Log in
Register|
Coja66 ☆ 2013-01-16 11:12 (4501 d 13:23 ago) Posting: # 9862 Views: 6,911 |
|
|
Hi all, For a client, I am performing the PK for a BE study using acceptance ranges of 0.50-2.00 (which are way to wide for my preference by the way). Now the results show that 90% CI are included in these ranges, but the 1 is not included the CI. I know this is not relevant for assessing BE, but for some reason worries me, especially since the acceptance ranges are so wide. Is there indeed a reason to worry, or not ? Thanks for the input ! Coja |
|
ElMaestro ★★★ Denmark, 2013-01-16 12:38 (4501 d 11:57 ago) @ Coja66 Posting: # 9863 Views: 5,627 |
|
|
Dear Coja66, ❝ Is there indeed a reason to worry, or not ? Yes, you have good reason to worry: Multi-resistant tuberculosis bacteria, the fiscal cliff, political instability on several continents, disappearance of the coral reefs and much more. 1.0 not included in the 90% CI should not keep you awake at night. — Pass or fail! ElMaestro |
|
d_labes ★★★ Berlin, Germany, 2013-01-16 16:07 (4501 d 08:28 ago) @ ElMaestro Posting: # 9866 Views: 5,666 |
|
|
My dear! ❝ 1.0 not included in the 90% CI should not keep you awake at night. Did you really forgot the Danish twist? Although the power calculation for their "BE decision rule" was implemented in the famous EFG? Can't believe that  .@Coja: Your BE acceptance range is really wide. Where did it came from? If your study is aimed for the European market no go! The widest acceptance range allowed in the EMA guidance is 69.84% ... 143.19% given that your study is a replicate crossover study and your intra-subject CV of the Reference from that study is >=50%. Note that the widening is only allowed for Cmax. If your study is targeted to the FDA a simple widening of the acceptance range is not the correct method. Search the Forum for "scaled average bioequivalence" or "RSABE". — Regards, Detlew |
|
ElMaestro ★★★ Denmark, 2013-01-16 18:46 (4501 d 05:49 ago) @ d_labes Posting: # 9873 Views: 5,582 |
|
|
Dear d_labes, ❝ Did you really forgot the Danish twist? Although the power calculation for their "BE decision rule" was implemented in the famous EFG? Can't believe that Not forgotten, but ignored. I don't think the Dabish Authorities are enforcing the requirement. They would be hammered flat in a CMD(h) refferal should it come to that. — Pass or fail! ElMaestro |
|
The Outlaw Torn ★ Europe, 2013-01-17 14:27 (4500 d 10:08 ago) @ ElMaestro Posting: # 9884 Views: 5,456 |
|
|
And a flat danish is just not very appetising.  |
|
bjkim97 ☆ Korea / Seoul, 2013-02-06 06:56 (4480 d 17:39 ago) @ d_labes Posting: # 9969 Views: 5,162 |
|
|
❝ Dear d_labes! ❝ If your study is aimed for the European market no go! The widest acceptance range allowed in the EMA guidance is 69.84% ... 143.19% given that your study is a replicate crossover study and your intra-subject CV of the Reference from that study is >=50%. Note that the widening is only allowed for Cmax. Why this CV(Intra) is >=50%? Is this CV(Intra)>=30%?. Is not that widening is more than >=30%? |
|
d_labes ★★★ Berlin, Germany, 2013-02-06 10:27 (4480 d 14:08 ago) @ bjkim97 Posting: # 9973 Views: 5,300 |
|
|
Dear bjkim97! The EMA allows widening of the BE acceptance limits based on the CVintra of the Reference according to the formula [U, L] = exp [±k·sWR] with k=0.760This widening is allowed for Cmax only and if CVintraR>30%. If CVintraR≤30% the usual acceptance limits 80 ... 125% apply. If CVintraR>50% a cap is imposed on the BE limits and they are held at 69.84 ... 143.19%, the values for CVintraR=50%. That was what I'm talking about in stating "widest acceptance range allowed in the EMA guidance". An additional requirement for scaled ABE is the constraint to the point estimate (ratio T/R) to be within the range 80.00 ... 125.00%. Hope this helps against confusion. BTW: Such a cap is not imposed in the FDA approach — Regards, Detlew |
Ing. Helmut Schütz