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Elena777 ☆ Belarus, 2018-01-20 12:13 (2277 d 20:51 ago) (edited by Elena777 on 2018-01-21 08:46) Posting: # 18229 Views: 4,212 |
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Dear participants of forum, I am relatively new to R and RStudio. And I really need your advise to clear some questions up which are important for my self-education and professional skills. 1. A BE study of Sotalol HCl 160 mg tablets (Mylan) and Betapace 160 mg tablets (Berlex Laboratories) with standard 2x2 cross-over design was described in one of the applications on FDA (application number 75-725). They planned to enroll 24 subjects. But in fact that study was conducted with 23 subjects. I would like to calculate CV from CI using data of that study. What data should I write for arguments "n" and "design"? If I input such data: CVfromCI(pe = 0.99, lower = 0.87, upper = 1.13, n = 23, design = "2x2", alpha = 0.05, robust=FALSE)RStudio gives me a result but with the following note: CVfromCI(pe = 0.99, lower = 0.87, upper = 1.13, n = 23, design = "2x2", alpha = 0.05, robust=FALSE)Can I use this result for futher calculations of CVpooled by means of using PowerTOST or should I correct my data? 2. While calculating CV from CI with data from another study I`ve got the following result: CVfromCI(pe = 0.96, lower = 0.9075, upper = 1.0089, n = 24, design = "2x2", alpha = 0.05, robust=FALSE)My input is correct because numbers are taken from that application not from my head. Should I pay attention to this warning message and can I use this result for futher calculations of CVpooled by PowerTOST? 3. While calculating CV from CI is it prefered to use CI for log-transformed parameters (for example LCmax) or for non-transformed parameters(Cmax)? Big thanks in advance.  |
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Helmut ★★★   Vienna, Austria, 2018-01-21 18:56 (2276 d 14:08 ago) @ Elena777 Posting: # 18241 Views: 3,379 |
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Dear Elena, ❝ 1. A BE study […] planned to enroll 24 subjects. But in fact that study was conducted with 23 subjects. […] If I input such data: ❝ ❝ ❝ ❝ RStudio gives me a result but with the following note: ❝ ❝ ❝ Unbalanced 2x2 design. n(i)= 12/11 assumed. ❝ [1] 0.2617363 ❝ ❝ Can I use this result for futher calculations of CVpooled by means of using PowerTOST or should I correct my data? The function does not “know” how many subjects in each of the sequences were dosed. The function tries to keep a 2×2 study with an odd number of subjects as balanced as possible (here 12 subjects in one sequence and 11 in the other) and throws this message. CVfromCI(pe=0.99, lower=0.87, upper=1.13, n=23, design="2x2")If you know the subjects per sequence and specify them in the argument n, you get the same result but without a message.CVfromCI(pe=0.99, lower=0.87, upper=1.13, n=c(12, 11), design="2x2")But the study might have been even more unbalanced. Let’s try 14 subjects in one sequence and 9 in the other: CVfromCI(pe=0.99, lower=0.87, upper=1.13, n=c(14, 9), design="2x2")Given that if you don’t know the subjects / sequence the code’s attempt to keep the sequences as balanced as possible gives you the highest (i.e., most conservative) estimate. For the background see this presentation (slides 25–29). ❝ 2. While calculating CV from CI with data from another study I`ve got the following result: ❝ ❝ ❝ [1] 0.1071475 ❝ Warning message: ❝ sigma based on pe & lower CL more than 10% different than sigma based on pe & upper CL. Check input. ❝ ❝ My input is correct because numbers are taken from that application not from my head. Please check it again. The PE is given by \(\sqrt{lower \times upper}\). In your case that’s \(\sqrt{0.9075 \times 1.0089} = 0.9568577\). The function checks the input for plausibility. Hence, the message is correct since your 0.96 is different to 0.9568577. ❝ Should I pay attention to this warning message Yes. Check the PE. ❝ and can I use this result for futher calculations of CVpooled by PowerTOST? I would (after checking the data for correctness) suggest the ones with the highest numeric precision. ❝ 3. While calculating CV from CI is it prefered to use CI for log-transformed parameters (for example LCmax) or for non-transformed parameters(Cmax)? The former. According to all guidelines the analysis for Cmax (and AUC as well) is done on log-transformed data. — 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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Elena777 ☆ Belarus, 2018-01-27 11:02 (2270 d 22:02 ago) @ Helmut Posting: # 18295 Views: 3,198 |
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Dear Helmut, thanks, I really appreciate it. |
Ing. Helmut Schütz