Galleri Test: Exciting Results From Blood Test for 50 Cancers

They always could! Diagnostics are a bit different than therapeutics, which need that big Phase 3 trial before you can start selling a new therapy.

There are two regulatory regimes for diagnostics in the US:

1) Lab developed tests (LDTs) licensed under the CLIA legislation (I think from the 1980s). These are verified by a Lab Director with a professional license in diagnostics, that allows them to sign out clinical results from the test. There are professional organizations that perform regular inspections of the lab, its condition, its paperwork, its tests, the SOPs, and the internal validations that have been performed at the lab director's direction to assess performance of the tests. These are limited to a single site, the kits for the test can not be sold except for Research Use Only, and if a second site wants to start doing a similar test the lab director at the other site needs to do all the same validation all over again as at the first site.

2) FDA approval for diagnostic medical devices. These can be simple and straightforward for Class 1/2 devices, which do not directly provide medical advice but mere physical readouts (to greatly bastardize the distinction between Class 1/2 and 3). Or the device approval can be quite complex for Class 3 devices, and would require a huge trial like the one described here. If you want to sell the device for others to use, rather than just testing as service, you want to go this route. Though there are still single-site "devices" especially for DNA sequencing tests, that want the FDA label.

Neither of these will result in getting reimbursement for a test. For that, you need to pursue coverage determinations from all the payers, basically one on one. For complex sequencing tests like this that mostly affects older populations, getting CMS coverage (Medicare) can pave the path for others. For other conditions... well... get all your trials and papers together and hope that your patient population is super sympathetic or you can show the insurance company some savings.

A large clinical trial like this one can help with getting coverage for the test, but it has to either show a big medical benefit, or show economic benefits within five years for the payor. Or ideally both. Early cancer detection has potential for this, but I have not heard optimistic things up until now at Galleri's chance for reimbursement any time soon.

It could be that GP participated in a study, or simply had a cool doctor willing to pull a few strings.

More like classic Bayes. Taleb's pop-sci came a few decades later.

Their advertised sensitivity and specificity put them in the ballpark of what other liquid biopsies advertise. The ones I know of target high-risk cohorts where the benefits of other screenings already outweigh the risks of taking them. It doesn't make sense for the average person to be getting periodic full chest CT scans for instance, but it might for a decades-long smoker.

But if you got one test saying "Detected a fragment of pancreatic cancer DNA" two days later another saying "Didn't see any cancerous DNA fragments" what would the actual effect on the doctor or patient be? Who'll take the risk and say "the first was a false positive"?

Also, these tests are a grand a pop if I'm reading it directly (which I may not be)

Probably not. They are not likely independent. Whatever it is about you that caused the false positive yesterday might likely cause it tomorrow.

No, the factors causing the false positives are usually correlated. The most common cause is mutations causing unrelated proteins to mimic an epitope (binding site) of the biomarker protein. Another cause is analytical interference where some other molecule absorbs the wavelength used to measure the assay.

Running the test using multiple different labs helps eliminate contamination and handling errors but most false positives are due to genetics and long term environmental factors.

If the stats were as good as the hyperbole in the article, it would clearly state the only 2 metrics that really matter: predictive value positive (what's the actual probability that you really have cancer if you test positive) and predictive value negative (what's the actual probability that you're cancer free if you test negative). As tptacek points out, these metrics don't just depend on the sensitivity and specificity of the test, but they are highly dependent on the underlying prevalence of the disease, and why broad-based testing for relatively rare diseases often results in horrible PVP and PVN metrics.

Based on your quoted sections, we can infer:

1. About 250 people got a positive result ("nearly one in 100")

2. Of those 250 people, 155 (62%) actually had cancer, 95 did not.

3. About 24,750 people got a negative test result.

4. Assuming a false negative rate of 1% (the quote says "over 99%") it means of those 24,750 people, about 248 actually did have cancer, while about 24,502 did not.

When you write it out like that (and I know I'm making some rounding assumptions on the numbers), it means the test missed the majority of people who had cancer while subjecting over 1/3 of those who tested positive to fear and further expense.

> I might decide to spend $1000 on an additional diagnostic, even knowing that I'm still very likely to be negative.

The problem is that diagnostics aren't necessarily risk-free. For example, there's a non-zero risk of death while getting a colonoscopy, to the point that false positives from unnecessary testing can increase all-cause mortality for patients.

There are Silicon Valley startups increasingly selling these directly to consumers, so I wouldn't assume tests like this are always intermediated by a medical professional.

Edit: There is in fact another comment on this thread of someone doing exactly this: https://news.ycombinator.com/item?id=45652535

> The doctors who perform these tests are trained to understand this type of stuff. They're not just blindly accepting any single test result

They're "trained to understand this type of stuff" in the sense that it will get a mention in medical school. Overwhelmingly, they aren't "trained to understand this type of stuff" in the sense that if you pose them a simple problem of this type, they'll be able to calculate the answers.

Hyperbole.

I am not going to avoid any reasonable treatment/screen because of it. It was intended to catch asymptomatic cancer. Additional invasive screenings are voluntary and like all treatments they carry risk. I weigh all treatments based on their risks at the time.

For everyday people increased screening of all types has risks, but overall the benefits massively outweigh the risks. If I was a frail 80yo, I might see the risk profile differently.

In my career I've encountered many people who "don't want to know" about medical tests of any kind. I'm not one of those people. Minimally invasive screens early and often please.

> A common logical fallacy for our human brains is that we think, "Oh, I just got a test, so it's less likely I have cancer today," which is not how probability works.

Given my interactions with my doctors and their tests, they did seem to hold this belief, too.

In any case, the real mistake people make is failing to update their beliefs when new evidence (symptoms) appears. Rookie mistake. My doctors love to do (or rather, not do) this. Who needs differential diagnosis and re-evaluation when they can just keep the diagnosis and continue receiving a fuckton of money after you based on a secore-based system we have here?