the interventions are as horrific as most of our current cancer treatments.

This is the reason for the recent recommendations for both breast and prostate cancers to reduce screening unless you have actual risk factors (family history, obesity, smoking, etc.)

I think people will be having monthly or weekly blood tests in the future. It will require just a drop of blood and many more conditions will be detected much cheaper and faster than now

I think that is an awful idea! Overdiagnosis and overtreatment is a huge problem right now! Here is a basic overview: https://www.sciencebasedmedicine.org/screening-for-disease-i...

You are right, my brother is a doctor and he has been telling me about this.

I do think though that this is due to our lack of understanding of health on many levels, and will be alleviated by better understanding of how these complex systems work. Machine learning will help a lot here

Are there stored sources of testable blood (blood banks?) that would be suitable? I would imagine that making predictions where we already know the outcome would be useful.

This is the idea of the deep freeze biorepositories that have been funded (and defunded). One of my friends is a molecular pathologist who does the MaterniT21. The data is quite tantalizing, because you're just going along looking for trisomy 21 and, wham, there's this case with tons of cell-free DNA that doesn't align, you call the provider, and the woman's been having constipation, the GI doc does a colonoscopy and she's got a fungating mass in her cecum.

But that's a long way from detecting small tumors. Which is something I'm not sure people understand: you need a big tumor to spill enough cell-free DNA to detect.

First step is remission monitoring.

For cancer screening? That doesn't make much sense.

No, in the regulatory pathway, it's easier to start with people who are already terminal and work your way back toward less sick people.

I've often wondered about things like this, I've wondered if improving medical technologies like this end up disadvantaging the poorer countries. If by increasing the life span of the wealthy west we pull more resources away from the rest of world? It seems as we get better at keeping ourselves alive we require more and more to do so.

I have no idea if I'm even close to correct in my speculation, but I bring it up as the Gates foundation investing in this seems to go against my hypothesis.

The premise of your hypothesis is that resources are zero-sum, when globalization, modern capitalism, and scientific progress have made this moment the greatest for poor people in all of human history. At the same time, the rich have gotten richer.

To answer your specific question, whether rich people living longer is good for poor people -- it would be, because those longer-living rich people aren't just consuming more, they are creating more. In other words, if we aren't losing as many people from cancer, our productivity goes up, and wealth abounds in all areas of human endeavor. If an engineer in Kansas didn't die of cancer, maybe he'll go on to invent a new method of soy cultivation that brings prices down and saves lives in Africa.

I think that to deny that health, life, thriving are good things, one must believe that humans are liabilities instead of assets. But they aren't. Humans aren't sandbags on human achievement, they are a necessary input.

WTF? You don't think that cheaper technologies are going to be available to other countries?

How much do we spend on cancer in the US alone? It's astronomical. If a simple blood test can catch it faster, that's going to save us a bunch of money, and increase productivity (people living longer). Why would this not also benefit third-world nations? It'll probably have a bigger effect there because instead of people dying because they can't afford expensive treatments for later-stage cancers, they'll be able to get cheap treatments early on and live.

This complaint of yours sounds like someone in 2006 saying "we shouldn't have these smartphones because people in poorer countries can't afford them, and it'll give us too many productivity and economic advantages over them". Meanwhile, here in 2015, everyone and his brother in India and China has a smartphone, and in fact third-world nations in general have done a much better job of pushing cellular technology to the masses than the US has, thanks to our telecom cartel which keeps service plan prices absurdly high.

I'm sorry I didn't mean to offend. My comment was not meant as a complaint, or a statement of fact, but as wild speculation. It was my hope that by voicing such wild speculation I'd learn something, and I have.

In no way do I think it's a bad idea to seek better medical treatments ever, I just worried that it might further the gap between the haves and the have nots. If one solution creates another problem sometimes best solution can be to fix the new problem.

Sorry if I was a bit harsh, but it just seemed to me that your comment seemed a bit like some schools of thought which basically amount to "no one should have any advantages over anyone else because it's not fair, so we should handicap everyone to the same level", but with nations instead of individuals. Or maybe "we shouldn't implement any new technologies until we can make them equally available to everyone worldwide".

The thing is, if you look at new technologies, they've revolutionized things not only here in first-world nations, but in thirld-world nations too. Phones are a prime example of this: a few decades ago, there were lots of 3rd-world nations where they didn't have widely-deployed telephones. The US and Europe had them of course, because they had spend oodles of money over many decades installing twisted-pair copper lines everywhere, giving us 1950s-level phone tech. Then along came cellphones, and they were expensive at first, so only businesspeople (like realtors) and rich people bothered to pay for them. Should the US have held back deploying cellular infrastructure, in order to wait for the 3rd world countries to deploy basic twisted-pair POTS? Heck no. Because after a decade or so, the costs came down so much and phones got so cheap that the 3rd-world nations just went ahead and installed cell towers everywhere, and skipped landlines altogether. There's a lot of 3rd-world nations with better cellular coverage than a lot of places in America! It's a lot cheaper to install a cell tower to service hundreds of people than it is to install twisted-pair wiring to hundreds of homes, so that's exactly what they did: they took advantage of superior and less-expensive technology to catch up with the developed nations faster. It would have been stupid and wasteful for them to deploy the older POTS technology.

It's like that with all technologies: costs get driven farther and farther down, and people in developing nations are able to take advantage of that, so those economies are improving rapidly, and the quality of life in those nations is rising greatly.

The way I see it, this "gap between the haves and the have nots" is not a problem, and doesn't even exist, if you're looking at a worldwide scale. It is a problem here in the US because things are so corrupt and broken, but that's an entirely separate issue. For the most part, things are improving a lot for people in developing nations, with some obvious exceptions in the Middle East.

This sort of test can reduce the cost of treating cancer. I saw a thing about it on the TV, the false positive rate is low, so it makes it possible to intervene earlier, which is a significant factor in treating cancer.

It also identifies what mutations are involved in the cancer, which may help in choosing effective treatments.

Take AIDS for example. While drugs remain expensive in the USA on the order of a $1000 a month, they are less than $200 a year in many poor countries, thanks to Bush laws and Clinton Foundation. Still they are reaching less than half the infected people due to broken local governments and money shortages. However we have several million people living when they would have miserably died.

Well presumably the beneficiaries of a cutting edge technology like this is going to be the upper echelons of the developed world.

The spoils of the productivity gains and economic growth in the developed world go to the knowledge worker and capitalist classes in the developed world, and the recipients of outsourced work in the developing world. So one hypothesis would be that increased lifespan of the wealthy in the developed world will increase the spoils the developing world will have access to.

Just a straw man of course.

No, because Western countries' populations aren't going up in the same way that poorer countries' populations are.

If the problems in Japan over the last few decades are any indication, keeping people alive longer will not advantage rich countries in an economic sense.

People will continue to retire in their sixties and live longer with progressively more expensive medical treatment. Not exactly a road to riches, although riches aren't everything.

Most of Japan's problems have nothing to do with demographics. That's just a fraudulent cover story used to hide the keynesian disaster. Debt and incompetent public spending that has been asphyxiating the private sector through malinvestment, has been the core problem (to go with continually bailing out zombie corporations). They loaded up on both debt and public spending since ~1990, and they got negative net real GDP out of it (even while their population increased).

Germany by contrast has seen zero population growth over 40 years and did not have similar growth (or debt) problems of the sort that Japan created for itself. Germany's GDP has increased nominally by 750% over those 40 years (their economy also tripled in size in the 15 years before the Berlin Wall fell, with zero population growth).

If demographics mattered that much, Germany's economy would be - and would have been - a disaster like Japan's is.

As long as the solutions can be digitalized or automated via technology it will always be to the benefit to everyone else. (unless it requires some rare materials of course)

As long as they can be "digitized or automated" and as long as we make sure IP restrictions won't get in the way.

Hehe sure that to, but even over time it will be less of an issue.

In light of today's news, I think it really sucks that they didn't have this technology available earlier so that David Bowie could still be with us, and also Lemmy from Motorhead who also died of cancer just a week or two ago.

I'd rather have my mom back, but you're right! David Bowie would improve the world so much!

Indeed. Moreover, if you consider the number of people who die every day, it's almost - no, it's precisely cruel our civilization is mostly ignoring the problems of aging and death. We should be pouring much more resources and people into this.

Meh, humanity is pretty good at producing more humans.

Would you maintain that attitude when confronted with your own or your loved one's diagnosis for something terminal and agonizing? Or is that cavalier, pretentiously "utilitarian" stoicism reserved for the young and invincible?

And even if you don't value your own health, substituting another warm body in place of a cold one does not undo the suffering caused by disease and death. All those people you don't care about deserve better than your "meh." And thank goodness we have so many people who disagree with it.

The same goes for the billions of people to have died of cancer so far.

We don't have the technology now either. It'll be at least 3 more years at best. That's probably a decade too late for Bowie.

We can't change the past but perhaps we can do something to discover more cures in the next decade. Almost 6 million people in the US alone die of cancer every decade. Many people are robbed of a few more good years.

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