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Achievwin ★★ US, 2022-05-20 06:44 (937 d 05:47 ago) Posting: # 23005 Views: 3,637 |
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Question for study design experts. If we want to introduce assessment or claim using BE study which design is more appropriate? 3-way cross over partial study or 4-way cross full replicate design. Please share your experience. Sincerely, Achiewin Edit: Category changed; see also this post #1. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2022-05-20 11:17 (937 d 01:14 ago) @ Achievwin Posting: # 23006 Views: 3,085 |
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Hi Achievwin, population BE (prescribability) and individual BE (switchability) are of historic interest only. Both are not assessed in any of the currently recommended approaches (average BE, reference-scaled BE, average BE with expanding limits). ❝ If we want to introduce assessment or claim using BE study which design is more appropriate? Define ‘appropriate’. An appetizer. — 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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Achievwin ★★ US, 2022-05-20 16:19 (936 d 20:12 ago) @ Helmut Posting: # 23007 Views: 2,966 |
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❝ population BE (prescribability) and individual BE (switchability) are of historic interest only. Both are not assessed in any of the currently recommended approaches (average BE, reference-scaled BE, average BE with expanding limits). Thanks for the clarification I vaguely recall when you don't have subject by formulation interaction in a replicate study design (4-period full replicate design???) you can request switchability (Metadate ANDA I guess) My question is can we assess this subject by formulation interaction in a 3-period partial replicate design?) what additional statistical test one needs for documenting this? |
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Helmut ★★★ Vienna, Austria, 2022-05-20 17:33 (936 d 18:58 ago) @ Achievwin Posting: # 23008 Views: 3,112 |
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Hi Achievwin, ❝ I vaguely recall when you don't have subject by formulation interaction in a replicate study design (4-period full replicate design???) you can request switchability (Metadate ANDA I guess) No idea (too lazy to search). ❝ […] can we assess this subject by formulation interaction in a 3-period partial replicate design?) what additional statistical test one needs for documenting this? Not sure whether it will work. The partial replicate is a nasty beast (for potential problems see there). IIRC, in the late 1990s concerns about the Subject-by-Formulation interaction emerged. Temporarily studies had to be performed in a replicated design. After assessing the results, the FDA concluded that the S × F interaction is practically not relevant and the temporary requirement was lifted. Furthermore, none of the simulations performed by various authors or by the FDA which lead to RSABE contained an S × F-interaction term in the model. — 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 |
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Achievwin ★★ US, 2022-05-21 01:32 (936 d 10:58 ago) @ Helmut Posting: # 23010 Views: 3,030 |
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Thanks Helmut |
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Brus ★ Spain, 2023-06-06 13:02 (554 d 23:29 ago) @ Helmut Posting: # 23577 Views: 2,214 |
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Dear Helmut, I don't understand the subject-by-formulation effect, can it only be studied in full replicated designs? If the subject-by-formulation effect is the change between test and reference difference means from one subject to another, in a 2x2 design it should be possible to study it. Right? And in that case it could also be measured in partial replicate. Right? Maybe I'm confused or don't understand something. Thank you so much Best regards, |
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Helmut ★★★ Vienna, Austria, 2023-06-07 12:34 (553 d 23:56 ago) @ Brus Posting: # 23580 Views: 2,193 |
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Hi Brus, ❝ I don't understand the subject-by-formulation effect, … ❝ … can it only be studied in full replicated designs? ❝ If the subject-by-formulation effect is the change between test and reference difference means from one subject to another, in a 2x2 design it should be possible to study it. Right? Adding S × F will not work. Didn’t try it yet. Either you get zero degrees of freedom in a fixed effects model or a mixed-effects model will collapse. ❝ And in that case it could also be measured in partial replicate. Right? — 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 |
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Achievwin ★★ US, 2023-06-08 12:21 (553 d 00:09 ago) @ Helmut Posting: # 23581 Views: 2,180 |
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I agree switchability can only be studied by full replicate design, follow up question is now that partial replicate or reference replicate are GONE (??? really) in the new statistics guidance can we study switchability by 3-period replicate design (as it is balanced).... and Can we measure the additional parameter needed for NTIDs by 3-period replicate (balanced design) "Applicants should use the average bioequivalence approach with BE limits of 80-125%. The within-subject variability of test and reference products should be compared and the upper limit of the 90% confidence interval for the test-to-reference ratio of the within-subject variability should be ≤ 2.5. For details about the Method for Statistical Analysis comparing within-subject variability of test and reference products, refer to Guidance on Warfarin Sodium." Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Helmut] |
Ing. Helmut Schütz