## Validation of FDA's RSABE on NTIDs [RSABE / ABEL]

Thank you for your quick response.

❝ THX! Below my results obtained in Phoenix WinNonlin 7.0 in full precision.

❝ s_{wR} 0.124392768691665, s_{wT} 0.0557209092013223

Yes, sWR and sWT can be calculate manually. So my results are indentical to yours.

❝ lower CL 0.293238291752988, upper CL 0.684266752752176

❝ The guidance might be confusing. See the last bullet point below the formula

- here
*α*= 0.1.

I am not sure the guidance is correct or not.

But from the formula in the guidance (page 4, line 5) with Alpha=0.1, I

**guess**the guidance is right, it calulates 90% CI of Swt/Swr, but not 95% CI.

Need your clarification? or FDA is wrong?

❝ I have only Excel 2000. Up to v2003 the inverse distributions were wrong. Maybe you have to use `F`

or the old workaround **.**inv(alpha,df1,df1)`Finv(`

. Duno. The correct **2***alpha,df1,df1)*F*-values (ν_{1}=ν_{2}=16) are:

❝ *F*_{α∕2,ν1,ν2} 2.33348362746764, *F*_{1−α∕2,ν1,ν2} 0.428543825304327

In Excel 2003,

Finv(0.05,16,16) = 2.33348362835

Finv(0.95,16,16) = 0.428543825142279

In Excel 2013

Finv(0.05,16,16) = 2.33348362746764

Finv(0.95,16,16) = 0.428543825304327

F.inv(0.05,16,16) = 0.428543825304327

F.inv(0.95,16,16) = 2.33348362746764

❝ According to the guidance s_{WR} and s_{wT} are estimated from complete data only (not an issue with *this* data set) *ignoring* its structure (solely 'sequence' in the linear model). Your values are correct. Hence, as usual \(CV = \sqrt{e^{s_{w}^{2}} - 1}\). Therefore, we get CV_{wR} 12.49% and CV_{wT} 5.58%.

Thanks.

❝ Personally I would prefer to run a mixed effects model with restricted maximum likelihood which takes the entire information into account (*i.e.*, the FDA’s code of the 2001 guidance and also in the ABE-part of the progesterone guidance). In this model you could have incomplete data and the variances of R and T are simultaneously estimated. I guess that’s impossible in Excel (as it is in R)…

❝ I got: CV_{wR} 15.86% and CV_{wT} 5.73%. Interesting.

I guess your result of 15.86% and 5.73% are obtain from the sheet of "Final Variance Parameters" from ABE results using PHX WNL.

let

a = Var(Period*Formulation*Subject)_21 (the value is 0.024828963992548 from PHX WNL)

b = Var(Period*Formulation*Subject)_22 (the value is 0.003281299568883 from PHX WNL)

CVwr = 100 * SQRT(EXP(a)-1)

CVwt = 100 * SQRT(EXP(b)-1)

I got the same results sa you.

Here the CVwr and CVwt are different from those calculated from Swr and Swt.

I prefer the result calculated from Swr and Swt.

What's your opinion?

### Complete thread:

- Validation of FDA's RSABE on NTIDs yicaoting 2017-08-22 18:01 [RSABE / ABEL]
- Validation of FDA's RSABE on NTIDs Helmut 2017-08-22 20:25
- Validation of FDA's RSABE on NTIDsyicaoting 2017-08-23 05:30
- Validation of FDA's RSABE on NTIDs Helmut 2017-08-23 15:00
- Validation of FDA's RSABE on NTIDs yicaoting 2017-08-30 14:33
- Validation of FDA's RSABE on NTIDs Helmut 2017-08-30 15:04

- Validation of FDA's RSABE on NTIDs yicaoting 2017-08-30 14:33

- Validation of FDA's RSABE on NTIDs Helmut 2017-08-23 15:00
- Clarification needed: Validation of FDA's RSABE on NTIDs CECIF 2018-02-19 22:20
- FDA's RSABE on NTIDs in R d_labes 2018-02-20 14:10
- FDA's RSABE on NTIDs in R CECIF 2018-03-01 21:08
- FDA's RSABE on NTIDs in R Helmut 2018-03-01 23:39

- FDA's RSABE on NTIDs in R CECIF 2018-03-01 21:08

- FDA's RSABE on NTIDs in R d_labes 2018-02-20 14:10

- Validation of FDA's RSABE on NTIDsyicaoting 2017-08-23 05:30

- Validation of FDA's RSABE on NTIDs Helmut 2017-08-22 20:25