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Nirali ★ India, 2008-12-18 08:29 (5601 d 03:53 ago) Posting: # 2936 Views: 6,360 |
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Dear Sir, Which method should be used for Cpd analysis to prove steady state? Study has been conducted for EU regulatory. Thnks & Regards, Nirali |
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Helmut ★★★   Vienna, Austria, 2008-12-18 16:23 (5600 d 19:58 ago) @ Nirali Posting: # 2946 Views: 6,000 |
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Dear Nirali! ❝ Dear Sir, Don’t forget the Madams on the forum!  ❝ Which method should be used for Cpd analysis to prove steady state? Study has been conducted for EU regulatory. First search the forum! To quote the policy:
There’s no guideline for human studies and not even a consensus amongst scientist. Maybe one of my lectures (slides 27/28) helps. The only regulatory document I know of is FDA’s veterinary bioequivalence guidance (Oct 2006): When conducting a steady-state investigation, data on the minimum drug concentrations (trough values) observed during a single dosing interval (CMIN) should also be collected. Generally, three successive CMIN values should be provided to verify that steady-state conditions have been achieved. Although CMIN most frequently occurs immediately prior to the next successive dose, situations do occur with CMIN observed subsequent to dosing. To determine a steady state concentration, the CMIN values should be regressed over time and the resultant slope should be tested for its difference from zero. (my emphases)For another approach see also the mixed effects model in Chow & Liu’s textbook (all editions). — 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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Nirali ★ India, 2008-12-19 08:59 (5600 d 03:23 ago) @ Helmut Posting: # 2949 Views: 5,436 |
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Dear HS, Thanks for that valuable inputs  However as per Canadian guideline, they have recommended RMANOVA with Day and Day*Treatment effects to be considered. Here, I am prefereing to do a ONE WAY ANOVA (as I am considering last three pre-dose). Will this approach fulfill the regulatory requirement, as the study is for Europe territory? Thanks & Regards, NIRALI |
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Helmut ★★★ Vienna, Austria, 2008-12-19 16:00 (5599 d 20:21 ago) @ Nirali Posting: # 2954 Views: 5,546 |
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Dear Nirali! ❝ However as per Canadian guideline, they have recommended RMANOVA with Day and Day*Treatment effects to be considered. Here, I am prefereing to do a ONE WAY ANOVA (as I am considering last three pre-dose). Have you read my linked slides? The problem with all global assessments is the dichotomous outcome (steady state: yes|no), whereas the regression approach allows exclusion of particular subjects. ❝ Will this approach fulfill the regulatory requirement, as the study is for Europe territory? Why not? Since there’s no consensus, you must come up with some procedure in the protocol anyhow. I never had any problems with both of the following methods: Hotelling’s T² and individual regressions. — 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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kram ☆ India, 2010-02-15 16:16 (5176 d 20:06 ago) (edited by kram on 2010-02-16 05:24) @ Helmut Posting: # 4764 Views: 4,953 |
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Dear HS, according to your post i hav some doubts, please guide me... ❝ Generally, three successive CMIN values should be provided to verify that steady-state conditions have been achieved. Here, is it three successive CMIN values means last Three pre dose values ? ❝ Although CMIN most frequently occurs immediately prior to the next successive dose, situations do occur with CMIN observed subsequent to dosing. But Cmin occurs in between Last dose and AUCtau then how above statement is possible ? ❝ To determine a steady state concentration, the CMIN values should be regressed over time and the resultant slope should be tested for its difference from zero. If I have performed ANOVA (using last three pre dose values (time point x, y, z) and result (p-value=0.3241) shows there is no significant difference between three pre dose values. And for same study I have regressed Cmin over Tmin and resultant slope tested for its difference from zero and result shows (p-value = 0.0219), slope is different from zero. From above both result shall I conclude that steady state achieved after (or at) time point x? Thanks and Regards, Ram |
Ing. Helmut Schütz