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.

So: totally reasonable.

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.

Many physicians are terrible at interpreting results of screening tests:

http://www.bmj.com/content/333/7562/284

For screening tests where the problem being screened for is rare, most results will be false positives, but the result is not intuitive.

Doctors being lousy Bayesians is (if anything) an argument in favor of services like 23andme!

Right. IF 23 And Me can show that its test are accurate. But they can't (or have refused to do so). That's the whole point.

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.

Safety isn't part of a long and happy life?

> 23 And Me should only have to prove that it is better than the alternative,

23andMe isn't even doing that.

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?

There are at least three different products in the space and to claim similarity would be to likely invite over-regulation:

- "full scan" companies, that do a full genetic scan and do not limit the scan to SNPs

- personal genomics companies that focus on SNPs

- medial diagnostics like the MSAFP test

> 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?

I don't know a single person who thinks Elvis is alive...

Why more than 1 follow up test?

Multiple unneeded follow-up tests across the population, not per person.

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 don't think people would commit suicide or become unduly despondent if they learned they have a gene.

What if the gene essentially means "you and your husband shouldn't have children?"

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:

https://www.23andme.com/howitworks/ (near bottom of page) http://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA...

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.

They'd probably feel a hundred times worse if they found out by observing the symptoms in those future children.

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.

Don't take away my freedom to trust test results.

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.

Public health isn't nanny statism.

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.

no, because presumably a licenced doctor would rely on a test provider that was FDA-approved.