What is ground truth: home meter or lab venipuncture?

[pem]

Hi. I'm beside myself

I've been home testing with an InRatio monitor from Alere and running parallel tests from the lab. It turns out the readings covary almost perfectly (see attached graph), but there is a spread between the two results that is bigger when my INR is higher (I've seen other anecdotal reports of that effect on this forum).

I have a formula that allows me to predict almost perfectly what the lab result will be based on what the home meter result is. That formula, in case it is useful to someone else, is to take the meter result, raise it to the power of 0.85 (use a scientific calculator - the windows calculator has a scientific mode with X^Y as a function). The "Adjusted Home" line on the graph is based on this formula.

So this might seem like good news in that I can use my home monitor to predict with almost perfect accuracy the lab result. It speaks well for both methods, because they are internally consistent and consistent with each other. The problem is that when the home meter says I have an INR of 4.3, the lab tends to say my INR is around 3.2. Only one of these can be true. I can convert back and forth between my meter and the lab value and they will always be different in predictable ways, but a medical decision needs to be made about whether to change my Coumadin levels. To further complicate this, my cardiology office tends to believe the lab result, while Alere says that different sensitivity levels (ISI) in the reagents used at the lab make the lab results very unreliable. I find this confusing because from what I understand the ISI value is used to normalize lab results by adjusting for the different sensitivity levels. In other words, in the past, without ISI values, labs would just report the prothrombin time (PT), which would be different from one lab to another because of the different sensitivity levels. But now that manufacturers provide the ISI value, it can be used to take a given PT value and adjust it to an INR ("Normalized") value so that it would be consistent across labs. I spoke to the lab that measures my INR and found that their ISI value is 1.80.

So does anyone have any ideas about which value is actually the true value between my home meter and the lab result?

Thanks!
pem

 

[wcasey5]

I went through this myself. Neither is true but both are true. As long as I am in range, I'm good.

 

[Bina]

Blood labs doing vein draws, and home monitors using capillary blood will both use different reagents to complete the test.
This is why we have an accepted variance of approx .2 for an INR reading using both methods; and it is also why we have
an INR range given to us of 2.0--3.0 or 2.5--3.5
INR numbers are not really an "exact" science but they are pretty darn close for what is required.

 

[dick0236]

Hi. I'm beside myself ....
.....So does anyone have any ideas about which value is actually the true value between my home meter and the lab result?

Thanks!
pem

Uh-Uh. Nope. As long as I stay anywhere within my numbers, 2.5-3.5, I don't worry about it. I have had some occasions where the finger stick was significantly "out of my normal" and have had lab draws done. Sometimes the lab draw and finger stick are reasonably close (never the same) and sometimes significantly diffrent.... then its a question of "which is right". Thankfully, it doesn't happen often. I do not know the chemistry behind the two testing methods, but I understand that th methds are not an exact "apples to apples" comparison. I agree that INR is not an exact science and problems usually arise only if you are way out of range. I only get concerned when I dip below 2.0 or above 4.5.....several months ago, it was an 8+ that turned out to be a malfunctioning meter in my docs office. My own experience is that while I periodically will have numbers a little above or below my range, any significantly different number is test error.....and using the other test usually suggests that the initial finger stick test was flawed.....but "only the shadow knows" which test is correct...but most docs put more faith in the lab tests???

 

[Protimenow]

I used to have a lot of faith in my meters. A few years ago, I had a concussion. The day before, I tested with a ProTime meter and had a 2.9. The day of my concussion, the hospital's lab results were 2.92. It made me pretty confident in the meter's results. When I got my InRatio, I tested on both machines and got the same result. I was pretty confident in the accuracy of the InRatio.

When I had a low INR reported by the InRatio machine, I also checked on my CoaguChek S and got very similar results. With an increase in Warfarin levels, I quickly resolved my low INR within a few days (which was safe, according to published protocols).

On Wednesday, I had a stroke - not too much damage (it's only four days later and I'm able to type this). As soon as I felt the strange symptoms, I tested my blood with the InRatio and took two aspirins. The InRatio reported 2.6. The hospital lab result - a day later - was 1.7. The next day, it was 1.6.

This makes me wonder about the InRatio machine -- how could it give me a 2.6, when a blood draw showed the below range 1.7? If it was underreporting my actual INR, how long was it doing this? Why weren't the quality controls on the strips showing errors? How long was I in the unsafe range, and did this erroneous reporting of my tests contribute to my stroke?

I took my warfarin EVERY night and never missed it (until the night I was in the E.R. for this damned thing). I was consistent with diet and activity. I trusted the meter. HOW COULD THIS HAVE HAPPENED?

I'm going back to the hospital on Monday for a blood draw. Although I don't like the idea, I may get involved with the hospital's coumadin clinic. I'll be talking to Alere - and maybe have an attorney give them a call, too.

It's hard NOT to trust these meters - especially because clinics and labs use, and rely on them. However, from my recent experience, I wonder about their continued accuracy and the quality of their QC tests.

 

[pem]

It's hard NOT to trust these meters - especially because clinics and labs use, and rely on them. However, from my recent experience, I wonder about their continued accuracy and the quality of their QC tests.

Protimenow,

I'm so sorry about your recent stroke. I'm glad there wasn't too much damage. Don't be discouraged as the brain is phenomenal at re-wiring itself to compensate for damage - it just takes time.

Were they able to tell you from diagnostic studies definitively whether it was an occlusive (clot) or hemorrhagic (bleeding) stroke? I would guess the former based on your low INR, but just thought I'd double-check.

It is indeed disconcerting that the InRatio meter could overreport your INR to that apparent extent. As you can see from my own graph, my InRatio meter consistently overreports with respect to the lab value. But if I apply my conversion formula to your 2.6, I would have predicted a lab value of 2.2, which is still out of range, but not 1.7. I started out with a different InRatio monitor, but after a difference of 4.5 to 3.3 (home vs lab), they gave me another meter. I did side-by-side tests between the old and new meter and with the lab. The old meter was a bit higher than the new meter, but both were still quite a bit higher than the lab value. Alere would have me believe that their monitors are more accurate than the lab values but, quite frankly, I am skeptical. The basis for their position on this is that there are lots of factors (different phlebotomists, time from draw to test, temperature consistency with samples, etc.) that could cause variability in lab results. On top of that they seem to think that different ISI values will preclude apples-to-apples comparisons between labs (in fact, ISI values were developed specifically to adjust for different reagent sensitivity levels). Since my home meter and lab vary consistently with each other, I can rule out those variability factors. So that leaves just this fundamental difference in the overall magnitude of the INR number. As I said in my earlier email, they cannot both be correct. Based on my most recently testing, either my INR is currently 4.3 (home) or it is currently 3.0 (lab). At this point, I'm inclined to believe the lab. Your recent experience also seems to support the accuracy of the lab result.

Anyway, thanks for writing in and sharing your experience. I wish you a speedy recovery. Also, my current guidance is to take my meter to the cardiology office on Thursday and check the result against their Coaguchek monitor. I have some methodological concerns about the validity of this method of checking, but I will take any additional data I can get and then treat it appropriately as best I can.

Thanks again and best,
pem

 

[pem]

I went through this myself. Neither is true but both are true. As long as I am in range, I'm good.

Thanks for your reply. Unfortunately, I'm faced with a situation in which one is in range and the other is out of range and I have to decide which I believe.

pem

 

[pem]

Blood labs doing vein draws, and home monitors using capillary blood will both use different reagents to complete the test.
This is why we have an accepted variance of approx .2 for an INR reading using both methods; and it is also why we have
an INR range given to us of 2.0--3.0 or 2.5--3.5
INR numbers are not really an "exact" science but they are pretty darn close for what is required.

Hi Bina,

Thanks for your reply!

It seems the variation I am seeing between lab and home exceeds that 0.2 accepted variance. I have been told by many that INR numbers are not an exact science, but there are aspects of this science that can be more exact by using controls. If my INR values on my home meter are consistently 0.5 or more higher than the lab result, then to me, either the lab or the home meter needs to be recalibrated. There is an exact definition of prothrombin time, and INR is just a manipulation of that number based on reagent sensitivity. There is a variance associated with reagents of different sensitivity levels, and using a higher ISI can magnify normal variability. All of these aspects are "known" factors in interpreting INR values. However, if I take 10 readings from home and lab, and home is consistently higher than lab by a certain amount, then we are not seeing a variance effect, we are seeing a statistically AND practically significant difference between the two measurement methods.

Let's say I went to 5 different labs each using a different reagent and got the following INR numbers: 3, 3.2, 3.0, 3.1, 3,1
Let's say I then used my home meter, pricking on three different fingers and got: 4.3, 4.2, 4.3
Should I believe the average lab value or the average home meter value?

Best,
pem

 

[pem]

Uh-Uh. Nope. As long as I stay anywhere within my numbers, 2.5-3.5, I don't worry about it. I have had some occasions where the finger stick was significantly "out of my normal" and have had lab draws done. Sometimes the lab draw and finger stick are reasonably close (never the same) and sometimes significantly diffrent.... then its a question of "which is right". Thankfully, it doesn't happen often. I do not know the chemistry behind the two testing methods, but I understand that th methds are not an exact "apples to apples" comparison. I agree that INR is not an exact science and problems usually arise only if you are way out of range. I only get concerned when I dip below 2.0 or above 4.5.....several months ago, it was an 8+ that turned out to be a malfunctioning meter in my docs office. My own experience is that while I periodically will have numbers a little above or below my range, any significantly different number is test error.....and using the other test usually suggests that the initial finger stick test was flawed.....but "only the shadow knows" which test is correct...but most docs put more faith in the lab tests???

Hi Dick,

Thanks for the data point. Wish I could find a study out there that compares home meters to labs to other labs. Do you get consistent values between your home meter and your lab? Which meter do you use? Which lab?

Thanks,
pem

 

[Protimenow]

Pem:

Thanks for the interesting comments. Yes, the brain can recover from many injuries rather quickly. I was lucky that this was small and in an area that wasn't as critical to normal functioning as, say, the sensory areas. I'm working on retraining my brain so that I can walk more normally. My typing has already returned to normal.

This was an ischemic stroke - not hemorrhagic. The difference between my meter's value (2.6) and the lab's value (1.6) is disturbing to me -- I'm wondering HOW LOW my INR actually was for the past few weeks. Although I've seen protocols that say bridging is unnecessary for low INRs - as long as dosage is increased and the return to range is rapid (like, say, withing a week), in my current case, because I have a bridging medication and a negative history, I AM bridging. A few days below range may not be very life threatening -- but the two or three weeks that I may have been in that range, after relying on the meter's accuracy, are distressing.

I'm going to contact Alere, which now makes the InRatio, and let them know about this problem with the meter (and the stroke that resulted from being way out of range).

Yes - mishandling of reagents, mishandling of samples before they get to the labs, etc., could all make lab results a bit less than consistent from lab to lab (or even from phlebotomist to phlebotomist), and in theory the meters have their reagents carefully calibrated and should be consistent, but, given my recent experience, I'm more inclined for the short term to trust lab first and MAYBE LATER trust a new meter and new strips.

 

[pem]

Yes - mishandling of reagents, mishandling of samples before they get to the labs, etc., could all make lab results a bit less than consistent from lab to lab (or even from phlebotomist to phlebotomist), and in theory the meters have their reagents carefully calibrated and should be consistent, but, given my recent experience, I'm more inclined for the short term to trust lab first and MAYBE LATER trust a new meter and new strips.

I don't blame you. Not one little bit.

 

[ElectLive]

Wish I could find a study out there that compares home meters to labs to other labs.

Are these home meters not required to document clinically studied accuracy/precision in any way as part of their standard FDA approved literature (like what you'd find packaged up with the test strips, for instance)? This is standard for blood glucose test strips, as an example, and often includes in depth statistical analysis, regression analysis charts, etc. I also wonder if there are FDA approval documents for these home meters available as well, including even more detailed testing and verification, similar to what we can find for our various replacement valves.

Pem - By the way, do you think your blood disorder is also influencing all of this? Ever get any more details on that?

 

[ElectLive]

Protimenow - So sorry to hear of your stroke. I know just from casually browsing threads here that you have always seemed to be one of the most diligent proponents of frequent home testing, so it is very disconcerting to read of potential device errors such as these. You know, as a diabetic, I am very used to home testing inaccuracies, but it's night and day really, since diabetics have symptoms of highs and lows, and are able to apply common sense verification to suspicious readings. Obviously, for INR, that is not possible.

Best wishes to you in recovery, and for everyone's sake, I hope progress is able to be made in getting answers to very important questions such as these.

 

[pem]

Are these home meters not required to document clinically studied accuracy/precision in any way as part of their standard FDA approved literature (like what you'd find packaged up with the test strips, for instance)? This is standard for blood glucose test strips, as an example, and often includes in depth statistical analysis, regression analysis charts, etc. I also wonder if there are FDA approval documents for these home meters available as well, including even more detailed testing and verification, similar to what we can find for our various replacement valves.

Pem - By the way, do you think your blood disorder is also influencing all of this? Ever get any more details on that?

Great idea - thanks. I was wondering about FDA studies on these recently, but your posting prompts me to actually dig a little.

Good memory! Alere asks about a Lupus diagnosis with regard to home testing, but does not ask about Thalassemia minor. I conducted some parallel tests with the help of the home nurse immediately following surgery. She used coagucheck and venipuncture side by side (with the latter sent to a lab), and I think except for one early discrepancy, they were consistent. I will go back and see if I can find those numbers. But I think those numbers gave me confidence that the test was robust to Thalassemia minor. If I can find them, I'll post them.

Great ideas and questions - thanks!
pem

 

[dick0236]

Hi Dick,

Thanks for the data point. Wish I could find a study out there that compares home meters to labs to other labs. Do you get consistent values between your home meter and your lab? Which meter do you use? Which lab?

Thanks,
pem

A couple of years ago I did "home test" for about a year. I returned to using the "finger stick" in my PCP office because of difficulties I had with insurance and Alere.

 

[pem]

A couple of years ago I did "home test" for about a year. I returned to using the "finger stick" in my PCP office because of difficulties I had with insurance and Alere.

Got it. Thanks, Dick.

Best,
pem

 

[newmitral]

Protimenow - Along with the others, I'm so sorry about your recent stroke, and I hope you recover quickly and completely.

PEM - I've only been home testing with my Inratio2 meter for about 5 months, and have had only one occasion where I have both a meter test and a lab test taken from blood drawn within an hour or two of the meter home test. On that occasion, the home test result was 3.4 and the lab test result was 2.8
I just assumed the truth was somewhere in the middle, around 3.1, or that the lab test was probably wrong since the blood wasn't actually tested until the next day after shipment from the doctor's office to the lab.

But, your formula of home-test-raised-to-the-power-of-0.85 works perfectly for the 3.4/2.8 home/lab difference on the one data point I can add from my Inratio2 meter.

This, along with Protimenow's experience makes me a bit nervous too. If your formula is true for my Inratio2 meter as well, then to stay within a lab-draw reading range of 2.5-3.5, I should strive for a home-test range of 2.9-4.4
I have no problem with the 2.9 side, but if my home reading is 4.4, I usually consider that well out of range and adjust my warfarin accordingly.
To be within range under both test types, it would appear I should strive for a home test range of 2.9 to 3.5 on my home meter. From my history so far, this tighter home-test target range will be difficult, if not impossible for me to achieve.

I would also be interested in hearing from others as to whether their Inratio2 meters show the same offset from lab-draw INR tests.

Another test I plan to perform when I do my next home test, is to make two different tests with my meter within 1/2 hour of each other just to test the repeatability of the meter itself with no other variables (same test strip lot number).

When I get a new batch of test strips, and have two with different lot numbers, I'll check the repeatability again by running two tests within 1/2 hour of each other using strips from different lots.

I'll post with my results after these tests, but I would be interested to know if anyone has already done such tests and what their results were.

---------------------

UPDATE to Post:
I just found the following from the FDA website after a bit of googling:
http://www.accessdata.fda.gov/cdrh_docs/reviews/K092987.pdf

Although there is no date on the report, it does make for some interesting reading.

In the "analytical performance" part of the report, because Biosite/Alere is using the venous blood draw as the basis for the purported accuracy of the meter & test strip readings, it would seem that "Ground Truth" would be the venous blood draw method test results.

The other item that caught my eye is that there can be a +/- 0.5 INR offset, with a +/- 30% relative bias of the test strips within the therapeutic range for INR values of 2.0 to 4.5. I am making an assumption that the absolute offset and relative bias of the test strips is what is calibrated out when the test strip lot code number is entered into the Inratio2 meter for a given manufacturing lot.

The report seems to say that there is a residual overall accuracy level of about +/- 8.5% So, for a nominal reading of INR=3.0, this gives an allowed uncertainty of +/- 0.25 on the INR reading.

From PEM's results, and my own single point comparison with a blood draw test, it would seem that these accuracy results may not always be met. Perhaps some other factors are at work to skew the results, but I plan to get a few more test comparisons to blood draw tests for my own meter if I can.

 

[Bina]

Newmitral,
Try not to make yourself crazy interpreting various results. Pick one method and go with it. My Coaguchek XS just happens to test the
same as my blood Lab, but I still like my INR at around 3.1 so that any normal testing variances won't be an issue. If one or the other
is up or down by a couple of points I am still in range and safe.

 

[Protimenow]

Are these home meters not required to document clinically studied accuracy/precision in any way as part of their standard FDA approved literature (like what you'd find packaged up with the test strips, for instance)? This is standard for blood glucose test strips, as an example, and often includes in depth statistical analysis, regression analysis charts, etc. I also wonder if there are FDA approval documents for these home meters available as well, including even more detailed testing and verification, similar to what we can find for our various replacement valves.

Pem - By the way, do you think your blood disorder is also influencing all of this? Ever get any more details on that?

This is about Pem's question regarding clinical studies comparing meters to lab results.

Yes -- there are a LOT of research studies available. If I recall, the ITC site (manufacturers of the ProTime meters), and, I think, the InRatio (Alere) sites both have links to extensive studies that compare the results from THEIR meters to lab studies - and all come out with the meters looking extremely good, and well within range of the labs. Last year, one company had a new meter in testing that was not able to get FDA approval -- the FDA is very careful about these things. If you check out the professional pages at the meter manufacturers' sites, you'll probably find a variety of papers.

One thing that everyone may have missed -- and that may have contributed to my recent stroke -- is that all the testing and comparing is being done on a NEW meter. Even with the quality controls and other safeguards that are built into strips or code chips, can you be certain that an OLD meter retains its accuracy? Can my five year old meter - having passed all its QC tests for each strip - just routinely OVERREPORT my INR. Could a 2.6 on my old meter have actually been closer to the 1.7 that the hospital lab determined a day later? Should the FDA look into this issue?

I still believe that having your own meter is empowering. I'm just not sure if it will be entirely trustworthy three, four, five or more years down the line.

 

[Protimenow]

A few things:

First - thanks to everyone for their good wishes. Fortunately, the ischemic damage was small, and was in an area (controlling my right lower leg and right hand), and I've already mostly retrained my neurons in that area (or some area) so that I can still type quickly, and can walk with a barely noticeable limp. I'll be careful for a while, slow down for a few weeks (until my INR is in range again), and continue to pursue my interest in coagulation management.

I am getting a new (maybe a refurbished?) InRatio 2 meter, and some strips, tomorrow. I'm also going to be going to an Anticoagulation Clinic that draw blood -- I don't know how long I'll be going to the lab - but I don't plan to NOT still do self-testing.

Once the effects of my bridging medication are completely gone, I'll do a test with a new batch of strips, using my InRatio 2 and InRatio (classic?) - using two fingers - and within minutes of each other, and compare the results. I'll probably also check on my InRatio2 at around the same time as my clinic's blood draw. They tell me that, out of 1000 patients, they only have one or two people who have a meter. I may SHOW them how easy the meter is to use, and they can compare the lab results with the InRatio2's results.

I don't think my 'erroneous' 2.6 was operator error. I'm suspicious of the accuracy of my old meter. It may be something that the FDA should look into.

One more thing -- although I wasn't sure if my lower right leg weakness was DEFINITELY a stroke, I was concerned. The first thing I did was take two full dose aspirin -- I tested my INR a few minutes later. I'm not sure if the aspirin helped - but my doctors seemed to think so. If any of you are unlucky enough to have strange symptoms, like I did, it would probably be worth considering immediately taking an aspirin or two. (And, since I suspected that this may have been more than a pinched nerve, OF COURSE, I should have called 911 or gone to the nearest emergency room. Without insurance, I chose to wait. The next day, after this thing only partially resolved, I drove myself to a county-run ER, where I got great care - eventually.)