Bioequivalence and Bioavailability Forum • Baseline correction examples

Baseline correction examples [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2015-09-17 17:44 (3137 d 16:56 ago) – Posting: # 15423
Views: 19,325

Dear Ohlbe,

two examples of baseline-corrections.

A stable baseline

The theoretical T/R for AUC is 90%. The baseline is 25. What we measure:

If we work with uncorrected concentrations the AUC_t-ratio with 94.87% will be biased (here the T looks better, but can be the other way ’round as well). The C_max-ratio is also affected (92.00%). Extrapolate? Forget it. The estimated λ_z is only ~10% (!) of the true value… Instead of the theoretical extrapolated fraction of 0.33% we get ~45%!

Let’t subtract the baseline:

As expected everything matches the theoretical values. No bias for any PK metric. Mission accomplished.
A circadian rhythm in the baseline

I followed your example (if I understood it correctly). The maximum of the baseline is at 6 a.m (50) and the minimum at 6 p.m. (20). The baseline at 8 a.m (administration) is 48 and at 8 p.m 22. The theoretical T/R for AUC and C_max is 50%; t_max for both at 2.56.

The thin green line is the baseline. Thin blue/red lines are theoretical profiles of R and T. Thick lines are observed profiles.

Let’s see what we get for the two baseline-correction methods.

If we subtract the pre-dose (that’s ~48 at 8 a.m.) we get the thin lines. Humbug. T/R for AUC_t is 33.30% (worse than the true value). The T/R for C_max is 44.92%. Good luck with extrapolation. Not only AUC and C_max are affected but t_max is shifted towards earlier time points (T 1.8, R 2.1).

If we subtract the entire baseline, we get the theoretical profiles (thick lines) and no bias in PK-metrics.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Complete thread:

Baseline correction vs non-baseline correction jag009 2015-09-15 20:29 [Regulatives / Guidelines]
- Baseline correction vs non-baseline correction Lucas 2015-09-16 14:16
  - Baseline correction vs non-baseline correction Relaxation 2015-09-18 10:25
- Baseline correction or supra-therapeutic dose Helmut 2015-09-16 15:16
  - Baseline correction or supra-therapeutic dose Ohlbe 2015-09-16 17:55
    - Baseline profile prior to each period? Helmut 2015-09-16 18:15
    - Baseline correction examplesHelmut 2015-09-17 15:44
      - Baseline correction examples Lucas 2015-09-18 14:19
        
        Baseline correction examples Helmut 2015-09-18 17:28
        
        Baseline correction examples Mauricio Sampaio 2016-02-07 03:05
        
        Baseline correction examples Lucas 2016-02-10 11:48
        
        Postmenopausal women Helmut 2016-02-10 12:26
        Baseline correction examples Mauricio Sampaio 2016-02-11 01:38
        Baseline correction examples Dr_Dan 2016-02-11 09:22
        
        Postmenopausal women Mauricio Sampaio 2016-02-12 03:24
        
        Postmenopausal women Dr_Dan 2016-02-15 17:45
    - Baseline; another example Helmut 2015-09-18 17:16
      - Baseline; another example nobody 2016-02-12 09:10
        
        Baseline; another example Helmut 2016-02-12 13:37
        
        Baseline; another example nobody 2016-02-12 14:08
        
        Slowly going OT: BE study simulations Helmut 2016-02-12 15:47
        
        Slowly going OT: BE study simulations nobody 2016-02-12 16:15
        
        Religious debate Helmut 2016-02-12 17:04
        
        Religious debate nobody 2016-02-12 17:26
        
        Religious debate ElMaestro 2016-02-13 12:53
        
        Religious debate nobody 2016-02-14 15:23
        
        Slowly going OT: BE study simulations Ohlbe 2016-02-13 13:10
        
        Slowly going OT: BE study simulations Helmut 2016-02-13 15:02
        
        Slowly going OT: BE study simulations lizhao 2016-02-25 17:31
        
        Business as usual Helmut 2016-02-25 17:44
        
        Business as usual lizhao 2016-02-25 17:59