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shankar ★ India, 2008-11-24 08:10 (6014 d 02:55 ago) Posting: # 2778 Views: 10,813 |
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Hi Everyone, One of our client want to conduct the bioavailability of particular drug with same volunteer in two different studies. I think we may get pharmacokinetic pattern of two different formulations in same volunteers. I am not sure whether it's right or wrong. What else we can achieve this type of studies. I am expecting your valuable comment on the same. Regards, — Shankaranarayanan |
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Helmut ★★★   Vienna, Austria, 2008-11-24 15:32 (6013 d 19:32 ago) @ shankar Posting: # 2789 Views: 9,610 |
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Dear Shankar! ❝ One of our client want to conduct the bioavailability of particular drug ❝ with same volunteer in two different studies. Yes, this happens from time to time. ❝ I think we may get pharmacokinetic pattern of two different formulations ❝ in same volunteers. I am not sure whether it's right or wrong. Sure. If you want to compare between studies and the same subjects were attending, you may use a paired comparison (only fixed effects: subject+study+subject(study)). ❝ What else we can achieve this type of studies. A lower variability than if different subjects would have been used (parallel design). In other words, if you calculate BA between studies your confidence intervals will be tighter - and your point estimates more reliable. — 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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BE ☆ 2008-11-25 07:01 (6013 d 04:04 ago) @ Helmut Posting: # 2791 Views: 9,515 |
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Dear HS, I agree with you that this concept has its own advantages. But is it accepted by the regulatory, especially the stats. Best Regards, BE |
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d_labes ★★★ Berlin, Germany, 2008-11-25 11:06 (6012 d 23:58 ago) @ BE Posting: # 2795 Views: 9,522 |
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Dear BE, ❝ [...] But is it accepted by the regulatory, especially the stats. With the new EMEA Draft the answer is no. See this thread. — Regards, Detlew |
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shankar ★ India, 2008-11-25 07:50 (6013 d 03:15 ago) @ Helmut Posting: # 2792 Views: 9,548 |
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Dear HS, Thanks for your valuable comment. Here the issue is already we conducted one bioavailability study, which was held on 1 year back. Now they want to repeat the study with same volunteers. What I feel that after a year the anthropometric parameters of volunteers may changed. This may cause chances of variance. And one more issue here, difficult to get the same volunteers for the study. Thanks with Regards, — Shankaranarayanan |
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d_labes ★★★ Berlin, Germany, 2008-11-25 10:56 (6013 d 00:08 ago) @ shankar Posting: # 2794 Views: 9,516 |
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Dear Shankar, Could you give us some more detail? -Why do you (they) want to repeat the study. First failed? -Same products in both studies? Or reformulated? -Why the need for exactly the same volunteers? -Design of previous and repeated study? Cross-over, parallel? Then our answer could be more specific. — Regards, Detlew |
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shankar ★ India, 2008-11-25 12:12 (6012 d 22:53 ago) @ d_labes Posting: # 2796 Views: 9,474 |
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Hi DLabes, It was crossover design and the study failed. Now they want to repeat the study with same formulation and same study design. The reason for same volunteers may be to find out the variance between the studies. I hope I answered your all queries. Regards, — Shankaranarayanan |
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d_labes ★★★ Berlin, Germany, 2008-11-25 12:52 (6012 d 22:12 ago) @ shankar Posting: # 2797 Views: 9,493 |
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Dear Shankar, Sounds a little bit strange to me to repeat a failed study without any modifications. IMHO it's dicing with the devil  (<-this one).Of course its possible that the new study will result in success, because power (usually 80%) allows for failing to state bioequivalence only by chance. But that depends on the grade of failing. I would opt for using at least some more subjects in the new study to increase power. If the new study is done, you have two options in my opinion: 1. Pool the studies as Helmut has suggested. But check for regulatory acceptance. In Europe according to the new EMEA Draft it will not accepted. Here they want to see both results (not pooled). See this thread. Pooling does not necessary imply to recruit the same subjects. 2. If you have actually the same subjects, you could opt for a evaluation as a replicate design. But the wash-out phase between periods 2/3 of one year in comparison to the ordinary wash-out in each study questioned that approach. Regulatory acceptance? I couldn't guess  .— Regards, Detlew |
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Helmut ★★★ Vienna, Austria, 2008-11-25 13:25 (6012 d 21:40 ago) @ d_labes Posting: # 2800 Views: 9,566 |
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Dear Dlabes, I agree to all your points, but without the information given later on in this thread I did not suggest to ❝ 1. Pool the studies... I assumed that the sponsor made some modifications of the formulation and wants to make a comparison between studies - which is more powerful in a paired design (same subjects) than in a parallel design (different subjects). Sometimes we've performed a new cross-over BE study and (exploratorily) made a comparision with the 'old' formulation between studies in order to support the chosen modification. — 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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d_labes ★★★ Berlin, Germany, 2008-11-25 14:14 (6012 d 20:50 ago) @ Helmut Posting: # 2803 Views: 9,576 |
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Dear Helmut, now I got the real idea behind your suggestion. But may it be you don't like the word pool? I like it best as pool billiards  .Nevertheless it's some sort of with respect to variability estimation. — Regards, Detlew |
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Helmut ★★★ Vienna, Austria, 2008-11-25 14:20 (6012 d 20:44 ago) @ d_labes Posting: # 2804 Views: 9,695 |
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Dear DLabes, ❝ But may it be you don't like the word pool? ❝ I like it best as pool billiards Hhm, I'm heavily biased towards Carom billiards (actually I've got a table at home)... ❝ Nevertheless it's some sort of with respect to variability estimation. Yes. — 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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d_labes ★★★ Berlin, Germany, 2008-11-25 14:28 (6012 d 20:37 ago) @ Helmut Posting: # 2805 Views: 9,372 |
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Dear Helmut! ❝ (actually I've got a table at home)... Congratulation! This is one of my dreams. But my home is to small. — Regards, Detlew |
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Ohlbe ★★★ France, 2008-11-25 12:54 (6012 d 22:10 ago) @ shankar Posting: # 2798 Views: 9,456 |
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Dear Shankar, Could one of the subjects in the initial study be considered as an "outlier", and is this why the study failed ? If this is the case, was the subject an "outlier" for the test product, the reference product, or both ? Regards Ohlbe |
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shankar ★ India, 2008-11-25 13:24 (6012 d 21:41 ago) @ Ohlbe Posting: # 2799 Views: 9,459 |
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Dear Ohlbe, They are not informed us that which authority they are going to submit. The aim of this study is to compare the Pharmacokinetic behaviour (Bioavailability) of drug in same volunteers in two different studies. Regards, — Shankaranarayanan |
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Helmut ★★★ Vienna, Austria, 2008-11-25 13:29 (6012 d 21:36 ago) @ shankar Posting: # 2801 Views: 9,567 |
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Dear Shankar! ❝ They are not informed us that which authority they are going to submit. That's bad business conduct. Since guidelines vary between countries you are left out in the rain. ❝ The aim of this study is to compare the Pharmacokinetic behaviour ❝ (Bioavailability) of drug in same volunteers in two different studies. IMHO that's not a valid rationale for a study according to ICH E6 and E9... — 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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shankar ★ India, 2008-11-25 13:45 (6012 d 21:20 ago) @ Helmut Posting: # 2802 Views: 9,475 |
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Dear HS, Ya of course its true guidelines vary from country. I will check the same and get back to you very soon. Thanks, — Shankaranarayanan |
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shankar ★ India, 2008-11-29 08:06 (6009 d 02:59 ago) @ shankar Posting: # 2832 Views: 9,374 |
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Hi Everyone & HS, This study is for non regulatory submission. Kindly share your valuable comments on the same issue. Thanks, — Shankaranarayanan |
Ing. Helmut Schütz