weiguo2122 ☆ 20230419 16:43 (400 d 14:09 ago) (edited by on 20230419 17:13) Posting: # 23527 Views: 2,021 

Hi, Please help on the issue. when I compared the ABE (Proc Mixed) output between SAS (FDA Draft Guidance on Progesterone, SAS code) and WinNonlin, they are not matched. For the given dataset (see code and dataset below) SAS ratio/ unscabe_lower/ unscabe_upper 135.096 / 115.546 / 157.954 WinNolin BE tool: Ratio_%Ref_/ CI_90_Lower/ CI_90_Upper Ln(Cmax)/ 74.0214/ 63.3096 /86.54555 Phoenix FDA RSABE Full Replicate template v1.4: Dependent/ Ratio_%Ref_/ CI_90_Lower/ CI_90_Upper/ Data/ 74.021385/ 63.3096/ 86.54555/ However, if I change “TRT 1 1” to “TRT 1 1” in “ESTIMATE 'T vs. R' TRT 1 1 /CL ALPHA=0.1 in below SAS code ” I got them matched. ratio/ unscabe_lower/ unscabe_upper 74.021385/ 63.3096/ 86.54555 I am wondering. 1. If anyone have same issue? 2. if we should change ESTIMATE 'T vs. R' to “TRT 1 1” since discussion in this Forum and FDA SAS code indicate we should use “TRT 1 1” not “TRT 1 1” 3. If not how to deal this issue to make it consistent for results from two side? Thanks David data Pk; input subj per seq$ trt$ Cmax; datalines; 1 1 RRT R 8592.1516 1 2 RRT R 9991.7692 1 3 RRT T 7877.606 2 1 TRR T 18119.532 2 2 TRR R 13082.5504 2 3 TRR R 20443.9168 3 1 RTR R 9964.4028 3 2 RTR T 7849.2956 3 3 RTR R 9930.2392 4 1 RRT R 11545.9044 4 2 RRT R 9931.7044 4 3 RRT T 4738.6024 5 1 RTR R 24863.772 5 2 RTR T 18131.4312 5 3 RTR R 18598.8372 6 1 RTR R 18767.834 6 2 RTR T 9631.2328 6 3 RTR R 13983.2816 7 1 TRR T 12357.3376 7 2 TRR R 12691.0256 7 3 TRR R 18033.464 8 1 RRT R 12490.2528 8 2 RRT R 29039.6884 8 3 RRT T 7453.3548 9 1 TRR T 13225.8472 9 2 TRR R 16836.392 9 3 TRR R 18455.9432 10 1 TRR T 7004.77 10 2 TRR R 16164.5532 10 3 TRR R 14568.2016 11 1 TRR T 24770.8476 11 2 TRR R 18791.1712 11 3 TRR R 20901.2328 12 1 RTR R 13570.0112 12 2 RTR T 13299.33 12 3 RTR R 14449.334 13 1 RRT R 16827.2456 13 2 RRT R 18581.1544 13 3 RRT T 13971.156 14 1 RRT R 10933.23 14 2 RRT R 15124.9448 14 3 RRT T 7768.3136 15 1 RTR R 10889.7196 15 2 RTR T 6809.4608 15 3 RTR R 10329.3052 16 1 RRT R 16119.3252 16 2 RRT R 20508.9744 16 3 RRT T 21888.374 ; run; data pk; set pk; lauct=log(Cmax) ; run; PROC MIXED data=pk; CLASS SEQ SUBJ PER TRT; MODEL LAUCT = SEQ PER TRT/ DDFM=SATTERTH; RANDOM TRT/TYPE=FA0(2) SUB=SUBJ G; REPEATED/GRP=TRT SUB=SUBJ; ESTIMATE 'T vs. R' TRT 1 1 /CL ALPHA=0.1; ods output Estimates=unsc1; title1 'unscaled BE 90% CI  guidance version'; title2 'AUCt'; run; data unsc1; set unsc1; ratio=exp(estimate)*100; unscabe_lower=exp(lower)*100; unscabe_upper=exp(upper)*100; run; 
BEQool ★ 20230420 08:21 (399 d 22:31 ago) @ weiguo2122 Posting: # 23528 Views: 1,671 

Hello! I don't know if this is the answer you are looking for but 74.021385 is an inverse of a number 135.096 (1/1.35096=0.740214). So in this case you just have to change which treatment (T or R) will act as a reference. For the explanation see this post  question 2 Hope it helps BEQool 
Helmut ★★★ Vienna, Austria, 20230420 10:13 (399 d 20:39 ago) @ weiguo2122 Posting: # 23529 Views: 1,633 

Hi weiguo2122$2gmail.com, please give something closer to a human name in your profile. Maybe better: Suggest another nick and I will change it in the database. ❝ when I compared the ABE (Proc Mixed) output between SAS (FDA Draft Guidance on Progesterone, SAS code) and WinNonlin, they are not matched. 74.02% (90% CI: 65.69–83.41%) is correct. Confirmed in Phoenix/WinNonlin, R, and ‘manually’ in a spreadsheet. See BEQool’s post above for the likely explanation. I don’t speak SAS; try to remove to dollarcharacters from the headers in your data statement. PS: Your lauct=log(Cmax); is funny. — Diftor heh smusma 🖖🏼 Довге життя Україна! _{} Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 
PharmCat ★ Russia, 20230420 21:58 (399 d 08:54 ago) @ Helmut Posting: # 23531 Views: 1,592 

Hi weiguo2122$2gmail.com! ❝ 1. If anyone have same issue? ❝ 2. if we should change ESTIMATE 'T vs. R' to “TRT 1 1” since discussion in this Forum and FDA ❝ SAS code indicate we should use “TRT 1 1” not “TRT 1 1” ❝ 3. If not how to deal this issue to make it consistent for results from two side? 1. This not an issue. 2. “TRT 1 1”  this only mean what level is a base, just from what you doing subtraction (you should define it in accordance with your data) 3. This is no problem just set it “TRT 1 1” 
weiguo2122 ☆ 20230421 16:15 (398 d 14:37 ago) @ Helmut Posting: # 23534 Views: 1,576 

❝ 74.02% (90% CI: 65.69–83.41%) is correct. Confirmed in Phoenix/WinNonlin, R, and ‘manually’ in a spreadsheet. See BEQool’s post above for the likely explanation. ❝ I don’t speak SAS; try to remove to dollarcharacters from the headers in your data statement. Thanks all for your replying. 1. I accidentally put "weiguo2122$2gmail.com" as my username, now it is hard to make a change because "edit profile" do not allow me make change". If possible, please change my username as "Weiguo21224" at your end. 2. I carefully reviewed previous discussion. My understanding is that "T" and "R" in FDA code do represent the "Test drug" and "Reference drug" respectively. It should be: ESTIMATE 'T (the large/later one in lexical order, Reference drug) vs. R (the small/early one in lexical order, Test drug') TRT 1 1/CL ALPHA=0.1; Right? Best! David Edit: 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 #5! [Helmut] 
Helmut ★★★ Vienna, Austria, 20230421 17:45 (398 d 13:07 ago) @ weiguo2122 Posting: # 23535 Views: 1,555 

Hi David or Guo, ❝ 1. […] please change my username as "Weiguo21224" at your end. Done. ❝ 2. I carefully reviewed previous discussion. My understanding is that "T" and "R" in FDA code do represent the "Test drug" and "Reference drug" respectively. Correct so far. ❝ It should be: ❝ ❝ ESTIMATE 'T (the large/later one in lexical order, Reference drug) vs. R (the small/early one in lexical order, Test drug') TRT 1 1/CL ALPHA=0.1; ❝ ❝ Right? In your example and the FDA’s code, yes and no. Alphanumeric codes are internally converted to factors in lexical order and integers by default. At least in all software I know. Examples in :
R – T instead of the desired T – R .— Diftor heh smusma 🖖🏼 Довге життя Україна! _{} Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 