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xz ● 2009-04-29 20:43 (6256 d 10:14 ago) Posting: # 3637 Views: 6,361 |
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Hello all, This is a great forum! I did learn a lot from it. Thank you all for sharing your ideas and expertise. I have some questions regarding a one-sequence, two-period drug-drug interaction study. Each subject is dosed with A in Perid 1 and A+B in Period 2. Could somebody please let me know what need to be modified in the SAS code for the regular 2x2 cross over study? I would assume that we need to take out the sequence and period in the ANOVA model. But I'm not sure about the formulas to calculate the CI and power etc. Thanks in advance for your input. If you can guide me to some relative information that will be great. Thanks again, xz |
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Helmut ★★★   Vienna, Austria, 2009-04-29 20:56 (6256 d 10:01 ago) @ xz Posting: # 3638 Views: 5,323 |
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Dear anonymous! ❝ I have some questions regarding a one-sequence, two-period drug-drug interaction study. Each subject is dosed with A in Perid 1 and A+B in Period 2. Oops, that's a wrong design! PK interaction studies must be performed as a cross-over. Imagine a situation, where you have a 'true' period effect. In a cross-over study the treatment effect will not affected. In the paired design you suggested it is not possible to separate any period effect from the treatment effect! BTW, don't forget that PK interaction studies are to be perfomed in steady state (FDA: recommended, EMEA: mandatory). Other users will help you with ![[image]](img/uploaded/image2.gif) — 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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xz ● 2009-04-29 22:45 (6256 d 08:12 ago) @ Helmut Posting: # 3640 Views: 5,267 |
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Hi Helmut, Thanks very much for your prompt reply! ❝ Oops, that's a wrong design! PK interaction studies must be performed as a cross-over. Imagine a situation, where you have a 'true' period effect. In a cross-over study the treatment effect will not affected. In the paired design you suggested it is not possible to separate any period effect from the treatment effect! You are right about the period effect. In the design I mentioned, it is impossible to separate the period effect from the effect. But the following FDA guidance says: "A study can use a randomized crossover (e.g., S followed by S+I, S+I followed by S), a one-sequence crossover (e.g., S always followed by S+I or the reverse), or a parallel design (S in one group of subjects and S+I in another)." http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf Is this true? ❝ BTW, don't forget that PK interaction studies are to be perfomed in steady state (FDA: recommended, EMEA: mandatory). Sorry, I forgot to mention that Drug B will be dosed for several days right before the A+B dose in period 2. Thanks, xz -- Edit: Link corrected for FDA's new site. [Helmut] |
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Helmut ★★★ Vienna, Austria, 2009-04-29 23:02 (6256 d 07:55 ago) @ xz Posting: # 3641 Views: 5,234 |
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Dear xy (what a nick!) ❝ […] it is impossible to separate the period effect from the effect. But the following FDA guidance says: ❝ "A study can use a randomized crossover (e.g., S followed by S+I, S+I followed by S), a one-sequence crossover (e.g., S always followed by S+I or the reverse), or a parallel design (S in one group of subjects and S+I in another)." ❝ Is this true? You are quoting correctly. I don't have the slightest idea what was going on in the minds of FDA's gurus when they suggested a »one-sequence crossover design«. Of course you can evaluate such a study, but imagine a situation when there's no 'true' PK interaction, but only a period effect (like: sunshine in period 1 and a thunderstorm in period 2). What will you get? If you really want to follow this track, see this post - just the other way 'round (i.e., you assume than any effect is due to treatment and there's no period effect). Since FDA also suggests a cross-over as one of the alternatives why don't you do it the 'easy way'? — 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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ElMaestro ★★★ Denmark, 2009-04-30 19:30 (6255 d 11:27 ago) @ Helmut Posting: # 3642 Views: 5,142 |
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❝ (like: sunshine in period 1 and a thunderstorm in period 2). What will you get? A nice tan and wet hair? EM. |
Ing. Helmut Schütz