Should personal genetic testing be regulated? Battle of the blogroll

On the side of less regulation is Alex Tabarrok in “Our DNA, Our Selves”:

At the same time that the NSA is secretly and illegally obtaining information about Americans the FDA is making it illegal for Americans to obtain information about themselves.
In a warning letter the FDA has told Anne Wojcicki, The Most Daring CEO In America, that she “must immediately discontinue” selling 23andMe’s Personal Genome Service . . .

Alex clarifies:

I am not offended by all regulation of genetic tests. Indeed, genetic tests are already regulated. . . . the Clinical Laboratory Improvement Amendments (CLIA) . . . requires all labs, including the labs used by 23andMe, to be inspected for quality control, record keeping and the qualifications of their personnel. . . .

What the FDA wants to do is categorically different. The FDA wants to regulate genetic tests as a high-risk medical device . . . the FDA wants to judge . . . the clinical validity, whether particular identified alleles are causal for conditions or disease. The latter requirement is the death-knell for the products because of the expense and time it takes to prove specific genes are causal for diseases. Moreover, it means that firms like 23andMe will not be able to tell consumers about their own DNA but instead will only be allowed to offer a peek at the sections of code that the FDA has deemed it ok for consumers to see. . . .

From another section of my blogroll comes a pro-regulation argument from Kaiser Fung, “For a change, the FDA earned my trust”:

For a change, the FDA is doing something right for consumers, without waiting 10 or 15 years. . . . These tests have never been tested clinically and the company never applied for approval from the FDA. Given that it is not that hard to conduct proper testing of this product, especially if it is looking for diseases that have clear genetic markers, one suspects that the makers know that the tests would not pass rigorous testing.

There may be a day in which such tests are possible but the day hasn’t arrived yet. I also think the chance that most diseases can be turned into equations that say if you have gene X, then you will develop disease Y is overly reductive.

So what? Why should we care? Kaiser continues:

One of the lesser studied effects of screening tests is the psychological impact of false results. If you tested positive for say breast cancer, and even if the biopsy showed the result was a false positive, there is always lagging doubt – every next time you feel something, part of your brain will make you worry. Then, there are those who take a better-safe-than-sorry attitude and elect to do procedures regardless – and some of these procedures have harmful side effects, which are frequently not properly explained.

Much of the discussion at both blogs was interesting. A particularly instructive bit came from a commenter who wrote: “As someone with a Master’s degree in Human Genetics, I chose to have this testing to enhance my knowledge of my own genome, fully mindful of the limitations. I learned that I am likely sensitive to Warfarin, a potentially serious health risk when you are unaware of your sensitivity. Now, I already knew I had a family history of this, but prior to taking this test, it never would have occured to me to mention it to a doctor. . . .” This comment was interesting to me because it suggests that there is a special symbolic value of genetics, even beyond the (considerable) information supplied. We have a well-informed person who already knew she had a family history of a potentially serious health risk but, before the genetic test, it “never would have occurred” to her to mention to a doctor.

This story suggests to me that one of the things people value about the genetic profile is its scientific framing. I’m getting this story from a non-random N=1, and a self-report at that, so of course it’s not strong evidence for anything, but it’s interesting to me partly because it fits into some other issues regarding the communication of statistical information. In particular, Kaiser has written frequently on Lance Armstrong and other dopers, and one of his continuing themes is that people interpret blood tests as being more definitive than they actually are. According to Kaiser, a negative drug test on an athlete does not supply much information, but a positive drug test actually is pretty definitive—but this asymmetry is not always so clearly portrayed in the news media.

In the comments, Kaiser also writes that “23andme should market the genealogical component as a separate product.” So maybe he and Alex aren’t so far apart on the merits of the case, they just have different views on what should be the default position.

P.S. Alex points to this discussion from Lior Pachter on the statistics of the genotyping.

12 thoughts on “Should personal genetic testing be regulated? Battle of the blogroll

  1. What the anecdote doesn’t consider is the downside of my having no Warfarin sensitivity but running around scared that I do.

    If I advertised a “Scientifically proven medical prediction” service and took $1000 and did nothing other than merely telling every guy that he has an especially elevated heart disease & stroke risk I’d probably do society a net good (if people believed me) but I think we’d still frown on such a fraud.

    One other downside to allowing half-baked, unvalidated stuff like 23andme is that a future firm that has indeed a real predictive diagnostics breakthrough to offer will get a very skeptical response.

    • Why net good? This is dangerous wishful thinking… Do not forget the nocebo effect! Nowadays we know how real and significant it is (so that the whole clinical trial procedure should be redesigned); and stress is a well known risk factor to both various cancers and heart diseases.

  2. I think the issue of what data should be available to consumers is distinct from what context should be given. I signed up for 23&me with a PhD in a relevant field, with very little trust of the risk prediction algorithms and very high faith in the genotyping lab QC. I’ve enjoyed being able to query my genome for variants I had prior knowledge about and wanted to know my genotype. In one case this was silly (confirming that I am a homozygote recessive null mutant for the bitter taste receptor – I really can’t taste bitter) and in one case this was serious (informing a treatment decision).

    I think it’s irresponsible to frame things as having a very strong prior when it’s not strong evidence that an association is causal, and I think 23andMe implicitly does this when it estimates predictive models based on possibly-unreplicated SNP associations but presents a “biologically causal” interpretation of result for laypeople who may have different distributions of effect modifiers than the training set.

    Why can’t FDA allow a CLIA-approved lab to do personal genotyping if it limits itself to reporting the results with appropiate disclaimers about interpretation? Calling genotyping “a medical device” seems like mislabeling. What does the device do?

    In general, people take much too deterministic a view of their genetics. 23andMe exploited that for marketing, but it could be a good (remedial) educational opportunity to explain about gene-environment interactions, epistasis, epigenetics, etc. at a digestible level for the public in the disclaimers so that people don’t look at results from one gene and decide they will for sure die of the associated disease.

    • “In general, people take much too deterministic a view of their genetics.” Absolutely true, but it is also true that “In general, people take much too deterministic a view of their PSA test.” It also seems to be true that “In general, people take $9.99 as signicantly different that $10.” The FDA has a role to play in assuring people that a test you paid for is run. They also arguably have a role is seeing whether or not the way 23andme characterize the result test is narrowly, logically accurate. (That’s Alex’s point.) It is entirely unclear whether they have any role to play in how people interpret that test result, since they have no expertise in what people think about things. In the past, that’s exactly how they’ve used that power, eg, allowing every vendor of aspirin to say “there is no better treatment than Bayer” and “no better treatment than St. Joseph,” even though we know that people interpret statements of equivalence as statements of superiority…. even when the equivalence is with respect to a placebo. Until the FDA becomes expert in how people will evaluate statements (and they have no expertise on that subject today) they should focus on strict accuracy.

      • “In general, people take $9.99 as signicantly different that $10.”
        No, in general people take $9.99 as essentially the same as $10, unaware that there’s a huge practical difference under the hoods, that’s the whole point of having such prices. And your comment confirms this. Kahneman and “anchoring” for a reference, but you may know it already.

  3. We probably need a better definition of the mission of the FDA than we have now. If you check out any vitamin supplement that purports to “support heart (or brain, prostate, etc) health, you will see a disclaimer that the product has not been submitted to the FDA and does claim to treat or diagnose any disease. This is in fine print, but it is pure poppycock no matter what size the print.
    From the discussion in the Lior Pachter article, I see that people are being informed about relative risks of 1.1 to 1.7. Those are also poppycock.
    People have a poor grasp of the meaning of probability. I get quite nervous on take-off but am calm when getting in my car on a similar length trip. Do we need the government to protect us from our misunderstandings and miscalculations? To some extent we do, but we should have an open and non-prejudiced discussion about the borders. Of course, that will happen when pigs fly.

  4. President Clinton wildly oversold the medical benefits of the Human Genome Project back in 2000, while simultaneously claiming that it also proved that Race Does Not Exist. The irony is that, so far, most of the utility of genome analysis has been in racial genealogy — e.g., “Oh, well, I guess I’m not part Cherokee like family lore claims” — while directly usable medical knowledge remains thin on the ground.

    • Clinton did this in 2000? What incentive would he have had to do this? You make it sound like a knowing deception — the man’s a politician with lawyer’s training. Personally, I’ve always supposed it was researchers applying for NIH grants who oversold the potential of genomics; they’re the ones who had every reason to overestimate its value.

      • Here are excerpts from the press conference of June 26, 2000 celebrating the Human Genome Projects quasi-conclusion:

        Bill Clinton: “We are here to celebrate the completion of the first survey of the entire human genome. . … With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal. Genome science will have a real impact on all our lives — and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

        “In coming years, doctors increasingly will be able to cure diseases like Alzheimer’s, Parkinson’s, diabetes and cancer by attacking their genetic roots. …

        “After all, I believe one of the great truths to emerge from this triumphant expedition inside the human genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 percent the same.”

        Francis Collins: “I’m happy that today, the only race we are talking about is the human race. (Applause)” …

        Craig Venter: “The method used by Celera has determined the genetic code of five individuals. We have sequenced the genome of three females and two males, who have identified themselves has Hispanic, Asian, Caucasian or African American. We did this sampling not in an exclusionary way, but out of respect for the diversity that is America, and to help illustrate that the concept of race has no genetic or scientific basis.

        “In the five Celera genomes, there is no way to tell one ethnicity from another.”

        You could excuse Clinton’s and Collins’ weasely words on race as not quite saying what everybody thought they were saying, but Venter went there directly and said something he must have known at the time was not just misleading, but false. This single press conference set back public understanding of the human sciences considerably.

  5. “23andme should market the genealogical component as a separate product.” Other companies (eg do this. I don’t know if they let you download the complete SNP array result like 23andme does. I think that personal genomics is really neat, but that this should be regulated like a screening test where it both has to have technical accuracy and demonstable predictive accuracy in at least one setting. Unlike most screening tests, 99% of MDs aren’t going to want to go through these, but some professional interpreter is probably required if they’re going to have YOU ARE DOOMED as a result. We’re on the cusp where huge numbers of people could get genotyped (or even sequenced if you have a few thousand to spend) “for fun” and let us really tease apart some genetics, so it would be a real shame to just shut it all down.

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