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Back to the forum  Query: 2017-07-25 10:52 CEST (UTC+2h)
 
Ladi
Junior

Thailand,
2017-02-23 02:58

Posting: # 17097
Views: 1,421
 

 Calibration and QC point with same concentration [Bioanalytics]

Dear All,

I was wondering if concentration of a calibration point can be equal to a QC point? For example, concentration of MQC and CC5 is equal, although CC and QC both were weighed and prepared independently. Do guidelines allow that or is just common sense that they should be different?

Thanks,
Ladi
Ohlbe
Hero

France,
2017-02-23 10:21

@ Ladi
Posting: # 17098
Views: 1,271
 

 Calibration and QC point with same concentration

Dear Ladi,

As far as I know: common sense only.

Regards
Ohlbe
Relaxation
Junior

Germany,
2017-02-23 15:24

@ Ladi
Posting: # 17099
Views: 1,261
 

 Calibration and QC point with same concentration

» Dear All,
»
» I was wondering if concentration of a calibration point can be equal to a QC point?
»...
» Do guidelines allow that or is just common sense that they should be different?

And a "Dear All" from me, too.
I am also not aware of any guideline giving a requirement that there should be different concentrations.
As this is not what I observed in most trials I was involved in and I had not heard of such a rule at all until today, I think I might learn something new here.

So my follow-up question:
is there really any rule, that CC and QC concentrations have to differ at all? And why would it be common sense, that they should be different, as long as I do not use the same stock solution?
I just can't see a reason (but I am also by no means a bioanalyst).

Best regards,

Steven.
Helmut
Hero
Homepage
Vienna, Austria,
2017-02-23 15:41

@ Relaxation
Posting: # 17100
Views: 1,254
 

 “Punkteinwaage”

Hi Relaxation,

» I am also not aware of any guideline giving a requirement that there should be different concentrations.

There is none.

» is there really any rule, that CC and QC concentrations have to differ at all? And why would it be common sense, that they should be different, as long as I do not use the same stock solution?
» I just can't see a reason (but I am also by no means a bioanalyst).

I was an analytical chemist. ;-)
If you use different stock solutions you would get identical concentrations only if the analyst managed to achieve a <lang="de"> Punkteinwaage </lang="de"> (sorry, don’t know the English term), i.e., weigh-in identical – desired – amounts. Since this is very difficult, it is common sense that concentrations of calibrators and QCs generally differ (slightly).

[image]All the best,
Helmut Schütz 
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Ohlbe
Hero

France,
2017-02-23 16:15

@ Helmut
Posting: # 17101
Views: 1,242
 

 “Punkteinwaage”

Dear Helmut,

» If you use different stock solutions you would get identical concentrations only if the analyst managed to achieve a <lang="de"> Punkteinwaage </lang="de"> (sorry, don’t know the English term), i.e., weigh-in identical – desired – amounts. Since this is very difficult, it is common sense that concentrations of calibrators and QCs generally differ (slightly).

What some labs do is that they adjust the volume of stock solution or intermediate solution that they take, to compensate for the slight difference between the desired weight and the actual weight, so that they get concentrations with round figures (e.g. pipet 998.5 µl instead of 1 ml). I don't see the point, but that's their choice. In the same way, it would be possible to adjust the volumes taken from both solutions to get the same nominal concentration for a QC and a calibration sample.

Regards
Ohlbe
Ohlbe
Hero

France,
2017-02-23 16:20

@ Relaxation
Posting: # 17102
Views: 1,242
 

 Calibration and QC point with same concentration

Dear Relaxation,

» And why would it be common sense, that they should be different, as long as I do not use the same stock solution?

The LQC sample has to have a concentration of maximum 3 times the LLOQ, and it is in the lab's interest to have it close to 3 times (lower variability than e.g. 2 times, less chances to fail). You don't necessarily have a calibration sample at the same level of concentration.

Same for the HQC. You don't necessarily have a calibration sample in the desired zone.

It is actually only for the MQC that you could easily have the same concentration. But then, may I turn the question back: why would you want it to be at the same level of concentration as a calibration sample ?

Regards
Ohlbe
Relaxation
Junior

Germany,
2017-02-23 17:29

@ Ohlbe
Posting: # 17103
Views: 1,237
 

 Calibration and QC point with same concentration

Dear All.

Thanks a lot for the interesting points of view!

With regard to Ohlbe's example with the 998.5 µl. I think that this is a specific mind-set as I clearly remember two groups of students during my time at university (although it does get faded).

Those that got back from the scale within minutes having written down any roughly fitting number for their analysis AND
those spending literally hours at the "4 decimal places" scale, because the Ph.Eur. says for the assay of the API "Weight 0.500 g" :crying:.
And I am sure, we all remember an example of this kind of people.

For me it seems that there is a lot of consensus here. And any apparent difference might simply be due to the fact that "should be different" for some sounds like
"have to be different" (which is not the case) and for some like
"are expected to be different in most cases, as identical real values would be a coincidence".

I think, the outcome, getting also back to Ladi's question, at the moment is simply: they are independent and can be identical, but by no means have to.
Naturally, I may have misread all prior post - again..., so any correction is welcome.

Thanks, best regards and, as making this post longer than really necessary took me to 5.30 P.M:

Have a nice evening/Schönen Feierabend!

Steven.
ElMaestro
Hero

Denmark,
2017-02-23 22:02

@ Relaxation
Posting: # 17104
Views: 1,217
 

 Calibration and QC point with same concentration

Hi Steven,

» I think, the outcome, getting also back to Ladi's question, at the moment is simply: they are independent and can be identical, but by no means have to.

That's the winning statement.


Now, for the independence part of the story I am still struggling a bit, and I have been for long. I usually like to think about myself that I am capable of applying some measure of common sense when I consider BE-related issues. But independent prep. of stock solutions: I see the reason, but I am not sure how to define independence based on common sense. Independent weighing only? Different glassware, different pipettes, too? Different scales? Different lots of ref. std.? Different staff? Different pipette tips? As far as I know it is independent weighing only. But why? Where does independence start and where does it stop? :confused::confused:
Ooooh, almost forgot, there are cases where the CROs buy the ref. standard in solutions with a certified potency. That means no weighing for the stock, and thus no independent preparation.... unless.... damn... I better take my medication now.:-)

I could be wrong, but…


Best regards,
ElMaestro

- since June 2017 having an affair with the bootstrap.
Ladi
Junior

Thailand,
2017-02-24 05:50

@ Relaxation
Posting: # 17105
Views: 1,192
 

 Calibration and QC point with same concentration

Dear All,

Thank you everyone for your insights. What happened is I accidentally set up my CC5 concentration the same as MQC (my bad). The method has been developed and validated and had passed many checking eyes. While finishing the MV report only the issue was spotted.

According to my boss, its "common sense" that the conc. shouldn't be same. Total CC points was eight so I think we can reprocess MV data with the problematic point removed and the curve will still have enough CC levels.

Anyway, in my opinion, the CC-QC points do not have to be different, but looks pretty if they are.

Ladi
Relaxation
Junior

Germany,
2017-02-24 10:29

@ Ladi
Posting: # 17106
Views: 1,180
 

 Calibration and QC point with same concentration

Hi.

» According to my boss, its "common sense" that the conc. shouldn't be same.

Hm, I took a different message home from this thread.

» Total CC points was eight so I think we can reprocess MV data with the problematic point removed and the curve will still have enough CC levels.

Actually, I even had a short discussion with a few (OK, 2, but both are no newbies) of my co-workers and one of them had an argument pro different concentrations (basically "I see this all the time") in case of clinical (!) laboratories.
But both (and me) would discourage omission of valid data from the calibration without proper justification (read: would start a discussion on re-calculating/re-validating including all CCs if we saw that in a bioanalytical/validation report).
Just my thoughts.


Best regards,

Steven.
Helmut
Hero
Homepage
Vienna, Austria,
2017-02-24 12:11

@ Ladi
Posting: # 17107
Views: 1,151
 

 Calibration and QC point with same concentration

Hi Ladi,

» What happened is I accidentally set up my CC5 concentration the same as MQC (my bad).

That’s not bad at all.

» According to my boss, its "common sense" that the conc. shouldn't be same.

I think that the conclusion of the thread (as Steven already noted above) was that an equal concentration of the MQC and one of the CC samples is unlikely but possible.

» Total CC points was eight so I think we can reprocess MV data with the problematic point removed and the curve will still have enough CC levels.

Please don’t do that. You will loose information. Citing the EMA’s GL on the calibration curve in BMV:

A relationship which can simply and adequately describe the response of the instrument with regard to the concentration of analyte should be applied.

It is up to you to demonstrate which model (linear, quadratic, …) and weighting scheme fits the data best. See this post (especially the excellent paper by Almeida et al. 2002).

» Anyway, in my opinion, the CC-QC points do not have to be different, but looks pretty if they are.

1. Yes and 2. Looking pretty is not a scientific category.

[image]All the best,
Helmut Schütz 
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
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d_labes
Hero

Berlin, Germany,
2017-02-24 13:17

@ Helmut
Posting: # 17108
Views: 1,142
 

 OT: Beauty of science

Dear Helmut,

» ... 2. Looking pretty is not a scientific category.

Some people, among them really famous ones, have here another point of view. For instance:
"It is more important to have beauty in one's equations than to have them fit experiment..." :cool:
Paul Dirac, paper on Magnetic Monopoles (1931)
(for more context see here or here)

Regards,

Detlew
ElMaestro
Hero

Denmark,
2017-02-24 14:05

@ Helmut
Posting: # 17109
Views: 1,140
 

 Calibration and QC point with same concentration

Oh dear,

» Looking pretty is not a scientific category.

Don't get me started :-D

Who wins the beauty contest:


Ms. Pretty : x = 5
or Ms. Ugly: x <- 5

?

If you vote for Ms. Ugly, try for consistency's sake if (x<-<-5) {cojones(x)}

And so forth...

I could be wrong, but…


Best regards,
ElMaestro

- since June 2017 having an affair with the bootstrap.
Helmut
Hero
Homepage
Vienna, Austria,
2017-03-03 16:06

@ ElMaestro
Posting: # 17128
Views: 925
 

 Beauty is in the eye of the beholder

Ahoy!

» Who wins the beauty contest:

» Ms. Pretty : x = 5
» or Ms. Ugly: x <- 5

Beauty is in the eye of the beholder.

» If you vote for Ms. Ugly, try for consistency's sake if (x<-<-5) {cojones(x)}

What do you expect from a syntactically wrong expression? See here and there. Most important:

The operator <- can be used anywhere, whereas the operator = is only allowed at the top level (e.g., in the complete expression typed at the command prompt) or as one of the subexpressions in a braced list of expressions.


BTW, in RStudio typing x[alt]_5 gives x <– 5. Note the two spaces. Two keystrokes less than your Ms. Pretty… :-D

[image]All the best,
Helmut Schütz 
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
ElMaestro
Hero

Denmark,
2017-03-03 20:18

@ Helmut
Posting: # 17130
Views: 881
 

 Beauty is in the eye of the beholder

Hi Hötzi,

» See here and there. Most important:

The operator <- can be used anywhere, whereas the operator = is only allowed at the top level (e.g., in the complete expression typed at the command prompt) or as one of the subexpressions in a braced list of expressions.


Impossible for me to understand what is meant, or what logic is behind all that. But clearly someone has a strong opinion.
Speaking in such tongues would have gotten you burned on the town square 400 years ago.:-D

I could be wrong, but…


Best regards,
ElMaestro

- since June 2017 having an affair with the bootstrap.
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