Evaluation of Uncertainty of In Vitro Diagnostic Kit Calibrators

K

kuertensun

#1
Dear all,

I am a guy in the in vitro diagnostic medical device industry. As ISO 17511 requires, an uncertainty should accompany any calibrator enclosed in the in vitro diagnostic kit. In my company's product, the value of the calibrator is obtained from 4 parameter data reduction method and is calibrated by our national standard calibrator. In the evaluation of the uncertainty, I get some difficulties in how to calculate the uncertainties of the 4 parameters in the function.

Please anyone can help with this problem?

thanks,
 
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Stijloor

Staff member
Super Moderator
#2
Dear all,

I am a guy in the in vitro diagnostic medical device industry. As ISO 17511 requires, an uncertainty should accompany any calibrator enclosed in the in vitro diagnostic kit. In my company's product, the value of the calibrator is obtained from 4 parameter data reduction method and is calibrated by our national standard calibrator. In the evaluation of the uncertainty, I get some difficulties in how to calculate the uncertainties of the 4 parameters in the function.

Please anyone can help with this problem?

thanks,
Can someone with this expertise help?

Thank you!

Stijloor.
 
G

George Weiss

#3
It appears there is no one accepted way to determine the uncertainty value for your calibrator/material, in many cases.
This is a problem in your product field, which is under review for future guidance.
Your uncertainty process develops into the various GUM guidance documents.
You describe a 4 point, or a 4 parameter evaluation of a material/calibrator.
It suggests that you are talking about a biological material/calibrator?
There are many IVD tools and materials/calibrators for various tests.
Reviewing competitor values will give you a target, which is worth knowing.
You have a National Standard, which it was compared to, with uncertainties also.
You have given only limited information. I offer an uncertainty guide, which might help:
The Australian Health department has a Uncertainty guide for your type of product @
http://www.health.gov.au/internet/main/publishing.nsf/Content/86A3CE312C612377CA257283007BC92D/$File/dhaeou.pdf
I found some BIPM uncertainty budgets, which might head you in the right direction @
http://www.bipm.org/utils/common/pdf/final_reports/QM/K6/CCQM-K6.pdf
The uncertainty budget in pharmaceutical industry @
http://www.pharmchem.tu-bs.de/forschung/waetzig/dokumente/DPhG_2005_Heydorn.pdf
NIST Special Publication 260-162 @
http://ts.nist.gov/MeasurementServices/ReferenceMaterials/upload/SP260-162.pdf
A common comment is that the question poster offer up more information. Sometimes within these added points is enough to plot a course for you. Some uncertainty wiz-guys want the numbers to work with.
SO, what kind of calibrator.material is it? A complex ASR?
I am not the expert, just passing on some general help.
 
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BradM

Staff member
Admin
#4
Dear all,

I am a guy in the in vitro diagnostic medical device industry. As ISO 17511 requires, an uncertainty should accompany any calibrator enclosed in the in vitro diagnostic kit. In my company's product, the value of the calibrator is obtained from 4 parameter data reduction method and is calibrated by our national standard calibrator. In the evaluation of the uncertainty, I get some difficulties in how to calculate the uncertainties of the 4 parameters in the function.

Please anyone can help with this problem?

thanks,
OK, first are the different components of the total uncertainty:
1. The uncertainty attributed by the national standard calibrator
2. Uncertainty associated with the error of someone using the calibrator enclosed with the product. I would think there could be some potential error there. Given human nature as it is:D, there is no task so simple that people can't mess up.:) So I would think that would be a contributor.
3. Are there any more contributors? Shelf life? Environmental factors?

To your question.... I realize you probably need to be vague about these four parameters, as you certainly don't want to divulge anything too confidential and such. However.... it's awfully generic, and difficult to get a handle on what it is.

With this data reduction method.... is it an identical mathematical calculation, or is there some statistical inferences being made? Out of say 100 trials, what kind of error would be generated using the four parameters simply given the nature of the parameters?

Anyway, I'm pretty sure there is nothing helpful there.:D But possibly if you could add a little more explanation of the parameters, that might help.:)
 
K

kuertensun

#5
OK, first are the different components of the total uncertainty:
1. The uncertainty attributed by the national standard calibrator
2. Uncertainty associated with the error of someone using the calibrator enclosed with the product. I would think there could be some potential error there. Given human nature as it is:D, there is no task so simple that people can't mess up.:) So I would think that would be a contributor.
3. Are there any more contributors? Shelf life? Environmental factors?

To your question.... I realize you probably need to be vague about these four parameters, as you certainly don't want to divulge anything too confidential and such. However.... it's awfully generic, and difficult to get a handle on what it is.

With this data reduction method.... is it an identical mathematical calculation, or is there some statistical inferences being made? Out of say 100 trials, what kind of error would be generated using the four parameters simply given the nature of the parameters?

Anyway, I'm pretty sure there is nothing helpful there.:D But possibly if you could add a little more explanation of the parameters, that might help.:)
Dear BradM,

Thanks for your reply,

Actually, 4 parameter data reduction method is a commonly used regression method in the in vitro diagnostic industry, people in this field should know this model. There are 4 parameters in the function used to calculate concentration from the output signal, say, an absorbance. I read GUM, and it includes an example similar to my case, however, in the example, only 2 parameters need to be determined, and the example says the uncertainty of these 2 parameters are evaluated by well established equations, so I am thinking if there is also a well established theory for my case.

Hope this makes the question clearer.

Thanks.
 
Last edited by a moderator:

BradM

Staff member
Admin
#6
Dear BradM,

Thanks for your reply,

Actually, 4 parameter data reduction method is a commonly used regression method in the in vitro diagnostic industry, people in this field should know this model. There are 4 parameters in the function used to calculate concentration from the output signal, say, an absorbance. I read GUM, and it includes an example similar to my case, however, in the example, only 2 parameters need to be determined, and the example says the uncertainty of these 2 parameters are evaluated by well established equations, so I am thinking if there is also a well established theory for my case.

Hope this makes the question clearer.

Thanks.
:agree1: And I'm glad you mentioned

people in this field should know this model
I should have mentioned earlier that I am not in this industry, and am totally unfamiliar with the formula you mentioned. :) Of course, I think you figured that out fairly quickly.:tg::lol:

I am just trying to pitch in some on the calculation of the uncertainty. Now if you are performing regression, would the R Squared not be useful in estimating uncertainty? Maybe the lower R Squared would contribute more uncertainty than a higher R Squared?

I would look for some information at the N.I.S.T. site for you, if I understand better what I was talking about.:D

Here is a list of the publications that might help:

http://www.nist.gov/srm/publications.cfm


Here is their contact list:

http://www.nist.gov/public_affairs/contact.cfm

Maybe one of them can guide you to the perfect document for guidance, or, might be able to help you in an e-mail or something.
 
G

George Weiss

#8
Hello again,
Your comment, "There are 4 parameters in the function used to calculate concentration from the output signal, say, an absorbance." Was helpful.
you might be speaking of calibration points "A", "B", "C", "D", "E" of material/calibrator dilutions.
Calibration point "A" is the reference without material.
You might also be talking about standard reporting outputs of: "four parameters", or polygonal regression curve in linear or logarithmic scale.
There is a possibility that your 4-parameter term is one of the common IVD analyzer outputs, Curve-fitting options: linear, 4-P, 2-P (logit/log), cubic, quadratic, cubic spline, point-to-point. In the end you have a value or values. These values should compare with the national standard calibrator. The significance of these values, is their variance from the national standard calibrator. This variance/error is a combination of some of the uncertainties, which you are trying to describe.
The significant absolute uncertainty values are:
  1. national standard
  2. process & bias errors (pipette volume, time, temperature, sample-number, and others)
all of these combined via GUM RSS method will give you your IVD kit calibrator uncertainty.

.
Absorbency calibration @
http://www.cisbio-ivd.com/documents/chromoa-package-insert.pdf
A nice IVD calibration uncertainty method description @
http://www.edma-ivd.be/fileadmin/upl_documents/Position_Papers/Estimation_of_uncertainty.pdf
.
The extremely wide variety of in vitro diagnostic devices currently available made it apparent that a single experimental design would not be appropriate for all devices.
.
For complex-calibrators, there is a defined assigned uncertainty process @
http://www.clinchem.org/cgi/reprint/53/4/735.pdf
.
I am just rewording the thread comments to assist in the next poster developing an answer to the question:
"what is the formula for determining the uncertainty of my IVD kit calibrator/reference-material from my 4-parameter data"
 
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