Bioequivalence and Bioavailability Forum

Interpol! [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2010-02-02 01:02 (5616 d 08:17 ago) – Posting: # 4689
Views: 24,680

Dear D Labes!

❝ In section 4.1.4 Study conduct under Sampling times it is stated: "... In multiple-dose studies, the pre-dose sample should be taken immediately before (within 5 minutes) dosing and the last sample is recommended to be taken within 10 minutes of the nominal time for the dosage interval to ensure an accurate determination of AUC_(0-tau)...".

❝

❝ My questions:

• Do I interpret this correctly that this prohibits any interpolation in case of time deviations at the measurement of time point t=tau?
  
• Is extrapolation (as we discusses at times here in case of missing samples) also prohibited?
  
• Would that mean, we are not able to calculate AUC_(0-tau) in case
  of missing samples at t=tau?
  
• Does this all also apply to AUC_(0-72), truncated area?

Positive thinking!
I guess this section is a reminder to sample accurately at critical time points. I will continue to do exactly the same I did for many years:

• Imputation of missing values by interpolation; linear at t<t_max, loglinear at t≥t_max
  
• If a value is measured not exactly at tau, using the inter-/extrapolated one
  
• Detailed description in the protocol
  
• Never any questions

Following our discussion I changed my procedure. If the 72 h value is missing in a particular subject after only one formulation, I use an estimate. If both values are missing (theoretically - never seen that), I would use AUC_t instead of AUC₇₂ - for that subject only.

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


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• EMA BE guideline - final version Ohlbe 2010-01-28 18:31 [Regulatives / Guidelines] 
  • Final version published Helmut 2010-01-29 14:29
    • Final version published ElMaestro 2010-01-29 17:02
      • Statistix Helmut 2010-01-29 17:30
        • Statistix ElMaestro 2010-01-29 18:11
      • Calories ;-) Helmut 2010-01-29 19:22
        • Calories ;-) ElMaestro 2010-01-29 20:43
          • Calories ;-) Helmut 2010-01-29 21:08
        • Variable calories d_labes 2010-02-01 12:05
      • ANOVA only - no doubts Helmut 2010-02-10 23:41
        • ANOVA only - no doubts ElMaestro 2010-02-12 21:09
    • Final EMA oracle d_labes 2010-02-01 11:53
      • Final EMA oracle Helmut 2010-02-01 12:28
      • Final EMA oracle ElMaestro 2010-02-01 12:50
        • More then two EMA oracles d_labes 2010-02-01 13:30
          • Less of an issue ElMaestro 2010-02-01 15:29
            • Less or More of an issue d_labes 2010-02-01 16:53
              • Less or More of an issue ElMaestro 2010-02-01 17:22
          • Effective with 1 Aug 2010 Helmut 2010-02-02 00:55
          • Bias? ElMaestro 2010-02-04 11:27
            • Bias? Helmut 2010-02-05 02:03
              • Bias? ElMaestro 2010-02-05 09:33
                • Bias? Helmut 2010-02-05 10:21
              • Bias? d_labes 2010-02-05 13:59
              • Bias? ElMaestro 2010-02-05 16:00
                • Bias? Helmut 2010-02-05 19:14
        • Final EMA oracle Helmut 2010-02-01 13:43
          • Final EMA oracle ElMaestro 2010-02-01 14:54
            • Final EMA oracle d_labes 2010-02-01 15:20
              • Teaching Helmut 2010-02-01 16:07
    • Cmin really gone? tmax reappeared? d_labes 2010-02-01 14:02
      • Cmin really gone. tmax reappeared - but how? Helmut 2010-02-01 23:30
    • Interpol or not d_labes 2010-02-01 14:52
      • Interpol!Helmut 2010-02-02 00:02
        • Interpol! ray_be 2010-02-03 18:31
          • WinNonlin/Phoenix extrapolation to t=tau Helmut 2010-02-03 20:26
    • Meta-analysis Helmut 2010-02-07 17:41
    • Final version published Panks.79 2010-03-08 07:22
      • Cmin for MR-formulations? Helmut 2010-03-08 18:16
        • Cmin for MR-formulations? Marcel 2010-04-23 10:09
          • MR-Guideline? Helmut 2010-04-23 12:34
  • Overview of comments published Helmut 2010-02-10 18:33
    • Comments commented d_labes 2010-02-11 08:19
    • Definition of Cmin by EMEA Ravi 2010-03-13 12:05
      • The EMA’s Cmin & WinNonlin Helmut 2010-03-13 12:52