Brus ★ Spain, 20230614 18:34 (402 d 17:55 ago) Posting: # 23593 Views: 2,074 

Dear all, In a partial replicated design (3periods, 3 sequences), only reference is replicated, with a sample size of 45, CRO sent to me the following with proc GLM for ANOVA for the R/R comparison: Source / DF / SS / MS / P Also they sent to me the following 90% CI for the comparative R1/R2: Ratio = 110.79 The number of observations used for the calculation were 40 due to drop outs. But I have several doubts:  It surprises me a 90% CI so wide for a relatively low, at least not high, ISCV.  If I backcalculated the CV from this 90% CI with “CVfromCI” of PowerTOST, I obtain a CV of around 70%. Why?  In addition, I have tried to calculate the ratio and 90% CI with MSE and LSM according to the Helmut example from Pamplona lecture on 2018 "Basic Statistic on BE", slide 16 and 17: SE = √(MSE/nps), where nps = (n1 +n2)/2 ∆ = LSM (T) – LSM (R) PE (GMR = e∆) 90% CI = ∆ ± t(α = 0.05, df) × SE I used 0.043 from first table as MSE and I used the formula from Helmut presentation to convert it in SE and then to calculate the ratio and 90% CI. I obtained a ratio of 110,8 but a 90% CI of 102,44 – 119,94. Same ratio as CRO but different 90 % CI. This is strange although it is in line with the ISCV presented by the CRO. Furthermore, doing various tests, I have noticed that if you add the mean square obtained in the Sbj(seq) from first table to the MSE and you use the formula from Helmut presentation to convert this sum in SE and then to calculate the ratio and 90% CI, you obtain the same 90% CI as CRO. But, If the subj(seq) is significant, should it be calculated in this way?, why?, and should it be taken into account and impact the 90% CI range? So, what is the correct 90% CI? Thank you so much Best regards, 
Helmut ★★★ Vienna, Austria, 20230615 00:26 (402 d 12:02 ago) @ Brus Posting: # 23594 Views: 1,768 

Hi Brus, ❝ In a partial replicated design (3periods, 3 sequences), only reference is replicated, with a sample size of 45, CRO sent to me the following with proc GLM for ANOVA for the R/R comparison: ❝ … ❝ ❝ ❝ ❝ ❝ Also they sent to me the following 90% CI for the comparative R1/R2: ❝ ❝ ❝ ❝ There can be only one. There is no ‘R_{1}’ and ‘R_{2}’, only one R repeatedly administered in the sequences in different periods. Say, the sequences are TRR  RTR  RRT . Did the CRO call the first administration in each sequence R_{1} and the second R_{2} (while dropping T)?This gives after recoding: ░R_{1}R_{2}  R_{1}░R_{2}  R_{1}R_{2}░ ❝ But I have several doubts: ❝  It surprises me a 90% CI so wide for a relatively low, at least not high, ISCV. ❝  If I backcalculated the CV from this 90% CI with “CVfromCI” of PowerTOST, I obtain a CV of around 70%. Why? CI2CV(lower=0.8731, upper=1.4057, design="2x2x2", n=40) , right? That’s not what you have. After recoding (wild guess) you have an Incomplete Block Design. Other degrees of freedom, ❝  In addition, I have tried to calculate the ratio and 90% CI with MSE and LSM according to the Helmut example from Pamplona lecture on 2018 "Basic Statistic on BE", slide 16 and 17: ❝ … ❝ I obtained a ratio of 110,8 but a 90% CI of 102,44 – 119,94. Same ratio as CRO but different 90 % CI. This is strange although it is in line with the ISCV presented by the CRO. CI2CV() . But again, there is only one R. A ‘PE’ and ‘CI’ doesn’t make sense.❝ Furthermore, doing various tests, … why? ❝ So, what is the correct 90% CI? If you want, send me the raw data offlist. — 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 
Brus ★ Spain, 20230615 16:07 (401 d 20:22 ago) @ Helmut Posting: # 23598 Views: 1,693 

Hi Helmut, Sorry, because I am lego and I can´t understand all correctly. ❝ There is no ‘R_{1}’ and ‘R_{2}’, only one R repeatedly administered in the sequences in different periods. Say, the sequences are ❝ As said above, such a ‘comparison’ will not work. ❝ You tried ❝ These formulas are for a 2×2×2 crossover and are also implemented in ❝ You can only calculate the CV_{wR} according to the EMA’s or the FDA’s models. The results will be similar, though quite often the one of the FDA is a bit smaller. Edit: Standard quotes restored; see also this post #8. [Helmut] 
Helmut ★★★ Vienna, Austria, 20230615 16:49 (401 d 19:40 ago) @ Brus Posting: # 23599 Views: 1,686 

Hi Brus, ❝ Sorry, because I am lego and I can´t understand all correctly. ❝ ❝ There is no ‘R_{1}’ and ‘R_{2}’, only one R repeatedly administered in the sequences in different periods. Say, the sequences are ❝ Yes. But, although this is not the usual approach, if you set the R treatment as R1 and R2, you can make an R1 / R2 comparison, as if they were different treatments, right? ❝ And in this way, Is the 90% CI calculated by the CRO well calculated? It seems to me to be a very large interval for a CV of 20%. ❝ ❝ As said above, such a ‘comparison’ will not work. ❝ Why? Can you explain? In your partial replicate you ignored the apple and tried to compare oranges with oranges. What? Heck, they are the same. Only conditions differed. ❝ ❝ You can only calculate the CV_{wR} according to the EMA’s or the FDA’s models. The results will be similar, though quite often the one of the FDA is a bit smaller. ❝ But, although this is not the usual approach, if you set the R treatment as R1 and R2, you can make an R1 / R2 comparison, if you want to do it just for curiosity, considering them as different treatments, it will be feasible, right? And in this way, Is the 90% CI calculated by the CRO well calculated? Rose is a rose is a rose is a rose. Let’s explore the EMA’s reference data set II, both with the approach given in the Q&A as well as with yours. See the script at the end.
Not only the SEs are different but also the degrees of freedom and therefore, the MSEs / CVs. CI2CV() from the ‘pseudo R comparison’ does not work with any design argument.
— 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 
Achievwin ★ US, 20230619 21:42 (397 d 14:47 ago) @ Brus Posting: # 23604 Views: 1,631 

Rose is a rose is a rose is a rose Not always... .... there are some blessing from hell formulations..... 