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beman ☆ 2011-08-18 14:49 (5429 d 00:31 ago) Posting: # 7282 Views: 6,027 |
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Dear All, according to the new EMA-Guideline we want to perform a study in a 2 Formulation - 3 Periods replicative crossover design to extent Cmax acceptance limits. In Literature and FDA-Guideline (1999) only following sequences are recommended: RTR (2 Times R) TRT (2 Times T) This design was needed for individual bioequivalence (because you need the CVintra of the Reference and the Test Formulation. To extend the acceptance limit (average bioequivalence) we only need the intrasubject CV of the reference formulation. Therefore it is more sufficient to use only sequences with '2 Times R', for example Proposal 1: TRR RRT or Proposal 2: TRT RTR TRR The answers in the comments to the EMA-Guideline allow this design. Is there any statistical disadvantage of that design ? Proposal 2 is the better one. But it is possible to use proposal 1, or are the disadvantages to big ? Thank you for you response in advance Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2011-08-18 18:17 (5428 d 21:03 ago) @ beman Posting: # 7283 Views: 4,855 |
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Dear beman! ❝ In Literature and FDA-Guideline (1999) only following sequences are recommended: ❝ RTR (2 Times R) ❝ TRT (2 Times T) … and some of others: TRR|RTT, TRR|RTR|RRT, TRT|RTR|TRR|RTT ❝ This design was needed for individual bioequivalence (because you need the CVintra of the Reference and the Test Formulation. Right. ❝ Proposal 1: ❝ TRR ❝ RRT ❝ ❝ or ❝ ❝ Proposal 2: ❝ TRT ❝ RTR ❝ TRR Don’t forget the partially replicated design TRR|RTR|RRT quoted in FDA's progesterone guidance. ❝ Proposal 2 is the better one. But it is possible to use proposal 1, or are the disadvantages to big ? I would also say that #2 is better, because in #1 you never dose T in period 2. Imagine a (rather hypothetical) situation where you have a large period effect in period 2. Both designs are not balanced, but the bias on the treatment effect would be larger in #1 as compared to #2. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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beman ☆ 2011-08-22 17:10 (5424 d 22:10 ago) @ Helmut Posting: # 7285 Views: 4,743 |
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❝ ❝ Proposal 2: ❝ ❝ TRT ❝ ❝ RTR ❝ ❝ TRR ❝ ❝ Don’t forget the partially replicated design TRR|RTR|RRT quoted in FDA's progesterone guidance. You are right. Sorry, it was a typing error, i mean RRT instead of TRT. Thanks Beman |
Ing. Helmut Schütz