Bioequivalence and Bioavailability Forum

Main page Policy/Terms of Use Abbreviations Latest Posts

 Log-in |  Register |  Search

Back to the forum  Query: 2017-07-22 10:51 CEST (UTC+2h)
 

SAS and R (?) for variability comparison (FDA NTID Guidance) [General Sta­tis­tics]

posted by M.tareq - 2017-04-14 15:04  - Posting: # 17239
Views: 1,216

Dear all,
notation clarification for a newbie ,
using EMA's sample data set I -full replicate- after removing the subject that didn't complete all periods
regarding this post : ddubins post
for calculation of CV-intra in full replicate design using FDA SAS code provided in appendix E
FDA Guidance
according to ddubins entry about Covariate Parameter Estimates:
Residual Subject Treatment A 0.124 <---- (sig_WT^2, the within-subject standard deviation) for the Test product
Residual Subject Treatment B 0.242 <---- (sig_WR^2, the within-subject standard deviation for the Reference product)

however when using the code given in fda guidance for warfrain sodium and following the same idea here to Calculate the 90% confidence interval of the ratio of the within subject standard
deviation of test product to reference product σWT/σWR by using the residual terms in covariates estiames to calculate the upper bound as follows:
[image]
guidance for warfrain sodium
and calculating the SWr for the critical bound ,the numbers aren't same ,
Covariance Parameter Estimates
Cov Parm Subject Group Estimate
FA(1,1) Subject   0.8454
FA(2,1) Subject   0.8232
FA(2,2) Subject   0.02062
Residual Subject Formula R 0.2097
Residual Subject Formula T 0.1202

and Swr obtained from proc mixed step -same idea as Shuanghe- there's slight difference :confused::confused:
CovParm  Estimate s2wr  theta      y       boundy sWR     critbound
Residual 0.4080 0.20401 1.11006 -0.22647 -0.17419 0.45168 -0.14657

my first question is and -sorry for the silly long post,the residual terms in covariates estimates is an estimate of the variance for both Test and reference and not the standard deviation as ddubins said?
and that means the calculation will be as follows :
sqrt(Residual Subject Formula R)
and same for Test to obtain the variability ratio?

2nd question,

Regarding Helmut lecture about Reference Scaled Average Bioequivalence (part II: NTIDs)
RSABE NTIDs
using the data set provided: CNS drug data set
when using the fda code for NTID mentioned above in warfarin guidance i get the following values:
Cov Parm Subject Group Estimate
FA(1,1) Subject   0.2473
FA(2,1) Subject   0.2680
FA(2,2) Subject   0
Residual Subject Formula R 0.02483
Residual Subject Formula T 0.003281

and
CVwt=SQRT(EXP(0.003281)-1) --> 5.73%
CVwr==SQRT(EXP(0.02483)-1) --> 15.86%

CL: 93.90% - 103.35%
CovParm    Estimate   s2wr    theta          y         ]boundy     sWR       critbound
Residual   0.03095   0.015474   1.11006   -0.017177   -0.010451   0.12439   -0.009828289

when using these estimates to obtain the upper bound for variability comparison i get : 0.60080159
the number checks out with what's in your lecture regarding EMA values but why there's a difference between FDA values ?:confused::confused:

Thanks in advance and Best Regards

Complete thread:

Back to the forum Activity
 Mix view
Bioequivalence and Bioavailability Forum | Admin contact
17,091 Posts in 3,666 Threads, 1,051 registered users;
30 users online (0 registered, 30 guests).

There is one certainty in drug development
and statistics that one can depend on:
the data are always late.    Scott Patterson and Byron Jones

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
XHTML/CSS RSS Feed