Bioequivalence and Bioavailability Forum

tlast (Common) [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2016-07-20 12:48 (2834 d 18:08 ago) – Posting: # 16495
Views: 12,518

Hi Kumar,

THX for posting this  amazing  scary article ( free resource). Some observations:

• I checked the CVs; the study had enough power. Hence, the results are likely not by pure chance.
  
• See my remarks about the EMA’s GL in this post above. When we think about a “representative batch of the reference product” this study opens a can of worms.
  
• We discussed numerous times (f.i. here) the potential bias of AUC-ratios if t_last of T and R are different. Quote from the article:
  • As previously reported,* within-subject differences in the time of the last quantifiable drug concentration (t_last) between PK profiles that differ in magnitude (and therefore fall below assay limit of quantitation [LOQ] at different times) can lead to bias in the AUC_(0-t) geometric mean ratio. This is simply a consequence of comparing AUC_(0-t) values that have been calculated using different time windows, and is remedied by use of a common t_last for all profiles for a given subject and analyte (the revised PK parameter is referred to as AUC_(0-tcommon)). As expected, Table 4 displays this phenomenon, with all AUC_(0-t) geometric mean ratios differing from 100% more than the corresponding AUC_(0-tcommon) ratios.
  I love it.

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• Fisher D, Kramer W, Burmeister Getz E. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: t_last (Common). J Clin Pharm. 2016; 56(7): 794–800. doi:10.1002/jcph.663. free resource.

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


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Science Quotes

Complete thread:

• inter-batch variability? Dr_Dan 2010-08-04 10:29 [Regulatives / Guidelines] 
  • inter-batch variability? Pavidus 2010-08-04 11:57
  • inter-batch variability? d_labes 2010-08-04 13:58
  • inter-batch variability? ElMaestro 2010-08-04 17:09
    • Between study variability common for HVDs Helmut 2010-08-04 19:45
      • Between study variability common for HVDs ElMaestro 2010-08-04 21:01
        • Representative batches? Helmut 2010-08-04 23:42
          • Representative batches? ElMaestro 2010-08-05 08:40
            • Representative batches? Helmut 2010-08-05 12:30
          • Representative batches? Dr_Dan 2010-08-05 08:58
            • Representative batches? Helmut 2010-08-05 12:45
              • Confidence intervals vs. point estimators Dr_Dan 2010-08-06 09:55
                • Confidence intervals vs. point estimators ElMaestro 2010-08-06 12:34
                  • Confidence intervals vs. point estimates Helmut 2010-08-06 13:20
                  • Confidence intervals vs. point estimators Dr_Dan 2010-08-06 14:44
                    • Confidence intervals vs. point estimators ElMaestro 2010-08-06 15:01
                      • meta analysis? martin 2010-08-06 17:25
                        • meta analysis? ElMaestro 2010-08-06 17:57
                          • meta analysis? Helmut 2010-08-06 18:31
                        • meta analysis? Ohlbe 2010-08-06 23:21
                          • No chance against RMS? Dr_Dan 2010-08-10 12:27
                            • No chance against RMS? ElMaestro 2010-08-10 16:26
    • Batch-to-Batch Pharmacokinetic Variability kumarnaidu 2016-07-20 07:16
      • tlast (Common)Helmut 2016-07-20 10:48
        • tlast (Common) nobody 2019-02-21 15:20
          • tlast (Common) ElMaestro 2019-02-21 16:32
            • tlast (Common) nobody 2019-02-21 17:02
              • tlast (Common) ElMaestro 2019-02-21 18:02
                • tlast (Common) nobody 2019-02-21 18:17