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Naveen Kumar ☆ India, 2014-06-23 15:19 (3952 d 10:19 ago) Posting: # 13124 Views: 6,358 |
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Dear All, Please suggest, can we design full replicate bioequivalence study (molecule is highly variable) in stages for EMEA submission. My concern is Power will play pivotal role in stage design, which not be in replicate (full) designs. Regards, Naveen Kumar.SR Edit: Category and subject line changed. [Helmut] |
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ElMaestro ★★★ Denmark, 2014-06-23 15:32 (3952 d 10:06 ago) @ Naveen Kumar Posting: # 13125 Views: 5,229 |
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Hello Naveen, ❝ Please suggest, can we design full replicate bioequivalence study (molecule is highly variable) in stages for EMEA submission. Yes, that should be a possibility but:
❝ My concern is Power will play pivotal role in stage design, which not be in replicate (full) designs. Not understood - can you explain what you mean? — Pass or fail! ElMaestro |
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Helmut ★★★   Vienna, Austria, 2014-06-23 16:53 (3952 d 08:46 ago) @ ElMaestro Posting: # 13128 Views: 5,298 |
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Hi ElMaestro & Naveen, ❝ 1. There are no publications about two-stage BE trials combined with replicated designs. Correct. ❝ You might be asked to prove by your own simulations that type I errors are controlled at max 5% or so. Correct again. But – unless one has access to a supercomputer or grid-computing – I would say that’s science fiction. The problem lies in the intermediate power calculation and sample size estimation for the second stage. Contrary to 2,2,2 crossovers and parallel designs there is no explicit formula… Although the convergence is pretty fast, we still would need 105 sim’s (the 104 the two Lászlós used in their paper was too low). With Power2Stage (or your famous C-code) on a reasonably fast machine 2,2,2 sim’s run for ~two days. If we add sim’s within the sim’s that would mean ~2,700 years. I don’t believe in immortality.  If you start tomorrow, ask a fortune teller for the adjusted α to validate, buy every year the latest hardware, and believe in Moore’s law then you’ll be done in twenty years. — 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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Naveen Kumar ☆ India, 2014-06-28 09:26 (3947 d 16:12 ago) @ Helmut Posting: # 13163 Views: 5,170 |
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Dear ElMaestro and Helmut, Thank you for the suggestions, one more  with out two stage in full replicate design, can i have a chance for interim analysis (EMEA).Regards, Naveen Kumar.SR |
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Helmut ★★★ Vienna, Austria, 2014-06-28 14:09 (3947 d 11:30 ago) @ Naveen Kumar Posting: # 13165 Views: 5,160 |
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Hi Naveen, ❝ […] with out two stage in full replicate design, can i have a chance for interim analysis (EMEA). Would you please so kind and describe in simple words the purpose and performance of the interim analysis you have in mind? What decisions will you make? What measures will you take to maintain the patient’s risk? <nitpicking> EMEA mutated into EMA back in 2005. </nitpicking>— 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 |
Ing. Helmut Schütz