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yjlee168 ★★★   Kaohsiung, Taiwan, 2015-12-07 10:18 (3396 d 06:26 ago) (edited on 2015-12-07 11:14) Posting: # 15699 Views: 31,236 |
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Dear all, I have released bear v2.7.0 to sourceforge. One minor change in this release is to check all dataset first to make sure that all subjects' λz (terminal-phase elimination rate constant, or 'ke' or 'kel') can be calculated before going to NCA, based on selected λz calculation method (ARS, AIC, TTT, TTTARS or TTTAIC). This error has been reported by some users (such as here and here). The error messages are something like Error in NAToUnknown.default(x = ke, unknown = 0) : 'x' already has value “0”Basically, ARS or AIC uses the same criteria to check the dataset (OK if > 2 data points after Tmax). TTT and its combination forms use the criteria of "OK if > 2 data points after 2*Tmax". The not-OK subject's data will be listed on R console/terminal. If there is any subject found not meet the criteria of selected λz, bear will be aborted and go back to the top menu. If this is the case, users need to decide to (i) change the λz calculation method (manual selection?); or (ii) consider to delete the entire subject from dataset if necessary. That's it and thank you for reading. Ps. The dataset checking function was built inside the original codes (not on the menu list); so if the dataset is OK, bear continues as usual. [added after OP] — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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ElMaestro ★★★ Denmark, 2015-12-07 11:12 (3396 d 05:32 ago) @ yjlee168 Posting: # 15700 Views: 29,178 |
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Hi yjlee, ❝ I have released bear v2.7.0 (...) Good work. I think Bear is coming close to being a solution for CROs that do not have access to expensive commercial software. In a future version, could you add an option to generate randomisation schemes for the various BE designs?  — Pass or fail! ElMaestro |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-07 11:55 (3396 d 04:49 ago) @ ElMaestro Posting: # 15701 Views: 29,017 |
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Dear Elmaestro, ❝ [...] In a future version, could you add an option to generate randomisation schemes for the various BE designs? Thank you so much. It's a really great idea. I will put this into the top of to-do-list. The other one is considering BE dataset simulation based on the in-vitro dissolution profile and PBPK (IVIVC + PBPK -> IVIVE??). Also there is a TSD waiting for years... — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Helmut ★★★  Vienna, Austria, 2015-12-07 15:01 (3396 d 01:43 ago) @ yjlee168 Posting: # 15703 Views: 29,321 |
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Hi Yung-jin, ❝ ❝ [...] In a future version, could you add an option to generate randomisation schemes for the various BE designs? ❝ ❝ […] It's a really great idea. I will put this into the top of to-do-list. One option is to include Detlew’s package randomizeBE as a dependency when building the package. Then you don’t have to re-invent the wheel and only need to handle the in-/output within bear.❝ The other one is considering BE dataset simulation based on the in-vitro dissolution profile and PBPK (IVIVC + PBPK -> IVIVE??). Wow! ❝ Also there is a TSD waiting for years... According to EMA’s Q&A (Rev.7 of 2013-02-13) the model for the final analysis (pooled data) is: stage, sequence, sequence × stage, subject(sequence × stage), period(stage), formulation.— 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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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-07 19:51 (3395 d 20:53 ago) @ Helmut Posting: # 15705 Views: 28,994 |
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Dear Helmut, ❝ One option is to include Detlew’s package Excellent package! I'll study randomizeBE more to see how to arrange I/O (just install it  ).❝ According to EMA’s Q&A (Rev.7 of 2013-02-13) the model for the final analysis (pooled data) is: ❝ Thank you for your information. Same as this by Detlew. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Astea ★★ Russia, 2015-12-10 17:36 (3392 d 23:08 ago) @ yjlee168 Posting: # 15717 Views: 28,723 |
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Dear yjlee168! Firstly, thank you a lot for your unique program! I've got some questions about calculations. Do I understand correctly that BEAR can calculate only AUCall but not AUClast? What is the formula for AUCinf calculation? I guess it is like AUCinf=AUCall+C/lambda_z, where C is the observed concentration in the last point, so AUCinf is actually AUCinf_obs, based on AUCall, am I right? Why does BEAR crash when there is a zero-concentration in the last point? (I change only one point: last point in concentrations of the first subject in the Single2x2x2 demo-data and BEAR returns: Error in lm.fit(x, y, offset = offset, singular.ok = singular.ok, ...) : NA/NaN/Inf in 'y' It allows calculation only for the manual selection of points. Thats very uncomfortably especially when we want to get primary information on the confidence intervals for AUC and Cmax. There is no need to calculate lambda_z and AUCinf if we just want to calculate AUC and Cmax... — "Being in minority, even a minority of one, did not make you mad" |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-10 18:23 (3392 d 22:21 ago) (edited on 2015-12-10 18:55) @ Astea Posting: # 15718 Views: 28,890 |
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Dear Astea, ❝ I've got some questions about calculations. Do I understand correctly that BEAR can calculate only AUCall but not AUClast? No, bear calculates AUC0-last first, then AUC0-inf which is equal to AUC0-last + Clast/λz (Clast: the last measurable conc., not the last conc.). ❝ What is the formula for AUCinf calculation? I guess it is like AUCinf=AUCall+C/lambda_z, where C is the observed concentration in the last point, so AUCinf is actually AUCinf_obs, based on AUCall, am I right?  Yes, I guess you're correct if your AUCall is AUC0-last here by definition.❝ Why does BEAR crash when there is a zero-concentration in the last point? (I change only one point: last point in concentrations of the first subject in the Single2x2x2 demo-data and BEAR returns: I see. log(conc.) vs. time (x). The error is due to log(0).[edited] You should remove the last point that its conc. value is zero; Alternatively, you can input as 'NA' instead of zero. Usually these are the conc. below the lower quantitative limit. They are not really zero, I think.❝ Error in ❝ lm.fit(x, y, offset = offset, singular.ok = singular.ok, ...) : ❝ NA/NaN/Inf in 'y' ❝ It allows calculation only for the manual selection of points. Not quite correct here. You may not require manual selection for data points if you remove the zero conc. after Tmax or just input as 'NA'. ❝ ...There is no need to calculate lambda_z and AUCinf if we just want to calculate AUC and Cmax... Agree (in some countries or areas). But most of time, we need to calculate AUC0-inf. Thus, the calculation of lambda_z will be required. BTW, if you just need Cmax and AUC, removing the data points with conc.= 0 will not affect the final results. I will consider to remove the data points with conc.=0 after Tmax automatically in next release. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Astea ★★ Russia, 2015-12-10 21:50 (3392 d 18:54 ago) @ yjlee168 Posting: # 15720 Views: 28,785 |
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Dear yjlee168! Thanks a lot for your answer! The problem is in understanding definitions, there are so many AUC (see this thread)... WinNonLin use definitions AUClast for AUC to the last mesuarable concentration and AUCall for all square under the curve. There are also two types of AUC0-inf: predicted and observed. I think, BEAR calculates AUC0-inf=AUClast+Cobs/lambdaz, isn't it? ❝ ❝ It allows calculation only for the manual selection of points. ❝ ❝ Not quite correct here. You may not require manual selection for data points if you remove the zero conc. after Tmax or just input as 'NA'. I've made several calculations and came to the conclusion that when we manually select points in the situation with last zero point we get wrong results on AUCinf. Correct method as you already pointed out was to exclude the last point or to name it NA: There are some my calculations below: initial data: "subj","seq","prd","time","conc" 1,2,2,0,0 1,2,2,0.25,36.1 1,2,2,0.5,125 1,2,2,0.75,567 1,2,2,1,932 1,2,2,1.5,1343 1,2,2,2,1739 1,2,2,3,1604 1,2,2,4,1460 1,2,2,8,797 1,2,2,12,383 1,2,2,24,0 that is demo 2x2x2 data with zero last point. If we try to calculate this set with manual selection of points (3) we get: BEAR: AUC=AUCall=14013.275 AUCinf=AUCinf_obs on AUCall=14013.275 Alternative calculation in another program ("by hand" in excel): points 3: 9 to 11 Cmax 1739 AUClast 11715,275 AUCall 14013,275 AUCinf_pred on AUClast 14054,16 AUCinf_obs on AUClast 14004,99 AUCinf_obs on AUCall 14013,275 But when we exclude the last point or name it "NA" the calculations are correct: exclude point: "subj","seq","prd","time","conc" 1,2,2,0,0 1,2,2,0.25,36.1 1,2,2,0.5,125 1,2,2,0.75,567 1,2,2,1,932 1,2,2,1.5,1343 1,2,2,2,1739 1,2,2,3,1604 1,2,2,4,1460 1,2,2,8,797 1,2,2,12,383 BEAR AUC 11715.275 AUCinf 14004.992 Alternative: AUClast 11715,275 AUCall 11715,275 AUCinf_pred on AUClast 14054,1622 AUCinf_obs on AUClast 14004,9918 Naming the last point "NA": "subj","seq","prd","time","conc" 1,2,2,0,0 1,2,2,0.25,36.1 1,2,2,0.5,125 1,2,2,0.75,567 1,2,2,1,932 1,2,2,1.5,1343 1,2,2,2,1739 1,2,2,3,1604 1,2,2,4,1460 1,2,2,8,797 1,2,2,12,383 1,2,2,24,NA BEAR: AUC=AUClast=AUCall=11715,275 AUCinf=AUCinf_obs on AUClast 14004,9918 Alternative calculation: AUClast 11715,275 AUCall 11715,275 AUCinf_pred on AUClast 14054,1622 AUCinf_obs on AUClast 14004,9918 — "Being in minority, even a minority of one, did not make you mad" |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-11 04:28 (3392 d 12:16 ago) @ Astea Posting: # 15721 Views: 28,822 |
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Dear Astea, ❝ The problem is in understanding definitions, there are so many AUC (see this thread)... Thank you for your pointer. So bear uses Method #4 to calculate AUC0-inf.❝ ... I think, BEAR calculates AUC0-inf=AUClast+Cobs/lambdaz, isn't it? Yes, that's correct. ❝ I've made several calculations and came to the conclusion... In order to verify your results as posted, could you please tell me (1) what AUC calculation method you used with bear ('all linear' or 'linear-up/log-down')? (2) what λz values you got with bear (when input 'NA' for the last data point) and with excel? and (3) what λz calculation did you use with non-manual selection of data points? Thanks again. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Astea ★★ Russia, 2015-12-11 10:39 (3392 d 06:05 ago) @ yjlee168 Posting: # 15723 Views: 28,719 |
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Dear yjlee168! I'm very grateful for your reply! ❝ In order to verify your results as posted, could you please tell me (1) what AUC calculation method you used with bear ('all linear' or 'linear-up/log-down')? (2) what λz values you got with bear (when input 'NA' for the last data point) and with excel? and (3) what λz calculation did you use with non-manual selection of data points? Thanks again. 1). I used linear-up/log-down method (1) 2). When 'NA' is marked for the last point BEAR gets λz in the following form (below I attach all the results for the verification): << NCA Outputs:- <Subj.# 1 > (Ref.)>>And when we leave "0" and choose manual selection (three points): << NCA Outputs:- <Subj.# 1 > (Ref.)>>It seems to me very strange that λz in BEAR are slightly different: 0.16708 and 0.16727. And the question is why the first method (that is calculating with manually selected 3 points) fails. — "Being in minority, even a minority of one, did not make you mad" |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-11 18:16 (3391 d 22:27 ago) @ Astea Posting: # 15724 Views: 28,578 |
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Dear Astea, ❝ 1). I used linear-up/log-down method (1) ❝ 2). When 'NA' is marked for the last point BEAR gets λz in the following form (below I attach all the results for the verification): OK. Thanks. ❝ ... ❝ And when we leave "0" and choose manual selection (three points): ❝ ❝ ❝ ❝ ❝ ❝ ❝ ❝ ❝ The zero-Clast should not be included even using manual selection method, though it will not cause any error in bear. This is because the extrapolated AUC (i.e. AUCt-inf) will become zero (since Clast is zero). I don't think this is a correct approach. Looks like that I have to take care of this error with bear. ❝ ... ❝ It seems to me very strange that λz in BEAR are slightly different: 0.16708 and 0.16727. And the question is why the first method (that is calculating with manually selected 3 points) fails. Oh? any error message? Thanks again. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-15 11:21 (3388 d 05:23 ago) (edited on 2015-12-15 19:48) @ yjlee168 Posting: # 15729 Views: 28,165 |
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Dear all, I have released bear v2.7.1 to sourceforge. The major change was to fix the reported error. The error will occur if there is any zero conc. included when calculating λz (the terminal-phase elimination rate constant). It's because log(0) is equal to -Inf as shown in error message. If switching to manual selection of data points to avoid this error (not to select any zero conc.), it may complete the run without any error. However, it will result with AUC0-t = AUC0-inf and AUCt-inf (extrapolated AUC) = 0 since Clast = 0. Actually, I don't know if we should call it as AUC0-t or AUC0-inf by definition. Although this has been mentioned in bear's website about data input, I decided to fix this error by throwing 'NA' to replace any conc. = 0 occurring at time ≠ 0. This error was also reported elsewhere (1 & 2) at this Forum by other users. Thanks for reading.❝ ❝ Error in ❝ ❝ lm.fit(x, y, offset = offset, singular.ok = singular.ok, ...) : ❝ ❝ NA/NaN/Inf in 'y' — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Astea ★★ Russia, 2015-12-15 20:32 (3387 d 20:12 ago) @ yjlee168 Posting: # 15733 Views: 28,063 |
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Dear yjlee168! Great thanks for your attention to this problem! ❝ I decided to fix this error by throwing 'NA' to replace any conc. = 0 occurring at time ≠ 0 What about zero-samples that are not in the last elimination part of the curve? I mean that theoretically there can be a zero-concentration point between other non-zero values (for example for the drugs with entero-hepatic recirculation)? The result of the calculation would depend on whether this point is marked like "zero" or "NA", wouldn't it? — "Being in minority, even a minority of one, did not make you mad" |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-15 21:17 (3387 d 19:26 ago) @ Astea Posting: # 15734 Views: 28,038 |
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Dear Astea, ❝ What about zero-samples that are not in the last elimination part of the curve? I mean that theoretically there can be a zero-concentration point between other non-zero values (for example for the drugs with entero-hepatic recirculation)? The result of the calculation would depend on whether this point is marked like "zero" or "NA", wouldn't it? Good question. Well, theoretically there should be no real zero conc. at all after taking a medicine for a reasonable sampling time period of a BE/BA study. Of course, there may have some conc. below LLOQ, occurring at any time point. I don't quite understand why we will possibly have real zero conc. for the drug undergoing entero-hepatic recirculation. Are they just below LLOQ? Could you explain more? Thanks.— All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Helmut ★★★ Vienna, Austria, 2015-12-16 02:45 (3387 d 13:59 ago) @ yjlee168 Posting: # 15735 Views: 28,011 |
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Dear Yung-jin, Astea, and all others, ❝ Well, Strong agree. ❝ I don't quite understand why we will possibly have real zero conc. for the drug undergoing entero-hepatic recirculation. Yep, very likely they are. See these threads: #14584, #14925, #10603, #4182. I like Simon’s term “embedded BQLs”. I think that is very difficult for a silicon-based life form to guess which PK may underly such profiles. The easiest way to avoid them is a more sensitive bioanalytical method… I know, I know. Shit happens. Whatever one chooses to do – it should be done consistently across all subjects and treatments. Sorry for no better news. Don’t blame the messenger. — 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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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-16 12:38 (3387 d 04:06 ago) @ Helmut Posting: # 15736 Views: 27,890 |
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Dear Helmut, Thank you for your pointers of previous discussions. From the current practice of a BE/BA study, I still don't know, when we get a BQL for a conc. from analytical report, how to judge it's real zero (as illustrated by weidson's example/plot. subject# 16) or a BQL. My question is: has any analytical lab. had a chance to report real zero measured conc. in the analytical report? ❝ ❝ ... why we will possibly have real zero conc. for the drug undergoing entero-hepatic recirculation. ❝ ❝ Yep, very likely they are. See these threads: #14584, #14925, #10603, #4182. I like Simon’s term “embedded BQLs”... — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Helmut ★★★ Vienna, Austria, 2015-12-16 13:40 (3387 d 03:03 ago) @ yjlee168 Posting: # 15737 Views: 28,044 |
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Hi Yung-jin, ❝ […] From the current practice of a BE/BA study, I still don't know, when we get a BQL for a conc. from analytical report,  Current practice is to give a non-nunmeric value. Sometimes I see zeros in reports, but that’s stupid for any t > 0 (for theoretical reasons – as we discussed above). Furthermore:
❝ how to judge it's real zero (as illustrated by weidson's example/plot. subject# 16) or a BQL. IMHO, the chance that it is “real zero” is ≈0. ❝ My question is: has any analytical lab. had a chance to report real zero measured conc. in the analytical report? They have. If the analysts are no-brainers and follow stupid SOPs, 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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yjlee168 ★★★ Kaohsiung, Taiwan, 2015-12-16 19:22 (3386 d 21:22 ago) @ Helmut Posting: # 15738 Views: 27,884 |
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Dear Helmut, Thank you so much for your great information and explanations. I will try to keep all these in my mind.— All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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Astea ★★ Russia, 2016-01-30 18:11 (3341 d 22:33 ago) @ yjlee168 Posting: # 15901 Views: 26,367 |
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Dear yjlee168! Please check the calculation of AUC_last in the situation when we have two zero (BLLOQ) points in concentration data. It seems to me that there are appeared an error in the latest version of BEAR. May be it is closely connected with the corrections you've made to improve data with BLLOQ in the elimination part of the curve. Let's start with the Single2x2x2_demo: if we will change the second concentration to zero the AUC_0t would be 14451,88, that is greater on 0.25*1/2*125 from the real value: 14436,25. Data set: "subj","seq","prd","time","conc" 1,2,2,0,0 1,2,2,0.25,0 1,2,2,0.5,125 1,2,2,0.75,567 1,2,2,1,932 and so on AUC calculation method: 1 (all linear) Please correct me if I'm wrong... — "Being in minority, even a minority of one, did not make you mad" |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-01-30 20:00 (3341 d 20:44 ago) @ Astea Posting: # 15902 Views: 25,863 |
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Dear Astea, I see your points. You are absolutely right. Apparently bear calculates the first AUC from time zero, not from the second data point at time 0.25 when it has zero conc. since it has been removed. I probably should remove the data point at time zero in this situation and keep the one at time 0.25. Interesting issue. I will think how to fix this later. Thanks a lot. ❝ [...] ❝ Let's start with the Single2x2x2_demo: if we will change the second concentration to zero the AUC_0t would be 14451,88, that is greater on 0.25*1/2*125 from the real value: 14436,25. ❝ [...] — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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mittyri ★★ Russia, 2016-02-01 23:16 (3339 d 17:28 ago) @ yjlee168 Posting: # 15911 Views: 25,558 |
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Dear Yung-jin, What about more tricky datasets? Data set: "subj","seq","prd","time","conc" 1,2,2,0,0 1,2,2,0.25,0 1,2,2,0.5,0 1,2,2,0.75,1 1,2,2,1,0 1,2,2,2,5 1,2,2,3,100 1,2,2,4,200 I think you are close enough to pre-processing of datasets (as in PHX - BQL rules, I can send you PDF guide if needed, there are some examples of rules), so the users can define their own rules of data handling (missing, BLOQ depending on position of data). Good luck! — Kind regards, Mittyri |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-02-02 11:59 (3339 d 04:45 ago) @ mittyri Posting: # 15915 Views: 25,814 |
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Dear mittyri, Yes, I have already taken your example dataset into consideration since last Astea's message. That's why I am still thinking how to fix it once for all. The situation is possible for delayed oral absorption (there is a Tlag), though I still wonder how to make sure if it is due to a delayed absorption or it is a true BLOQ (as we have had a lot of discussions at this Forum). Anyway, the time of first data point with conc. = 0 is critical for AUC calculation. ❝ What about more tricky datasets? ❝ Data set: "subj","seq","prd","time","conc" ❝ 1,2,2,0,0 ❝ 1,2,2,0.25,0 ❝ 1,2,2,0.5,0 ❝ 1,2,2,0.75,1 ❝ [...] ❝ I think you are close enough to pre-processing of datasets (as in PHX - BQL rules, I can send you PDF guide if needed, there are some examples of rules), so the users can define their own rules of data handling (missing, BLOQ depending on position of data). Thank you so much for your kindness. But that won't be necessary. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-02-02 22:30 (3338 d 18:14 ago) (edited on 2016-02-03 08:46) @ mittyri Posting: # 15921 Views: 25,504 |
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Dear Astea and mittyri, I think that I have found the solution for your datasets. This time I keep all user's input data unchanged. It used to assign a 'NA' to any conc.=0 except the first data point (time =0). Calculations for AUC and AUMC are fine for all-linear trapezoidal method. If linear-up/log-down trapezoidal method is applied, the following situations will switch to all-linear: (1) Ci=Ci-1; (2) Ci>Ci-1; and (3) Ci=0 or Ci-1=0 (new) for the trapezoidal calculation between the data point of (ti-1, Ci-1) and (ti, Ci). So for Astea's dataset (all linear),I got And with same Astea's dataset (linear-up/log-down), for mittyri's dataset (all linear), The only thing remained unsolved is how to do a semi-log plot for these zero conc.? It will be skipped if included for the plot. Then we will see a broken line since log(0) cannot be plotted. Any suggestion for this? Thanks in advanced. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-02-03 10:04 (3338 d 06:39 ago) @ mittyri Posting: # 15922 Views: 25,568 |
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Dear mittyri and others, I guess the issue (zero, BLLOQ or missing) may not be solved quickly. Thus I leave the decision to users if it is a real zero conc. (0) or a missing (NA), or a BLLOQ (0 or NA). Basically, the drug plasma conc. should be input as either a zero or a NA in bear. If it is a NA, it will be ignored (or deleted). If it is a zero conc., it will be treated as a number in AUC/AUMC calculation. However, since a zero conc. cannot be used to estimate λz, any zero conc. will not be counted as a valid data point. Like the following example: -> the subj# 1 (Ref.) in sequence# 2, period# 2,❝ I think you are close enough to pre-processing of datasets (as in PHX - BQL rules, I can send you PDF guide if needed, there are some examples of rules), so the users can define their own rules of data handling (missing, BLOQ depending on position of data). — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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mahmoud-teaima ★ 2016-02-08 22:28 (3332 d 18:16 ago) (edited on 2016-02-09 00:48) @ yjlee168 Posting: # 15959 Views: 25,261 |
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Dear yjlee168, i got almost the same error message with bear_2.7.5 on R3.2.3 for mac. --- the list of problematic subject data --- -------------------------------------------- -> the subj# 18 (Test) in sequence# 1, period# 2, λz (kel) cannot be calculated with ARS or AIC.. subj seq prd drug time conc-> the subj# 19 (Test) in sequence# 1, period# 2, λz (kel) cannot be calculated with ARS or AIC.. subj seq prd drug time concis there any solution for it yet? is there any option to work with these cases (2 subjects with error message) to calculate the parameter by manual selection of 2-6 point after Cmax? Greetings. Edit: formatted using BBCodes. Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe] — Mahmoud Teaima, PhD. |
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Ohlbe ★★★ France, 2016-02-09 01:51 (3332 d 14:53 ago) @ mahmoud-teaima Posting: # 15960 Views: 25,161 |
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Dear mahmoud-teaima, When replying to a message, please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post. We had to edit most of your posts today. — Regards Ohlbe |
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mahmoud-teaima ★ 2016-02-09 05:55 (3332 d 10:49 ago) @ Ohlbe Posting: # 15961 Views: 25,094 |
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Thanks for editing my posts. I wish anyone have a solution for the problem and error in my previous post?. Many thanks in advance. — Mahmoud Teaima, PhD. |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-02-09 07:40 (3332 d 09:04 ago) (edited on 2016-02-09 10:38) @ mahmoud-teaima Posting: # 15962 Views: 25,168 |
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Dear mahmoud-teaima, Can you please check your dataset file (*.csv) carefully once again, especially for these two subjects? Focus on if there are the extra spaces or positions of numbers, etc.. BTW, what csv format do you use? It looks unlikely having such errors. Yes, you can try manual selection for data points. Go to *Edit setup files to change the selection for λz estimations. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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mahmoud-teaima ★ 2016-02-09 16:00 (3332 d 00:44 ago) @ yjlee168 Posting: # 15963 Views: 25,174 |
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Dear YJLee, thanks for your instructions. i create the .csv file of my data using macoffice 2011, i did it more than a time. when i used the ARS method for calculation of Kel, the same error method for subjects 18 and 19 pop up and when i tried to change to the manual selection for calculation of Kel, i got the following error message. " Point Selection for Lambda_z Estimation ------------------------------------------------------------------------------- This method is about to select data points for lambda_z estimation based on the manual selection from each subject's log(conc.) vs. time plot. 1. MS-Windows OS: Please use your mouse to click the data point on the graph to select the data points for linear regression. Once you want to stop selection for each plot, click the 'Stop' menu on the left corner of th plot and click 'Stop locator.' Alternately, you can use click mouse right- button to bring up hidden menu and click 'Stop' to stop selection. 2. Linux/Unix (Ubuntu) PC OS: Use your mouse left (1st)-button to select and mouse right (2nd)-button to stop selection. 3. Mac OS X: Use your mouse button to select and hold down the Control key and click (Control-click) to stop selection. When finishing the current subject and the next subject's plot will show up. Do the same procedures until finishing all subjects. Note: The # of data points should be at least 2's and max. is 6. Please do NOT choose any data point before Tmax. ............................................................................... Press Enter to proceed... **************************************************************************** Data for the Ref. Products: ---------------------------------------------------------------------------- AUC(0-t), AUC(0-inf), AUMC(0-t), AUMC(0-inf), λz, Cl/F, Vd, MRT, and half-life (T1/2(z)) **************************************************************************** Error in if ("y" %in% log && any(ii <- y <= 0 & !is.na(y))) { : missing value where TRUE/FALSE needed Please advise me. Greetings — Mahmoud Teaima, PhD. |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-02-09 16:38 (3332 d 00:05 ago) @ mahmoud-teaima Posting: # 15964 Views: 25,012 |
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Dear mahmoud-teaima, Interesting. Could you e-mail me (yjlee168 at gmail.com) your dataset as .csv file format? I can take a look on it. Sorry about this. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
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yjlee168 ★★★ Kaohsiung, Taiwan, 2016-02-09 20:14 (3331 d 20:30 ago) @ mahmoud-teaima Posting: # 15965 Views: 25,181 |
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Dear mahmoud-teaima & useR, After checking the dataset, there are two errors found: ... However, bear/R still run without any warning message. Then some weird things happened. R totally misinterpreted the input data for all subjects. For example, subj seq prd drug time concIf I replaced the underline with 'NA' for subject #5, then everything was back to normal. subj seq prd drug time concVery interesting dataset.  — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
Ing. Helmut Schütz