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ViPraj ☆ India, 2017-07-27 09:05 (2844 d 16:36 ago) Posting: # 17618 Views: 9,053 |
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Dear Is there any difference between within-subject variance and within-subject variability ? If yes, how to calculate one from another ? Edit: Category changed; see also this post #1. [Helmut] — Regards VP |
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Helmut ★★★   Vienna, Austria, 2017-07-27 20:08 (2844 d 05:33 ago) @ ViPraj Posting: # 17619 Views: 7,859 |
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Hi VP, ❝ Is there any difference between within-subject variance and within-subject variability ? Variability is a term statisticians use when desperately trying to communicate with members of the real world (physicians, patients, the boss).  In statistics two parameters describe a distribution. One gives the location (mean, median, …) and the other dispersion (variance or standard deviation, interquartile range, …). You have to figure out yourself from the context what is meant. In BE (log-transformed data) most common: \(CV = \sqrt{e^{s^2}-1}\). — 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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ViPraj ☆ India, 2017-08-01 08:31 (2839 d 17:10 ago) @ Helmut Posting: # 17639 Views: 7,661 |
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Dear Helmut Thanks for your response. Actually while reading the USFDA reference scaled BE guidance of Progesterone and Warfarin this question came in my mind.I was thinking that S2w (S square w) is within subject variance and Sw is within subject variability (assumption was based on the formula mentioned for variance and standard deviation in various literature) . Pl. confirm if it is true or false. Also i was interested in knowing how we can calculate S2w (S square w) from available Sw value. — Regards VP |
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Shuanghe ★★ Spain, 2017-08-01 12:07 (2839 d 13:34 ago) @ ViPraj Posting: # 17640 Views: 7,647 |
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Hi Vipraj, ❝ I was thinking that S2w (S square w) is within subject variance and Sw is within subject variability (assumption was based on the formula mentioned for variance and standard deviation in various literature) . Pl. confirm if it is true or false. Yes. In fact, the step 1 of method description before the SAS code in FDA's guidance already clearly mentioned it as "Determine SWR, the within-subject standard deviation (SD) of the reference product, for the pharmacokinetic (PK) parameters AUC and Cmax. ..." ❝ Also i was interested in knowing how we can calculate S2w (S square w) from available Sw value. Now I'm lost. You mean other way than just square it? Back to your original question ❝ Is there any difference between within-subject variance and within-subject variability ? Like Helmut said, depending on the context. Sometimes they mean the same thing, sometimes they don't. In the "additional comments" of the same FDA guidance, they tell us in order to apply the scaled method the criterion is "within-subject variability ≥ 30%)", so clearly here the variability is not equal to variance since you need to do sqrt(exp(s2w) - 1) to get it.  — All the best, Shuanghe |
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Helmut ★★★ Vienna, Austria, 2017-08-01 18:55 (2839 d 06:46 ago) @ Shuanghe Posting: # 17643 Views: 8,510 |
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Hi Shuanghe, ❝ In the "additional comments" of the same FDA guidance, they tell us in order to apply the scaled method the criterion is "within-subject variability ≥ 30%)", so clearly here the variability is not equal to variance since you need to do Yep, sloppy as usual. […] please provide evidence of high variability […] (i.e., within-subject variability ≥ 30%). \(\sqrt{\log(0.294^2) + 1} = 0.2935604 \ldots {\color{Red} \neq} 0.294\) \(100\sqrt{e^{0.294^2}-1} = 30.04689\ldots\% {\color{Red} \neq} 30\%\) Who cares about the fourth significant digit… Regulators love simple numbers. What does the EMA tell us? The switching variability is clearly defined as CVwR 30% (based on the paper of the two Lászlós). That would translate into a regulatory σ0 of 0.29356… and a switching condition \(\theta_s = \log(1.25)/\sigma_0 \equiv -\log(0.80)/\sigma_0 = 0.760128 \ldots\) Well, what do we have to use? 0.760. IIRC, Panos Macheras complained about it in one his papers about reference-scaling. Picky: In code assessing ABEL (SAS, Phoenix/WinNonlin) only the 90% CI should be rounded to two digits, not the expanded limits themselves. Otherwise a discontinuity will appear close to CVwR 50%:
— 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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Ing. Helmut Schütz