## Misunderstanding? [Regulatives / Guidelines]

Hi ElMaestro,

» If we look at SAS documentation e.g. here and here, then

» 1. I do not understand the underlying math (just try and look into the spectral decomposition things mentioned as part of DDFM derivation; it sends my head spinning).

Wooaah!!

» 2. Whatever SAS does, it seems to require that we work in V through

Seems so.

» It would be

Definitely not me…

» However, since FDA now threw the mixed model out for semi-replicate designs, …

What on earth gives you this impression? I’m talking about

» …

Nope. Talk to John about his data sets which didn’t converge. Given,

» But who knows - until someone does it and explores it, it is not known if there is an advantageous property hidden somewhere.

Might be.

» If we look at SAS documentation e.g. here and here, then

» 1. I do not understand the underlying math (just try and look into the spectral decomposition things mentioned as part of DDFM derivation; it sends my head spinning).

Wooaah!!

» 2. Whatever SAS does, it seems to require that we work in V through

`ZGZ`^{t}+R

in order to estimate CI's for the fixed effects.Seems so.

» It would be

*interesting*to see someone who has solid understanding of matrix theory and stats to work out the equations when the between and within-variability for T cannot be separated.Definitely not me…

» However, since FDA now threw the mixed model out for semi-replicate designs, …

What on earth gives you this impression? I’m talking about

**ABE**(Stats guidance Appendix E, Progesterone guidance page 8, ANDA guidance page 29):The following codes are an example of the determination of unscaled average BE for LAUCT with a partially replicate 3-way BE design:

**PROC MIXED**

data=pk;

CLASSES 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;

unscabe_lower=exp(lower);

unscabe_upper=exp(upper);

**run**;

» …

*interesting*may in reality just mean academically attractive but possible not too useful at this moment.Nope. Talk to John about his data sets which didn’t converge. Given,

`FA0(1)`

did – with a warning – but I think there is a data set posted at Certara’s forum where *nothing*worked. Study done, no result. THX, .» But who knows - until someone does it and explores it, it is not known if there is an advantageous property hidden somewhere.

Might be.

—

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

*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

### Complete thread:

- Desperate reader Helmut 2021-08-27 15:51 [Regulatives / Guidelines]
- Desperate reader ElMaestro 2021-08-27 22:18
- Misunderstanding?Helmut 2021-08-27 23:54
- Misunderstanding? ElMaestro 2021-08-28 10:00
- Here we are Helmut 2021-08-28 10:38

- Misunderstanding? ElMaestro 2021-08-28 10:00

- Misunderstanding?Helmut 2021-08-27 23:54
- Papers Mahmoud 2021-09-17 13:31
- FDA: PROC MIXED (‼) for ABE Helmut 2021-09-17 15:15
- FDA: PROC MIXED (‼) for ABE Mahmoud 2021-09-17 15:24
- FDA: PROC MIXED (‼) for ABE Helmut 2021-09-17 17:11

- FDA: PROC MIXED (‼) for ABE Mahmoud 2021-09-17 15:24

- FDA: PROC MIXED (‼) for ABE Helmut 2021-09-17 15:15

- Desperate reader ElMaestro 2021-08-27 22:18