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luvblooms ★★ India, 2011-06-14 08:19 (5084 d 18:37 ago) Posting: # 7117 Views: 7,505 |
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Dear All Good morning  For a molecule showing Intra-subject variability of 40-50% in Cmax and 33% in AUC, which study design will be more appropriate, Partial replicate(RTR---RSABE) or Full replicate (RTRT)? Thanks Luv — ~A happy Soul~ |
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GSTATS ☆  India, 2011-06-14 08:53 (5084 d 18:03 ago) @ luvblooms Posting: # 7118 Views: 6,557 |
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Dear Luv, Good Morning ❝ For a molecule showing Intra-subject variability of 40-50% in Cmax and 33% in AUC, which study design will be more appropriate, Partial replicate(RTR---RSABE) or Full replicate (RTRT)? Both designs are appropriate to be used for Reference scaling. But full replicate design has one extra arm (period) as "T" which is not required in reference scaling while in partial replicate design, (if you are new to this design) statistical calculations are bit complex. I will suggest you to go with partial replicate. Regards, GSTATS — Let Noble Thoughts come from Every Side: RIG VEDA |
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Dr_Dan ★★ Germany, 2011-06-14 10:49 (5084 d 16:07 ago) @ GSTATS Posting: # 7119 Views: 6,554 |
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Dear both I am not a statistician but isn’t it true that if you do a full replicate design you double your Test vs Reference comparisons and by this you have a higher power for the study to show bioequivalence? That’s why I would suggest to go with a full replicate. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
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luvblooms ★★ India, 2011-06-14 11:07 (5084 d 15:50 ago) @ Dr_Dan Posting: # 7120 Views: 6,636 |
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Dear Dr. Dan and GSTATS ❝ if you do a full replicate design you double your Test vs Reference comparisons and by this you have a higher power for the study to show bioequivalence? I totally agree to you on this!!! Besides, I recently had an experience with the same molecule for Canada submission. Where we have done a full replicate and BINGO!!!!! The study passed (no CI limit for CANADA required  but also very comfortable CI for AUCs with using 30 volunteer per period. Cmax-110%, AUC 110 with CI of 102-119, with ISCV for reference 50% and for test: 40%)But when the same formulation was dosed for EMEA submission with 30 volunteer/period, we got comfortable results for Cmax (falling in the extended CI range) and higher AUC (upper limit 128  and ISCV of 40% for Cmax and 33% for AUC) Does this difference in the study is because of number of volunteers in each study or study design and there is no difference in the innovator and test release pattern. (Class II molecule with more than 90% release in 10 min in all the media) Luv — ~A happy Soul~ |
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rajneesh singh ☆ 2011-06-14 15:47 (5084 d 11:09 ago) @ luvblooms Posting: # 7124 Views: 6,513 |
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Dear Luv, If the ISCV >30% then we go with both reference scale or Fully Replicate study design. In Reference Scale Design The Statistical Analysis little be complicated, BE Limit can widen according to variability of reference product and only one ARM for Test drug & Two Arm for reference drug is used. My Suggestion is with reference scale design. Regards, RS Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
Ing. Helmut Schütz