Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-23 22:11 (3839 d 07:25 ago) Posting: # 13781 Views: 13,288 |
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Only for specialists! Can you guess what these plots might represent? If yes, can you name the guideline(s) leading to them? ![]() ![]() — 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 |
nobody nothing 2014-10-23 22:37 (3839 d 06:59 ago) @ Helmut Posting: # 13782 Views: 11,580 |
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Not a specialist, but: two-stage design, alpha max inflation, depending on sample size in stage 1 and 2? — Kindest regards, nobody |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-23 22:58 (3839 d 06:38 ago) @ nobody Posting: # 13783 Views: 11,619 |
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Ὀδυσσεύς ❝ Not a specialist, but: two-stage design, alpha max inflation, depending on sample size in stage 1 and 2? Nice try. ![]() \(\small{\alpha=0.05,\;k=2}\) — 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 |
ElMaestro ★★★ Denmark, 2014-10-24 00:47 (3839 d 04:49 ago) @ Helmut Posting: # 13784 Views: 11,543 |
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Hi Hötzi, A wild guess: I think you are fiddling around with WHO Technical Report Series, No. 937, annex 7 (Multisource BlahDeeBlah), specifically you might be looking at section 6.3.2: "If the bioequivalence study was performed with the appropriate number of subjects but bioequivalence cannot be demonstrated because of a larger than expected random variation or a relative difference, an add-on subject study can be performed using not less than half the number of subjects in the initial study, provided this eventuality was anticipated and provided for in the study protocol." as well as 6.11.3: "the total sample size of the initial bioequivalence study is not less than 20 (n = 10/group) or pooled sample size of the initial and add-on subject studies is not less than 30;" -which lend from the PMDA guidelines section 2.5. In a nutshell you are trying to figure out how the overall alpha behaves for various scenarios, incl. adjusted alphas, anticipated to comply with the Japanese add-on recommendations. — Pass or fail! ElMaestro |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-24 01:08 (3839 d 04:28 ago) @ ElMaestro Posting: # 13785 Views: 11,530 |
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Ahoy! ❝ A wild guess: […] Bingo! ❝ In a nutshell you are trying to figure out how the overall alpha behaves for various scenarios, incl. adjusted alphas, anticipated to comply with the Japanese add-on recommendations. That is not correct. No adjustment in 日本. Tried to convince them. No success. So you got 50/100 points. What about the lower panel? — 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 |
ElMaestro ★★★ Denmark, 2014-10-24 01:19 (3839 d 04:17 ago) @ Helmut Posting: # 13786 Views: 11,654 |
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Oh... ❝ That is not correct. No adjustment in 日本. Tried to convince them. No success. ❝ ❝ So you got 50/100 points. What about the lower panel? Oh...lemmefink.... so you did not adjust alpha but did just use 0.05 and 0.025...Upper versus lower panels show that if you pick a common alpha for both the main and the add-on then the applicable alpha will fall between 0.05 and 0.025 if convergence towards 0.05 is a goal. Paste some curves to show us how Pocock's alpha of ~0.0294 or somethink like that will give curves that converge towards 0.05 overall, please? — Pass or fail! ElMaestro |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-24 01:27 (3839 d 04:09 ago) @ ElMaestro Posting: # 13787 Views: 11,544 |
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O-hoy! ❝ so you did not adjust alpha but did just use 0.05 and 0.025... ![]() ❝ Upper versus lower panels show that if you pick a common alpha for both the main and the add-on ![]() ❝ then the applicable alpha will fall between 0.05 and 0.025 if convergence towards 0.05 is a goal. ![]() Read the second sentence of my OP again. ❝ Paste some curves to show us how Pocock's alpha of ~0.0294 or somethink like that will give curves that converge towards 0.05 overall, please? ![]() — 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 |
ElMaestro ★★★ Denmark, 2014-10-24 01:37 (3839 d 03:59 ago) @ Helmut Posting: # 13789 Views: 11,427 |
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Hmmm, ❝ ❝ then the applicable alpha will fall between 0.05 and 0.025 if convergence towards 0.05 is a goal. ❝ I still believe that conclusion would be valid if the purpose were to identify the common alpha level that would preserve convergence at overall alpha 0.05, even though your perspective happens to be another (assuming your curves are correct, of course). What second sentence - are we missing some guideline stuff? — Pass or fail! ElMaestro |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-24 02:20 (3839 d 03:17 ago) @ ElMaestro Posting: # 13791 Views: 11,509 |
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Hoho-hoy! ❝ ❝ ❝ then the applicable alpha will fall between 0.05 and 0.025 if convergence towards 0.05 is a goal. ❝ ❝ ❝ ❝ I still believe that conclusion would be valid if the purpose were to identify the common alpha level that would preserve convergence at overall alpha 0.05,… Yep. But this is an answer to a question I didn’t ask. ❝ … even though your perspective happens to be another (assuming your curves are correct, of course). Well, the second one would lead to Bonferroni’s correction, which is related to… ❝ … are we missing some guideline stuff? Now you got it. The first GL (upper panel) screws up whereas the second one (lower panel) doesn’t. — 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 |
d_labes ★★★ Berlin, Germany, 2014-10-24 15:13 (3838 d 14:24 ago) @ Helmut Posting: # 13797 Views: 11,378 |
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Dear Helmut, ❝ ... The first GL (upper panel) screws up whereas the second one (lower panel) doesn’t. Let me try: Second one: Canada. — Regards, Detlew |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-24 15:19 (3838 d 14:18 ago) @ d_labes Posting: # 13798 Views: 11,530 |
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Dear Detlew, ❝ Let me try: ❝ Second one: Canada. 99 p(o)ints! It was stated in the 2009 draft, but they dropped it in the current (2012) guidance. — 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 |
ElMaestro ★★★ Denmark, 2014-10-24 16:19 (3838 d 13:18 ago) @ Helmut Posting: # 13799 Views: 11,544 |
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Hi all, to round this off, can it be mathematically proven that upper type 1 error asymptotes exist for any level of common alpha smaller than 1? I bet that should be possible, too. I'd love to see how. I imagine that to deliver the proof one would have to one way or another get aorund to Owen's Q and non-central t. So I am very certain that would improve yours truly's understanding of statistics for BE. — Pass or fail! ElMaestro |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-24 16:54 (3838 d 12:42 ago) @ ElMaestro Posting: # 13801 Views: 11,481 |
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Hi ElMaestro, ❝ to round this off, can it be mathematically proven that upper type 1 error asymptotes exist Yes. At least this is what my stats friends told me. Note that Bonferroni is the most conservative method in adjusting for multiplicity.* IMHO, you could gain a little solving the quadratic equation \(\small{1-(1-x)^2=\alpha}\), which leads for α 0.05 to \(\small{(2-\sqrt{4-4\alpha})/2=0.02532057\ldots}\) Others (f.i. Holm, Hochberg) are less conservative but may lead to a CI which doesn’t include the PE any more. Counterintuitive, but my stats friends just smile about it. See also EMA’s 2012 workshop on multiplicity. If you – really! – have nothing better to do, watch the six (‼) hours of video. ❝ for any level of common alpha smaller than 1? Smaller than one? ❝ I bet that should be possible, too. I'd love to see how. I imagine that to deliver the proof one would have to one way or another get aorund to Owen's Q and non-central t. So I am very certain that would improve yours truly's understanding of statistics for BE. Yep. People are working on it (for three years now)…
— 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 |
nobody nothing 2014-10-24 16:25 (3838 d 13:11 ago) @ Helmut Posting: # 13800 Views: 11,445 |
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Bonferroni in a Guidance! Wow! Didn't know that! — Kindest regards, nobody |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2014-10-24 17:01 (3838 d 12:35 ago) @ nobody Posting: # 13802 Views: 11,381 |
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— 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 |