## Inter-subject variability in Full replicate design [RSABE / ABEL]

like ElMaestro I’m not a

**SAS**ian and my knowledge is limited.

» […] I am not able to calculate the inter-subject variabilities for test and reference treatments. Please help me with this calculation.

With the EMA’s example ‘Data set I’ (download CSV) you should get sumfink like:

` Covariance Parameter Estimates`

Cov Parm Subject Group Estimate

FA(1,1) SUBJ 0.8530

FA(2,1) SUBJ 0.8284

FA(2,2) SUBJ 8.339e-07

Residual SUBJ TRT R 0.2021

Residual SUBJ TRT T 0.1174

In Phoenix/WinNonlin slightly different terms.

`Final variance parameter estimates:`

lambda(1,1)_11 0.852995

lambda(1,2)_11 0.828407

lambda(2,2)_11 8.33919e-007

Var(PER*TRT*SUBJ)_21 0.202118

Var(PER*TRT*SUBJ)_22 0.117394

The first two lines give \(\small{\widehat{s_\textrm{bR}^2}}\) and \(\small{\widehat{s_\textrm{bT}^2}}\) and the last two \(\small{\widehat{s_\textrm{wR}^2}}\) and \(\small{\widehat{s_\textrm{wT}^2}}\). Ignore the third, which is the Subject-by-Formulation Interaction. Then as usual \(\small{100\sqrt{\exp \left ( \widehat{s_{\ldots}^2} \right )-1}}\).

Here \(\small{CV_\textrm{bR}=116.0\%,\;CV_\textrm{bT}=113.6\%,\;CV_\textrm{wR}=47.3\%,\;CV_\textrm{wT}=35.3\%}\).

As ElMaestro wrote, you can get the estimated between-subject variances also from

`Col1`

of the estimated `G matrix`

, where the 1^{st}Row is for R and 2

^{nd}for T.

» But when I use the proc varcomp procedure in SAS, I am able to generate the Variabilities (Inter and Intra) for test and reference treatments.

Out of curiosity: Do they are agree with the results of

`Proc Mixed`

as outlined above?» My doubt is that whether it is acceptable by FDA regulatory?

The between-subject variabilities are not required for RSABE (in the FDA’s Summary Table 3B you have to give only the within-subject variance and standard deviation of the reference).

For ABE (Table 3A) variances are not required at all.

Post 22,000…

*Dif-tor heh smusma*🖖

_{}

Helmut Schütz

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

Science Quotes

### Complete thread:

- Inter-subject variability in Full replicate design MGR 2021-09-30 07:35 [RSABE / ABEL]
- Inter-subject variability in Full replicate design ElMaestro 2021-09-30 14:04
- Inter-subject variability in Full replicate designHelmut 2021-09-30 15:25