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Back to the forum  2018-07-16 07:06 CEST (UTC+2h)
GM
Junior

India,
2018-06-29 05:47

Posting: # 18992
Views: 320
 

 Drug concentration <LLQ [Bioanalytics]

Hello All,

Hope all are doing well.

As per the Bioanalytical guidance of FDA, all values <LLQ should be declared as zero.

But my doubt is, is there any possibility to use the actual values measured for calculating key parameters?

If yes, how this can be justify?

B’coz, we are not getting best fit (Rsq<0.8) when considering zero instead of actual values.

Thankyou in advance.

GM.
Ohlbe
Hero

France,
2018-06-29 12:00
(edited by Ohlbe on 2018-06-29 17:11)

@ GM
Posting: # 18995
Views: 273
 

 Drug concentration <LLQ

Dear GM,

» As per the Bioanalytical guidance of FDA, all values <LLQ should be declared as zero.
»
» But my doubt is, is there any possibility to use the actual values measured for calculating key parameters?

In BE ? Not the slightest. Nada. Forget it.

» B’coz, we are not getting best fit (Rsq<0.8) when considering zero instead of actual values.

So what ? Who says it has to be < 0.8 ?

The question is rather: was your LLOQ low enough ? What you're describing sounds a bit like you're not able to follow the terminal elimination phase but are getting a mix of distribution + elimination. If you messed up, you can't make up for it by extrapolating below your LLOQ, you'll have to re-develop your method, validate, re-assay.

What is your LLOQ, and what is the Cmax range in your study ?


Edit, to make sure there is no misunderstanding: when you write
» B’coz, we are not getting best fit (Rsq<0.8) when considering zero instead of actual values.
I hope you're not using these values as 0 to calculate Kel, right ? These sampling points should just be ignored. They were to be reported as 0 in the tables of the concentration in the report, not to be used as 0 in the calculations. As pointed out by Helmut, in any case they now have to be reported as BQL. [Ohlbe]

Regards
Ohlbe
Helmut
Hero
avatar
Homepage
Vienna, Austria,
2018-06-29 12:15

@ GM
Posting: # 18997
Views: 269
 

 Report as BLQ

Hi GM,

» As per the Bioanalytical guidance of FDA, all values <LLQ should be declared as zero.

No more – see this thread. For the other points I agree with Ohlbe.

Cheers,
Helmut Schütz
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jag009
Hero

NJ,
2018-06-29 20:49

@ Helmut
Posting: # 18999
Views: 226
 

 Report as BLQ

Hi Helmut!

» » As per the Bioanalytical guidance of FDA, all values <LLQ should be declared as zero.
» No more – see this thread. For the other points I agree with Ohlbe.

I have never seen values below LLQ declared as 0 in any reports. :confused:
Helmut
Hero
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Homepage
Vienna, Austria,
2018-06-29 21:00

@ jag009
Posting: # 19001
Views: 225
 

 Report as BLQ

Hi John!

» » » As per the Bioanalytical guidance of FDA, all values <LLQ should be declared as zero.
» » No more – see this thread. For the other points I agree with Ohlbe.
»
» I have never seen values below LLQ declared as 0 in any reports. :confused:

Lucky you. Was indeed stated in the FDA’s 2013 draft. Bizarre. Was a big issue at the first Crystal City (aka Arlington I) conference in 1990. People were shouting at each at other. It was very strange that “zero” reached out from the grave in the draft…

Cheers,
Helmut Schütz
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