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

Hi Zhang Yong,

» Hope you are well.

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

» I manually calculate the sWR and sWT in Excel sheet, they are 0.124392769, 0.055720909, respectively. Are my results EXACTELY right?

s

» In your slides, you have present the upper 95% CL of sWT/sWR 0.68427 ≤2.5.

» I have calculated

» lower 95% CL of sWT/sWR = 0.293238292

» upper 95% CL of sWT/sWR = 0.684266753 (this is nearly the same as your result)

lower CL 0.293238291752988, upper CL 0.684266752752176

» As US FDA's Guidance on Warfarin required, the upper 90% CI should be used, I also calculate the following:

» lower 90% CL of sWT/sWR = 0.322597242

» upper 90% CL of sWT/sWR = 0.621992961

» Are the above results right?

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

» I use the function Finv(0.1,16,16) and Finv(0.9,16,16) for the calculation of 90% CL of sWT/sWR,

» and Finv(0.05,16,16) and Finv(0.95,16,16) for the calculation of 95% CL of sWT/sWR. Do I use the right function?

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

» Would you please guide (step by step) me how to calculate CVwr CVwt? As shown in your slides, they are CVWR 12.49%, CVWT 5.58%. Although these two values are not used in calculation of "upper 90% CL of sWT/sWR".

According to the guidance s

Personally I would prefer to run a mixed effects model with restricted maximum likelihood which takes the entire information into account (

I got: CV

Hope that helps.

» Hope you are well.

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

» I manually calculate the sWR and sWT in Excel sheet, they are 0.124392769, 0.055720909, respectively. Are my results EXACTELY right?

s

_{wR}0.124392768691665, s_{wT}0.0557209092013223» In your slides, you have present the upper 95% CL of sWT/sWR 0.68427 ≤2.5.

» I have calculated

» lower 95% CL of sWT/sWR = 0.293238292

» upper 95% CL of sWT/sWR = 0.684266753 (this is nearly the same as your result)

lower CL 0.293238291752988, upper CL 0.684266752752176

» As US FDA's Guidance on Warfarin required, the upper 90% CI should be used, I also calculate the following:

» lower 90% CL of sWT/sWR = 0.322597242

» upper 90% CL of sWT/sWR = 0.621992961

» Are the above results right?

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

- here
*α*= 0.1.

» I use the function Finv(0.1,16,16) and Finv(0.9,16,16) for the calculation of 90% CL of sWT/sWR,

» and Finv(0.05,16,16) and Finv(0.95,16,16) for the calculation of 95% CL of sWT/sWR. Do I use the right function?

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

`F`**.**inv(alpha,df1,df1)

or the old workaround `Finv(`**2***alpha,df1,df1)

. Duno. The correct *F*-values (ν_{1}=ν_{2}=16) are:*F*_{α∕2,ν1,ν2}2.33348362746764,*F*_{1−α∕2,ν1,ν2}0.428543825304327» Would you please guide (step by step) me how to calculate CVwr CVwt? As shown in your slides, they are CVWR 12.49%, CVWT 5.58%. Although these two values are not used in calculation of "upper 90% CL of sWT/sWR".

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%.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.Hope that helps.

—

Helmut Schütz

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

Science Quotes

*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:

- Validation of FDA's RSABE on NTIDs yicaoting 2017-08-22 18:01 [RSABE / ABEL]
- Validation of FDA's RSABE on NTIDsHelmut 2017-08-22 20:25
- Validation of FDA's RSABE on NTIDs yicaoting 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 NTIDs yicaoting 2017-08-23 05:30

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