Bioequivalence and Bioavailability Forum

Critical review of EU BE guideline (Rev.1) [Regulatives / Guidelines]

posted by d_labes  – Berlin, Germany, 2008-08-22 17:42 (6521 d 11:27 ago) – Posting: # 2234
Views: 29,134

Dear all,

here are some of my additional points:

Evaluation of data from several bioequivalence studies, page 13 (lines 533-542)
'1. If after the failed trial or trials some well justified modifications have been made [...] A positive study in this situation is not downgraded by previous negative results.'

Da bin ich aber froh! (How lucky I am).
I can not get the point. What has the failed study to do with the study now showing BE? The formulation for which now BE is claimed is the reformulated, a new product.
Generalizing this would mean that all unsuccessfull efforts and attempts during pharmacists or other work within the development must be reported.

Evaluation of data from several bioequivalence studies, page 13/14 (lines 537-542)
'2. [...] It is not acceptable to pool together two ambigous studies to reach a positive conclusion.'

This may be OK from the regulators point of view (He would like to see at least one study showing BE), but it is against all principles of a meta analysis. Pooling together studies and obtaining a clearer picture is why meta analysis was invented.

Evaluation of data from several bioequivalence studies, page 14 (lines 543-547)
'3. If a failed study(s) clearly show that the test product is bioinequivalent [...] additional study(s) will be needed until evidence for bioequivalence clearly outweights the evidence against [...] It is not acceptable to pool together positive and negative studies in a meta analysis.'

This is nonsense IMHO. How many studies must be done additionally until achieving outweighting evidence? 1, 10, 100 or thousand? Since we are dealing with statistics we have alway the chance of an unlucky finding (set by our alpha to 5% for the patient and by sample size planning to 20% for the producer, if we set power to 80%)! Again the last sentence is against the principles of meta analysis.

Complete thread:

• Critical review of EU BE guideline (Rev.1) Helmut 2008-08-22 14:30 
  • Critical review of EU BE guideline (Rev.1)d_labes 2008-08-22 15:42
    • Critical review of EU BE guideline (Rev.1) Helmut 2008-08-23 02:02
      • Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 09:14
        • Variations Helmut 2008-08-25 11:06
  • Critical review of EU BE guideline (Rev.1) Jaime_R 2008-08-23 16:47
    • Critical review of EU BE guideline (Rev.1) Ravi 2008-08-25 08:19
      • Two Stage Design Helmut 2008-08-25 11:43
        • Two Stage Design JPL 2008-08-28 09:44
          • Two Stage Design Helmut 2008-08-28 11:50
            • Two Stage Design d_labes 2008-08-28 12:09
            • Sequential Design Helmut 2008-11-05 13:22
    • Critical review of EU BE guideline (Rev.1) banusunman 2008-08-26 16:56
      • Washout Helmut 2008-10-15 16:02
  • Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 09:49
    • Critical review of EU BE guideline (Rev.1) Helmut 2008-08-25 12:11
      • Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 13:03
      • Urban legend? Helmut 2008-11-21 16:06
        • Urban legend? d_labes 2008-11-24 15:06
  • Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 11:16
  • Critical review of EU BE guideline (Rev.1), tmax, MRT, LZ d_labes 2008-08-25 11:32
    • Critical review of EU BE guideline (Rev.1), tmax, MRT, LZ Helmut 2008-08-25 13:10
    • tmax, nonparametrics Helmut 2008-10-13 15:38
      • tmax, nonparametrics d_labes 2008-10-14 08:33
        • tmax, nonparametrics Helmut 2008-10-14 11:29
        • tmax, Canadian approach Helmut 2008-11-21 15:41
          • tmax, Canadian approach d_labes 2008-11-24 13:53
            • Early exposure, Canadian approach: GMR only! Helmut 2009-02-08 00:44
              • Early exposure, Canadian approach: GMR only! d_labes 2009-02-09 08:50
          • tmax; another example Helmut 2008-12-25 15:59
  • Automatic integration janmacek 2008-08-27 12:21
    • Automatic integration Ohlbe 2008-08-27 14:49
      • Manual reintegration! H_Rotter 2008-08-28 11:28
        • Manual reintegration! ElMaestro 2008-08-28 12:44
  • Subject accountability, Proc MIXED or equivalent d_labes 2008-09-02 11:13
    • Subject accountability, Proc MIXED or equivalent Ohlbe 2008-09-02 15:20
      • Subject accountability, Proc MIXED or equivalent d_labes 2008-09-02 16:30
  • partial AUC, early exposure d_labes 2008-09-03 08:35
  • HVDs? Helmut 2008-09-23 12:52
    • HVDs? d_labes 2008-09-23 14:20
    • HVDs? Helmut 2009-01-20 14:33
    • E.g., omeprazole Helmut 2009-03-06 17:21
  • BCS-based Biowaiver Helmut 2008-09-25 15:48
    • Dissolution update Helmut 2008-10-13 12:43
  • EUFEPS workshop Helmut 2008-12-23 17:03