This seems absolutely reasonable. The letter indicates that the FDA has notified 23andMe that their products are not satisfactorily cleared, they're reached out to them several times, and they've offered assistance through a group they specifically set up to help companies in this situation.
Meanwhile, 23andMe went ahead and began marketing and selling their product, despite the FDA's concerns.
Relevant quotes:
> Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasions.
> However, to date, your company has failed to address the issues described during previous interactions with the Agency or provide the additional information identified in our September 13, 2012 letter for (b)(4) and in our November 20, 2012 letter
> To date, 23andMe has failed to provide adequate information to support a determination that the PGS is substantially equivalent to a legally marketed predicate for any of the uses for which you are marketing it; ...
> ...we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification.
> As part of our interactions with you, including more than 14 face-to-face and teleconference meetings, hundreds of email exchanges, and dozens of written communications, we provided you with specific feedback on study protocols and clinical and analytical validation requirements, discussed potential classifications and regulatory pathways (including reasonable submission timelines), provided statistical advice, and discussed potential risk mitigation strategies...
> Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS.
If you look at the FDA's website, it's littered with dozens of communications begging 23andme to submit some documentation about their product so that the FDA can evaluate the medical claims they're making.
All the FDA wants in this letter is some kind of understanding that their genetic tests are actually valid and correct, since they are making medical claims regarding their accuracy:
> 23andMe has never submitted information on the analytical or clinical validity of its tests to FDA for clearance or approval. However, your website states that the 23andMe Personal Genome Service™ is intended to tell patients in advance how they will respond to certain medications including warfarin and clopidogrel. It also states that the data generated from the 23andMe Odds Calculator, a feature ofthe 23andMe Personal Genome Service™, includes the contribution of single-nucleotide polymorphisms (SNPs) to disease risk. Consumers may make medical decisions in reliance on this information.
The FDA then establishes its ability to regulate this (remember, it's legally required to do this):
> During a meeting between 23andMe and FDA on July 29, 2009, you described the 23andMe Personal Genome Service™ as consisting of a software program that analyzes genetic test results that are generated by an external laboratory in order to generate a patient specific test report. Thus, the 23andMe Personal Genome Service™ is a diagnostic device and subject to all applicable requirements of the Act.
They then very helpfully point them to all the forms, documents, etc., necessary to satisfy the legal requirements:
> For a device requiring premarket approval, the notification required by section 510(k)of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b).
There's even a helpful mailing address and fax number:
> Please direct your questions and response to: James L. Woods, Food and Drug Administration, 10903 New Hampshire Avenue, W066-5688, Silver Spring, MD 20993
Honestly, this sounds like 23andme has been getting away with something for a while and the FDA is tired of giving them leeway.
The bio on the guy who sent the letter you linked is interesting; not the "career civil servant maybe with a JD" you'd expect from an enforcement action:
As an aside, I think this is not as uncommon as one might think. It's a big government and obviously not perfect at hiring and promotion, but in my experience the upper-middle tier of employees generally know their shit.
I suspect 23andMe didn't provide documentation because they very much want to avoid being treated as a medical service, and fear submitting this documentation would serve to further put them on this path.
There is a bit of a contradiction here that "natural supplements" get this huge pass from the FDA, but applying some math to very, very natural genetic data doesn't.
Blame Congress. While the executive branch may write regulations, they must operate within the mandate defined by Congress.
The DSHEA of 1994 (authored by Orrin Hatch) explicitly forbids the regulation of dietary supplements by the FDA so long as they do not make health claims. Unless that bill is repealed, the FDA has no authority over supplements.
Natural supplements are effectively marketed as medication (despite a label indicating the FDA has not evaluated the claims). Many people I have spoken to genuinely believe natural supplements to be actual medicine based on the way they are marketed.
The issue with incorrect diagnosis is might lead to incorrect or ineffective treatments. "Natural supplements" are the incorrect or ineffective treatments themselves: the unregulated claims they make is very similar in substance and effect to the quasiregulated claims that 23andme is making.
And which ballpark would you say is closer to the area of a "food" or "drug"?
If you look at the FDA's mandate, it is pretty strongly oriented to products for treatment, not medical diagnosis. The medical diagnosis angle is mostly there due to certain forms of quackery.
I develop medical devices use for diagnosis for a living. Some organization has to watch over this stuff, it just so happens to fall to the FDA. What's your proposal? Do you believe that these devices should not be regulated?
Moreover, it appears from the letter that the concerns are about marketing; ie, presumably the FDA was simply asking for 23AM to clarify their copy to remove any implication that you could use the product as a substitute for a doctor's assessment of your e.g. cancer risk.
It's actually kind of hard to tell -exactly- what the FDA wants without reading the original 510(k) submission. The claims by the FDA directly tie into the original claims by 23andMe as their intended use.
In any case, the FDA right now doesn't just want a change of copy. By "cease marketing", I presume they don't mean advertise it differently, they mean stop offering the product to customers - period.
While the FDA certainly appears to be taking issue with the specific marketing copy, they seem to be more annoyed that 23andMe has basically failed to complete the regulatory submission process - amongst other things failing to provide evidence to the FDA that their product actually works as intended.
"[...] we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification [...]".
Incidentally, the FDA is lagging a lot of other criticism and restrictions on the 23AM service; for instance, you can't even buy the service in Maryland, which forbids any home lab testing for health conditions not administered by licensed professionals. Similarly, there have been many critiques in the media and elsewhere about the lack of rigor in the 23AM analysis, relative to the importance of some of the conditions the service is implicated in.
> It's actually kind of hard to tell -exactly- what the FDA wants without reading the original 510(k) submission
Well, you don't get this far into trouble with a regulatory agency without having a contact within the agency that you are working with. So, I'm fairly certain that 23andMe probably knows what the FDA wants, but they might disagree. I'll be disappointed in the company if they have ignored the FDA all these years when it was obvious that they'd need to have some sort of approval (even if it was an FDA acknowledgement that they didn't fall under regulation).
What I really want to know is what 23andMe's response to the FDA will be. They must have known this was coming and should have a press release today.
"For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery"
Uh, you don't think the surgeon is going to demand a second BRCA test be done before performing the surgery?
Without an appropriate study to determine reasonable efficacy, it is possible that the diagnostic technique could result in a large number of false positives.
This could result in a large number of unnecessary follow-up BRCA tests which could potentially increase the waiting time for test results or unduly raise costs for lots of patients. Not to mention the stress of feeling like you may be suffering from a potentially expensive and life-threatening illness.
Your verdict of reasonableness depends on the idea that physicians are not going to be able to properly advise patients who they think might have gotten a false positive result.
Considering that over half of American adults believe Elvis is alive, I think the small percentage who may slightly overreact to the kind of presentation that 23andme gives of these kinds of results is a complete non-issue.
23 And Me should only have to prove that it is better than the alternative, not that it is accurate (to determine whether the service is of net benefit to the public). Depending on the counter-factual, 23AM could provide a relatively inaccurate test that would still be better than no test.
Unfortunately for us, the FDA is on a quest for "safety"; the agency does not try to help the citizenry live longer or happier.
You seem to believe the average doctor is well-versed in the mechanics of genetic testing, or (perhaps equivalently) that the average doctor isn't wholly dependent on the mechanisms of FDA approval for product selection.
Any doctor educated in the past two decades is well versed in genetic testing, and any doctor specializing in areas where genetic testing is a frequently used aspect of planning/diagnosis (such as OB/GYN) will be highly familiar even if trained long ago.
The 23andme product explains explicitly how it should be used by a physician, and there are all kinds of warnings and checkboxes before the user is shown any data that falls into the area of overlap.
Perhaps any one of several trained medical professionals on HN could chime in here to explain (a) how suitable 23AM's current product is for clinical use and (b) how competent a typical physician is at evaluating clinical genomics products without FDA's assistance. 'carbocation? 'niels_olson?
('carbocation has already expressed some tacit support for FDA's action, but I'm not qualified to interpret it in the context of this particular subthread).
> The 23andme product explains explicitly how it should be used by a physician
Generally, for diagnostic tools, drugs, etc., it is not enough that the product labelling explains how it should be used, but it is required to demonstrate to the FDA that there is evidence that it works as marketed when used according to those directions. The FDA Warning Letter specifically calls out 23andMe's failure to either identify existing approved products on the market to which the product is equivalent (which wouldn't reduce the requirements for proving this) or to meet the requirements for demonstrating the effectiveness of their offering as a new product without existing, approved equivalents.
> How do you think 23andme should answer that question?
I don't know enough about 23andMe's operations and those of what appear from the outside to be generally similar services to answer that. Assuming that they really are an innovative service, they would need to conduct and provide the studies supporting the validity of their innovative service.
Any doctor educated in the past two decades
is well versed in genetic testing
I'm not sure what definition of "well versed in genetic testing" you had in mind but this is untrue for most or all reasonable definitions.
any doctor specializing in areas where genetic testing
is a frequently used aspect of planning/diagnosis
(such as OB/GYN) will be highly familiar even if trained long ago.
Also an overstatement. The trouble is that "genetic testing" is a large and complex field. Are you referring to a single-gene test for a well-known and well-characterized disease? Or whole exome sequencing? Because in the coming years doctors will come into contact with both. In general these tests will require specialist interpretation; not general physicians or OB/GYNs.
Regardless of whether physicians are skilled or not at helping their patients interpret the results of a proprietary test, the point I was making is that if the test produces an unacceptably high number of false positives then this would result in an unnecessary increase in the number of times physicians have to actually have those conversations.
If physicians are forced to waste huge amounts of time and effort to console an influx of patients who have been wrongly told they have some terrible disease, this is going to reduce the amount of time they have available to work with patients with actual terrible diseases.
If other medical device/diagnostic makers have to comply with the law, so should 23andme.
What if it results in some accurate positives and saved lives? You think the FDA should limit access to information curious people can obtain for $100 about their own genome that might help them behave proactively toward their own health just in case it results in more patients behaving proactively?
There is always a point in any discussion of medicine where broad "public health" concerns creep in.
If we really cared about public health we'd have a drastically different system.
In any case I think it's hard to make a persuasive argument that if the members of the public were only kept more naive about their own health risks, public health would improve.
The point isn't necessarily the second test (which would have to be done). It's also the emotional distress caused by a potential false positive, which could be severe. You could imagine in an extreme case some one finding a result with a poor prognosis and deciding to commit suicide. Now, if that result was a false positive, you can see where you'd want to have some assurances that their test was accurate.
This is an extreme example, and I have no knowledge that it ever happened, but it is possible.
This might not even require a technical fix with the test, but rather a marketing and reporting of results.
From what I understand, the test doesn't attempt to diagnose an existing condition. Instead, it shows whether you have a gene that indicates a predisposition to the condition. In that case, prophylactic measures can be taken, once confirmed and if desired. This is what drove Angelina Jolie's decision to have a double-mastectomy.
That's a hugely significant difference vs. actually being diagnosed with a life-threatening condition. I don't think people would commit suicide or become unduly despondent if they learned they have a gene. They would just know they need to take action, get further testing, be vigilant, etc. It's not much different (in spirit) from knowing that your family history predisposes you to a certain condition.
It's all about education and results reporting. Where you or I might see a result as a predisposition to a phenotype with a statistical probability, someone else might see a death sentence.
That could be one area that the FDA might be trying to address.
I agree that it has to be clearly reported and explained.
But, you know, there are in-home HIV tests that are FDA-approved. They tend to stress professional counseling and/or follow-up testing, etc. They also explain such somewhat-technical details as the window between infection and antibody formation, so it's an education process there as well. But, I think the availability of such a test is testament to the fact that easier access to important knowledge re: one's status may be worth the risks.
HIV tests are pretty simple, from a diagnostic test point of view. It's really a boolean - HIV present, or not present. The meaning of a particular genetic variant is much more ambiguous.
It's odd to me that you're saying HIV tests can give definitive devastating diagnoses to people alone in their homes, yet they are OK; but genetic testing provides a range of possibilities and recommends further investigation, but they are somehow so devastating that they would drive someone to despair or suicide.
I'm not trying to equate things to HIV tests, and it's probably a poor example. I'm not sure what the reporting process for an in-home HIV test would be. I recently had a doctor tell me that she's not allowed to actually give the results of an HIV test over the phone for fear of patient reactions.
What I was trying to say was that that class of test should be easier to use and get a definitive yes/no answer with a smaller false positive rate.
I think one can make a million hypothetical arguments against the testing. But, I just don't see people taking the test at face value and making major life decisions without further follow-up. I think most reasonable people would consider it a screen.
If the testing was wildly inaccurate, then that's another issue. It almost becomes more an FTC consumer protection-type matter at that point. But, there is no indication that this is the problem. They go on to state that their testing is done in CLIA-certified laboratories:
BTW, I'm not really defending the service, per se. In fact, I have issues with it that are more along the privacy lines. I just don't see where there's any proof that it has an outsized chance of ruining lives any more than, say, in-home HIV testing.
People get wacky when facing things like this. Remember the stories of Steve Jobs turning to crazy diets instead of treating his cancer medically?
If you dump a bunch of information in front of people who may or may not be prepared from an intellectual or emotional perspective to deal with it, they may take dramatic and unwarranted action.
Dont take my freedom to decide because of homeopathic weirdos like Jobs. I'm not one to usually complain about the nanny state, but this is deep into nanny statism here.
Have you lived or travelled extensively in countries that don't have public health or regulatory infrastructure?
Organizations like the FDA and EPA were created in response to very real failings. The problem for many of us who grow up benefitting from these safety nets is that we don't have a sense of how hard-won these battles were. Life is good and so we start chipping away at the "nanny state" to get a tiny little bit more freedom. Actually more like a lack of inconvenience, not really freedom.
I've been thinking about this a lot lately. Is this just a natural social cycle?
I don't think it's a natural social cycle, it's the outgrowth of the general mistrust of government that has festered over the last 30-40 years or so. I don't think that our political institutions have dealt with the changes in the media well.
The ideology that inspired the construction of these safety nets is gone for the most part -- we've degraded to bread and circuses. The political machinery on one side focuses on handing out stuff in exchange for votes, and the other side focuses on vilifying "those people". Nobody believes in anything anymore.
When there is no qualitative requirement to make effective medicines, you'll find (literally) the industry degenerate into snake oil and the types of patent cures that ultimately led to the creation of the FDA.
That really doesn't matter. The responsibility for correct results falls on the Device Manufacturer (in this case 23&me), not on the physician that ordered the test.
I work for a large Medical Device manufacturer and questions like this come up all the time when we do Hazard Analysis. While the physician (or lab rules) may require a second confirmatory test, and that may give us warm fuzzies, it really can't be considered to be a hazard mitigation. It's still up to the manufacturer to not make the mistake in the first place.
But if another company like 23AM pops up, they could be the "second company". If companies are not required to prove that they are reliable, then you could too easily get multiple false positives.
The primary path to approval to market for a new device or drug is the PMA (pre market approval). This is fairly extensive an costly for the company (e.g. clinical trials). A 510(k) filing allows you to take a short cut by identifying a "predicate device" that is "substantially equivalent". In other words you are saying "we do the same as X but we [also do Y/do this differently/etc.]". At least, you are claiming this for the scope of your "indications for use" (which are the only uses you can market your device for).
This doesn't let you off the hook entirely at all. You still need to demonstrate safety and efficacy, perform risk analysis, follow standard manufacturing and product development methodologies (e.g. ISO13485, IEC60601, etc. ), but it is a lot faster and less involved than a PMA.
If you don't use one of these accelerated paths, you'll need a PMA before you can market your product in the US.
The key issue here is that 23andme has filed one or more 510(k)'s, but have failed to support them properly.
As far as I can tell, you could translate that as "existing product". Given A and B, if A is already legally marketed, and B is basically the same thing, B has a lower bar to clear. Googling for "legally marketed predicate" turns up results like a 501(k) for a catheter[1] that the manufacturer says is "substantially equivalent" to another catheter already on the market.
Am I the only one this seems completely reasonable to? There are probably people who take action over the results they get from the service and if the results are incorrect the actions could have negative impact on their health. Therefore the service should have to prove the results are accurate before advertising it as a first step in prevention.
> Am I the only one this seems completely reasonable to?
No. I'm not actually a big pro-regulation kind of guy. But there is a knee-jerk reaction favoring tech-ish companies getting regulatory compliance letters that I don't share. Most of the time, it just seems like the agency in question doing its statutorily-sanctioned job. It's not like sympathetic cases where a company falls into a Kafka-esque quagmire of obscure regulations that only tangentially apply to what they're doing. When I see cases like this, or AirBnB, or Uber, they fall directly within the scope of the relevant agency, and the action being taken is justified on the same basis that justifies the agency itself.
Right. There are some areas where more due diligence is required than to wave one's hands and chant "Disrupt!" And in this case, at least from their perspective, the FDA hasn't been unwilling to work with 23-and-me.
> Am I the only one this seems completely reasonable to?
No, particularly from an "FDA" rather than "Congress" viewpoint. That is, independently of whether the law should have the FDA regulating devices used to diagnose disease, the facts seem to be:
1) The FDA does have that responsibility under the FD&C Act,
2) 23andMe began the process of getting FDA clearance for a device intended to diagnose a disease, and
3) 23andMe, when the FDA found the application wasn't sufficient and asked for more information to support that the device met the requirements for approval, failed to respond with more information and just accelerated public marketing of the device.
Unless there is substantial dispute over these facts -- which I don't see any indication of -- there doesn't seem to be any basis for criticizing the FDA action.
No. This letter is a model of clear communication and reasoned argument. I think 23andme is a great concept and admire what they're doing; I hope they get their ducks in a row so they can develop their offerings more effectively.
Nope, you're not the only one. I've been wondering for years how 23andMe has been getting away with what is clearly a flagrant violation of FDA marketing rules.
Of all the things that have a clear negative impact on health, 23andme's existence and business practices do not (in my opinion) merit a single hour of agency/burocratic time.
FDA interest in 23andme is driven solely by rent-seeking incumbents trying to keep 23andme out of the game.
Every single piece of information on 23andme is accompanied by confidence estimate, and most of it is very low confidence. Every single concern mentioned in that letter is clearly and obviously addressed by the site as part of its core functionality.
As a happy 23andme customer I wish the FDA would stop harassing a company I enjoy doing business with so that it can get on with releasing new data and building new features rather than just hiring lawyers.
> FDA interest in 23andme is driven solely by rent-seeking incumbents trying to keep 23andme out of the game.
No, FDA interest in 23andMe is driven by:
1) The fact that 23andMe's product is within the clear scope of what FDA is tasked to regulate under the FD&C Act, and
2) The fact that, having initiated the process of seeking regulatory clearance for their product as required, 23andMe abandoned that process and continued marketing the product.
> Every single concern mentioned in that letter is clearly and obviously addressed by the site as part of its core functionality.
Really? The lack of studies supplied by 23andMe establishing the validity of their process in delivering the outputs it gives is "addressed by the site as part of its core functionality"? How?
Just responding to your first point. The FDA scope of jurisdiction is breathtakingly large and arbitrarily enforced, so the fact that it can fall under their jurisdiction and that they claim it is a weak statement. In policy it is like writing laws which make everyone a criminal and only enforcing it when you feel like it.
Is this a fair comparison for the FDA? Yes, because in the current system you are guilty until you prove your own innocence to their standard of evidence, which tends to vary based on who you are. One could argue that the potential harm of unregulated supplements is clear and present, yet the FDA chooses not to act.
To whom shall we write our complaints about the unregulated aspects of the food and drugs which have the potential to cause massive harm (but which apparently don't because people on aggregate are not as helpless as they sometimes appear)?
I'd address your first point with a simple question: Suppose 23andme did no data analysis/interpretation and simply returned the raw data, would that increase or decrease the scope of appropriate FDA involvement?
To your second point, the site has a few "locked" areas that are described as containing potentially upsetting or confusing information, and the user is advised to consult his/her physician before looking at the results. There is also downloadable information available to physicians.
> I'd address your first point with a simple question: Suppose 23andme did no data analysis/interpretation and simply returned the raw data, would that increase or decrease the scope of appropriate FDA involvement?
Reducing the scope of the product would inherently reduce the scope of the FDA involvement, not that that is in any way relevant to any point I made.
> To your second point, the site has a few "locked" areas that are described as containing potentially upsetting or confusing information, and the user is advised to consult his/her physician before looking at the results. There is also downloadable information available to physicians.
I don't see how that's relevant to anything I said. Particularly, its not relevant to either the second point in the first paragraph (which concerns 23andMe abandoning the regulatory clearance process) or the point of the second paragraph (which concerns 23andMe failing to provide studies supporting their claims about the accuracy of the reports).
It's possible 23andme has been sloppy with its compliance practices.
If you take the raw data and download various utilities that match SNPs with the literature, the result is far more scary and misleading -- and it reveals just how thoughtful and reserved 23andme's approach is.
23andme provides ample links to evidence for every single result. The confidence metric is a function of the study size and reproducibility for the studies pertaining to each and every result. Most have very low confidence.
IMHO the only legitimate beef is with the underlying scientific assumption behind 23andme, which is that statistical genetics is both useful and accurate. I consider it more of a form of entertainment than a likely way of gathering actionable information.
> It's possible 23andme has been sloppy with its compliance practices.
Then no one should be surprised that they are in trouble with a regulatory agency responsible for holding participants in the market they are in to compliance standards.
Actually I think it's quite surprising. Why would a well-funded company pursuing a business model that clearly falls into a regulatory gray area gamble with its future by simply not complying?
Seems to be not-too-rare practice with startups -- don't comply and hope the rules adapt to them rather than vice versa (either by legislation or litigation.)
AirBnB, Uber/Lyft, 23andMe previously (with then-current California regulation requiring tests of the type they provide to be physician-ordered) have all done this with varying degrees of success.
> Every single piece of information on 23andme is accompanied by [a] confidence estimate, and most of it is very low confidence.
Another customer here, and this has also been my experience. I have found their results presentation very responsible and low-key. A lot of these correlations are quite weak, and they're very clear about that.
I wonder if the real dispute here is over whether giving confidence estimates is good enough. Perhaps the FDA thinks that the general public are not well enough trained to interpret them.
Seems pretty stupid to me. I've enhanced DNA signals using the enzyme used for this in lab class plenty of times, and ran analysis on them. It's pretty trivial nowadays. 23andme does this and runs the result over a gene array and reads out the answers. There should be nothing illegal about this. If you want to slap a disclaimer that it isn't perfect on the mailing envelope, fine, but it's none of the government's business to say we can't have someone do it for us IMO. They should be hunting down fraud and not killing useful lab tests with pointless paperwork.
The FDA is not trying to prevent you from doing this with your own genes. They are trying to prevent unlawful marketing of a medical device. Despite the similarities that you point out, these are in fact quite different things.
Its a simple procedure but from an epidemiological prospective, different screening methods are ideal for different slices of the population. If something has a very high false positive rate, it's a terrible screening tool... I think a lot of the concern is that someone might receive bad news and change their anti-coagulant dose because of a false positive. Even if that only happens to 0.1% of people, it could kill people. The point is that doctors don't market these tests to the public like that.
Has 23andme killed anyone yet? How many customers has 23andme had? Suppose the answers are "no" and "1 million". Then it's probably not worth worrying about until something changes.
It is safe to use. It's how people react to it that is the concern. I think it's perfectly fine to take a reactive approach for that. Similarly, one in a million people might not pay attention to the maximum consumption of many (otherwise safe) medicines. It doesn't mean those medicines should be sold pill-by-pill until we know the number of people who will read instructions.
It's a cost benefits analysis. Medicine does this, and is constantly updating their recommendations for screening based on the data that comes back. For example, it used to be recommended that all women perform a breast self exam every month, then data showed us this didn't prevent cancer and actually caused harm because it lead to needless surgeries and biopsies. (Sources here: http://en.wikipedia.org/wiki/Breast_self_exam)
Things like Prostate-specific antigen screening of healthy men is no recommended by the United States Preventive Services Task Force because "the potential benefit does not outweigh the expected harms." (Source in: http://en.wikipedia.org/wiki/Prostate-specific_antigen)
The Cochrane analysis of screening indicates that it is "not clear whether screening does more good than harm". According to their analysis one in 2,000 women will have her life prolonged by 10 years of screening, however, another 10 healthy women will undergo unnecessary breast cancer treatment. Additionally, 200 women will suffer from significant psychological stress due to false posivitive results.[10] Newman points out that screening mammography does not reduce death overall, but causes significant harm by inflicting cancer scare and unnecessary surgical interventions.[11] The Nordic Cochrane Collection notes that advances in diagnosis and treatment of breast cancer actually may make breast cancer screening no longer effective in decreasing deaths in breast cancer, and therefore no longer recommend routine screening for healthy women as the risks might outweigh the benefits
This is why we use science and do studies and always question if we are doing the right thing.
If you believe 23AM's technology is so important that its use will save lives, it's hard to understand how you might believe the FDA is out of bounds in regulating it. Unless your argument is that the FDA should be abolished entirely.
It all depends on what is meant by "regulate". If the FDA just wants 23andMe to make it clearer to their customers that:
1. Like any screening, their results could be inaccurate.
2. Before making any changes based on their results—aside from eating more healthfully, exercising more, and sleeping better—they really need to talk to a doctor.
... then few people would have a problem with it. And maybe that's all the FDA is trying to do! I don't really know.
Sadly, when an activity or product could result in a bad outcome, certain types of people are incredibly eager to ban (or heavily regulate) it.
Those people don't realize that by doing so, they themselves are actively harming the people who benefit from that activity or product by preventing or heavily limiting their access to it.
Just like we shouldn't ban health discussion boards (and we shouldn't make it illegal to participate in health-related discussions without government-mandated credentials), we shouldn't limit people's freedom to choose services like these. It's wrong.
We just need to make sure the services aren't lying about what they're offering.
That in fact appears to be what the FDA is interested in; their letter references attempts to clarify 23AM's "labeling". Presumably, the FDA would like 23AM to stop overtly mentioning health conditions in their marketing; they could write copy that refers to the importance of genetic testing in health management while explicitly stating that their consumer service is not intended as a medical diagnostic.
It seems clear that FDA does not in fact want to shut 23AM down, but that they do want 23AM to radically change their marketing. Which seems fair, because 23AM's marketing is disquietingly clinical.
Sorry, you're right, I was being imprecise. Obviously, I think (2) is the only viable option here; 23AM doesn't appear to be set up for clinical genomics. But that bias was built into my comment implicitly, not stated directly like it should have been.
And because of that, perhaps you should be getting that test (or not getting the test), with the help of a physician who is better equipped to help you interpret the results.
Or at maybe for particular results the company should just refer you straight to a doctor for more information.
These are the questions that I think the FDA will be interested in having the company addressing.
But often people get certain tests when they have certain symptoms or risk factors. For example, smokers are much more likely to have lung cancer. Screening them for lung cancer is a good idea, even if the screen has some false positives because there's a reason why the the group has above average risk for the disease.
People are screened for the BRCA gene when they have a history of certain cancers in their family. If you get a positive result, there's a small chance its wrong. But, if you took all of American and gave them that test, there'd be thousands of people getting positive results, living in fear, and sometimes taking medical action.
It's more about the labeling. I can't market french fries as lowering chances of breast cancer because my tests only included males. How does the agency know whether your procedures are being done proberly unless you work with them on it.
23andMe offers a very low cost way to open the door to a whole new world of having people understand something about their genetic makeup and the possible impact upon their lives.
The work that they're doing to show how genetic features correlate with the observed tastes, behaviors, and propensities of users of the site seems remarkably useful.
The FDA is doing exactly what it always does, stifling innovation while justifying its existence using the voluminous laws created by politicians justifying their existences.
If the FDA were useful, it would be helping 23andMe rather than trying to take them down.
How the hell should the FDA be trying to help 23andMe?
Did you even read the letter? The FDA is making serious and legitimate claims. Amongst other things, the FDA is claiming that 23andMe has said that they were in the process of completing their validation studies. 23andMe has already submitted their 510(k) (which is the form/clearance required for -any- medical device), but failed to provide the required evidence to back up their claims in their submission.
Note that the FDA is that claiming that 23andMe has not provided sufficient evidence (as in they don't like the study you did) rather the FDA is claiming that 23andMe has not submitted the required evidence at all. As in there should be this big ass binder full of test results comparing 23andMe's test results against the ground truth, but that binder doesn't exist.
This is hardly stifling innovation. 23andMe has had 5 years since they started selling their product to produce an analytical or clinical study proving their product's effectiveness, and they failed to do so, despite clearly knowing that it was required, to the point of claiming that they were in fact working on it.
5 years for a clinical study? That's a laughably short amount of time. You don't just write a test suite and get your answer out. Moreover, this is kind of uncharted territory: If you've got a device that, say, estimates an 'elevated' risk of alzheimer's in 20 year olds, how long of a clinical trial period do you suspect would be reasonable to run the test?
5 years for an analytical/clinical study for a DNA test? Absolutely in the cards. 23andMe isn't discovering new mutations that it then claims are linked to some phenotypical difference. They are going through all the SNPs that have ever been studied by someone else, testing you for it, and then telling you that "You have this SNP which is linked to clopidogrel metabolism" for example.
The study that the FDA would have required from 23andMe is to show that the genetic testing provides the correct results at the bare minimal. They would require 23andMe to quantify their actual error rate of their product in use by customers. Depending on 23andMe's claims in their 510(k) submission regarding their intended uses, then the burden of proof may go higher.
The point is that if 23andMe can't actually prove that this test result predicts elevated risk of Alzheimer's (either by their own study, or through other relevant studies) then they sure as hell shouldn't say that their test predicts Alzheimer's risk.
Case in point, clopidogrel response. The link between CYP2C19 and clopidogrel response is well studied. There are already other tests on the market based on this relationship. Given this, 23andMe would not have to prove by themselves that clopidogrel and CYP2C19 are linked, they would merely have to prove their their CYP2C19 test provided correct results.
Case in point, clopidogrel response. The link between CYP2C19 and clopidogrel response is well studied. There are already other tests on the market based on this relationship. Given this, 23andMe would not have to prove by themselves that clopidogrel and CYP2C19 are linked, they would merely have to prove their their CYP2C19 test provided correct results.
It's not entirely clear to me that this is what the FDA is demanding. Quantifying the lab error rate is easy, and while it's possible that 23andMe is failing to do so, it's almost like not doing that would take effort.
Having worked at a company that went through the FDA process for a genetic test product, where the link between gene in question and phenotype were fairly well characterized, what we want to do for our analytical studies were to basically push the tests out to their failure modes. That meant seeing what happened with common contaminants, what happens with incorrect sample collection technique, what happens with incorrect storage, etc. For our clinical tests, we had to prove not the lab rate, but the actual customer use rate.
For example, 23andme ships you a test package, you sample it yourself, send it back and then they process it. While quantifying that last rate is simple (as you say), it's crucial to understand how well the product will work in practice, with an actual customer on the other end.
For something like 23andme, that would likely mean getting a whole bunch of untrained test subjects, having them preform the sample collection as instructed by the instructions shipped with the sample collector, having them shipped over by standard means to the lab, and then processed. The test subjects would likely then have to have their DNA fully sequenced with some gold standard test, and then the results compared. 23andMe would be given leeway, in the sense that inconclusives don't "really" count as a wrong result.
Since the field is new, it is not clear to me that the FDA has a set standard procedure to determine one thing or another, so it is possible that the FDA is requiring a higher level of review that may or may not be equivalent to what you experienced. It is also possible that 23andMe is being totally negligent.
You are not allowed to just make things up. How do they know there is an elevated risk if they have not studied it? This is pretty basic science. I think you are probably suggesting a hypothesis, as in a bunch of 60 yo patients with Alzheimer's has this genetic marker, you at 20 have this same genetic marker, therefore you may be at elevated risk. That seems like a reasonable hypothesis, but that is all it is until tested. Until then, you don't get to make claims.
No the FDA is saying that they need to see proof that the test has a high level of accuracy and isn't just snake oil. 23andMe tried saying "you shouldn't actually use our test for diagnosing disease" to which the FDA said "then stop marketing it that way."
23andMe both wants to _say_ they have a totally accurate test, but doesn't want to pay to do the testing to prove it is totally accurate. The FDA is saying you can't have it both ways.
have you actually used 23andMe? All over the place, it says, the information is based on academic studies, these figures are only n star (on a rating from 1-5) reliable, it only is conclusive for ethnicities X, etc, etc, etc. Now, it is not clear to me that people read all that (in the aldehyde dehydrogenase test, a lot of caucasians don't realize that it only applies to asians, even though it says that in bold, font right underneath the title). There is no such thing as a totally accurate test and I don't think 23andMe says that anywhere.
I'm not sure total accuracy is the point. Rather, I think it's about the claimed value being correct. If 23andMe say a test has a 20% accuracy, they should be able to prove how they came by that number.
There's a big difference between telling someone they have a 5% chance of something and telling them they have a 25% chance of something - even though both are uncertain.
The issue isn't them saying "you have a higher likelyhood of disease." The problem the FDA has is 23andMe saying "you have the gene variation XYZ." If you take your 23andMe results to a doctor, the doctor should at best order a REAL FDA approved diagnostic test to see if you really do have variation XYZ because 23andMe hasn't proven that their test is accurate.
> The work that they're doing to show how genetic features correlate with the observed tastes, behaviors, and propensities of users of the site seems remarkably useful.
Oh man are you going to be upset when we regulate all that out of existence. Trying to correlate genetics to tastes, behaviors, and propensities, while scientifically interesting, is a total political non-starter.
> The FDA is doing exactly what it always does, stifling innovation while justifying its existence using the voluminous laws created by politicians justifying their existences.
This action is the FDA acting within the core of its jurisdiction, and within the core of a law that was passed with tremendous public support. This is not to say that agencies don't do what you're describing, but in this case, it's pretty much the FDA's job to control this sort of "innovation."
Oh man are you going to be upset when we regulate all that out of existence
I guess you're being sarcastic, but it's not that I fear progress will stop. What I see instead is a great deal of needless friction that prevents efficiency. When you consider how innovations and businesses build on one another over the years - any friction in the process compounds the amount of time for "the future" to be here.
I doubt anyone here on HN doesn't realize that in the future our genetic code will be understood and manipulated like we do with computers and software today. Will this golden age of genetic self determination be 50 years from now or 500 years from now?
Roadblocks we put in front of progress now will mean many decades of delay for the advances down the road that are dependent upon today's advances and the intervening thousands of others.
law that was passed with tremendous public support
Doesn't at all make it right, good, or mean I won't bitch about it.
> I guess you're being sarcastic, but it's not that I fear progress will stop.
I'm not being sarcastic. Any technology that tries to correlate genetic markers with behavioral characteristics will be regulated out of existence. I'm not taking a position one way or the other as to whether this is a good idea, but I'd bet money on it being the outcome.
> Doesn't at all make it right, good, or mean I won't bitch about it.
Sure. But what it does mean is that it's an intended consequence, rather than an unintended consequence as your characterization suggested.
Any technology that tries to correlate genetic markers with behavioral characteristics will be regulated out of existence
I'm sure that there are those who would like to make all such pursuits illegal. Such a slippery slope, though. Where will that line be drawn? Which 23AM style correlation question should be illegal for inclusion in their correlation determination system?
1. Do brussel sprouts taste bitter and unpleasant?
2. Are you more active in the mornings?
3. Do you prefer blondes to brunettes?
4. Do you carry debt on your credit cards month-to-month or pay them off?
5. Did you graduate college?
6. Do your joints ache after rigorous exercise?
7. Have you ever been arrested for a felony?
8. Are people with a great deal of money more lucky than clever?
9. Does hard work tend to lead to financial success?
You're one of those people who sees "needless friction" in the previous sentence and tries to make an out-of-context argument against a position that I obviously don't hold.
It's hard to tell what position you hold, since the kernel of your argument seems to be that 23AM is a low-cost democratizing alternative to existing licensed medical technology, and should therefore be free to market itself without FDA approval. Do you also believe that of the companies who sell apricot pits as a cancer cure? I doubt it, but the logic you use sustains both arguments.
Where oh where did I say anything about "alternative to existing licensed medical technology"? Where has 23AM indicated such a thing whereby I'm supporting that argument by proxy?
Where did I or 23AM indicate that they had a cure for anything whatsoever?
The answers are "nowhere", "nowhere", and "nowhere".
I do have a point, because it's possible for one factor among several to weight someone's choice. However, you're nitpicking at my paraphrase, while ignoring the content at the link which I supplied (which was why I supplied it.
The specific claim made by 23andme, without disclaimers, is: 23andMe empowers you to better manage your health and wellness. This seems to me like a straightforward claim of diagnostic value; the fact that it's non-exclusive is beside the point.
I disagree. certainly, the risk of misdiagnosis is is inverse proportion to the degree of supplementarity, but that can still affect an awful lot of people and result in significant economic loss. It seems to me that some people want to argue this on a binary basis, ie since 23andme does not purport to replace the advice of a primary physician, its liability for misdiagnosis therefore should fall to zero. To me, though, it seems quite likely that if 23andme suggests a risk factor that is greater than the probability spread between different options offered by a patient's physician(s), then it's very likely that the 23andme data will be given excess weight given the notoriously poor grasp of Bayesian inference among the general population (and even among some groups of clinicians).
If anything, the supplementary nature of 23andme's test data should make compliance easier, since their burden will drop proportionately under the B<PL formula employed to assess tort liability in the US. http://en.wikipedia.org/wiki/Calculus_of_negligence
I wonder if you and other folks who seem to be espousing this binary approach live in or hail from states with contributory negligence regimes.
For whatever it's worth for you to know, it would have been easy to make that same point without being nasty about it, and I think the nastiness harms your argument. "But it doesn't so you don't" makes one sound like an angry teenager; it's a wordier way of saying "so there!". You don't see a lot of adults tacking "so there!" onto the ends of their arguments, because it's a self-evidently silly thing to add.
My position is that the FDA should have better things to do with its limited budget that never seems enough to keep up with the drug and treatment approval process than to go after innovative companies like 23AM.
As though lives are more likely to be lost because 23andMe is putting more information out there than are going to be lost because of all the years behind we would be without extra information.
Take down the giants upon whose shoulders we could be standing upon and be happy that no one is so tall that they can fall and hurt someone.
there have definitely been, uh, attempts at eugenics in the past. less sophisticated, overt attempts, but you can not remove the smell of certain things, no matter the scientific veneer pasted over them.
When you put it in the same sentence as 'tastes and behaviors' you're creating a very different context from things like heart disease. Imagine, for example, a genetic test that says that you, Crusso, are 29% more likely to commit a criminal act involving deception than the median person. Now imagine that your genetic testing service has a data breach and suddenly you have immense difficulty getting hired, getting credit, or getting a table in a restaurant.
One has only to glance back to the last century to see overconfident claims along the same lines from eugenicists, for example. Or look at the dreadful state of science journalism and the broken logic that prevails in many internet comment/forum sections to see how easily a statistical correlation can be substituted for fact - to say nothing of poor statistical work in scientific research, where publication strongly favors positive results and replication is often under-prioritized.
Now please return to your preventive custody zone, non-citizen.
That's got nothing to do with PC or any such nonsense, it's got to do with you taking as your starting point that it's possible to reduce highly complex, multivariate and environmentally influenced phenotypes down to useful genotypes.
anigbrowl's comment argued that correlations were bad, and did not mention whether useful ones were possible. Blame them for bringing up political correctness, not crusso.
Would you care to provide your interpretation of "Now imagine that your genetic testing service has a data breach and suddenly you have immense difficulty getting hired, getting credit, or getting a table in a restaurant."
The meaning of that is self-evident - you could be discriminated against because people considered you to be untrustworthy due to the results of the test mentioned in the preceding sentence. Where you and crusso see political correctness - perhaps in the belief that I'm describing such a test as a proxy for some identity group - what I'm actually concerned about is the accuracy and/orpredictive power of such tests. I really doubt that you would be OK with finding yourself on the receiving end of such an evaluation.
Obviously you're just dragging your feet here. He is not saying whether the discrimination itself is correct, but that if the validity of the tests is not correct this can lead to incorrect discrimination here, the chance of this data ruining someones life in the wrong hands is very high.
Avoiding performing measurements because you're worried about how the results could possibly be misused is a political motivation, not a scientific one.
The primary concern is fragility, not in truth-space. Scientists have ethical responsibilities and pretending that this isn't true is probably how NSA mathematicians justify their work.
If the FDA were useful, it would be helping 23andMe rather than trying to take them down.
It's not their mandate to help 23andme, their mandate is to protect the general public. Their enforcement letter clearly spells it out: the FDA had had concerns about the validity of some of their tests, and they gave 23andme opportunity to address there. Since they failed, the FDA is taking action.
The FDA protects the public, but only from new things, it does not protect new from a disease, but it does protect you from a potentially unproductive test or treatment. One could say the FDA exists to ensure that all statistical errors are of type II.
> If the FDA were useful, it would be helping 23andMe rather than trying to take them down.
If the FDA were trying to take 23andMe down rather than helping them, they wouldn't have been working with them for several years to get them into compliance and only issued a Warning Letter after 23andMe walked away from the process.
Exactly. The FDA takes this shit seriously and will order you to take products off the market or shut you down completely if you fail to comply with their orders. Abbot famously ran afoul of this 10 years ago and it looks like they're having trouble again. http://www.mddionline.com/node/5701
I think most people view their service as fun thing that comes back with results that, if revealing of a concern, would cause you to seek proper and more detailed testing from a real medical practitioner.
It's not like a physician prescribes a 23 & me writeup.
You think diagnostic services sold to doctors aren't a concern for the FDA? Virtually every medical product or service the FDA regulates is marketed primarily to doctors.
Anyways, my comment was a response to the commenter who claimed 23AM was marketed as "entertainment". Horseshit.
No, they need to prove to the FDA that their tests do each of those things. If they say the test lets you find out "if your children are at risk for inherited conditions", should the FDA just trust them about that? I mean, that's a pretty serious thing to be testing for.
> I think most people view their service as fun thing
If they were marketing as an entertainment product, this wouldn't be an issue. They are marketing it as a diagnostic product (and apparently submitted applications for FDA clearance as such, but then just decided to ignore that process and continue marketing it for diagnosing risks.)
Literally, my mom is the one who got me to send off my spit to 23andMe. She thinks it's fun and interesting but at no point has she indicated that she's thinking of it as a medical service - especially not one that replaces seeing a doctor.
>> "I think most people view their service as fun thing"
The problem is that's not how they are marketing it as others have pointed out. They market it as a serious health evaluation tool you can use as a step in preventing future illness.
Should personality and health quizzes in magazines also need FDA approval?
Q: Have you eaten fast food more than 3x this week?
A: If yes, you may be at risk for obesity (or just plain lazy)! See a medical professional for verification and treatment options! By the way, check out this insurance plan! And these nutritional supplements!
I mean there's a whole industry of publications, websites, media, and more dedicated to getting people to self-diagnose and self-treat all kinds of conditions and doing it without FDA approval...
I don't even think I've gotten to most of the egregious ones because they use trickier to find names. But they're all basically promoting self diagnosis and self-treatment of conditions that may or may not exist or methods of managing or treating conditions that do in fact exist.
Besides this not being part of the FDA's charter, what you're ignoring is that articles assist you (correctly or otherwise!) in self-diagnosis. An article does not in and of itself diagnose you with a disease or condition and thus can't by any stretch of the imagination be considered a Device.
Yes, that's what I view it as, as a subscriber to 23 and Me. Though, fortunately, I also haven't seen anything that as a real concern that I didn't already know about from family history.
I wonder if it _does_ apply. I am not certain if it doesn't.
In general, products sold to diagnose diseases -- including software products -- may be subject to regulation. See this article (on WebMD cause I found it when googling to answer the original question, heheh)
> The U.S. Food and Drug Administration on Monday drew a line between which smartphone medical apps it will regulate and which ones it will not, saying it will focus only on those that turn the phone into an actual diagnostic tool.
> In essence, those applications include software that enables the phone to read a patient's heart rhythm, take a blood pressure reading or measure a person's health in some other way.
> For example, an ECG machine that diagnoses heart rhythms is "still an ECG machine whether it is the size of a breadbox or the size of a smartphone," Shuren said. "It's not about the platform, it's about the functionality. An ECG is an ECG.
Ah, it sounds like it probably wouldn't apply to the 'symptom checker', they've decided their regulatory regime only applies to devices that... actually directly take medical readings themselves, it sounds like? That doesn't seem unreasonable. And, yeah, a service/process/system that takes your saliva as input seems in that category.
My gut feeling is that it's an issue of manpower: they're choosing their battles.
I've been in the Medical Device industry for over 10 years as a software engineer. Soon after I started, during one of our mandatory Quality Systems training sessions, it was pointed out that there are many software-only companies whose products were Medical Devices under the FDA definition, but the FDA simply didn't have the manpower to police all of them. In many cases, the companies themselves probably didn't know they fell under FDA regulation.
The objections are based on the second part (and the marketing for it), which seems by itself to be very equivalent to WebMD. I don't think there's any suggestion that abstract-genetic-marker-finding is the problem here.
It seems to me that it's the link between those two parts that is problematic! If someone sold genetic tests that just output a list of markers, and the clients consulted publicly available literature to discern the meaning of those results, then no one would have taken the responsibility of giving advice to a client. By packaging a specific, curated set of information with the test results, 23andme has crossed over from offering tools to offering expertise - and has therefor taken on responsibilities.
Any lab test is going to have those two parts, a lab procedure and an analysis. I would expect both parts to be governed by the FDA to ensure reliable results.
There is a difference between mechanical analysis and medical analysis. Obviously they need to analyze the raw signals coming out of the machine to figure out what markers are present. But they could stop there, saying "with four nines certainty you have genes ABJ2, CBI8, LOC9, JOLO, ZZT". The FDA is objecting to doing a medical correlation/explanation beyond that point, doing the things WebMD does.
To be honest, I think they have to do both things to get regulated under the FDA. The FDA is involved because they consider it a "device" that is "intended for use in the diagnosis of disease or other conditions." If they just did the analysis based on provided data, I don't think that would count as a device.
1. They sign a terms of use agreement.
2. 23andMe asks for "are you sure, this can have impact on your health?" when you want to see your health risks.
3. 23AndMe interface has health risks with a "confidence level", for example, my Alzheimer's probability is 10% higher than avg risk and confidence level is 4/4.
I find your argument invalid. If they get an approval from FDA, is it going to change their data processing logic or data set?
> I find your argument invalid. If they get an approval from FDA, is it going to change their data processing logic or data set?
I guess it would depend on if the FDA finds their data processing logic to result in valid and reliable medical determinations, right?
They also might have to change their marketting materials to comply, something specifically mentioned in the FDA letters. Regulation to prevent misleading marketting of medical products is definitely a pretty core part of the FDA's remit.
If they get an FDA approval, it would mean that there has been review that their outputs are actually appropriate. That's why the FDA is required by law to review items marketed for diagnosing disease.
Summary:
5 years ago, 23andMe started marketing a test for among other things a BCRA indicator
July and Sept 2012 - 23andMe submits a form to the FDA saying "our test isn't really useful for diagnosis and thus shouldn't fall under these rules"
Nov 2012 - FDA says we don't agree with you you need to either prove your effectiveness or change your marketing
Jan 2013 - 23andMe says "it will take us a couple months to do the tests, we'll get back to you"
Nov 2013 - FDA says, "its been 11 months and you never got back to us. Stop selling and let us know within 15 days what you're going to do explicitly because you ignored us for close to a year"
Exactly. I am no fan of the FDA, but what 23andMe did here was extraordinary: they essentially ignored the agency. If Anne Wojcicki was CEO of a similarly-sized medical device company she would have gotten her walking papers today.
Why is ignoring a government agency when they ask you to follow the law praiseworthy? The law says you cant market a diagnostic test without testing to know the accuracy of the test. I don't want to praise the snake oil salesmen who would also want to break this law so why should I praise what 23andMe did?
Because, in this case, the Government agency and the laws they enforce are unconstitutional, and actually harm the people they're supposed to be protecting.
Care to explain how the FDA is harming the people it should protect? It seems to me that they're simply trying to get 23AndMe to accurately market their product. Since 23AndMe is making claims of a medical nature, it falls neatly under the jurisdiction of the FDA as granted by Congress.
Care to explain where in the Constitution the Federal Government is granted the power to regulate medicine? I think you'll find that that power is reserved for the states. With respect to harm, take a look at how many people are killed by delays in drug availability caused by the approval process.
Nothing the FDA does that is legitimate couldn't be better handled through the courts at a state level. And you wouldn't have to ignore the Constitution in the process.
I'd like to point out that -- as much as I'm sure most people love 23andMe -- it's not really a scrappy start-up. It's a nearly 8 year old company which has received something like a hundred million in funding.
So this isn't really a case of the gov't stomping on the little guy before he has a chance to grow; 23andMe has had its chance to grow into a fairly big deal, and now it's time to start playing by the rules.
The average drug costs around a billion dollars to bring to market and decades in development and approval. 23andme might not be a small fish by internet standards, but they are by medical industry standards.
But 23andme do not make drugs. They do diagnostic tests. The cost of development for those are much lower. 23andme aren't giants in that field for sure, but they're pretty big. It's absolutely nonsensical to compare them to a drug company.
More specifically they are busted for interpreting diagnostic tests not doing the tests. If they were two cooperating companies, and one did tests and squirted out results and the other sold diagnostic and interpretive services, the diagnostic services company would be busted but the test company would not be in trouble, as I interpret it at this time.
Skip all the exotic genetic issues and think about personal experiences with something boring, like blood pressure. No legal problem with testing someones blood pressure and giving them numerical results and maybe a medically sane set of typical ranges. My local pharmacy has a machine that does it for free. However, it would be a big issue for a non-MD using that data to diagnose high blood pressure, or a high likelihood of it anyway, then providing some treatment plans.
The issue seems to be selling services. If they just did testing, and provided a free downloadable immense data set and some statistical analysis tools and let the user come up with their own interpretations, they'd probably be in the clear (at least with respect to this individual problem). Now having a cloud service to hold the data and do the math is getting gray area ish but probably still OK as long as its the end user drawing the conclusions and not "the company" drawing the conclusions.
> Skip all the exotic genetic issues and think about personal experiences with something boring, like blood pressure. No legal problem with testing someones blood pressure and giving them numerical results and maybe a medically sane set of typical ranges.
Actually, the device used to take the blood pressure reading, if I understand things right, did have to be approved by the FDA.
The FDA's letter keeps referring to 23andme as a 'device', so it seems like the FDA's authorization/responsibility is specifically to regulate devices rather than services, actually, but they've decided 23andme can be technically classified as a 'device' under the relevant laws/regulations.
If it was instead considered a 'service'... I wonder if there'd instead be a problem with practicing medicine without a license, if it's not MD's who are providing the 'service'!
"the device used to take the blood pressure reading, if I understand things right, did have to be approved by the FDA"
that is true, the FDA would bust a mfgr of a device that claimed to report blood pressure but instead did astrology. This specific example of 23andme is, as near as I can tell, getting busted for interpreting the results, not for using 'cat /dev/urandom' to generate the results and then interpreting them.
Kind of like the same FCC that gets excited about out of band RF interference also got sorta excited by janet jackson's halftime show.
I am not sure there is as big a black-and-white distinction between 'providng' and 'interpreting' as you suggest.
23andme is a 'device' that takes a bodily fluid sample as input, and provides genetic information as output.
A an automated blood pressure cuff is a device that, well, I don't know how it works, but wikipedia says it "They do not measure systolic and diastolic pressures directly, per se, but calculate them from the mean pressure and empirical statistical oscillometric parameters", whatever that means, and produces some blood pressure numbers as output.
23andme is obviously a much more complex 'device'. Both both take some sort of measurement of your person, and then provide medical information.
Even if you could somehow draw a line at some point in this process of translation from physical measurements to medical information, some point at which the 'interpretation' begins, I'm not sure why one would suggest that either side of that line would be exempt from FDA regulation!
>23andme is a 'device' that takes a bodily fluid sample as input, and provides genetic information as output.
I don't think that's true, which is the problem. They don't just provide genetic information. They provide information detailing the impact of those genes, as medical science understands them.
>Even if you could somehow draw a line at some point in this process of translation from physical measurements to medical information, some point at which the 'interpretation' begins, I'm not sure why one would suggest that either side of that line would be exempt from FDA regulation!
Neither side would be exempt, but the physical side would be trivially approved as "yes, this does in fact measure those genes, good work everyone, pop the champagne".
He didn't fail to notice they're different agencies.
He is asserting that they both (being both government agencies) have each been inconsistent in their regulation.
> So this isn't really a case of the gov't stomping on the little guy
Last time I checked, the US federal government had an annual funding rate of $3.45 trillion compared to "a hundred million in funding" total for 23andMe.
So yeah, government stomping on the little guy definitely fits the picture. Then again, it would fit the picture no matter who the government decided to stomp on. Perhaps we should focus on less stomping and on more cooperative behavior?
That's disingenuous. The FDA's 2012 budget was $4.3B. The fact that our government chooses to pour $1/2T into the military, that has very little sway on this.
Make no mistake -- after having stomped on this "not little guy", any new little guy that comes along is definitely going to get stomped on. Which of course means that no new little guys are going to come along. This is the process whereby established players obtain a monopoly. In other words, what doesn't kill 23andMe will make it stronger.
This reminds me of a blog post in German [1] by a person who due to a software bug had been falsely diagnosed by 23andMe with limb-girdle muscular dystrophy. (Fortunately, he was able to identify that it was a misdiagnosis.) It appears that in this case potential misdiagnoses aren't just a theoretical problem.
This is what 23andMe said about that person's genome:
"Has two mutations linked to limb-girdle muscular dystrophy. A person with two of these mutations typically has limb-girdle muscular dystrophy."
Of course this not a diagnosis in a technical sense, but to a lot of people it will sound like it is. Specifically, I don't see how this is "very clearly" not a diagnosis.
23andMe empowers you to better manage your health and wellness.
$99 [Add a kit]
There are no disclaimers on this page, just an aphorism, an assertion, and a call to action. Now I like the idea of 23andme, I like the company, and I'm educated and skeptical enough to enjoy some fluffy scientism for a hundred bucks, but don't tell me they're not selling the hell out of this.
As usual, the government is trying to meddle with companies. Read the letter, but make no mistake - the "kind" tone, especially when reminding how they did they best to get in touch, have meetings, help insuring compliance etc. is just a decoy. The truth is with "must immediately discontinue marketing the PGS".
The gov wants to decide what's best for the people. Should the people decide differently, using their wallets for example, this anomaly will be quashed.
This trend is especially strong in the medical field - gov approval required everywhere, then people wonder why medical things are so damn expansive.
I use 23andme and I'm happy with the information provided. I know it's not reliable - it's not a lab test anyone will use to base important decisions on, since it is not a full sequence of genes.
Yet, by being commercially available and easy to use, it is paving the way for commercial offers of full genome sequencing, which I damn well intend to use when they reach the $500 threshold.
However, gov actions like this one may very well make that impossible, making sure the only full genome sequencing offers there will be will be "FDA cleared" at a huge markup.
Suggestions to "medical" like companies - get out the gov eye. Move your business to Asia, the caribbean or wherever the gov will not get in your way like this. I want to keep using (and recommending) your products!
> The gov wants to decide what's best for the people. Should the people decide differently, using their wallets for example, this anomaly will be quashed.
Wallets are incredibly poor judges of medical efficacy. The FDA rules are in place for very good reasons, namely to prevent snake-oil salesmen and other unscrupulous merchandisers from foisting their -- potentially harmful -- products upon an unsuspecting public.
I would much rather have FDA clearance for medical products and devices than the alternative that you seem to be proposing.
I don't think anyone is going to argue about the FDA's role in ensuring drugs are safe, but most countries don't require positive proof of effectiveness and, frankly, have better health outcomes than the US. Doctors are quite capable of reviewing the evidence to see if drugs are effective, and the FDA doesn't in practice do anything to prevent the sail of non-poisonous snake oil.
A number of western countries take a strategy that tries to make questionable-but-safe drugs legal-but-rarely-used. For one, they ban direct-to-consumer advertising; the USA and New Zealand are the only two developed countries where it's legal to advertise to consumers. And for another, state health-care systems will typically not pay for drugs that lack evidence of efficacy, and most people are used to getting their healthcare through the state health system. That leaves it technically legal for consumers to buy, out-of-pocket, a drug that can't be advertised to them. In practice a handful of people do so, but not too many.
It looks like they do sell this in Europe. Although I'm not sure if that's because it's approved at all, or just because Europe considers it some kind of novelty product rather than a medical device; the FDA and EU categorization of drugs/devices/etc. is a bit different.
Doctors encompass the entire range of people (from morons to geniuses). As a group, they aren't some magnificent godlike all knowing figure.
"Programmers are quite capable of reviewing the evidence to see if code is effective" — yet, we end up with thousands of people using MongoDB based off fad and hype and losing data by the day.
(Wait, did I just advocate for a government-level code approval board? In the right hands it would probably help if it prevented more Mongos and Hadoops from entering the world.)
Doctors make mistakes, but there isn't anything preventing that in any event. In theory a doctor can prescribe any drug for any ailment (though there are lots of checks and consequences), and prescribing drugs for things other than their FDA approved use is very common[1]. You have to rely on doctor judgment at some point and efficacy trials don't substitute for competent doctors. And sometimes the whole process goes awry because a drug is approved for one problem, later becomes the only treatment for some people with a second problem, then the FDA withdraws approval because there are now better treatments for the first problem, leaving those with the second problem in the lurch.[2]
I think the US's for profit healthcare system makes the FDA very important. Here in the US, we have pharmaceutical salesman who come in and schmooze the staff to then get to the doctors. Pharmaceutical rep is a job known to be very amenable to attractive women with little skills outside of flirting.
Your definition of "for profit" is somewhat misleading, as many Canadian doctors, nurses, pharmacists, etc. are the residual claimants ('profiteers') of almost any course of testing or treatment; and I suspect that this is true of many countries with less strict drug regulations.
Can you please give example of such a country? I can't think of any country with working healthcare where you are allowed to claim anything medical (or heaven forbid perform) before clearing it with the authorities.
> Wallets are incredibly poor judges of medical efficacy.
So are bureaucrats who are subject to the influence of lobbyists. Snake-oil salesmen and peddlers of alternative medicine do sell their stuff under the current system, while true innovation is crushed, as is evident in this case.
Any hospital offering primary care has a lab at their disposal that can do this. Genotyping is nothing new...but as for competitors in 23&me's area (aka public access genotyping for cheap an that I can remember off the top of my head): deCODEme, lumigenix, Dna Genotek and MapMyGenome
Navigenics, with Navigenics Health Compass, was a competitor to 23andMe with their PGS offering, but Navigenics appears to have discontinued the competing offering (Navigenics was received initial contact from the FDA at about their product at the same time 23andMe did, they also went through similar rounds with the State of California for licensing to operate their before that.)
There's a number of other offerings that have been made in the same general space, as well.
>Wallets are incredibly poor judges of medical efficacy. The FDA rules are in place for very good reasons, namely to prevent snake-oil salesmen and other unscrupulous merchandisers from foisting their -- potentially harmful -- products upon an unsuspecting public.
There is snake oil for sale in every store, and no one has ever been hurt from their test.
> The gov wants to decide what's best for the people. Should the people decide differently, using their wallets for example, this anomaly will be quashed.
There are huge information asymmetries involved when it comes to medical drugs, and also huge barriers to experimenting with different products. "Voting with your wallet" is appropriate for determining which cell phone should be popular, not which medical drugs or medical tests.
We as a society have determined that the appropriate risk versus innovation trade-off when it comes to medicines and drugs is less risk at the potential cost of less innovation. The FDA exists to safeguard that policy.
It's funny that you mention Asia, because the trend in Asian countries is to follow the American/European model. Asians have had enough of thinking "is this rat meat?" every time they bite into a lamb kebob, and are regulating their food and drug industries. And by "asians" I mean the Chinese, because the Japanese and Koreans have adopted the Western regulatory model long ago.
The Chinese have the death penalty for food adulteration with toxic or non-food products[1]. It's funny seeing people complain about heavy handed regulation in comparison.
> There are huge information asymmetries involved when it comes to medical drugs...
This is what the FDA should be doing. Correcting information asymmetries. With labeling requirements, unbiased PSAs, drug pamphlets and literature. Not telling people what they can and can't put in their bodies, or what businesses can and can't sell on the open market.
In fact, I'd say most government regulatory functions should be set up this way. Clearly inform and educate your citizens, don't opaquely dictate the behavior of your subjects.
Well, but this is exactly what they are doing here - the letter claims that they required corrections in the marketing claims (which would be correcting information asymmetries / labeling requirements), this wasn't done properly for a long time, so they are now enforcing it.
For any reasonable requirement, if people/companies don't comply then it has to escalate to [threats of] harsher actions in order to force the reasonable thing to actually happen.
I know you're responding to a more general point, but I don't think any of your post applies to this situation. This is about marketing materials, and more importantly the factual information therein.
> I know it's not reliable - it's not a lab test anyone will use to base important decisions on, since it is not a full sequence of genes.
If they made that more clear, then they wouldn't have had to send the letter. It's why you see "This is not intended to diagnose, treat, or cure any disease" on all the non-FDA-approved supplements/energy drinks. My money is on them paying the fine and scaling back the marketing.
The purpose behind these FDA rules are to make sure things aren't marketing as "cures" when they aren't. People's health is serious business; there's no room for failure. If 1.0 doesn't work (or makes things worse), then the people that need it might not live to see 1.1.
That's true, but it's not a slam-dunk case for rushing ahead without sufficient testing. There's a reason that "first, do no harm"[1] is considered one of the fundamental principles of medical ethics. Medical interventions can have disastrous side effects.[2]
It's not a slam-dunk case, just keep in mind it's very easy to measure the harm done by things like Thalidomide, but not so easy to measure the amount of people dead or maimed by not getting treatment due to the glacial pace of regulatory approval. "First, do no harm" could just as easily apply to not dragging your feet in giving someone potentially life-saving treatment.
I'm curious, are there any other examples than Thalidomide? It's a true horror story, but there should be a limit to how much precaution one disaster justifies in the future. Many other drugs with ultimately fatal but initially undiscovered side effects have made it through FDA approval, too.
This example is rather famous in the legal world because a) the drug was off-patent for many years before the problems were identified, and so there were many different manufacturers, and b) the problems were often not apparent until decades after exposure had occurred - two factors which make it very difficult to fairly ascribe liability to those who suffered avoidable injuries. This led to some innovative thing in damages/liability allocation which is now an essential part of understanding tort law.
I mention this because I've had some conversations with libertarian legal thinkers where they bring up this same argument of Thalidomide vs. opportunity cost - and its true that the barriers to approval were so low back in the late 50s that it's very unlikely such a drug could ever get on the market these days. Also, the effects were so drastic that that they were quickly noticed, and the number of birth defects ascribable to Thalidomide are in the low 10,000s. By contrast, millions of people are living with the impact of DES, and the magnitude of the affected class is also a factor in the legal significance of the damages formula. So any lawyer who's talking about balancing innovation and regulation in the drug market without addressing DES is being a bit disingenuous, and you should weight your judgment accordingly.
That's fascinating. The Wikipedia links cover the landmark nature of how liability was distributed, but I'm as curious about how liability was established. I don't know much about tort law, but is it essentially automatic that a manufacturer would be liable for a product that caused such damage, no matter how difficult it would have been for them to have been aware of that potential?
FYI I like tort law but am not a lawyer, just a law school dropout. My view is that liability depends on the degree to which the manufacturer was in a position to be aware of the risks, and also on the relative ability of the consumer to discern such risks.
To take the latter point first, drug consumers are generally in a poor position to evaluate the risks of a given medication. If I set up a wheel manufacturing business, and sell square wheels, you are in a poor position to complain about the resulting bumpy ride [1] because the superiority of round wheels is so glaringly obvious. Unless you hold a medical or pharmaceutical degree, though, your ability to evaluate a drug's safety and efficacy is probably very limited. I'm smart enough to read and get the gist of a biochemistry paper to have an idea of what a drug does, but nowhere near knowledgeable enough to review or spot all but the most egregious errors. So while I am the sort of person who reads all the fine print on drug labels and sometimes digs into the academic research, in the end I'm taking a great deal on faith whenever I take medicine. by contrast, the drug manufacturer has not just one biochemical expert, but whole teams of them. This certainly puts them in the best position to foresee and even look for potential problems.
Now back to the first point: drug discovery is not the exact science we'd like it to be due to the gaps in our knowledge. Accordingly, drug companies must be given some leeway, compared to other manufacturers who enjoy a greater degree of foreseeability. suppose I set up a ladder company, but the ladders I manufacture employ such thin metal rungs that they cannot bear any weight above 100 pounds. They look good enough, but soon consumers begin suffering accidents when using them. I could not claim the accidents were unforeseeable since the tensile properties of metals are so well known and the tests are so easy to perform, that I should have realized the risk when designing my product, never mind before shipping it! It would be unfair to hold drug manufacturers to that degree of liability, but on the other hand a) experimental protocols exist precisely to address this problem and are widely understood within the drug industry, and b) since DES was on sale from 1941 onwards and class action lawsuits were brought against manufacturers in the late 1960s, more than enough time had elapsed for industry participants to have apprised themselves of the risk and limited the risk to consumers to a greater extent than they did.
If you read Judge Mosk's opinion, in footnote 24 [2] he summarizes a 7-point test for establishing (rather than allocating) liability. The answer you seek is there:
The suggested requirements are as follows:
1. There existed an insufficient, industry-wide standard of safety as to the manufacture of the product.
2. Plaintiff is not at fault for the absence of evidence identifying the causative agent but, rather, this absence of proof is due to defendant's conduct.
3. A generically similar defective product was manufactured by all the defendants.
4. Plaintiff's injury was caused by this defect.
5. Defendants owed a duty to the class of which plaintiff was a member.
6. There is clear and convincing evidence that plaintiff's injury was caused by a product made by one of the defendants. For example, the joined defendants accounted for a high percentage of such defective products on the market at the time of plaintiff's injury.
7. All defendants were tortfeasors.
This is a very brief abstraction of a key theory in a law review article written by a student at Fordham University, referred to in the opinion as 'the Fordham comment.' This unusually influential article [3] basically sets out a whole theory of 'enterprise liability' and damages allocation addressing why the manufacturers should share liability in the context of the DES in much greater detail, although it's rather painful to read for people who are not legal nerds as it approaches some sort of footnote event horizon. Whether the Sindell court's findings allow the legal academy to be held liable for typographically-induced brain trauma remains unresolved.
Doesn't exactly answer your question, but here's a list of formerly approved drugs that were withdrawn due to risks to the patient (22 in the last decade).
That's kind of my point. Does that mean we should ratchet up FDA's precautionary attitude dramatically further, to the point where that number is perhaps 2 instead of 22? I don't think so. There's a sensible tradeoff to be made, but tuning exactly where that tradeoff should be isn't the kind of thing you settle with dramatic examples of things gone wrong.
It's difficult to measure how many lives were saved or made substantially more livable because the FDA was not more cautious than it has been. Surely that number is not zero, and perhaps it's greater than the net harm done by drugs whose effects might have been caught by more prolonged testing. I don't think we know.
There's another aspect to tradeoffs where Lumiracoxib was introduced to compete with Celecoxib. Celecoxib has a known acknowledged issue where it increases the risk of heart attack although its relatively easy on the liver. Unfortunately Lumiracoxib occasionally destroys livers. So superficially you'd think having both on the market would be a great idea, because people with a personal or family history of liver disease would probably be better off with Celecoxib but people with a personal or family history of heart attack would be better off with Lumiracoxib. However, worldwide in general all the .gov disagree with me, and as the new guy on the block Lumiracoxib more or less got the boot. It never even made it to market in the USA as far as I know. Probably has something to do with relative incidence of fatality.
BTW these are not made up names although they look like it. Google them for a good time if you're bored. I'm more interested in the chemistry issues than the politics or biochemisty, so I'd be more comfortable (authoritative?) talking about the location of the methyl groups than liver toxicity, but my first paragraph has no known intentional errors (although it probably has some unintentional errors LOL).
I guess the point of this ramble is if a company exists to provide highly personalized customized services, then using a metric of "joe average" is probably not overly meaningful. The response of joe average to a disease percentage is maybe not relevant to the response of someone with a high percentage to the same result.
We have a pretty good medical system designed for joe average, and its intersection with radically personalized services is unsurprisingly going to be an epic disaster.
Another interesting side effect is most mass shooters were on anti-depressants, although that's probably not the kind of direct fatal side effect you're looking for. Its a challenging google game to track down the toxicology reports for each mass shooter weeks after the smoke clears and identify which anti-depressant they were on at the time. Sometimes its a different kind of med, sometimes they're not on any med at all, although thats kind of rare.
The cost to over-rapid approval is that unborn children are mutilated by medicine taken by the pregnant mother, or that very many people are harmed by side-effects from expensive meds that are no more efficient (sometimes less so) than existing meds.
>very many people are harmed by side-effects from expensive meds that are no more efficient (sometimes less so) than existing meds
That one is easy: don't fast track drugs that are only marginally better than their peers, if at all, because by definition they aren't as important.
I don't have as clear an answer for pregnancy, other than exempting pregnant users from the fast track approval, but I'm not sure how a slower process actually protects pregnancies in the first place.
A lot of the modern pharmaceutical marketing regulation, and the regulations that makes approving new drugs a slow process, came in the wake of Thalidomide, which I think still provides a fairly strong case for why we should thoroughly test new medicines, and shouldn't rush them to market.
People die from the opposite approach as well from drugs that shouldn't have been on the market and aren't safe or effective. People dying is not a reason to just allow anything. Regulation is good when it comes to forcing companies to prove a drugs effectiveness by actually doing the science.
That's a good point. I don't know as much as I should about the clinical trial process or the ability of terminally-ill patients with nothing to lose to seek experimental drugs. In a better world, it'd be as simple as patient and doctor both giving an informed and well-reasoned consent, knowing the risks involved but choosing to take that risk anyway.
This is more complex than the simplistic picture you paint.
I'm moderately on the side of government not interfering where possible. But medicine and medical devices is one area in which such interference is quite likely a positive influence, on the whole.
Fact is, we don't want a return to the era of patent medicines. For every user of 23andme who is well-informed enough to know that the information is not reliable, experience shows that there will be another who is not. And these people will base life- and health-affecting decisions on the results provided by unregulated products. Then maybe they'll get sick or die.
That's why there are regulatory standards for medical devices and services. These standards don't prevent the sale of 23andme's services, but require that they are either a) regulated and proven to work, or b) explicitly and clearly described as not being so.
Yes, there are rampant inefficiencies within this system. But I'd wager that it's probably better than the alternative.
For every user of 23andme who is well-informed enough to know that the information is not reliable, experience shows that there will be another who is not.
The funny thing here, is that barring lab errors, which I think are highly unlikely unless they are being incredibly shoddy, which would take effort, the information that 23andMe provides is very reliable. Now it is debatable as to whether the individual's interpretation is (for example in the Alcohol Dehydrogenase gene, many, many, many caucasian users don't bother to read that the test is only informative for asians, but it's definitely there, in bold letters, etc.)
Could you explain a scenario where basing life and health decisions on 23andMe's product could lead to sickness and death? Maybe it's "because I'm sophisticated", but this biochemist can't really see that happening.
The funny thing here, is that barring lab errors, which I think are highly unlikely unless they are being incredibly shoddy, which would take effort, the information that 23andMe provides is very reliable
That's the point of certification - is the process reliable? Are the warnings clear? I won't cast any aspersions on the product (because it's pretty awesome), but I do see these as risks and requirements.
Could you explain a scenario where basing life and health decisions on 23andMe's product could lead to sickness and death?
"I've got all these symptoms of diabetes. But 23andme said I had a low risk! It's probably nothing. Guess I'll eat another pie."
If 23andme has shoddy lab practices, or unclear explanation of the limitation of their testing, then that's a risk. The process of certification involves managing that risk.
(this study is about mammograms of healthy women, another example of a health screening tool)
We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).
Numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42) for the two adequately randomised trials that measured this outcome; the use of radiotherapy was similarly increased.
So women who get more screening get more treatment but didn't live longer (unnecessary treatment)
Study continues:
This means that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false positive findings. It is thus not clear whether screening does more good than harm. To help ensure that the women are fully informed of both benefits and harms before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk.
yes, but getting a mammogram has an additional layer of regulation in between the end-user of 23andMe. A licensed radiologist should look the person askew when they insist on getting extra mammograms because of 23andMe, and order a follow-up BRCA test before proceeding.
A mammogram is a screening test. 23andMe is another type of screening test. You aren't getting extra mammograms because of 23andMe, they are the same thing.
Mammogram can screen you for early detection of a serious disease. 23andMe can do the same (they advertise - this is what the FDA has a problem with).
More screening for all diseases doesn't mean better outcome, and can be harmful, depending on the test, the people screened, the disease, etc., etc. and can lead to more disease (needless treatment). Throwing more screening at the wall for every disease doesn't do more good all the time. Especially when we learn that some diseases (prostate cancer) cause no symptoms most of the time. Treating these asymptomatic prostate cancers is very harmful, because they are harmless unless they progress. The treatment is risky and has serious side effects (impotence!)
Every time we have a screening test, we have to look at the science. What are we screening for? What is the good? What is the bad? Who is helped? Who is harmed? Do the positives outweigh the negatives?
Another outdated screening tool is the breast self exam - it was found (in scientific studies) it didn't do any good and caused harm (http://en.wikipedia.org/wiki/Breast_self-examination) Lots of over treatment without a reduce in cancer rates. Also, just learning about it increases women's worry and anxiety about breast cancer. This is a harmful screening tool. This was studied and abandoned.
----
BRCA test has nothing to do with this example.
Mammograms are currently very common in women a certain age >40 or >50. Most women get them every few years as part of their health maintenance to check for the presence of cancer, tumors or lumps. Right now there is research coming out that is questioning that practice, but the practice hasn't caught up to the research and most doctors say "get your mammogram" without informing patients of the risks, they treat it like it is "all good." That was the point of this research to ask "are we doing the right thing here by screening all these healthy women with mammograms? Let's study that."
I will personally opt out of the mammogram hype when I reach the mammogram age. I'm also going to inform my mother of the current research on the matter, I know she's already had a few mammograms herself.
> The funny thing here, is that barring lab errors, which I think are highly unlikely unless they are being incredibly shoddy, which would take effort, the information that 23andMe provides is very reliable.
Certainly, there is science to support certain claims of the class made in the reports 23andMe provides being made with some degree of reliability based on the kind of inputs 23andMe takes in. Whether what 23andMe actually does from end-to-end makes the actual reports they provide reliable in real world condition is...well, exactly the question they have seem to have decided not to expend the effort to answer even after initiating the process of getting clearance from the FDA to market their diagnostic product.
Ah, the "people will vote with their wallets" argument against medical regulation.
I'm with you. I'd much prefer a bunch of people die first so the rest of us can "vote with our wallets" instead of having a government agency step in and try to fix things before anyone gets hurt. I mean, my start-up is going to sell baby food laced with arsenic because I once heard that arsenic makes babies smarter and I think I once ingested some accidentally and I didn't die. If it really does end up killing babies, well, the market will eventually correct itself. And no harm, no foul, man. Except the dead babies. But at least I wouldn't have some nebbish bureaucrat knocking at my door trying to tell this American how to live his life.
Just to pare back the hyperbole -- there's really no practical way for someone to die from a 23andMe kit. We should be able to agree on that.
There have been a bunch of concerns in this thread that are valid -- e.g., people might have to deal with bad news, or may see false positives, etc., that could cause them some inconvenience (though I would argue that 23andMe doesn't tell you that you have cancer, just maybe whether or not you're likely to).
Regardless, the idea that I could die from a 23andMe test is about as far-fetched as one can get.
What an absurd argument. If you sell baby food laced with arsenic, and babies die, you've committed murder. In a true free market, you wouldn't have a liability shield and would face severe consequences for putting out dangerous products. Just because it's a free market doesn't mean you get to do whatever you want with impunity. And also, the FDA is not some magic fairy dust that will shield you from bad products. Mountain Dew still has BVO in it, for example.
> In a true free market, you wouldn't have a liability shield and would face severe consequences for putting out dangerous products.
Liability for defective (whether through malice, negligence, or in some cases on a strict liability basis) products is government intervention in the marketplace, and is specifically designed to address one of the ways that reality does not align with the presuppositions under which an unregulated "free market" is ideal, to wit, that people generally do not, in fact, act with perfect knowledge of the outcomes of economic decisions when they engage in them.
It is no different than many other government interventions in the marketplace in its basis.
> And also, the FDA is not some magic fairy dust that will shield you from bad products. Mountain Dew still has BVO in it, for example.
That does not mean that its approval procedures (and procedures for reviewing products already on the market) do not have utility in providing clearer information on products within its regulatory domain and helping consumers avoid bad products.
You understand that the goal is to prevent the horrible thing from happening, right? Not to let the horrible thing happen and then try to fix something that's unfixable?
> I use 23andme and I'm happy with the information provided. I know it's not reliable - it's not a lab test anyone will use to base important decisions on, since it is not a full sequence of genes.
You have unwittingly affirmed the very argument you are attempting to refute. Their inability to make accurate functional predictions from genomic data has much less to do with the technology (sequence vs. array) than it does with the fact that, isolated instances aside, nobody knows how to do this well. I am a 23andMe user myself and, knowing a bit about statistical genomics, I was surprised how credulously the results of one or two GWAS papers are presented as an almost-diagnosis on their website. GWAS are plagued by all sorts of confounding issues and the statistical evidence in favor of their conclusions is often extremely weak. This is not something that the general public appreciates, so I can see why FDA might get involved.
Hey! You should check out Elixir Sulfanimide! It prevents infections, but it's available over the counter. So easy! And it's from a Massengill, an established pharma company, so you can trust it!
So actually you can't buy elixir sulfanimide anymore. Because it was poisonous. It resulted in more than 100 deaths in 1937. This was before the FD&C Act, requiring safety tests. The founder of Massengill refused to take responsibility for the results: "We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part." It should be noted that there was a sulfanimide craze on at the time, as the first commercial antibiotic, so there was much money to be made.
One woman wrote to President Roosevelt, about her dead daughter: "The first time I ever had occasion to call in a doctor for [Joan] and she was given Elixir of Sulfanilamide. All that is left to us is the caring for her little grave. Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane. ... It is my plea that you will take steps to prevent such sales of drugs that will take little lives and leave such suffering behind and such a bleak outlook on the future as I have tonight."
Massengill paid a minimum fine and continued on until it was acquired in 1971.
I don't mind that we have set up an agency to make sure that medical products and devices are safe to use and do what they say they are going to do. It's far more efficient than having to do it individually. And there's always, evidently, people who won't, because they trust their doctor or the brand. And, being medical products and devices, sometimes those people or their loved ones die.
I agree for the most part (I tend towards libertarian ideals if you've read any of my comments), but it's a difficult balance to maintain between allowing for medical innovation and preventing an objectivist distopia a la Bioshock. The government has a legitimate responsibility to ensure that medical technology is used and marketed responsibly, while at the same time giving companies some wiggle room to innovate.
Look how smallpox vaccine was discovered. Edward Jenner inoculated a young boy with cow pox, then attempted to infect him with smallpox a dozen times. Obviously we can't go around convincing young children to take infectious doses of deadly viruses. But we also cant send FDA thugs after every Silicon Valley startup pushing the boundaries of genomics research. So where do we draw the line?
There are lots of proposals to simplify FDA's approval process, for example, automatically approve it if it's already approved in a number of Western countries whose approval standards are high on average.
But in this specific case, seems FDA isn't being totally unreasonable. For example, from the letter
"Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS"
seems like a good idea to require companies to do this
This sounds like a false dichotomy:
"The government has a legitimate responsibility to ensure that medical technology is used and marketed responsibly"
So either the government ensures the above or it does not get accomplished? There are no third parties that could take this on? I find that hard to believe.
Non-government regulatory agencies aren't a cure all for complex products. For instance, check out the 2008 financial crisis. Sub-prime mortgage derivatives were rated AAA by private ratings agencies.
In fact, I would venture they are worse because they have to be paid somehow, and if they are paid by industry, you are ripe for regulatory capture. It can be difficult to get consumers to pay for it unless you include some kind of tax in the product they buy in which case you've arrived at a pseudo-government agency.
From what I hear from my co-workers in the quality department (I work in a medical device company) it's even harder to get approval to go through regulation in China than in the US. And you most certainly cannot just base your company from Asia and sell your stuff to the rest of the world (unless of course you go through regulation in the rest of the world).
You might be able to find countries where regulation is less strict or non-existent but I'd imagine that people's trust in medicine in said countries is less than in the regulated ones (as you most certainly would have rouge players abusing the lack of regulation).
Why be so snide, instead of actually writing an informative / useful reply? That would certainly take more effort, but this is Hacker News, there's supposed to be a higher standard of discourse here.
The original comment is nothing more than a generic libertarian rant, complete with the "gov" strawman, force-mapped to the matter at issue. It scarcely deserves more than the response to which you take objection.
What's the point of the down vote then, if not to enable an easy response (and influence) to something disagreeable without spurring entirely unnecessary and often negative comments?
Wrong. Derision begets derision and tends to create an anti-intellectual feedback loop. There is no place for that here. Flag the people throwing insults around and move on.
You're right. I shouldn't have done that but I just couldn't believe that that was the top/first comment. It was one of my first posts and if I wanted to comment I should have taken the time to write an useful response.
> For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist.
I cannot imagine someone getting surgery or chemo solely based on a 23andme heads up warning and without consultation with a specialist physician.
As someone working in medical devices, this dramatic language is extremely frustrating.
That example is a bit severe, but I think the Warfarin compliance example is spot-on. You receive a prescription for a drug, but your magic internet test tells you to take a lower dose, because you're "sensitive". Then you die of an aneurysm because the test was wrong.
People are completely stupid when it comes to medical issues. I heard a woman complaining that she couldn't eat honey because she was allergic to fructose. I work with at least 3 "gluten-sensitive" people (it's pretty unlikely they all have Celiac disease, it's not a big office), because it's a hip thing to do. Hell, didn't Angelina Jolie have a prophylactic double mastectomy?
edit: Since everyone is jumping on the Angelina Jolie example. I don't think her decision was made based on a single spit test. And I think she had doctors advising her. But the amount of publicity it got makes me worry that it could become needlessly popular based on self-diagnosis (like not eating gluten).
>Hell, didn't Angelina Jolie have a prophylactic double mastectomy?
The placement of this in your post seems to imply you think she was being stupid with her decision, or thought it was in some way "hip" to do. She has a family history of breast and ovarian cancer and has a defective gene that made her chances of getting breast cancer 87%. As she's pretty wealthy, I'm going to guess that she has pretty good doctors and didn't make the decision on a whim. Also since it was major surgery I'm going to also assume some doctor saw her at least once before the surgery and s/he didn't just take her word for it that the surgery was in her best interest.
Yes there are plenty of people who don't have a clue when it comes to medical issues, but I'm not sure why you felt the need to lump Jolie in with your other examples.
I don't think she did it to be hip - I'm sure she had many doctors advising her, and she underwent many tests before making her decision. But it was heavily publicised, and it set a dangerous precedent that people with less access to medical resources will send away this $100 test, see "cancer risk", and start pushing for unnecessary surgery.
I mean, it is major surgery. There is a pretty big difference from somebody cutting out gluten from their diet and somebody getting surgery. If I decide one day I'm allergic to gluten, I can stop eating it without consulting a doctor. Similarly, as the sibling comment mentions, if McCarthy thinks vaccines cause autism she can stop getting them for her and her children without consulting a doctor. Sure, maybe some women will start pushing for unnecessary surgery, but they will also have to find a doctor who is willing to accommodate them and perform the surgery in the absence of evidence (or perform it based on a website).
It just doesn't jive with me that they are remotely the same thing. I think Jolie is a particularly poor example here and serves as a distraction for an otherwise decent point.
Very very few people are going to understand what that means for them. Gerd Gigerenzer has a book that's a useful discussion of why presenting risks as percentages is bad.
Just because people don't have an M.D. doesn't make them automatically wrong. The patients that complain about gluten have access to information you do not have. Namely, they are able to experiment with their own diet. When they eat gluten, they feel bad. When they stop, they feel better. Who cares if it's placebo effect? If they feel better not eating gluten, tell them to stop eating gluten and support them in their decision instead of writing them off as part of a dietary fad.
And I certainly hope you have at least done some research on fructose metabolism before writing that woman off as a kook. Even if it is all in her head, you can make her at least happier, if not healthier by suggesting that she also avoid foods with sucrose or monomeric fructose, and substitute them with alternatives such as xylitol, glycerol, maltose, or ordinary glucose corn syrup.
If the patient is ignorant, that is a condition the doctor should be expected to cure. If the patient is stupid, they should find a less arrogant personal physician.
Diagnosing the true cause of someone's "gluten allergy" would allow them to start eating gluten again. Since gluten is pretty much everywhere, I'd say that'd be a nice quality of life improvement.
Or the diagnosis might confirm the patient's suspicions, and they might have to monitor their gluten intake for the rest of their life. Either way, there should be actual evidence available before a definite conclusion is reached.
Low-cost screenings, such as 23&Me mail-in swab tests, elimination diets, or common blood and urine tests are a great way to start building up that objective evidence without first doing harm to your patient's wallet.
The FDA just wants to make sure that 23&Me's tests are accurate, which could actually lead doctors to trust them more rather than replicating them at the patient's expense.
When you receive a Warfarin prescription, you begin very close monitoring that involves daily then weekly then monthly blood tests (for the rest of your life) to determine your dose and monitor the effect of the drug in your body. Someone choosing to take a lower dose because of 23andme results would be blatantly and intentionally disregarding the results of testing and the advice of their Drs. The 23andme result that you may be sensitive to Warfarin is something to mention at the outset of your treatment, and nothing more. Also, taking a lower than therapeutic dose of Warfarin would not cause an aneurysm, but would be more likely to cause a clot.
1) I dont see how 23andme results for Warfarin would in practice negatively effect a patients drug regime.
2) You seem to know very little about Warfarin and should take that into consideration when commenting on issues surrounding it.
Why is Jolie's decision stupid? If she had BRCA mutations she could have had over 50% lifetime risk of breast cancer. Seems like a reasonable step to take.
Anyone who thinks the FDA is overreaching here has little awareness of how stupid the majority of the world's population is. The people that this protects don't know how to even read this statement from the FDA.
Perhaps the startup echo chamber has more respect for unchecked opportunism; if that's the case, someone should make a startup called 23andMeFree (monetized by ads, duh) that has you spit in a tube, send it to some PO Box, then randomly generate positive and negatives across the board. If you wanted the scam to last longer, you could even generate random values based on statistics of certain characteristics. A true libertarian must support such a business.
WRT to libertarianism, you can't have a free market if virtually all of one side of a contract are too ignorant to participate rationally. If its designed to not be a free market and doesn't involve rational decisions, there's not much libertarian commentary on the topic. That political stance is orthogonal to the discussion.
One might easily argue that the majority of the population is too ignorant to participate in the computer market, the handheld device market, the automobile market, the housing market, the super-market, or any other market. Ignorance alone is not evidence that government intervention will improve outcomes in any situation.
As part of the world's population, isn't there a high chance that the FDA contains some fraction of the "stupid" majority? Is it possible that a majority of the FDA could be labeled "stupid"?
I'm not sure that libertarianism is coherent enough to admit the existence of "true" adherents, but surely you mean to say that a "true libertarian" must not support the outlawing of such a business? Typical libertarians often display preferences among businesses. E.g., a libertarian might prefer Taco Bell to Panera Bread.
The classic definition is what most people think of: socially liberal, fiscally conservative. These two ideas are coherent because they both require minimal intervention on the part of the state. But libertarians are often attacked for not supporting equal individual rights, which does require forceful intervention by a state. This dichotomy is what non-libertarians have trouble understanding. And when something is poorly understood, it is often vilified.
Edit: this should have been posted under the post above, but I meant to take issue with your comment on the division on economic issues. The only division I've seen is tactical, not philosophical. Can you provide an example of a deep philosophical division?
>Can you provide an example of a deep philosophical division?
The deepest divide (of American libertarianism) is probably deontological (natural rights) versus consequential (pragmatic) libertarianism. Most of the branch ideologies originate from one of the two.
A good read on the subject. The Ethics of Liberty by Murray Rothbard [1].
Sorry I return to this thread a bit late. Consequentialists, at least, often advocate their position in tactical terms (read Jeff Miron for example), so I'm not sure this divide qualifies as "deep" or "philosophical". Maybe it's simply the case that consequentialists see the divide as tactical while natural-rights enthusiasts see it as deep and philosophical. A disagreement the very nature of which inspires more disagreement seems... robust.
Since I have long been "socially liberal, fiscally conservative" I did for a time wonder if I were libertarian. However, enough libertarians have subsequently explained how my opposition to most military action, to drug prohibition, to immigration limits, and to financial bailouts is counter to their libertarianism that I am left confused. (I occasionally call myself anarchist but that seems to annoy "true" anarchists even more than "true" libertarians!)
Thus my skepticism of libertarianism's coherence. I certainly don't intend to "vilify" anything, but up above I tried to correct what I felt to be a misrepresentation of even the amorphous understanding of libertarianism I do have. That is, it's clear to me that libertarians don't "support" all business interests without question. Any particular business might be objectionable or simply uninteresting in any number of ways.
Fact check: libertarians think fraud is a rights violation, a crime that is properly punished.
On the other hand, governance by the FDA is tantamount to punishing for a crime not committed. It'd be like putting cameras in your home because you might abuse your children someday. And surely, a lot of stupid people abuse their children, right?
Well, get back to me when negligence is punished like fraud, since the impact on the victim can be just as drastic regardless of tortfeasor's intent or lack of same.
No, you stop advocating that the rights of innocents are violated for the sake of cases where there is evidence of fraud. Instead, advocate that cases of fraud are actually followed up on. Be an upstanding citizen, not part of the ignorant mob.
There's a presumption of innocence in fraud cases as well. I'm not proposing handing out fines in the absence of a conviction. I strongly disagree with his claim that governance by the FDA is equivalent to punishment, in fact I think it's total bullshit.
Of course it's punishment. You have to pay an extraordinary amount of time and money under threat of violence. And even when you do comply, from then on you have to start judging whether or not the next feature you add is worth the cost of compliance.
I understand the FDA getting pissy if I'm consuming/injecting a substance that may or may not harm me, but why this? I spit in a tube and get some results which may or may not be accurate. Go away, FDA.
People take action based on the results of the tests.
There are different ways to mitigate risk - ensure there's adequate genetic counselling and proper easy to understand information available for anyone taking the tests would be one way.
I lean towards favouring tight regulation of medical products. One person's 23andMe genetic test is another person's quackery - see some of the nonsense offered as medical advice by the quacks on other websites.
Academic science somehow manages to police itself fairly well with peer review processes. Wouldn't this type of paradigm work better than paying for the FDA to go through its approval process?
The FDA could still take action if they see that a company is doing something & claiming something that is not properly peer-reviewed and proven.
But why create extra red tape for everyone from the get-go?
For the same reason that the FDA tends to care if an MRI or a CT scanner displays accurate results. People make life/death decisions based on diagnostics.
When the FDA sends you a letter like this, you either pay a fine and change tactics or you embark on one of the most frustrating approval processes known to the world (all for people's protection.) Good luck with that.
It is only reasonable in the context of the standard operating procedures of the FDA. As this is essentially prior restraint upon speech and/or trade, it is unreasonable, but no more unreasonable than anything else the FDA does.
Ideally, the FDA would have independently-generated evidence indicating that the product in question is unreasonably dangerous or ineffective for some intended purpose before issuing a cease and desist order. Instead, they simply assume guilt and place the burden of proof upon the vendor.
Given that the FDA has vastly more resources than 23andMe, and companies like it, this makes the FDA seem like bullies against microbusinesses, and like the captured servants of agricultural and pharmaceutical megabusinesses.
The tone of the letter was surprising to me. I wouldn't expect the FDA to go quite so far in explaining the why behind the desist letter. I suppose that's because it was written just as much for public consumption as it was for 23andMe.
The most common sort of cease and desist letters we tech people are accustomed to are DMCA and patent-related. These letters are typically meant as precursors to private litigation. They are often sent out with commercial considerations in mind, and so tend to be light on details in order to be more threatening.
The FDA is a regulatory agency, which implies that their mission is less about intimidation and more about protecting the public good. Hence the more open tone, I suspect.
> The tone of the letter was surprising to me. I wouldn't expect the FDA to go quite so far in explaining the why behind the desist letter.
Its fairly typical of formal regulatory notices (or even informal notices -- much of the language is very similar to the 2010 letter in which the FDA first raised issues with the product) -- because they are typically directed at corporations with substantial legal resources and they are designed to convince them that they should voluntarily comply with the agencies direction because if they fail to do so regulatory action will be initiated which will be costly and unlikely to be reversed by subsequent litigation, so they lay out all the facts and authorities necessary for the recipient (and the recipient's counsel) to come to the desired conclusion.
Obviously 23andMe results are not a diagnosis from your physician. You should use 23andMe in conjunction with a real physician. For example, I used 23andMe back in 2010 and it told me I had a high risk for a certain genetic condition which I recalled one of my family members having, so I went to see my physician for a real diagnosis, armed with this newly found information.
23andMe helped me catch this early enough with the assistance of my physician that I was able to get treatment long before I would have developed symptoms. If I never used 23andMe I probably would not have had this diagnosed until years later.
Given https://www.23andme.com/health/all/, I don't think you're considering the negative case properly. If 23andMe's results say you don't have something on their list of 250+ things they're checking for, you might decide against certain treatments or tests based on that.
I think it's reasonable for the FDA to tell 23andMe that if they're going to interpret the results for their customers, they need to be able to guarantee the chain of processing is there, and they need to be able to justify each "detection point" their marketing claims.
Your outcome is positive. But positive is not the only possibility.
You are equating false negatives to harmful information, when in reality it is the same as simply not taking the 23andMe test. The only thing 23andme enables you to do is act sooner on things they get right, and any false negatives are irrelevant—you didn't ask for a diagnosis and they aren't claiming to give you a diagnosis. You cannot be harmed by a false negative any more than you will be harmed by not buying a 23andMe kit.
> you might decide against certain treatments or tests based on that
Since you are mentioning treatments means, you must misunderstand what the purpose of the test is for. If you have current medical problems that you need treatment for, you wouldn't use 23andMe's statistics in order to chose a treatment, you ask your physician to help you get the treatment you need. If 23andMe had a false negative on my condition instead of the true positive, I would still get diagnosed once I started developing symptoms eventually. Nobody who starts having health problems thinks "I should first consult my 23andMe results for things that I should specifically mention to my physician that I don't have".
I'm most curious to see how 23andMe is going to respond to this, because the more technical-regulatory language in this letter says essentially that in FDA's opinion the device is Class III (the highest risk of all medical device/diagnostics) and would require a PMA, unless 23andMe provides the evidence that allow FDA to de novo classify the device as Class II.
A Class III ruling would destroy the personal genomics market, because it would mean extensive clincial testing and documentation about the development of the device. I hope it doesn't stand.
> It took them 40 years to get the labeling for tylenol right.. [...]
> They are moving rather quickly on this one... my only question is, why/how??
You are comparing apples and oranges. It didn't take them 40 years to get to the point where Tylenol had to go through the procedure requiring FDA approval for marketing a drug (which is generally similar in origin to the parallel requirement for medical devices.)
Likewise, its quite possible that 40 years from now, there'll have been several rounds of changes to how an equivalent personal genomics kit will be marketed based on changes to what we know between now and then.
> Government agencies empowered to weild regulatory force against citizens are a threat to everyone
Yes! How dare those jack-booted thugs infringe on my freedom to sell "Dr." Smacktoward's Bona-Fide Health Elixir and Youth Restoring Tonic (99% water, 1% radium) to anyone dumb enough to buy it!
It's turning into a dang police state, I tell you!
Hyperbole aside, if "Dr" Smacktoward did actually develop a cheap and effective therapy that actually worked, the prior restraint employed by the FDA would likely keep it off the market. The same technique employed against snake oil may also be applied to real cures that might provide cost-effective competition to multibillion-dollar blockbuster patent medicines.
Yes, that's right; if you believe that you truly have developed a remarkable healing elixir in your garage, the burden is on you to obtain scientifically valid proof that it does what you claim it will do before you can go around selling it to people.
Whether or not you see this as a horribly unjust burden imposed by an unfeeling government will probably depend on whether you are the inventor or the person the inventor was planning on selling it to.
If you apply that standard to other products, such as software, what happens? If you cannot distribute software that is certifiably bug-free and algorithmically correct, that is warranted to be fit for a specific purpose, what happens? If you cannot sell a car if it cannot go 70 miles-per-hour, consuming fuel at 50 miles-per-gallon, and have zero fatalities in a head-on collision, what happens?
too bad they are not as rigorous with the food we eat. One example is that they don't even have the resources to check if the food manufacturers claims are true (you can't be sure what type of fish you eat nowadays).
This is a really critical point. People who are pro-regulation are under the premise that regulation actually does protect people. There are countless examples to the contrary.
(The finance sector is even much worse than the FDA in this regard---for example Bernie Madoff was regulated, leading people to think their money was safe with him---but in some ways, the FDA is just as bad.)
Of course it can help, some. I'm not going to deny the obvious. But it's highly imperfect, and it often hurts.
The only way to know it actually works is to do the necessary science, which unfortunately isn't cheap but them's the breaks. Stopping bad medication from being on the market saves lives, even if it prevents the occasional good one.
The FDA introduces a bootstrapping problem wherein the proceeds from selling a potential remedy cannot be used to test it, and no one other than the inventor can test it, because the product cannot be sold until after it is tested.
In any case, the only hurdle to selling should be "does it do harm?", and "does it work as advertised?" can be determined later, if and only if there is any doubt among the consumers.
Elsewhere in consumerland, the product is sold, and independent testing is performed on off-the-shelf samples. Think Consumer Reports or Underwriters' Laboratories. If a problem is found, a recall may occur. If none are evident, the testing body grants its approval to use its trademarks on the product. People look for that trademark from the trustworthy third party.
If the FDA did not apply prior restraint, and tested products already available to the consumer, it could regulate the usage of the phrase "FDA-approved" and make perfectly safe everyone who buys only the medicines bearing that approval for the purposes which have been tested.
> In any case, the only hurdle to selling should be "does it do harm?", and "does it work as advertised?" can be determined later, if and only if there is any doubt among the consumers.
Laws don't operate under the principle of what should be, they are past agreements hammered out by negotiation, not logic. You don't get to say what the hurdle "should" be, that's already been agreed upon and set and it's unlikely to change because a few don't like it.
> Elsewhere in consumerland, the product is sold, and independent testing is performed on off-the-shelf samples. If a problem is found, a recall may occur.
Sometimes, sometimes not, it entirely depends on the law in those areas. Recalls don't help people who are dying from bad medication, the FDA's role is preventative, not reactionary.
> If the FDA did not apply prior restraint
That's their job, it's why they exist.
> and tested products already available to the consumer,
Then they'd be useless.
> it could regulate the usage of the phrase "FDA-approved" and make perfectly safe everyone who buys only the medicines bearing that approval for the purposes which have been tested.
Sorry, but their job is to protect people who don't have the information/brains to protect themselves, which in the field of medicine is practically everyone. This solution is simply a libertarian fantasy that has no chance of working in the real world. As the other poster said, see homoeopathy as an example, consumers aren't smart enough to not kill themselves with idiocy, even the rich ones like Steve Jobs.
Federal law requires manufacturers and importers to test many consumer products for compliance with consumer product safety requirements. Based on passing test results, the manufacturer or importer must certify the consumer product as compliant with the applicable consumer product safety requirements in a written certificate that it must provide to retailers, distributors and, upon request, to the government.
As a point of order, you cannot refute a "there exists" assertion with any number of counterexamples.
My point was that it doesn't have to work in the way that the FDA (and other examples of other regulatory agencies) currently function, and your response did not address that.
The scientific community regards homeopathy as nonsense,[11] quackery[12][13][14] or a sham,[15] and homeopathic practice has been criticized as unethical.[16] The axioms of homeopathy are long refuted[17] and lack any biological plausibility.[18] Although some clinical trials produce positive results,[19][20] systematic reviews reveal that this is because of chance, flawed research methods, and reporting bias.[21][22][23][24] The postulated mechanisms of action of homeopathic remedies are not only scientifically implausible[21][25][26][27] but precluded by the laws of physics.[28]
"does it do harm?"
yes, it exists, so it prevents people from accessing real medicine. It is a distraction.
Steve Jobs is a good example...
"Despite his diagnosis, Jobs resisted his doctors' recommendations for medical intervention for nine months,[174] instead consuming a pseudo-medicine diet in an attempt to thwart the disease. According to Harvard researcher Ramzi Amri, his choice of alternative treatment "led to an unnecessarily early death."[206] Cancer researcher and alternative medicine critic David Gorski "disagreed with Amri's assessment," stating, "My best guess was that Jobs probably only modestly decreased his chances of survival, if that."[209] Barrie R. Cassileth, the chief of Memorial Sloan–Kettering Cancer Center's integrative medicine department,[210] said "Jobs’s faith in alternative medicine likely cost him his life.... He had the only kind of pancreatic cancer that is treatable and curable.... He essentially committed suicide."[211] According to Jobs's biographer, Walter Isaacson, "for nine months he refused to undergo surgery for his pancreatic cancer – a decision he later regretted as his health declined."[212] "Instead, he tried a vegan diet, acupuncture, herbal remedies and other treatments he found online, and even consulted a psychic. He also was influenced by a doctor who ran a clinic that advised juice fasts, bowel cleansings and other unproven approaches, before finally having surgery in July 2004."
Yet, it still exists, and people are still buying it, using it, and buying into it. That is an indication the free market doesn't work in drugs. I can go on and on and on, but we need to be protected from ourselves.
So you're advocating doing harm to my life (by blocking legitimate medicine), for the sake of supposedly protecting irrational hippies from themselves (which you may be able to do in this one area---but what about all the other ways they harm themselves)?
I can make my own decisions. Just like 99% of rational people, who are able to judge for themselves that homeopathy is nonsense.
Nobody is blocking legitimate medicine. It is just asked that you prove that it is legitimate medicine before you are allowed to sell it as medicine. That way consumers don't go into a store, find 30 "cures" 3 of which have actual evidence that they work. They might harm themselves by taking the treatment that doesn't work, thus delaying access to the evidence based treatment.
> Just like 99% of rational people, who are able to judge for themselves that homeopathy is nonsense
Rational people fall for pseudo science too, especially if it has a good salesperson behind it. Most people believe what others tell them without questioning. Very few look at the world skeptically. We need to blame the scam artist not the victim.
> The FDA introduces a bootstrapping problem wherein the proceeds from selling a potential remedy cannot be used to test it
To the extent that approval requirements applied by the FDA under the Food, Drug, and Cosmetics Act do that with remedies (which aren't at issue in this case, as it is about a diagnostic device not a tretment), that isn't what happened here, as demonstrated by the fact that the FDA allowed 23andMe to continue to operate for years after issuing the June 2010 letter in which they first raised the issue that the PGS fell within the FDA's regulatory ambit and that various approvals were needed to continue marketing it the way it was marketed.
The "stop now" letter wasn't set until 23andMe stopped working with the FDA toward meeting the requirements, so 23andMe in fact was able, had it chosen to do so, to use the funds from selling its device to test it.
> and no one other than the inventor can test it, because the product cannot be sold until after it is tested.
The FD&C Act doesn't prevent covered "remedies" (etc.) from being sold before they are tested, it prevents them being sold to prevent, treat, or diagnose disease until they've been tested. Products can be sold for, e.g., research purposes before being approved (and, in fact, often are -- one of the suppliers to 23andMe and other genetic testing services was dinged by the FDA for knowingly selling to 23andMe and other genetic testing services products for diagnostic use which were not yet cleared for such use but which were allowed for research use [1].)
> In any case, the only hurdle to selling should be "does it do harm?", and "does it work as advertised?" can be determined later, if and only if there is any doubt among the consumers.
This approach was tried in the health space for many, many years, and the results were deemed unacceptable. Of course, you may have a different opinion of what is desirable than that which motivated the Food, Drug, and Cosmetics Act, but simply asserting that the rules should be different is unconvincing.
> Elsewhere in consumerland, the product is sold, and independent testing is performed on off-the-shelf samples. Think Consumer Reports or Underwriters' Laboratories.
That's true for some consumer products, and its not true for others, generally driven by perceived risk levels.
While I agree that stopping bad medication from being on the market saves lives, medication is not at stake in the case of 23andMe. Information is what's at stake.
I am so glad of this. Without regulatory force we would se much more threats to everyone from other citizens (and that's why regulations came into being).
I'm actually an Objectivist---I agree with the philosopher who had 5% of her system ripped out of context and stolen by the libertarians (i.e. Ron Paul people).
He is too impatient to toil slowly through the years for the things he wants. Too uncompromising to succeed in the way of the popular men who know how to get along with those in power. Too intolerant to “get along” with anybody. Too passionate not to burn with disgust for life as he sees it and with humiliation at not being above the mob, crushing it under his feet, giving it orders instead of trying to satisfy it, of crawling before it for its good graces. He is unable to understand how he can act and live as an equal with those he knows to be inferior to him, those he despises and had a right to despise.
For the record, that was Ayn Rand talking about (one of?) her favorite serial killers, who became the basis for a character in an unfinished novel, about whom she wrote:
"[he] is born with a wonderful, free, light consciousness -- [resulting from] the absolute lack of social instinct or herd feeling. He does not understand, because he has no organ for understanding, the necessity, meaning, or importance of other people ... Other people do not exist for him and he does not understand why they should."
You are taking this completely out of context, and it is a dishonest slander of the lowest kind.
As evidence (to anyone else reading---no point in dealing with dishonesty), I present Atlas Shrugged, The Fountainhead, and Objectivism.
Ayn Rand is the only modern philosopher who can even present a reality-oriented reason not to partake in a life of crime. i.e., a reason not based on religion or appleal to emotion or simple common sense (though common sense is also correct on this issue and worth having).
I'm not sure what sort of context can explain away this real-life Randian superman. (and it's interesting that you mention Rand and crime and the Fountainhead, given that Howard Roark blew up Courtlandt Homes with dynamite)
This is some interesting reading that goes deeper into Rand's writing: http://michaelprescott.freeservers.com/romancing-the-stone-c...
All these are Rand's own words:
"The first thing that impresses me about the case is the ferocious rage of a whole society against one man. No matter what the man did, there is always something loathsome in the 'virtuous' indignation and mass-hatred of the 'majority.'... It is repulsive to see all these beings with worse sins and crimes in their own lives, virtuously condemning a criminal..."
And in regards to Hickman's jury: "Average, everyday, rather stupid looking citizens. Shabbily dressed, dried, worn looking little men. Fat, overdressed, very average, 'dignified' housewives. How can they decide the fate of that boy? Or anyone's fate?"
"Other people have no right, no hold, no interest or influence on him. And this is not affected or chosen -- it's inborn, absolute, it can't be changed, he has 'no organ' to be otherwise. In this respect, he has the true, innate psychology of a Superman. He can never realize and feel'other people.' "
"He shows how impossible it is for a genuinely beautiful soul to succeed at present, for in all [aspects of] modern life, one has to be a hypocrite, to bend and tolerate. This boy wanted to command and smash away things and people he didn't approve of."
> I'm not sure what sort of context can explain away this real-life Randian superman. (and it's interesting that you mention Rand and crime and the Fountainhead, given that Howard Roark blew up Courtlandt Homes with dynamite)
Well, if you want to be sure, read The Fountainhead and Atlash Shrugged.
The Fountainhead is actually an explicit repudiation of Neitzche (though it is more than that).
There is a Nietzschean hero in the book---and he is driven almost to suicide, and is completely destroyed.
Rand greatly admired one aspect of Hickman: that he wasn't influenced by other people; he was fully himself. The actual hero of The Fountainhead is like that, but rather than being a destructive parasite (of self and others), he uses his independence to achieve real goals and values in life in a way that does not vicitimize anyone.
He did blow up Cortlandt Homes; importantly, nobody was in the building and nobody was harmed, and he did it because the plans for the building were essentially stolen from him. He does it to make a point, which he does make.
Says you, but we don't live in a society where everyone gets to make their own rules. As a country, we've decided we do have the right to boss you around, so we do. :)
There is no logical chain of facts, starting with concrete perception of reality, that leads to the conclusion that society gets to coerce me. So, no, you do not have the right to coerce me.
However, there is a logical chain of facts, starting with concrete perception of reality, that leads to the conclusion that we should establish government for protection from coersion.
Society can pass a law to coerce people---at its own peril.
I see your problem, you think logic matters, it doesn't, this isn't that world. In this world, numbers matter, votes, not logic. Rights are a social construct, we have whatever rights we've all agreed we have and no more. Any talk about natural rights and logic and positive vs negative rights is just that, meaningless talk; policy comes from those who acquire power, not those with the best arguments and facts.
> Society can pass a law to coerce people---at its own peril.
Look around, turns out it's not really perilous at all. It's actually the normal way the world works.
Don't turn this around as "my problem." I don't have a problem. I look at reality and I derive the correct conclusions.
Including the fact that I live in a mixed economy.
I am not the one in conflict with reality.
Logic and talk are not meaningless. There are reasons that there once was an Enlightenment, ultimately culminating in the founding of the only contry originally based on the concept of individual rights---the United States.
And hopefully we can get there again. Greater than the tread of mighty armies, is the idea whose time has come.
Of course, to make the time come, much intellectual groundwork will have to be laid.
> Look around, turns out it's not really perilous at all. It's actually the normal way the world works.
It is perilous. For instance, the US is in a perma-recession. In the long run, this is quite dangerous.
You are explicitly advocating that we ignore reality. That should be enough to make my point and probably everything else I just said is just distracting from it.
Silicon Valley "It is better to ask for forgiveness" culture meets the worst of government "We'll need that in triplicate 5 years in advance of starting to look at the paperwork."
This should be interesting, if you have the patience to watch the fallout in slow motion.
CMS/HHS will look like idiots as mRNA sequencing dips below the $100 per test price point and doctors for the first time will have a histogram of genes turned on for use in their diagnosis.
Instead of whinging, FDA needs to partner with NIST to come up with quality control protocols so doctors know the error distribution in data that they receive.
I have to agree that this seems completely reasonable... glad to see so few commenters jumping to the expected conclusion that this is some kind of government oppression.
If you believe 23andMe is a sound source for the clinical diagnosis of medical conditions, you're probably not going to read the fine print telling you otherwise.
Never once did they attack the technology but rather the potential for error or the consequences if the public "can't handle the truth."
The closest they come to calling her a "quack" is when they state "...We still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses..."
The bigger question is why is the FDA having a seizure over this? Could it be the potential for added treatment and preventative healthcare measures that insurers vis a vis the Affordable Care Act and not looking forward to paying for? (Not a rhetorical question, just asking)
I think the line of reasoning makes sense: people will make medical decisions based on this information, but 23andme has never given us any reason to (or not to) believe their tests are accurate. Without someone reviewing their process, their error rate is unknown. That can be dangerous. This is similar to the problem with many alternative medicine claims. 'Alternative medicine' may be very helpful to an individual, but it's important not to overstate its effectiveness or reliability.
how would you define 'error rate'? Do you mean "lab handling error rate"? Or "information presenting" error rate? The way 23andMe works, is they run your DNA and they show "percentages" based on already done studies. Then they throw in caveats (like, if you're not of the correct race relative to what the study was done in). So what would you suggest? That the service track all of their users over a long-term and then see whether the percentage of their users that get condition X matches the percentage they predicted? And then do some sort of statistical analysis on a possibly moving number (because 23andMe updates their information if academic science improves) with a population that might turn out to have differing biases...? And then prove this information over what, 100000 SNPs on the chip?
What you are basically arguing is that 23andMe should not be allowed to offer its service.
Ultimately both error rates matter, and are measurable. It's not necessary that these error rates are zero, it's necessary that they are measured, controlled, and acknowledged, which is what 23andMe is not doing.
Even the FDA isn't arguing that 23andMe should not offer it's service, just that it shouldn't market it. And really, given that they don't seem to be following the basic quality assurance practices of the industry, they should not be marketing at all.
> Even the FDA isn't arguing that 23andMe should not offer it's service, just that it shouldn't market it.
They aren't even really arguing that either; they are more arguing that if they are going to market it, then they need to provide studies supporting the accuracy and take other steps to get it approved to be marketed for the particular uses it is being marketed.
They are saying in the Warning Letter that 23andMe must stop marketing the product because 23andMe has abandoned the approval process (and apparently was not preventing 23andMe from marketing the product as long as they were working through the approval process), not because the product is inherently unmarketable.
False. Read the letter carefully. They're specifically concerned with false positives and false negatives - these are both very real possibilities - one is documented up thread.
> The bigger question is why is the FDA having a seizure over this?
Um, they aren't having a seizure. 23andMe was informed of the regulatory requirements in a letter in June 2010 [1], and (as discussed in the Warning Letter just issued) submitted required documentation to begin the approval process in July and September of 2012. The FDA sent letters identifying issues with the submitted documentation and requesting additional information in order for the approval process to move forward on September 13, 2012 and received no response from 23andMe.
The FDA set follow up letters in March and May of 2013 indicating that due to 23andMe's failure to address the issues raised in the FDA's earlier letter, the applications submitted in 2012 were deemed withdrawn -- which meant that 23andMe was not only not in compliance, but no longer considered to be actively working toward compliance -- but still took no substantive action, giving the company time to begin working toward compliance again.
Now, more than a year since raising issues with 23andMe's original submission, more than 3 years since notifying them that they needed to come into compliance, and 6 months after notifying 23andMe that their failure to respond to the issues raised with their initial submissions had caused those submissions to lapse, they've given 23andMe notice that they will face regulatory action if they don't either stop marketing the products or provide an acceptable plan within 2 weeks.
I JUST bought the kit yesterday. The FDA is right though. Imagine making extreme decisions (e.g., double masectomy to avoid breast cancer) based upon the information. This is making me consider cancelling my order.
If you are screening for something, the first test should have a low rate of false negatives. Anyone testing positive on that test should take a second--possibly more expensive--test with a low rate of false positives.
If you remove big blobs of flesh from yourself on the basis of a single test, you are not making your medical decisions wisely. The only decision you should be making on the basis of 23&Me results is whether to take another test that is more specifically targeted at the potential problem.
If 23&Me says you have BRCA, you don't get a double mastectomy. You talk to your doctor. You perform self-exams more often and more thoroughly. You get additional screenings that are not cost-effective for the general public with a lower risk profile. That's the whole point of consumer-grade genetic screening.
If I did see something that suggested a possibility of something, I would go the direction of what you mentioned in the last paragraph.
Although I agree with the FDA's actions, a consumer getting a thorough genetic exam is possibly what prompted this. Check out the artidcle http://www.bloomberg.com/news/2013-11-25/fda-tells-google-ba.... Turns out United Healthcare raised a concern which I believe is might be money-related. If your test results suggest a high possibility of some health issue from an non-FDA approved company and you requested a more accurate test, then I can see the health insurance companies getting involved.
you would not take serious action in any condition based on an cheap DNA test, would you?
I would suspect that it might serve as a possible flag and then you can talk to your doctor to further investigate any issue.
Plus 23andme is clear when showing the results that everything is based on probabilities, there's not a single %100 change of anything, it just tells you that people with similar DNA markers (in X, Y or Z study) seem to have a higher/lower chance of X or Y.
Have a google image search for "coloidal silver". See the people who have turned themselves blue. permanently blue - it's not going to change.
People are stupid. This isn't a label on a chainsaw saying "don't lick the blade". This is reasonable regulation of a product being marketed as a medical product.
I wouldn't but some would. I am more interested in my genetic lineage. To get a more accurate test like the one Angelina Jolie did would be a better option.
This is simply the result of the medical lobby. This pressure is being put on them simply because it takes power from the gods of medicine. If I order my own bloodwork, (from the same labs that my medical foundation does), somehow the same bloodwork costs me 20% of what it would otherwise. This is about taking away the ability to monitor your own health, in order to enrich the medical community.
This will simply result in this type of testing to move beyond FDA borders. Great job FDA, you're helping kill a successful and profitable US company. Un-F-ing-believable.
Is there anyone else that sees this as a positive thing for the company? They've lived under the cloud of potential FDA regulation for a while, and I'm a bit surprised that it took this long for the FDA to step in.
Obviously, it would have been preferable to have the company and FDA work together to announce how FDA regulations apply before an enforcement action. But, now that it has happened, the process has started. If the company can come out of this with some kind of FDA approval, then that cloud will be lifted and they can keep on working. And then the company will know exactly what rules they'll have to play by. So, depending on how things work out, it could end up being a positive for the company.
Now that the FDA has played their hand, I'm very curious to know how the company will respond.
They have been in talks since 2009 to help 23andme understand what they need to file, and how to do it. 23andme has (repeatedly, it sounds like) failed to do that.
This notice is a standard corrective action taken by the FDA after failure to complete 510(k) submissions.
I'm not sure if 23andme's management team is totally out of touch or if they have genuinely mislead the public about their product's effectiveness. I'd assume the latter. They could have easily done periodic check-ins with the FDA to throw them a bone while gathering longitudinal data to support their claims.
You would think that before putting in so much money, time, and effort into 23andMe they would have had discussions with the FDA and actually responded with more information. I'm amazed that it didn't happen.
I wonder whether a company could bypass the FDA by simply giving people their genome data, without any interpretation or diagnosis, which could be left up to people's doctors, opensource software, etc.
Well yeah, they could totally get rid of the health part of their product and only report on ancestry, and I think the FDA would be perfectly fine with that.
Is there a list of government agencies IP addresses? I would like to block them from accessing my sites. And write in the ToS that they are not allowed to browse and read more.
If you read the article, you will see the large paragraph outlining the dozens of in-person meetings and hundreds of emails that the FDA has exchanged with 23andMe.
What you are noticing is a government agency that has exercised restraint for years, not one that was aloof.
Meanwhile, 23andMe went ahead and began marketing and selling their product, despite the FDA's concerns.
Relevant quotes:
> Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasions.
> However, to date, your company has failed to address the issues described during previous interactions with the Agency or provide the additional information identified in our September 13, 2012 letter for (b)(4) and in our November 20, 2012 letter
> To date, 23andMe has failed to provide adequate information to support a determination that the PGS is substantially equivalent to a legally marketed predicate for any of the uses for which you are marketing it; ...
> ...we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification.
> As part of our interactions with you, including more than 14 face-to-face and teleconference meetings, hundreds of email exchanges, and dozens of written communications, we provided you with specific feedback on study protocols and clinical and analytical validation requirements, discussed potential classifications and regulatory pathways (including reasonable submission timelines), provided statistical advice, and discussed potential risk mitigation strategies...
> Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS.