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sukimmm ● 2008-10-20 04:53 (6453 d 02:59 ago) Posting: # 2561 Views: 6,135 |
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Sorry if this is a basic question. I have to calculate a sample size for a parallel design with 1 test product and 3 references. We would like to know if the Test is Bioequivalent to the reference 1, then to the reference 2 and then to the reference 3 (not simulateneously of course !). Q1. Should I adjust for the multiplicity of tests error (i.e. as a Bonferroni adjustment to the alpha = alpha/number of planned comparisons) ? Q2. Should I use the sample size calculations as in a 0ne-test one-treatment parallel design (as in Julious's Tutorial pp. 1969-70-71, Stat in Medicine) ? Q3. Or maybe I should work on a alpha=0.05 with an allocation ratio (r in the equation) of 1/4 ? Your advices will be more than welcome. Thanks in advance Sukimmm |
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Helmut ★★★   Vienna, Austria, 2008-10-20 13:42 (6452 d 18:10 ago) @ sukimmm Posting: # 2564 Views: 5,407 |
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Dear Sukimmm! ❝ I have to calculate a sample size for a parallel design with 1 test product and 3 references. ❝ We would like to know if the Test is Bioequivalent to the reference 1, then to the reference 2 and then to the reference 3 (not simulateneously of course !). This sounds a little bit strange to me. I guess you will try to shoot three birds with a single bullet. Probably you want to run a BE study for a long half life drug to be submitted in different countries, each of them calling for their own reference. I would not recommend it, beacuse it's not possible to split the report accordingly. What if one of the T/R comparisons fails? ❝ Q1. Should I adjust for the multiplicity of tests error (i.e. as a Bonferroni adjustment to the alpha = alpha/number of planned comparisons)? Tricky. If you plan to submit the package to different countries with their respective references, I wouldn't see the reason for a correction (the patient's risk of one population is independent from the others). ❝ Q2. Should I use the sample size calculations as in a 0ne-test one-treatment parallel design (as in Julious's Tutorial pp. 1969-70-71, Stat in Medicine) ? Yes. Just for other readers: Julious SA. TUTORIAL IN BIOSTATISTICS. Sample sizes for clinical trials with Normal data. ❝ Q3. Or maybe I should work on a alpha=0.05 with an allocation ratio (r in the equation) of 1/4 ? No. The allocation ratio r is the ratio of sample sizes within arms (nR/nT). For equal sample sizes nR=nT r=1. — 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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sukimmm ● 2008-10-20 21:44 (6452 d 10:08 ago) @ Helmut Posting: # 2566 Views: 5,159 |
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Thanks for the reply. You are right, I am not sure about the scientific value of this design. It was asked by one of my clients. This study will be submitted at once with all the references. That's why I asked for the alpha correction. Thanks for your suggestions. I will ask the client if this is really what he want and let you know the results. Sukimmm -- Edit: Full quote removed. Please see this post! [Jaime] |
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Helmut ★★★ Vienna, Austria, 2008-10-20 22:10 (6452 d 09:42 ago) @ sukimmm Posting: # 2567 Views: 5,060 |
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Dear Sukimmm! ❝ This study will be submitted at once with all the references. That's why I asked for the alpha correction. What do you mean by ‘submitted at once with all the references’? Generally there’s one reference / country (e.g., the RLD in the USA). In the EU even for a national market authorization you may use a reference (only one!) from any EU member state. Extreme example: You apply in Germany, France, Spain and use a reference from the UK – that’s fine; no need to go for three (national) references. — 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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sukimmm ● 2008-10-20 23:11 (6452 d 08:40 ago) @ Helmut Posting: # 2568 Views: 4,953 |
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I know this sounds strange. I will re-verify with the sponsor. I cannot say much on this design except that teh reference is Xmg once a day, Xmg twice a day, etc. I really don't understand where the client wants to go with this design. As I said, I will speak to client again. Sukimmm |
Ing. Helmut Schütz