You're really out of the loop, Obamacare eliminated excluding due to prior conditions and differing premiums for anything except smoking. In exchange we all got higher premiums, higher deductibles, and worse coverage across the board.
And yet, insurance companies are still making healthy profits [1].
In any case the problem with the US healthcare system is not that now everyone has a sort-of right to insurance, the problem is on the spending side. Y'all spend many thousands of dollars more per capita than the Swiss [2] but have worse metrics across the board.
There are a confluence of reasons behind this state of affairs.
- A few fundamental flaws of Obamacare that broke the incentive structure of the healthcare and some regulatory capture. (Granted, the incentive structure has always been a little broken even before Obamacare)
- A broken, overly politicized healthcare system in general (something, everyone can agree with)
However, people always seem to gloss over this fact: The United States is responsible for vast majority of R&D and revenue in the healthcare sector. Frankly, the US taxpayer and consumer are subsidizing the rest of the world including the Swiss.
As a US person, I would love to stop this dynamic and stop hearing this tired, patronizing argument.
FDA authorization has nothing to do with insurance coverage. I know of a small manufacturer that's had an authorized product on the market for over 3 years, not a single insurance company will cover it.
Insurance coverage is basically a waiting game between manufacturers and insurance companies. If you have enough capital to wait it out and schmooze executives, then you can get coverage. If not, good luck to you.
FDA approval makes it considerably easier, and in many cases possible at all, to get reimbursement for these tests. I work in the field and this is a constant hurdle to overcome.
In many cases medical insurers outsource decisions on what tests to cover to care guideline vendors such as MCG and Change Healthcare (Optum). Those vendors periodically update their guidelines based on medical research and evidence-based medicine protocols. For a new test to be covered it generally has to demonstrate some clear benefit in terms of improved patient outcomes.
For clarification, it tests for 47 genes which are associated with increased risk of cancer. It doesn’t help tell you whether or not you have cancer, in contrast to blood tests like Galleri, which can do that.
As someone in the field, I can say with certainty to expect FDA approved liquid biopsy tests (for somatic variants) to start appearing on market in the next year, if not sooner.
I'll also point out that detecting germline variants (which is what Invitae is doing) is considerably easier than somatic variants, which is what tests ala Grail and PGDx do. Of course this doesn't discount the work of Invitae, absolutely sound tech behind it.
Yeah I'm willing to bet there are more than one liquid biopsy tests submitted and likely to get approved.
I worked at PGDx for ~5 years and wrote an appreciable chunk of their bioinformatics pipeline, though I moved on to a different industry back in 2020 and am now out of date by that much. Though if you had asked me then, I would have bet that the first liquid biopsy test would be out by now; when I left was a short while after they had the first solid tumor somatic test FDA-approved.
Grails test isn't for somatic mutations but cancer specific DNA methylation patterns. DNA methylation is slightly more challenging to work with due to how the methylation is identified from sequencing data. There's a chemical of enzymatic step to convert unmethylated bases to another base. In humans it's usually unmethylated cytosines to thymines. The analysis is also more complicated but mostly standard now. Nonetheless, DNA methylation has proven to be very useful for liquid biopsies.
Reading the FDA notice, a lot of them will probably get FDA approval soon given this accelerated pathway. Looks like they just want 99% sensitivity and < .01% false positives on the targeted genes/regions, and as long as you can show your WGS coverage you don't need to do trials or whatever.
In what way is any of that actionable? Are there specific recommendations besides "eat right, exercise, don't smoke"? Sounds like something that could just induce anxiety.
If you know you are at risk for specific cancers, then you would likely get tested more regularly and could potentially catch them at an earlier stage when they're usually more treatable.
I haven't looking into this specifically, so I have no idea if that works for the types of cancers this tests for. My point is applies to testing just generally speaking
Well if you have the FAP (Familial Adenomatous Polyposis) gene then the action is to get your colon removed during adolescence, 20 years before you certainly die of colon cancer. The recovery is much easier at 15 than at 35.
The comment you've replied to is about the Galleri test by Grail. It tests for early _detection_ of cancer, not likelihood of cancer. Meaning, you _have_ cancer. Knowing you have cancer (hopefully early) is actionable...
You would think so, but when I brought the information pamphlet to my GP (who does blood work in office and took 2 vials for other tests at the same visit) and told her I am happy to pay the $1k out of pocket, she took a couple of weeks to research it, but couldn't find a way to prescribe it in the hospital system. Since it is a prestigious research hospital, she even found clinical trials ongoing and tried to get me included but I was too young for any of their subject groups.
2 years later, I still haven't found a way to take this test and have it's results be meaningful to any actionable health outcomes.
I believe the only thing I can do is find a sketchy online doctor willing to prescribe it, and then roll the dice on whether any related testing or care based upon the results would be covered by insurance (my doctors biggest concern)
You can do this via Galleri web site where a doctor will prescribe it for you.
It's also weird that your doctor would be worried that insurance won't cover the costs of cancer being detected early. Saving money in this situation is not something that is on the top of my mind. Worst case I incur debt and then declare bankruptcy if I survive.
Insurance unlikely to reimburse you, but its not prohibitively expensive. Some top tier employers like McKinsey cover the costs for employees over the age of 40.
Without knowing the sensitivity or specificity there's no way of knowing if it's telling you that you definitely do have cancer or just may have cancer.
As a specific example, this includes BRCA1/2 mutation testing, mutations that are strongly associated with breast and ovarian cancer. Actionable outcomes from a positive result could go from something as small as getting more frequent screenings up to something like prophylactic mastectomy and/or oophorectomy.
> Since WGS technology has no PCR enrichment of targeted regions, non-human contamination has a higher impact on overall sample quality metrics and can cause higher sample failure rates in Saliva and Buccal specimens. Therefore, blood is the preferred specimen for the Invitae Exome, when available.
Saliva is fine if quality is good, but it's incredibly hard to get people to follow protocol (no eating or drinking for 30 minutes, fill up to the line, shake the tube...)
Blood you can't really mess up because a phlebotomist handles the protocol.
Often early detection does very little to change when people die. It will mean that 5 year survival rates get better, because you have earlier detection which means more people know they have cancer for five years before they die, rather than finding out they have cancer 3 years before they die.
For lots of people this means they'll get lots of testing, lots of treatment, lots of harm caused by testing and treatment, and some of them will die early, and some of them will die at the same time, and some of them will have their life extended by all this testing and treatment.
It's really complex for the general public to understand this because it involves probability and statistics and these are both things that are very tricky for people to understand. (See eg Monty Hall or regression to the mean or anything involving percentages).
Everything you say is correct, but I think it's easy to come away with the impression that early detection is not helpful in living longer when I'm certain that's not the case.
I'm certain that expected time of death is a nonincreasing function of detection time -- this would necessarily be the case if the treatment never harmed the patient, and even though that's sadly not the case, prescribing a course of treatment that on average shortens patient lives must surely contradict "First do no harm".
If you assign a low quality-of-life score to time spent undergoing certain harsh treatments like chemo, then you could certainly reduce your "total quality of life" (that is, the integral over your lifetime of quality-of-life-at-each-moment) by starting treatment too early. I think that's a reasonable way to frame it. But in terms of maximising lifespan, the earlier you detect it, the better.
False positive rates are a concern for any widespread medical testing. If you test everyone in the USA for a rare disorder, a super great test might have a 1% false positive rate and 1% false negative rate. It's good that you catch 99% of people with the disorder, but that might only be 10,000 people. At the same time, you'll get 3.3 million false positives which will absolutely swamp the medical systems for follow-up tests, some of which will also have false positives. This costs a ton of money at the very least for unnecessary follow-up testing, and realistically would overwhelm the medical systems designed for just those 10,000 people. It also causes a great amount of undue stress and financial burden on the 3.3 million affected families.
Some people will also be unlucky enough to get false positives on the follow-up test, and eventually you may end up performing unnecessary invasive interventions on 30,000 people who don't have the underlying condition.
It's not to say that:
> the earlier you detect it, the better.
Is wrong, per se. But we'll need to narrow down the criteria for who should be recommended to get these tests in order to minimize harms from false-positives. So you'd want to identify risk factors and have a way to check if someone has those risk factors before testing them.
Just because I don't have a genetic risk for some cancers doesn't mean that I'll be OK to smoke. Different cancers have different causes, not all of which are genetic.
It's like saying that since you don't live in an area prone to earthquakes, you can also ignore other possible natural disasters (flooding, tornadoes, landslides, etc).
I feel like GINA act is superseded by the ACA barring pre existing health conditions as a pricing or qualification criteria.
It is crazy that people still comment as if a health insurance company in the US can deny or price insurance based on healthiness.
It’s been over a decade since anyone would have been asked for anything but age/location/smoking status when getting health insurance.
You still get asked smoking status on the exchange. It affects subsidy levels. * edit to say, I think it actually asks about tobacco use, not specifically smoking. But the point remains.
That said, most people know absolutely nothing about health insurance or health care in the US beyond the memes.
That is what I meant, legally, health insurance companies can only take into account your age/location/tobacco use in their premium pricing, hence that is all they ask you.
My primary concern with these are: what will it mean in a possible future to know your risk profile, and your ability to get/maintain health insurance, also without having to pay premiums. I live in the Netherlands, so probably not too much, but US could be different, and who knows what the future holds. Anyway, this makes me less/not want to take them...
In the USA there is The Genetic Information Nondiscrimination Act from 2008 that bars insurance discrimination based on your genes. I assume this will become a landmark law in the next 50 years as society becomes familiarized with routine blood (I mean gene) tests to drive preventive care to the next level
It shouldn't be a problem in the US. The ACA requires insurers to insure people with pre-existing conditions. (And GINA is also relevant here, as sibling mentioned. I was struggling to remember its name.)
> It shouldn't be a problem in the US. The ACA requires insurers to insure people with pre-existing conditions.
The ACA requires insurers to cover people under the age of 65 with pre-existing conditions and, more importantly, requires them to provide coverage at the same prices regardless of those conditions (they can only set price using a few pieces of information: age, zip code, smoking status, etc.). However, there are a lot of ways that insurers already skirt that second part, such as offering "discounts" to patients for certain elections which are strongly negatively correlated with various pre-existing conditions.
Furthermore, the ACA has seen a number of challenges over the last few years - most recently, the requirement to cover preventive care at no cost to the patient was struck down a few months ago. There's plenty of reason to suspect that this provision will be challenged in the future as well, and could easily be overturned.
> However, there are a lot of ways that insurers already skirt that second part, such as offering "discounts" to patients for certain elections which are strongly negatively correlated with various pre-existing conditions.
I agree with you re: the ACA hanging around unscathed. That seems like a bad gamble. Striking it down completely seems politically unlikely, but then there's Roe v. Wade.
They aren't skirting anything, discounts were explicitly written in to the ACA to encourage behaviors the government and insurance companies both wanted.
I wonder if this could keep you from even being hired for a job. Given two otherwise equal candidates I can imagine some companies may wish to choose the one which doesn't have a risk for a major cancer.
The sci-fi use case is that an prognostic / diagnostic / active learning agent pulling information from EHRs would use this as a prior.
More low tech is that you and your physician are more vigilant when it comes to monitoring or testing for certain types of cancer if you have a high impact onco-variant.
Keep in mind that prognosis for cancer improves dramatically when you can detect it early.
Even more sci-fi might be drugs that can mitigate the risk. Notable is the recent cocktail of drugs that coax the defective protein in CF to functioning better. There is one cancer gene I know that causes people to develop polyps in their intestines which then go on to become cancerous. Imagine a drug that stops that.
One of the weird things about oncogenes that I have observed is that there is a balance. Perturb them too far one way and you get cancer. Perturb them too far the other and you get a developmental disorder. This is not at all rigorously documented or studied. Just an anecdotal observation.
Invitae is doing the lord’s work when it comes to commercializing high quality genetic diagnostic tests and offering them directly to consumers at reasonable prices. We used them for prenatal screening. They offered the circulating DNA test - which is only covered for geriatric pregnancies - for a reasonable price. I wish the payers would cover these so they could be compensated more for what they do, but the US healthcare system is bonkers.
Some of the problem with these types of genetic tests - especially for stuff like PGx - is that physicians have not integrated them into their practice / workflows, so even when they get actionable info from one of these tests they don’t really know what to do with it.
We did prenatal tests to ensure that the IVF process we went through actually prevented our CF-genes from combining and causing the fetus to have CF. Also we knew very early there was no Down syndrome.
Unlike eugenics, where otherwise perfectly normal humans would have been born, this use case is focused on negative traits that would have resulted in a lifelong tragedy for everyone involved.
> Unlike eugenics, where otherwise perfectly normal humans would have been born, this use case is focused on negative traits that would have resulted in a lifelong tragedy for everyone involved.
If the intention was to abort a genetically undesirable pregnancy, then that is literally textbook eugenics.
You're not wrong, that is the dictionary definition of eugenics. However painting "aborting a fetus with CF" and "sterilizing the 'undesirable' races" as equivalent is a pretty massive leap in my opinion.
There's historic context to eugenics and a nexus with racism, nationalism, fascism, and physiognomy that makes it a harmful ideology.
I don't think those factors are present in the case where people doing the eugenics are the parents and the phenotype being selected against is dying a slow, painful death in the absence of lifelong exotic drug therapy.
There are really good questions about where to draw the line here though. What if it's type-1 diabetes?
> However painting "aborting a fetus with CF" and "sterilizing the 'undesirable' races" as equivalent is a pretty massive leap in my opinion.
I didn’t make that leap. I was just saying that this is eugenics, because that seems like a factually accurate description to me.
I would agree that not all eugenic systems are created equal, and that while you could debate whether aborting a child with a hereditary condition might be a bad thing to do, it’s at least not bad for all the same reasons as sterilizing populations to achieve some sort of racial purity would be.
I’ve never been confronted with these sorts of decisions, so I can’t be entirely certain how I’d react. But this seems like an important topic to debate as these technologies mature. However one way I can imagine that debate being undermined is if the people developing and advocating for this technology were to succeed in reframing it as somehow being not-eugenics, which to me it seems as though it clearly is. While it might be far less problematic than the Nazi eugenics programs, it’s not clear to me how you could put this technology to use without eventually creating some sort of Gattaca-like situation, which is also deeply problematic, just for different reasons.
it also gets into pretty uncomfy territory when you consider hereditary diseases that have a 40-60% percent curable rate in 5 years and most likely 90% rate in 10. Do you still abort under such circumstances?
Sure, if you want to define eugenics strictly in terms of selecting for features, but I think there's a difference between "selecting for A" vs "selecting for !B", with the latter not limiting the existence of A, C, D, etc. On paper these might seem equivalent, but when applied by a society it becomes the difference between "let's breed blond haired blue eyes people" vs "let's not have kids with Down syndrome" and I think "eugenics" has been primarily used to describe the former application.
You’re still choosing who gets to live based on their immutable characteristics. Which I would say is still bad, but not for entirely the same reasons as the Nazi program was.
And as I mentioned in another response, if this technology eventually becomes very sophisticated, how do you prevent some sort of gattaca-like situation emerging?
You’re still discriminating upon who gets to live, and “at least it’s not racist” doesn’t seem like a particularly compelling defence of that idea to me. It also doesn’t impact the myriad of other potential downstream issues.
I did one of their tests for some IVF stuff. Frankly if you can do this it seems like it’s almost unethical not to check if you and your partner don’t have some sort of horrible incompatibility that you should try to work around with IVF.
23andMe works by checking ~1M sites along the genome, and using known correlations with pathogenic variants. This Invitae test actually sequences the (coding portion plus a bit of) the genes involved, and can detect rare[0] mutations. Additionally, Invitae puts a ton of effort into determining whether any particular variant (of which you certainly have very many) is benign or pathogenic.
Invitae has argued that (especially in certain under-represented populations), the 23andme approach is going to miss a lot of important variants [1].
_disclaimer: I’m a former Invitae employee and still holding the bag on what used to be a lot of stock . All opinions are my own. _
[0] Rare on the population scale. To a good approximation each person has only 0, 1, or 2 copies of any given polymorphism.
There's a big difference between what 23&Me includes in their technology and reports compared to solutions that are production grade medical tests. That said, 23&Me does tout their results as being medically relevant (https://www.23andme.com/brca/)
(for a while, only Myriad could do any tests with brca1/2 because they had a patent on the literal gene sequence. it went to the supreme court and the court said no, you cannot patent human gene sequences)
Invitae has done some good work scaling up genetic testing and increasing its accessibility, but tried to play a risky high growth game and paid the price when the economic landscape started to shift. Hopefully their efforts aren't lost if the company doesn't survive in its current form long-term.
Any Cancer-related news is exciting, but at the same time, I feel like knowing that I'm at an increased risk will make me obsess over it, and end up being a net-negative for me.
Can you give me some keywords to get started with this if you are acquainted with the field? I can try to work my way to something if it's just software that needs to be written and textbooks to read.
Would be appreciative. I will try on my own as well.
The variants in ClinVar will have genomic coordinates associated with them, each given with respect to a particular reference genome, e.g.
GRCh38 - chr2:41785474-41785474
or something like that.
You will need to align your FASTQ to one of these reference genomes using a short-read aligner such as BWA-MEM (assuming your genome was sequenced using something like Illumina NGS) to produce a BAM (binary alignment map) file, and then from there use a variant calling tool such as GATK's HaplotypeCaller or Google's DeepVariant to produce a VCF (variant call format) file, which will contain the mutations in your genome. Then you can see if any of the mutations found in your genome match those in ClinVar.
As humans are diploid, you will also need to be cognizant of the zygosity of each mutation, i.e., whether you have a particular mutation on just one of your two chromosomal homologs (heterozygote) or both (homozygous mutant), as this may affect whether or not the mutation is of concern, the variant caller will attempt to determine this for you and report it in the VCF file.
Does anybody know how much this costs? The website is not at all transparent about this.
I’ve been navigating a nightmare through my insurance trying to get BRCA testing because I’m not female despite an immediate familial history and non-trivial potential risks. I’m looking for options so I can understand my risks without paying thousands out of pocket.
Insurance doesn’t seem to have any interest in proactive screening, only in reactive which really sucks.
Even if they had a "perfect" analyzer, that could tell them all about every atom in the sample, Theranos's test still wouldn't have worked.
This is because Theranos's product wasn't just claiming to look at DNA. It claimed to measure things like cholesterol levels and pregnancy hormones, molecules that are circulating in the blood - all with a pinprick of fluid.
If you had a "perfect" analyzer, you would need just one cell to get someone's full genetic code. However, something like blood cholesterol is a statistical average - you need to take enough blood to ensure that the percentage of cholesterol in the sample is reasonably close to the percentage in the patient. It's a population sampling problem (same as how you wouldn't be able to predict a senate election by polling 50 people on who they were going to vote for, even if you could ensure they were 100% truthful with you - it's just not enough people). No tech can get around that.
What Theranos did was like promising a ticket to the Moon for 50 dollars one way.
No one doubts that you can fly to the Moon for 50 billion dollars. Perhaps, in the future, it will be feasible to fly there for 5 million dollars. But 50 dollars is beyond the realms of possibility.
I have serious doubts that any individual or company, starting from scratch not having previously built rockets, gets to the moon on $50b, especially with any sort of safety margin built in.
'Next-generation sequencing' was arguably invented in 2000, so it would have been available for Theranos. However, AFAIK they never really tried to sequence DNA, so the availability of 'next-generation sequencing' was irrelevant to the accuracy of their test.
I wonder what the advantage is of a blood based test over existing saliva based hereditary cancer screens (that do genome sequencing instead of 23andme type array testing).
What’s the cost of this test?
We’re going to see many DNA sequencing tests being available in the near future, but I hope they’re not going to be expensive so that diagnosis and prevention can be available to all.
This isn't a test for hereditary cancers. It is test for the gene's that indicate you have an increased risk for hereditary cancers. It matters as there are actual blood tests for cancer available now.
If interested, there's already DNA Genetic testing that screens for many conditions (more? Not sure about overlap). No blood draw necessary, only saliva. They also screen for partners who are hoping to conceive. Contact a Genetic Counselor.
I'm not a doctor, so standard disclaimers apply: I've followed the LEF's recommended list (https://www.lifeextension.com/magazine/2006/5/report_blood) since I was in my early 30s. Doing them every year or two, out-of-pocket using DirectLabs or similar, which frequently goes on sale for ~$250. The key mentioned on that LEF page, and echoed by longevity doctors, is that the standard test ranges are often too wide.
I also paid out of pocket recently (age 42) for a coronary calcium scan. It was surprisingly inexpensive (~$125), but did require a prescription.
One thing you will probably hear from your GP is that these kinds of tests are a waste of money for someone near 30, and speaking from population averages, they're correct. Odds are, there won't be anything in there that is actionable or useful, but I think there's value in establishing a baseline and observing trends over the years. Of course, if you fall into the rare case where your CAC shows a >0 score, that's a really valuable bit of info.
Those, to me, always seemed like the best value to $ spent, for someone younger than 50. I suppose an early (<45) colonoscopy might approach that value, but those would be thousands out of pocket.
I hope this is a first of many and that genetic testing of more conditions gets approved soon.
I’m currently paying for a test suite during my IVF process that will also test for things like ADHD risk, diabetes risk, and low IQ risk[1]. I think soon it will be basically immoral to not do these type of screenings and it should be accelerated.
If you're using GP, they don't do monogenic screening like the hereditary cancers described here (it's an assay that's good for GRS but can't do monogenics). Orchid does monogenic screening though[1], because it's WGS, you can get in touch.
In a scenario where embryo selection is possible, it does seem like new moral/ethical considerations arise if you have the ability to choose an embryo that is at a lower risk for long term issues.
That said, other questions arise like: what happens to the broader population when we start manually selecting for certain traits? It seems like unintended consequences could be lurking as well.
To suggest we should choose an embryo that is at lower risk of long-term issues reveals an underlying presupposition that suffering should be avoided or is bad. There are many examples throughout history of people who rose to great heights as a result of facing their suffering bravely.
While you will always find stories of people who've overcome great difficulties, there is no virtue in suffering for no reason, and when possible, we use medical interventions to prevent or avoid it. The success scenarios shouldn't imply that the state of suffering is itself desirable, even if it does sometimes lead to inspiring outcomes. There are plenty of examples of the opposite, with suicides providing a counterpoint at the extreme.
The way I see this, suffering is part of life, and isn't something we can entirely eliminate. When suffering happens, there are better and worse ways to handle it, and good can come from it. But most of cultural/societal evolution is focused on finding ways to reduce or avoid it, and that's a good thing. Obvious examples like improving food security and reducing the impact of previously debilitating illnesses come to mind. I personally grew up not knowing where the next meal would come from some days. That early experience influenced the person I am today. Poverty/starvation are still situations we should continue to try to solve.
So the question really becomes: what differentiates the standard ways we avoid unnecessary suffering from preemptive options that are on the horizon, if anything? i.e. if you have a bad knee, it makes sense to see someone and fix it. Given the choice, there's no reason to choose immobility. If an embryo has a high chance of developing lifelong congenital issues and a future parent has the option to choose an embryo that is significantly less likely to suffer the same fate, why not make that choice, especially if the affliction leads to high child mortality rates?
So yes, I think there is a presupposition that suffering should be avoided when possible (it is often not possible). And I think most of the world runs on this presupposition. This should not be conflated with believing that suffering is inherently "bad", nor should the possibility of positive outcomes lead one to believe that suffering is "good".
Yeah sorry didn’t make it clear - specifically in the IVF process when you get to the decision of which embryo to implant, it’ll be immoral not to screen them all and choose the one with lowest health risks.
I've been told by oncologists that blood testing is presently the wild west of cancer profiling. Getting blood testing like CARIS: https://www.carislifesciences.com/products-and-services/mole... or Guardant360: https://guardanthealth.com/products/tests-for-patients-with-... approved seems important from an insurance standpoint.