Bioequivalence and Bioavailability Forum

❝ untransformed

❝ PHX/WNL 6.2

❝ fixed:  sequence+formulation+period


❝ random: sub(sequence)


❝ Treatment   LSM      SE     LowerCI  UpperCI


❝ 1         235.1521 12.7463 213.1332 257.1711


❝ 2         231.8667 12.7463 209.8477 253.8856


❝ --------------------------------------------------------


❝         Estimate  StdError  P_value LowerCI    UpperCI

❝ 1 - 2  3.2854762 10.387277  0.75644 -15.009737 21.580689

❝

❝ fixed:  sequence+formulation+period+sub(sequence)

❝ Treatment   LSM      SE     LowerCI  UpperCI

❝ 1         235.1521 7.34491 222.2155 248.0888

❝ 2         231.8667 7.34491 218.9300 244.8033

❝ --------------------------------------------------------

❝         Estimate  StdError  P_value LowerCI    UpperCI

❝ 1 - 2  3.2854762 10.387277  0.75644 -15.009737 21.580689

As HS calculated, since WNL's
fixed: sequence+formulation+period
random: sub(sequence)
and
fixed: sequence+formulation+period+sub(sequence)
generates identical result on Diff 1-2 and it's SE 10.387277 and 90% CI -15.009737 21.580689, and this is what BE analysis TRUELY concerning about, so let's use this result as a temp "Golden Standard".

it can be seen:

when Proc GLM (GLM 3 and GLM 4) is used, never use
model AUC=sequence period formulation
even
random subject(sequence) / test;
is added.

However,
when Proc Mixed (Mixed 3) is used, you can use
model AUC=sequence period formulation;
but remeber to specify
random subject(sequence) / subject=subject;
as random effect.

Now, let's consider WNL's
fixed:  sequence+formulation+period+sub(sequence)
SE 7.34491
as a TRUE fixed effect analysis.

It can be seen that both GLM 1 and GLM 2 are in fixed mode even
random subject(sequence) / test;
is added (see GLM 2)
this is previously discussed as so called "… post hoc fashion …"

When Proc Mixed is used, once you specified
model AUC=sequence subject(sequence) period formulation;
SAS will consider subject(sequence) as random effect.(Mixed 1 and 2), regardless of specifying
random subject(sequence) / subject=subject;
or not, (Mixed 2) the results are identical.

Since all results of SAS's GLM 1, GLM 2, Mixed 1 and Mixed 2, identical
SEs for LSM of R and T are both = 7.344914

90% CI for 1 and 2 are
222.215471   248.088815
218.929995   244.803339

90% CI for diff is
-15.009741    21.580693

can we concluded that this result is reliable?

Besides, as shown is Mixed 2, can we manually obtain SE = 7.344914 from the result of
Type 3 Tests of Fixed Effects?
I have tried, but failed.

Mixed 3 gets right 90% CI for diff, but strange 90% CI for LSMs of R 212.70 257.60 and T 209.42 254.32.

WNL's default
fixed:  sequence+formulation+period
random: sub(sequence)
Treatment   LSM      SE     LowerCI  UpperCI
1         235.1521 12.7463 213.1332 257.1711
2         231.8667 12.7463 209.8477 253.8856
--------------------------------------------------------
        Estimate  StdError  P_value LowerCI    UpperCI
1 - 2  3.2854762 10.387277  0.75644 -15.009737 21.580689
are never obtained by SAS's any trying of Proc GLM or Proc Mixed with many optional settings. So may be it is time to suspect WNL's default setting in BE Wizard? Do you agree?

Thanks to HS, d_labes and ElMaestro for your kind patience on this topic.

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Edit: Sorry yicaoting, I tried to edit your post in order to get a more compact style. [Helmut]