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rahul dixit ☆ 2010-10-26 09:08 (5724 d 05:13 ago) Posting: # 6079 Views: 6,732 |
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Dear All, Greetings! This is a very informative forum. I wish to congratulate everyone who are sharing their knowledge and expertise using this forum. I have came across an approved ANDA of Labetalol tablets submitted by Watson lab for US submission. Watson lab had used a study design in which 30 volunteers were enrolled (ANDA application No is 75133. Information is available on CDER) The study conducted was crossover, two treatment, two period in which volunteers (N =30) were divided in two groups with subject 1 to 20 in group I and 21 to 30 in group II. The dosing was done in a cross over fashion to one group first and then to second group. As add on dsign is not acceptable in US, I am confused with this type of design. Kindly elaborate on this. My second query is: In add on study design, if the result of the first group is passing, then is it necessary to carry out the dosing for the second group? Can we divide the number of volunteers in 2:1 proportion in add on design? Thanks and best regards Rahul Dixit Unichem Laboratories Ltd India |
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Helmut ★★★   Vienna, Austria, 2010-10-26 16:00 (5723 d 22:21 ago) @ rahul dixit Posting: # 6081 Views: 6,083 |
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Dear Rahul, THX for the  !❝ (ANDA application No is 75133. Information is available on CDER) Can you come up with a link? ❝ The study conducted was crossover, two treatment, two period in which volunteers (N =30) were divided in two groups with subject 1 to 20 in group I and 21 to 30 in group II. ❝ The dosing was done in a cross over fashion to one group first and then to second group. Though I have not seen the application, from the details you gave I would say this was not an add-on study, but a study with a fixed sample size of 30 subjects, where due to logistic reasons two groups were dosed. This is acceptable with the FDA (see FDA's 2001 Guidance, Section VII.A.). ❝ As add on dsign is not acceptable in US, I am confused with this type of design. Oh no, an add-on design is acceptable. FDA was actually actively involved in the work published by Potvin et al. 2008 (see this post for the reference and this post for a flow-chart). Donald Schuirmann of the FDA is one of the co-authors and according to a conversation I had in May this year with Barbara Davit (Acting Director of the Division of Bioequivalence II, Office of Generic Drugs, CDER/FDA) the method is not only acceptable but supported by the FDA. ❝ In add on study design, if the result of the first group is passing, then is it necessary to carry out the dosing for the second group? If power in the interim is >80% and the study passes 80%-125% at alpha 0.05 (=90% confidence interval), stop. If power <80% and the study passes at alpha 0.0294 (=94.12% confidence interval), stop - otherwise go for the second stage. In the pooled analysis (stage 1 + stage 2), calculate the 94.12% confidence interval. For details see one of my lectures (slides 52-62). ❝ Can we divide the number of volunteers in 2:1 proportion in add on design? If you fail in the first stage at alpha 0.0294 perform a sample size calculation based on the CV from the first part. No fixed sample size of 1:anything. — 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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rahul dixit ☆ 2010-10-26 16:55 (5723 d 21:25 ago) @ Helmut Posting: # 6082 Views: 5,935 |
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rahul dixit ☆ 2010-10-27 11:49 (5723 d 02:32 ago) @ Helmut Posting: # 6086 Views: 5,899 |
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Dear sir, Greetings! I have already asked my library for that article published by Potvin et al. Do you know any references or published reports where add on study design is conducted and approved in US? We do not have our own Clinical center facility and we generally conduct the study outside. If we wish to carry out the study using add on design then what will be the procedure to get the study approval from US FDA. Thanks and best regards Rahul |
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rahul dixit ☆ 2010-10-30 10:52 (5720 d 03:28 ago) @ Helmut Posting: # 6096 Views: 5,680 |
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Dear All, Is there any way to find out that add on study design is acceptable in US? Is there any study reports by companies who had used add on design? Thanks and best regards Rahul Edit: Post linked to existing thread. [Helmut] |
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Helmut ★★★ Vienna, Austria, 2010-10-30 17:12 (5719 d 21:08 ago) @ rahul dixit Posting: # 6097 Views: 5,683 |
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Dear Rahul! See the Forum's Policy: If you feel that your post did not gain the attention you expected, you may reply to your own post [...]. A reasonable waiting period is two weeks or if the thread has left the entry page of the forum. Only one 'reminder' is suggested; consider the possibility that nobody has an answer or is not willing to share his/her experiences. ❝ Is there any way to find out that add on study design is acceptable in US? Concerning your questions I can only quote from Potvin's paper: It is our understanding that the FDA has accepted studies with designs like those considered here. Since FDA's Donald Schuirmann is one of the co-authors of the paper, you can assume that this statement is correct.  ❝ Is there any study reports by companies who had used add on design? No one I know of. Theoretically you could browse the ~3000 ANDAs under the FOI... — 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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rahul dixit ☆ 2010-11-09 12:30 (5710 d 00:50 ago) (edited on 2010-11-09 14:07) @ Helmut Posting: # 6119 Views: 5,637 |
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Dear all, I have came across one reported study on Clinical trilas @ GOV about sequential design. A Phase I, Open-Label, Randomized, Single-Center, 2-Stage Group Sequential Design, 2-Way Crossover Bioequivalence Study Comparing a Fixed-Dose Combination Capsule of Esomeprazole 40mg and Low-Dose Acetylsalicylic Acid (ASA) 325mg With a Free Combination of Esomeprazole Capsule 40mg and Low-Dose ASA. Looking at the title and the given information, can it be called as an add on study design? Thanks and best regards Rahul 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! [Ohlbe] |
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Helmut ★★★ Vienna, Austria, 2010-11-09 15:50 (5709 d 21:31 ago) @ rahul dixit Posting: # 6120 Views: 5,657 |
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Dear Rahul! ❝ I have came across one reported study on Clinical trilas @ GOV about sequential design. ❝ A [...] 2-Stage Group Sequential Design [...] ❝ Looking at the title and the given information, can it be called as an add on study design? The title says everything. Add-on designs (essentially evaluating for BE and adding a second group without alpha-adjustment) were in practice in Canada and Japan, but are currently abandoned because the patients' risk is (uncontrolled) inflated. So stop searching for 'add-ons' - but thanks for finding the nice example of a group sequential design! — 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 |
Ing. Helmut Schütz