4 ms·

I got a genetic test done with 23andme. It said I had a (greater probability of a) warfarin sensitivity. This was interesting because my grandma had a stroke af

by Drifter 13y ago

I got a genetic test done with 23andme. It said I had a (greater probability of a) warfarin sensitivity. This was interesting because my grandma had a stroke after being given warfarin. The stroke put her in a wheelchair for the rest of her life - it ended her independence and she had to go into a home with 24hr care. It was horrible. After this I got my entire family tested. As expected my mother carried the warfarin gene (the grandma was on her side of the family). Knowing this information is hugely valuable to me. I think it's awful that the FDA deems fit to prevent me getting information about myself.

freehunter 13y ago
The problem becomes apparent if someone is "diagnosed" by 23andme as having a predisposition to something that they don't actually have. For example, your test says you're sensitive to warfarin and you choose not to have that drug administered in a time when your doctor says it would be the best option. Not only are the results questionable, perhaps warfarin is the only good option. If you refuse it based on an invalid test and you are seriously damaged by the lack of proper care, that's a problem. I'm no expert, but it seems like the validity of these tests are being drawn into question. While it may help, it may also really hurt. Questioning these interpretations is exactly what medical science should be doing. You're not getting information about yourself, you're getting (to you) incomprehensible data and a guess as to what it means. Is that more valid than the family history that your doctor already has? Humans tend to make emotional decisions when it comes to their own health. The goal of medical science is to get past the emotion (look at what this drug did to my grandma) and find provable facts instead.
- dnautics 13y ago
  For example, your test says you're sensitive to warfarin and you choose not to have that drug administered in a time when your doctor says it would be the best option. Then you repeat the test. Your doctor may not have been considering that you may have a warfarin sensitivity, the doctor's family history may be incomplete, etc. etc. This is especially an issue with minority communities, whose medical issues are not as well dealt with by physicians, or medical science in general (minority = fundamentally less statistical strength). It's not a well-known fact, for example that asians tend to have statin sensitivity because of impaired clearance, a lower dose is equally effective in asians (although IIRC while effective in reducing cholesterol, endpoint efficacy of statins in preventing coronary disease is unknown in asians); to my horror I found my father was being prescribed the 'caucasian' dosage of statins, and then a year later, I took the 23andMe test and found that I'm homozygous to a codominant allele that is associated with dramatic increase the risk of myopathy when taking simvastatin. So here my dad is taking an inappropriate dosage of a drug that is likely making him sicker and maybe not even helping prevent coronary disease. Now, the question you have to ask yourself, is, is it worth it to deny responsible people like myself the power to easily and cheaply obtain these sorts of decisions just to protect people who are going to get hysterical about information, even when there's a second layer of professional expertise that intervenes before any medical action is taken? look at what this drug did to my grandma But that is exactly, scientifically valid evidence. I think you are placing an unreasonable reverence on the 'validity' of medical 'facts' or the competence of medical authorities. After all, proper scientists aren't necessarily seeking provable facts but rather, disprovable assertions.
  - dzhu 13y ago
    "Then you repeat the test." What if the test is inherently flawed? "look at what this drug did to my grandma" Uh, that is purely anecdotal, n of 1 data, which is not scientifically valid evidence. This is what scientifically valid evidence begins to look like: http://www.nejm.org/doi/full/10.1056/NEJMoa1310669 http://www.nejm.org/doi/full/10.1056/NEJMoa1310669, which suggests the _opposite_ of what 23andMe says about warfarin sensitivity. The point isn't that we shouldn't have tests for things such as warfarin sensitivity or statin sensitivity; it's simply that we need to have clinically VALIDATED tests for these medical conditions. Otherwise, without a clear understanding of the analytic and clinical validity of these tests, it's possible that many false positives or false negatives arise. There's a reason why other genetic tests (e.g. Genomic Health's Oncotype DX or Myriad's BRCAnalysis) haven't been pulled by the FDA (in fact, they're not even regulated by the FDA!) - that's because they've gathered sufficient data to support the clinical outcomes and utility claims that they've made. Put more simply, these other molecular diagnostics have actually verified their science. 23andMe has not - that's why they're being regulated.
    - girvo 13y ago
      You mean what if the doctors second test is inherently flawed? Then you're screwed either way :/
  - smtddr 13y ago
    Just FYI http://www.nytimes.com/2013/12/31/science/i-had-my-dna-picture-taken-with-varying-results.html?_r=0 http://www.nytimes.com/2013/12/31/science/i-had-my-dna-pictu... None of this DNA testing stuff is super-accurate.
  - Cass 13y ago
    look at what this drug did to my grandma And this is exactly the sort of crazy nonsense that happens when you give medical information to laypeople without explaining it properly. Warfarin doesn't cause strokes, or if it does, it does so as a crazy and crazy unlikely side-effect in a vanishingly small number of patients. The common, dangerous, life-threatening side effect of Warfarin, the one you need to be worried about with a Warfarin sensitivity, is bleeding. Of course, Warfarin, when administed in a careful, low dosage to people with the sensitivity, may fail to prevent a stroke, but Warfarin almost certainly did not give the previous commenter's grandma a stroke, and it's driving me slightly crazy that this thread is causing people to think that it's some sort of common side effect.
MichaelGG 13y ago
The FDA is _not_ trying to prevent this information. It's trying to prevent 23andme from marketing a diagnostic product that doesn't meet diagnostic regulations. They can't have it both ways. They can market and dump out your DNA data. Or they can meet regs, prove they are clinically accurate, then market it as a diagnosis product. We'd not like random companies starting up and misleading people and claiming to diagnose but really just flip a coin. That's all the FDA is asking.
- barry-cotter 13y ago
  The diagnostic regulations are too stringent . They are preventing people from getting information that they want to pay for, 23&me is willing to provide, and that 23&me can justify. It's not like they're taking information straight off of SNPedia, they survey the literature on the alleles of the henes they test.
  - mjn 13y ago
    But they're selling things that aren't actually valid diagnostics as if they were diagnostic tests. In what sense is prohibiting that too stringent a regulation? It's not DNA-specific; if you set up a random lab that claimed to diagnose diseases from blood samples that you invite people to mail in, your lab would be shut down pretty quickly if you never validated the analyses. If they want to sell DNA dumps and call them DNA dumps, that'd be truthful advertising. But if they want to make diagnostic claims, they need to actually back them up.
  - MichaelGG 13y ago
    >It's not like they're taking information straight off of SNPedia, they survey the literature That's the point. If they simply gave people raw results and told them to Google it, that'd be fine. They could even provide a report with hyperlinks to SNPedia. But that's not a very fun marketing message, is it? 23andme wants to sell itself as accurate diagnosis, without having to actually prove they're accurate. The FDA's letter said the FDA tried to contact them repeatedly about this issue, asked them to change language, and 23andme ignored them. What's the FDA supposed to do?
dzhu 13y ago
Warfarin sensitivity is _precisely_ why 23andMe needs to be regulated; 23andMe has NOT clinically (or analytically) validated any of the claims around the specific SNPs they've identified. All 23andMe does is link to research papers that may suggest that there are gene variants that are linked to warfarin sensitivity; however, these have not been validated to be clinically significant. In fact, just last month, the New England Journal of Medicine published a landmark study around the pharmacogenomics of warfarin dosing, which found that this very genetic data does NOT affect/improve warfarin dosing (http://www.nih.gov/news/health/nov2013/nhlbi-19.htm http://www.nih.gov/news/health/nov2013/nhlbi-19.htm, original paper: http://www.nejm.org/doi/full/10.1056/NEJMoa1310669 http://www.nejm.org/doi/full/10.1056/NEJMoa1310669). In light of this, this warfarin sensitivity information that you've obtained from 23andMe is almost certainly a false positive, and if you were on a prescribed warfarin treatment, 23andMe would've likely resulted in a change in your behavior that would be strictly detrimental to your health.
- mindcrime 13y ago
  In light of this, this warfarin sensitivity information that you've obtained from 23andMe is almost certainly a false positive, and if you were on a prescribed warfarin treatment, 23andMe would've likely resulted in a change in your behavior that would be strictly detrimental to your health. I don't think there is any valid basis for that claim. A rational person (and I only mean "somewhat rational", I'm not talking about an Econ101 "perfectly rational actor" here) would get their 23andMe results, go "hmmm, this is interesting" and line up a visit to their primary care physician to talk about the results, and what it might mean for their treatment... at which point additional tests might be indicated, or the doctor could more fully explain the various tradeoffs, implications, etc. There's no particular reason to assume that people are going to randomly adjust their medications based on 23andMe results alone. And, even if they do, so be it - the price of personal freedom is individual responsibility for the outcome of your actions.
  - vidarh 13y ago
    If only most people where sufficiently rational to respond that way to things, we could do away with a whole lot of regulation of all kinds of things.
Cass 13y ago
This comment is the perfect example of why the FDA needs to be involved with this. They gave you very important medical information. Did they a) make sure the information was accurate and b) explain it to you in a way that's understandable to a layperson? I can easily see a layperson reading that, and thinking "warfarin sensitivity"? As in "food sensitivity", meaning "this is something that isn't good for me, and I should avoid it?" Wait, isn't that the stuff that gave my grandmother a stroke? Holy shit, they killed my grandmother by giving her too much of a medicine that she's sensitive to!" All warfarin sensitivity actually means, though, as far as I understand it, is that you're likely to need a lower dose than the average patient. If your grandmother had a stroke, it's unlikely that she was overdosed, though - in fact, it's quite likely that she received too low a dose. If someone has a stroke under warfarin treatment, there are two likely causes: Either their warfarin dose was too low, or they had an artery-to-artery embolic stroke instead of the cardioembolic stroke the warfarin was supposed to prevent. (There are of course other, more rare cases of stroke, but those are the two big ones.) Do you see how there's a huge potential for misunderstandings here? I'm not saying you suffered this particular misunderstanding, or that laypeople should be stopped from getting this information. I'm just saying, if you're going to put something like that out there and claim it's a diagnostic tool, it needs to be accurate and it needs to be explained, and that's where the FDA needs to come in.

by Drifter 13y ago

freehunter 13y ago

The problem becomes apparent if someone is "diagnosed" by 23andme as having a predisposition to something that they don't actually have. For example, your test says you're sensitive to warfarin and you choose not to have that drug administered in a time when your doctor says it would be the best option. Not only are the results questionable, perhaps warfarin is the only good option. If you refuse it based on an invalid test and you are seriously damaged by the lack of proper care, that's a problem. I'm no expert, but it seems like the validity of these tests are being drawn into question. While it may help, it may also really hurt. Questioning these interpretations is exactly what medical science should be doing. You're not getting information about yourself, you're getting (to you) incomprehensible data and a guess as to what it means. Is that more valid than the family history that your doctor already has? Humans tend to make emotional decisions when it comes to their own health. The goal of medical science is to get past the emotion (look at what this drug did to my grandma) and find provable facts instead.

dnautics 13y ago
For example, your test says you're sensitive to warfarin and you choose not to have that drug administered in a time when your doctor says it would be the best option. Then you repeat the test. Your doctor may not have been considering that you may have a warfarin sensitivity, the doctor's family history may be incomplete, etc. etc. This is especially an issue with minority communities, whose medical issues are not as well dealt with by physicians, or medical science in general (minority = fundamentally less statistical strength). It's not a well-known fact, for example that asians tend to have statin sensitivity because of impaired clearance, a lower dose is equally effective in asians (although IIRC while effective in reducing cholesterol, endpoint efficacy of statins in preventing coronary disease is unknown in asians); to my horror I found my father was being prescribed the 'caucasian' dosage of statins, and then a year later, I took the 23andMe test and found that I'm homozygous to a codominant allele that is associated with dramatic increase the risk of myopathy when taking simvastatin. So here my dad is taking an inappropriate dosage of a drug that is likely making him sicker and maybe not even helping prevent coronary disease. Now, the question you have to ask yourself, is, is it worth it to deny responsible people like myself the power to easily and cheaply obtain these sorts of decisions just to protect people who are going to get hysterical about information, even when there's a second layer of professional expertise that intervenes before any medical action is taken? look at what this drug did to my grandma But that is exactly, scientifically valid evidence. I think you are placing an unreasonable reverence on the 'validity' of medical 'facts' or the competence of medical authorities. After all, proper scientists aren't necessarily seeking provable facts but rather, disprovable assertions.
- dzhu 13y ago
  "Then you repeat the test." What if the test is inherently flawed? "look at what this drug did to my grandma" Uh, that is purely anecdotal, n of 1 data, which is not scientifically valid evidence. This is what scientifically valid evidence begins to look like: http://www.nejm.org/doi/full/10.1056/NEJMoa1310669 http://www.nejm.org/doi/full/10.1056/NEJMoa1310669, which suggests the _opposite_ of what 23andMe says about warfarin sensitivity. The point isn't that we shouldn't have tests for things such as warfarin sensitivity or statin sensitivity; it's simply that we need to have clinically VALIDATED tests for these medical conditions. Otherwise, without a clear understanding of the analytic and clinical validity of these tests, it's possible that many false positives or false negatives arise. There's a reason why other genetic tests (e.g. Genomic Health's Oncotype DX or Myriad's BRCAnalysis) haven't been pulled by the FDA (in fact, they're not even regulated by the FDA!) - that's because they've gathered sufficient data to support the clinical outcomes and utility claims that they've made. Put more simply, these other molecular diagnostics have actually verified their science. 23andMe has not - that's why they're being regulated.
  - girvo 13y ago
    You mean what if the doctors second test is inherently flawed? Then you're screwed either way :/
- smtddr 13y ago
  Just FYI http://www.nytimes.com/2013/12/31/science/i-had-my-dna-picture-taken-with-varying-results.html?_r=0 http://www.nytimes.com/2013/12/31/science/i-had-my-dna-pictu... None of this DNA testing stuff is super-accurate.
- Cass 13y ago
  look at what this drug did to my grandma And this is exactly the sort of crazy nonsense that happens when you give medical information to laypeople without explaining it properly. Warfarin doesn't cause strokes, or if it does, it does so as a crazy and crazy unlikely side-effect in a vanishingly small number of patients. The common, dangerous, life-threatening side effect of Warfarin, the one you need to be worried about with a Warfarin sensitivity, is bleeding. Of course, Warfarin, when administed in a careful, low dosage to people with the sensitivity, may fail to prevent a stroke, but Warfarin almost certainly did not give the previous commenter's grandma a stroke, and it's driving me slightly crazy that this thread is causing people to think that it's some sort of common side effect.

MichaelGG 13y ago

The FDA is _not_ trying to prevent this information. It's trying to prevent 23andme from marketing a diagnostic product that doesn't meet diagnostic regulations. They can't have it both ways. They can market and dump out your DNA data. Or they can meet regs, prove they are clinically accurate, then market it as a diagnosis product. We'd not like random companies starting up and misleading people and claiming to diagnose but really just flip a coin. That's all the FDA is asking.

barry-cotter 13y ago
The diagnostic regulations are too stringent . They are preventing people from getting information that they want to pay for, 23&me is willing to provide, and that 23&me can justify. It's not like they're taking information straight off of SNPedia, they survey the literature on the alleles of the henes they test.
- mjn 13y ago
  But they're selling things that aren't actually valid diagnostics as if they were diagnostic tests. In what sense is prohibiting that too stringent a regulation? It's not DNA-specific; if you set up a random lab that claimed to diagnose diseases from blood samples that you invite people to mail in, your lab would be shut down pretty quickly if you never validated the analyses. If they want to sell DNA dumps and call them DNA dumps, that'd be truthful advertising. But if they want to make diagnostic claims, they need to actually back them up.
- MichaelGG 13y ago
  >It's not like they're taking information straight off of SNPedia, they survey the literature That's the point. If they simply gave people raw results and told them to Google it, that'd be fine. They could even provide a report with hyperlinks to SNPedia. But that's not a very fun marketing message, is it? 23andme wants to sell itself as accurate diagnosis, without having to actually prove they're accurate. The FDA's letter said the FDA tried to contact them repeatedly about this issue, asked them to change language, and 23andme ignored them. What's the FDA supposed to do?

dzhu 13y ago

Warfarin sensitivity is _precisely_ why 23andMe needs to be regulated; 23andMe has NOT clinically (or analytically) validated any of the claims around the specific SNPs they've identified. All 23andMe does is link to research papers that may suggest that there are gene variants that are linked to warfarin sensitivity; however, these have not been validated to be clinically significant. In fact, just last month, the New England Journal of Medicine published a landmark study around the pharmacogenomics of warfarin dosing, which found that this very genetic data does NOT affect/improve warfarin dosing (http://www.nih.gov/news/health/nov2013/nhlbi-19.htm http://www.nih.gov/news/health/nov2013/nhlbi-19.htm, original paper: http://www.nejm.org/doi/full/10.1056/NEJMoa1310669 http://www.nejm.org/doi/full/10.1056/NEJMoa1310669). In light of this, this warfarin sensitivity information that you've obtained from 23andMe is almost certainly a false positive, and if you were on a prescribed warfarin treatment, 23andMe would've likely resulted in a change in your behavior that would be strictly detrimental to your health.

mindcrime 13y ago
In light of this, this warfarin sensitivity information that you've obtained from 23andMe is almost certainly a false positive, and if you were on a prescribed warfarin treatment, 23andMe would've likely resulted in a change in your behavior that would be strictly detrimental to your health. I don't think there is any valid basis for that claim. A rational person (and I only mean "somewhat rational", I'm not talking about an Econ101 "perfectly rational actor" here) would get their 23andMe results, go "hmmm, this is interesting" and line up a visit to their primary care physician to talk about the results, and what it might mean for their treatment... at which point additional tests might be indicated, or the doctor could more fully explain the various tradeoffs, implications, etc. There's no particular reason to assume that people are going to randomly adjust their medications based on 23andMe results alone. And, even if they do, so be it - the price of personal freedom is individual responsibility for the outcome of your actions.
- vidarh 13y ago
  If only most people where sufficiently rational to respond that way to things, we could do away with a whole lot of regulation of all kinds of things.

Cass 13y ago

This comment is the perfect example of why the FDA needs to be involved with this. They gave you very important medical information. Did they a) make sure the information was accurate and b) explain it to you in a way that's understandable to a layperson? I can easily see a layperson reading that, and thinking "warfarin sensitivity"? As in "food sensitivity", meaning "this is something that isn't good for me, and I should avoid it?" Wait, isn't that the stuff that gave my grandmother a stroke? Holy shit, they killed my grandmother by giving her too much of a medicine that she's sensitive to!" All warfarin sensitivity actually means, though, as far as I understand it, is that you're likely to need a lower dose than the average patient. If your grandmother had a stroke, it's unlikely that she was overdosed, though - in fact, it's quite likely that she received too low a dose. If someone has a stroke under warfarin treatment, there are two likely causes: Either their warfarin dose was too low, or they had an artery-to-artery embolic stroke instead of the cardioembolic stroke the warfarin was supposed to prevent. (There are of course other, more rare cases of stroke, but those are the two big ones.) Do you see how there's a huge potential for misunderstandings here? I'm not saying you suffered this particular misunderstanding, or that laypeople should be stopped from getting this information. I'm just saying, if you're going to put something like that out there and claim it's a diagnostic tool, it needs to be accurate and it needs to be explained, and that's where the FDA needs to come in.