
Gates, Bezos invest in cancer blood test - ourmandave
http://quadrangleonline.com/2016/01/11/gates-bezos-invest-in-cancer-blood-test/
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cant_kant
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/...](http://www.fda.gov/downloads/MedicalDevices/ResourcesforYou/Industry/UCM464092.pdf)
( it is a pdf )

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jforman
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.

~~~
seren
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.

~~~
jonwachob91
A CBC (complete blood count) test is a class I...

~~~
niels_olson
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.

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dharma1
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

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nommm-nommm
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...](https://www.sciencebasedmedicine.org/screening-for-disease-in-
people-without-symptoms-the-reality/)

~~~
dharma1
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

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tcbawo
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.

~~~
niels_olson
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.

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sjg007
First step is remission monitoring.

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

~~~
niels_olson
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.

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xupybd
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.

~~~
Grishnakh
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.

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xupybd
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.

~~~
Grishnakh
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.

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Grishnakh
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.

~~~
TeMPOraL
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.

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guelo
Meh, humanity is pretty good at producing more humans.

~~~
driftvel
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.

