5 ms·

New study casts doubt on some fingerprick blood tests

57 points by pavornyoh 11y ago

Fede_V 11y ago
If this study is correct, and blood drops have a high variability in certain important clinical features, then, no matter how accurate the instruments are, it's impossible to actually get a clean measurement from low volumes of blood. This is one of the most obvious tests that should come to mind for anyone who wishes to create a blood diagnostic company. How could Theranos not know about this?
- JonFish85 11y ago
  I'm sure they do/did, and hope(d) that they could work around it in some way. Unfortunately for them, it sounds like they're going to have to pay the piper before they wanted to.
  - Fede_V 11y ago
    The best they can do is measure the sample with zero measurement noise - but that's no panacea if the variation is in the sample itself, and not the measurement.
- Plough_Jogger 11y ago
  Additionally important is the fact that the minimum required volume varies based on the feature that is being measured. This seems incongruent with Theranos' focus on a few standardized sample containers.
  - IanCal 11y ago
    That depends on the sizes. The article says > Only when the authors tested upwards of five drops combined (60 to 100 microliters) were they able to get accurate results. That still sounds pretty low volume to me. I can't read the actual article, so I can't comment in much more detail (also, I'm not a biologist).
- danieltillett 11y ago
  More importantly how did their sophisticated investors not know this? This issue has been known in the industry for years. The whole Theranos fiasco would not matter except for the damage it does to other biotech startups - when sentiment turns it does not matter if what you are doing is real or not, everyone is frozen out.
  - robbiep 11y ago
    Hype always beats science and reality, at least in the short term
  - JonFish85 11y ago
    If you look through their BoD, there's not a lot of biomed representatives as I recall...
    - danieltillett 11y ago
      That must be the understatement of the year. The board looks like the board you would put together if you were planning a coup of some central american country.
  - FireBeyond 11y ago
    I highly doubt their sophisticated investors are any more clued in than their board / executive management, which included prominent military figures, industrial complex powerbrokers, politicos, but zero or nearly zero medical expertise.
    - danieltillett 11y ago
      I need to be a little less subtle with my snark I think. If there ever was a company you could have avoid investing in by looking at their board it is Theranos [1]. 1. https://www.theranos.com/leadership https://www.theranos.com/leadership
      - deleted 11y ago
        [deleted]
- Jerry2 11y ago
  >How could Theranos not know about this? They probably did know but willfully ignored it because the monetary upside was great.
- such_a_casual 11y ago
  The study states that they got accurate measurements once they started taking 5 drops of blood which is less than 0.1 ml. A blood sample could vary from 3-10 ml according to the first thing I found on google. So it seems like all they have to do is take a few more drops to be accurate (which will still be an order of magnitude from the volume of traditional blood tests). first thing on google: https://ethnomed.org/patient-education/blood/how-much-blood-is-taken-spanish-english https://ethnomed.org/patient-education/blood/how-much-blood-...
  - danieltillett 11y ago
    To get 100 µl out you need more than a finger prick. Once you go this way you might as well cannulate. There might be some special cases where you can get 100 µl but not 3 mL, but this market is not going to support the weight of a unicorn.
    - such_a_casual 11y ago
      Are you claiming that 5 drops of blood cannot be obtained via finger prick?
      - thescriptkiddie 11y ago
        If he is, he's generally right. You get 1.5, maybe 3 drops out before it seals back up. Finger lancets are very tiny needles, even smaller than those used for insulin injections.
        replicatorblog 11y ago
        I worked in diabetes where finger stick tests are the lingua franca. 3 microliter sample sizes were common about 10 years ago for home use systems using relatively fine lancets. Using something just a bit larger would pretty easily get you 5 drops of blood.
      - danieltillett 11y ago
        Not out of one - well not easily or consistently.
- jacquesm 11y ago
  It's not so much the volume that is the problem from what I understand it is the way in which it is drawn. So if that same volume were drawn from a vein then the variability would be substantially less. > How could Theranos not know about this? Who says they did not know about this? Maybe they did but it did not agree with their plans, maybe they thought they could overcome it.
moultano 11y ago
I've found even glucose meters to be wildly inaccurate. There is often a 20% difference in readings between two meters moments apart, and thats enough to have consequences for how your care is managed.
- RA_Fisher 11y ago
  It's pretty heteroskedastic, which practically makes the errors not tooo bad. For example, say my wife is low (< 70), in that case the error rate will be small. That's where precision matters. Now suppose she's 200+, in that case the errors will be large but it doesn't really impact how to take care of it. In terms of error, What worries me much more is a server at a restaurant giving my wife a regular coke rather than a diet coke or vice versa. Where smaller blood is really beneficial is that it requires a less painful finger prick.
  - Fede_V 11y ago
    If the error is proportional to the measurement - can't you just take the log to make it additive again?
    - RA_Fisher 11y ago
      Hmm, it's not clear to me what the benefit of that would be in terms of information (a transformation). It's univariate data, it's been a bit since I looked at it but a histogram showed readings were lognormal / weibull / gamma distributed (point is asymmetric, right-skewed), I believe. In terms of inference, it's kind of mind-bending to think of a "population" of blood and each person having a specific variation.
- jonlucc 11y ago
  I've noticed this as well in rodents. Take 2 consecutive drops and the readings can be as much as 60 mg/dl off. It's not a problem for us because we take duplicate measures, and if they are too far off, we can remeasure. An individual with one meter and only one drop must be relying very heavily on a pretty inaccurate measurement.
m0rganic 11y ago
My wife's a nurse and she said if the test comes out high or low they always do a blood draw to double check. So this doesn't seem that ground breaking of a study.
- tedunangst 11y ago
  What do they do if the test erroneously comes out normal?
cant_kant 11y ago
Fingerpricks provide capillary blood mixed with tissue fluid. A venupuncture provides venous blood. The normal ranges and the error bars are different for finger prick blood.Virtually data and research on the normal ranges and ranges in various diseases has been done on venous blood. The thousands of journal articles that come out each week are done using results of venous blood.For instance, see this article from this week's NEJM http://www.nejm.org/doi/full/10.1056/NEJMoa1504720?query=featured_home#t=articleMethods http://www.nejm.org/doi/full/10.1056/NEJMoa1504720?query=fea... The glycated Hb readings referred to in this article are automatically taken to be on venous blood samples, as are the fasting glucose levels. Your physician relies on readings from venous blood. His training in medical school was on normal and pathological ranges in venous blood samples. Physicians are thrown a bit when given pathology readings from other countries ( mmol versus the old fashioned American mgs/litre are confusing. if the pathology printout is in German or Arabic, it adds even to the fun ). It breaks the flow of rapid data analysis while the physician breaks out bc https://www.gnu.org/software/bc/ https://www.gnu.org/software/bc/ or some other calculator to convert units. Add in the confusion and inaccuracy of fingerprick samples, and the potential for even more error, increases a bit.

57 points by pavornyoh 11y ago

If this study is correct, and blood drops have a high variability in certain important clinical features, then, no matter how accurate the instruments are, it's impossible to actually get a clean measurement from low volumes of blood. This is one of the most obvious tests that should come to mind for anyone who wishes to create a blood diagnostic company. How could Theranos not know about this?

JonFish85 11y ago
I'm sure they do/did, and hope(d) that they could work around it in some way. Unfortunately for them, it sounds like they're going to have to pay the piper before they wanted to.
- Fede_V 11y ago
  The best they can do is measure the sample with zero measurement noise - but that's no panacea if the variation is in the sample itself, and not the measurement.
Plough_Jogger 11y ago
Additionally important is the fact that the minimum required volume varies based on the feature that is being measured. This seems incongruent with Theranos' focus on a few standardized sample containers.
- IanCal 11y ago
  That depends on the sizes. The article says > Only when the authors tested upwards of five drops combined (60 to 100 microliters) were they able to get accurate results. That still sounds pretty low volume to me. I can't read the actual article, so I can't comment in much more detail (also, I'm not a biologist).
danieltillett 11y ago
More importantly how did their sophisticated investors not know this? This issue has been known in the industry for years. The whole Theranos fiasco would not matter except for the damage it does to other biotech startups - when sentiment turns it does not matter if what you are doing is real or not, everyone is frozen out.
- robbiep 11y ago
  Hype always beats science and reality, at least in the short term
- JonFish85 11y ago
  If you look through their BoD, there's not a lot of biomed representatives as I recall...
  - danieltillett 11y ago
    That must be the understatement of the year. The board looks like the board you would put together if you were planning a coup of some central american country.
- FireBeyond 11y ago
  I highly doubt their sophisticated investors are any more clued in than their board / executive management, which included prominent military figures, industrial complex powerbrokers, politicos, but zero or nearly zero medical expertise.
  - danieltillett 11y ago
    I need to be a little less subtle with my snark I think. If there ever was a company you could have avoid investing in by looking at their board it is Theranos [1]. 1. https://www.theranos.com/leadership https://www.theranos.com/leadership
    - deleted 11y ago
      [deleted]
Jerry2 11y ago
>How could Theranos not know about this? They probably did know but willfully ignored it because the monetary upside was great.
such_a_casual 11y ago
The study states that they got accurate measurements once they started taking 5 drops of blood which is less than 0.1 ml. A blood sample could vary from 3-10 ml according to the first thing I found on google. So it seems like all they have to do is take a few more drops to be accurate (which will still be an order of magnitude from the volume of traditional blood tests). first thing on google: https://ethnomed.org/patient-education/blood/how-much-blood-is-taken-spanish-english https://ethnomed.org/patient-education/blood/how-much-blood-...
- danieltillett 11y ago
  To get 100 µl out you need more than a finger prick. Once you go this way you might as well cannulate. There might be some special cases where you can get 100 µl but not 3 mL, but this market is not going to support the weight of a unicorn.
  - such_a_casual 11y ago
    Are you claiming that 5 drops of blood cannot be obtained via finger prick?
    - thescriptkiddie 11y ago
      If he is, he's generally right. You get 1.5, maybe 3 drops out before it seals back up. Finger lancets are very tiny needles, even smaller than those used for insulin injections.
      - replicatorblog 11y ago
        I worked in diabetes where finger stick tests are the lingua franca. 3 microliter sample sizes were common about 10 years ago for home use systems using relatively fine lancets. Using something just a bit larger would pretty easily get you 5 drops of blood.
    - danieltillett 11y ago
      Not out of one - well not easily or consistently.
jacquesm 11y ago
It's not so much the volume that is the problem from what I understand it is the way in which it is drawn. So if that same volume were drawn from a vein then the variability would be substantially less. > How could Theranos not know about this? Who says they did not know about this? Maybe they did but it did not agree with their plans, maybe they thought they could overcome it.

moultano 11y ago

I've found even glucose meters to be wildly inaccurate. There is often a 20% difference in readings between two meters moments apart, and thats enough to have consequences for how your care is managed.

RA_Fisher 11y ago
It's pretty heteroskedastic, which practically makes the errors not tooo bad. For example, say my wife is low (< 70), in that case the error rate will be small. That's where precision matters. Now suppose she's 200+, in that case the errors will be large but it doesn't really impact how to take care of it. In terms of error, What worries me much more is a server at a restaurant giving my wife a regular coke rather than a diet coke or vice versa. Where smaller blood is really beneficial is that it requires a less painful finger prick.
- Fede_V 11y ago
  If the error is proportional to the measurement - can't you just take the log to make it additive again?
  - RA_Fisher 11y ago
    Hmm, it's not clear to me what the benefit of that would be in terms of information (a transformation). It's univariate data, it's been a bit since I looked at it but a histogram showed readings were lognormal / weibull / gamma distributed (point is asymmetric, right-skewed), I believe. In terms of inference, it's kind of mind-bending to think of a "population" of blood and each person having a specific variation.
jonlucc 11y ago
I've noticed this as well in rodents. Take 2 consecutive drops and the readings can be as much as 60 mg/dl off. It's not a problem for us because we take duplicate measures, and if they are too far off, we can remeasure. An individual with one meter and only one drop must be relying very heavily on a pretty inaccurate measurement.

m0rganic 11y ago

My wife's a nurse and she said if the test comes out high or low they always do a blood draw to double check. So this doesn't seem that ground breaking of a study.

tedunangst 11y ago
What do they do if the test erroneously comes out normal?

cant_kant 11y ago

Fingerpricks provide capillary blood mixed with tissue fluid. A venupuncture provides venous blood. The normal ranges and the error bars are different for finger prick blood.Virtually data and research on the normal ranges and ranges in various diseases has been done on venous blood. The thousands of journal articles that come out each week are done using results of venous blood.For instance, see this article from this week's NEJM http://www.nejm.org/doi/full/10.1056/NEJMoa1504720?query=featured_home#t=articleMethods http://www.nejm.org/doi/full/10.1056/NEJMoa1504720?query=fea... The glycated Hb readings referred to in this article are automatically taken to be on venous blood samples, as are the fasting glucose levels. Your physician relies on readings from venous blood. His training in medical school was on normal and pathological ranges in venous blood samples. Physicians are thrown a bit when given pathology readings from other countries ( mmol versus the old fashioned American mgs/litre are confusing. if the pathology printout is in German or Arabic, it adds even to the fun ). It breaks the flow of rapid data analysis while the physician breaks out bc https://www.gnu.org/software/bc/ https://www.gnu.org/software/bc/ or some other calculator to convert units. Add in the confusion and inaccuracy of fingerprick samples, and the potential for even more error, increases a bit.