Bioequivalence and Bioavailability Forum • BLLOQ ≠ 0 ∀ t

BLLOQ ≠ 0 ∀ t > 0 [🇷 for BE/BA]

posted by Helmut – Vienna, Austria, 2015-12-16 13:40 (3387 d 02:40 ago) – Posting: # 15737
Views: 28,039

Hi Yung-jin,

❝ […] From the current practice of a BE/BA study, I still don't know, when we get a BQL for a conc. from analytical report,

~~Easy~~ hopefully: If it is <LLOQ. ;-)

Current practice is to give a non-nunmeric value. Sometimes I see zeros in reports, but that’s stupid for any t > 0 (for theoretical reasons – as we discussed above). Furthermore:

In calibration (regardless the model) we have an intercept. How likely is it that we “measure” something that will give after back-calculation exactly zero? Practically zero…
According to BMV-guidelines the LLOQ is defined as the lowest concentration which can be measured with acceptable (in)accuracy and (im)precision. Would that be possible for zero? No way. Even with a “wonder-method” how would one calculate the CV% = 100 × SD / 0 = ?
At the first Crystal City conference (1990) there were heated debates about this issue. The consensus was to not (!) report a result as zero. Wasn’t questioned ever since. Extrapolation <LLOQ and >ULOQ is not acceptable. Well, in the FDA’s draft guidance on BMV (September 2013) we read an amazing sentence: “Concentrations below the LLOQ should be reported as zeros.” Browsing the comments I’m pretty sure that this oddity will be trashed in the final version.

❝ how to judge it's real zero (as illustrated by weidson's example/plot. subject# 16) or a BQL.

IMHO, the chance that it is “real zero” is ≈0.

❝ My question is: has any analytical lab. had a chance to report real zero measured conc. in the analytical report? :confused:

They have. If the analysts are no-brainers and follow stupid SOPs, yes.

—
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Helmut Schütz

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Science Quotes

Complete thread:

bear v2.7.0 released yjlee168 2015-12-07 09:18 [🇷 for BE/BA]
- Suggestion ElMaestro 2015-12-07 10:12
  - Suggestion yjlee168 2015-12-07 10:55
    - Suggestion Helmut 2015-12-07 14:01
      - Suggestion yjlee168 2015-12-07 18:51
- bear v2.7.0 released Astea 2015-12-10 16:36
  - if Clast is zero in bear yjlee168 2015-12-10 17:23
    - if Clast is zero in bear Astea 2015-12-10 20:50
      - if Clast is zero in bear yjlee168 2015-12-11 03:28
        
        if Clast is zero in bear Astea 2015-12-11 09:39
        
        if Clast is zero in bear yjlee168 2015-12-11 17:16
    - bear v2.7.1 yjlee168 2015-12-15 10:21
      - bear v2.7.1 Astea 2015-12-15 19:32
        
        BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-15 20:17
        
        BLLOQ ≠ 0 with measured drug plasma conc. Helmut 2015-12-16 01:45
        
        BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-16 11:38
        
        BLLOQ ≠ 0 ∀ t > 0Helmut 2015-12-16 12:40
        
        BLLOQ ∋ { 0, ≈0, BLLOQ{...} ∀ t > 0} yjlee168 2015-12-16 18:22
        
        BLLOQ at first two time ponts, AUC calculation Astea 2016-01-30 17:11
        
        zero-zero with AUC calculation in bear yjlee168 2016-01-30 19:00
        
        BQL rules in bear mittyri 2016-02-01 22:16
        
        BQL rules in bear yjlee168 2016-02-02 10:59
        possible solutions? yjlee168 2016-02-02 21:30
        zero (0), missing (NA), or BLLOQ (0 or NA) in bear yjlee168 2016-02-03 09:04
        
        zero (0), missing (NA), or BLLOQ (0 or NA) in bear mahmoud-teaima 2016-02-08 21:28
        
        Please avoid Full Quotes (“TOFU”)! Ohlbe 2016-02-09 00:51
        
        error message in bear mahmoud-teaima 2016-02-09 04:55
        
        please check your dataset file yjlee168 2016-02-09 06:40
        
        please check your dataset file mahmoud-teaima 2016-02-09 15:00
        
        please check your dataset file yjlee168 2016-02-09 15:38
        
        A possible R bug? yjlee168 2016-02-09 19:14