Bebac user ☆ Egypt, 2023-09-09 08:34 (522 d 16:35 ago) Posting: # 23713 Views: 3,873 |
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The combination of Amlodipine and valsartan was published as two periods crossover but after checking the variability of Valsartan, it had more than 30%. Therefore, should I in those cases design this study as replicated or un-replicated ? |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2023-09-12 08:48 (519 d 16:21 ago) @ Bebac user Posting: # 23717 Views: 3,264 |
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Hi Bebac user, ❝ The combination of Amlodipine and valsartan was published as two periods crossover but after checking the variability of Valsartan, it had more than 30%. Therefore, should I in those cases design this study as replicated or un-replicated? There is no product-specific guidance of the EMA and the FDA recommends 2×2×2 crossovers (fasting and fed). Any replicated design can be assessed for (conventional, unscaled) average bioequivalence. However, if you aim at reference-scaling, I would be wary to base the sample size on the CVw of a 2×2×2 design because the CVwR is unknown (see this article). — 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 |
Kumarnaidu2 ☆ India, 2023-12-06 10:36 (434 d 13:32 ago) @ Helmut Posting: # 23781 Views: 2,643 |
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Dear All, For the product like Valsartan + Amlodipine or Telmisartan + Amlodipine, is it possible to plan a analysis with 3 way design for Valsartan/Telmisartan and 2 way design for Amlodipine in same study. For e.g. if we plan a 3 way Partial replicate in 48 subjects (RTR/TRR/RRT). For Val/Telm, sample size will be 48 (All three period) and for Amlodipine, sample size will be 32 (First two period and with sequence RTR and TRR only). Is there any statistical issues with such design? I know the ideal way is to analyse both Val and Aml in same way. |
dshah ★★ India, 2023-12-06 17:49 (434 d 06:19 ago) @ Kumarnaidu2 Posting: # 23785 Views: 2,650 |
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Hello Kumarnaidu2! ❝ For e.g. if we plan a 3 way Partial replicate in 48 subjects (RTR/TRR/RRT). For Val/Telm, sample size will be 48 (All three period) and for Amlodipine, sample size will be 32 (First two period and with sequence RTR and TRR only). Is there any statistical issues with such design?" I believe that for Amlodipine the ISCV would be LT 30%, so by default the ABE calculation becomes applicable. So what advantages would be there to have such statistical plan? Further- analysis of Amlodipine would be required to link any AE for last period. And if it is analyzed, what can be the justification for not using in PK stat? Regards, Divyen |
Kumarnaidu2 ☆ India, 2023-12-07 03:42 (433 d 20:26 ago) @ dshah Posting: # 23786 Views: 2,659 |
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Hello dshah ❝ I believe that for Amlodipine the ISCV would be LT 30%, so by default the ABE calculation becomes applicable. So what advantages would be there to have such statistical plan? ❝ Further- analysis of Amlodipine would be required to link any AE for last period. And if it is analyzed, what can be the justification for not using in PK stat? The reported ISCV for Amlodipine is around 9 to 12%. |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2023-12-07 10:01 (433 d 14:07 ago) @ Kumarnaidu2 Posting: # 23787 Views: 2,644 |
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Hi Kumarnaidu, ❝ For the product like Valsartan + Amlodipine or Telmisartan + Amlodipine, is it possible to plan a analysis with 3 way design for Valsartan/Telmisartan and 2 way design for Amlodipine in same study. ❝ For e.g. if we plan a 3 way Partial replicate in 48 subjects (RTR/TRR/RRT). ❝ For Val/Telm, sample size will be 48 (All three period) … ❝ … and for Amlodipine, sample size will be 32 (First two period and with sequence RTR and TRR only). ❝ Is there any statistical issues with such design? ❝ I know the ideal way is to analyse both Val and Aml in same way. There is a massive problem with the FDA’s RSABE in the partial replicate design if \(\small{s_\text{wR}<0.294}\) because the study has to be assessed for – conventional, unscaled – ABE.
PS: Why is the bloody partial replicate design still so popular? Beyond me. — 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 |