Bioequivalence and Bioavailability Forum

To Err is Human [General Statistics]

posted by preyes323 – 2010-07-16 04:28 (5418 d 22:46 ago) – Posting: # 5643
Views: 14,260

Hi All,

❝ Your implementation of the intra-subject contrast T-R (ilat in the guidance) is faulty. You must calculate T-0.5(R1+R2).

My bad on this. I went through my code a number of times but didn't even notice this!!! :-(

❝ • The SAS code given in the guidance is half-cooked. See here and here.

❝ First: To get a 95% upper CI of the scaled ABE criterion IMHO you must use

❝ alpha=0.05 in the intermediate analysis of ilat.

❝ • Second: The ominous x in the IGLM2 part of the code is IMHO wrong. What

❝ wee need here is (Y_T-Y_R)² and this would translate to me to x=estimate**2

❝ in the SAS code.

I revised this two as well (see way below for my codes :-D

). After revising, I ran my models however I got a different result than the one gotten by d_labes (see below). Mine is 0.023485. Is there something wrong with my implementation of the FDA guideline for the crit bound?

❝ (µ_T-µ_R)²-theta²*sigma²_WR = -0.03751

I am also confused with the difference between the S2wr results by the ABE SAS code by FDA (page 9 of progesterone guideline) using PROC Mixed and the S2wr formula for intra-subject contrasts. I tried using both as well. I produced the results that was earlier posted. Why is it that Sigma2WR values are different? Is this ok? I read in your other posts the Progesterone guidance makes use of MoM. Is MoM the approach really used for SABE then?

Thanks again.

Thanks and Regards,
Paolo

Code for IGLM


proc glm data=SABE.scavbe_Cmax;

   class sequence;

   model ilat = sequence/clparm alpha =0.05;

   estimate 'average' intercept 1 sequence 0.3333333333 0.3333333333 0.3333333333;

   ods output overallanova=SABE.iglm1_Cmax;

   ods output Estimates=SABE.iglm2_Cmax;

   ods output NObs=SABE.iglm3_Cmax;

   title1 'scaled average BE';

run;



Data SABE.iglm2_Cmax;

   set SABE.iglm2_Cmax;

   pointest=exp(estimate);

   x=estimate**2;

   boundx=(max((abs(LowerCL)),(abs(UpperCl))))**2;

run;

Code for Crit Bound

data SABE.upper_cmax;

   merge SABE.dglm1_cmax SABE.iglm2_cmax;

   theta=((log(1.25))/0.25)**2;

   y=-theta*s2wr;

   boundy=y*dfd/cinv(0.95,dfd);

   sWR=sqrt(s2wr);

   critbound=(x+y)+sqrt(((boundx-x)**2)+((boundy-y)**2));

run;

Complete thread:

SABE Reference Variability and CI Computation preyes323 2010-07-12 17:12 [General Statistics]
- Dataset Helmut 2010-07-12 17:26
  - Dataset preyes323 2010-07-12 18:20
    - Data format Helmut 2010-07-12 18:38
      - Data format preyes323 2010-07-13 01:16
        
        SAS and/or Phoenix/WinNonlin-experts around? Helmut 2010-07-13 02:29
        
        Phoenix/WinNonlin-experts around? d_labes 2010-07-13 12:15
        
        Phoenix/WinNonlin-experts around? Helmut 2010-07-13 13:42
        
        Mixed interest d_labes 2010-07-13 15:11
        
        Mixed interest Helmut 2010-07-13 19:19
        
        lme() answer and beyond ... d_labes 2010-07-14 10:41
        
        lme() answer and beyond ... Helmut 2010-07-14 13:47
        
        AIC, BIC and that all ... d_labes 2010-07-15 12:01
        
        To Err is Human d_labes 2010-07-13 11:51
        
        To Err is Human, but... Helmut 2010-07-13 13:45
        
        ... to Arr is Pirate d_labes 2010-07-13 15:47
        
        Brilliant page!!! ElMaestro 2010-07-14 21:03
        
        To Err is Human preyes323 2010-07-14 14:45
        
        Heads up! Helmut 2010-07-14 15:17
        To Err is Teacher d_labes 2010-07-15 11:05
        
        To Err is Humanpreyes323 2010-07-16 02:28
        
        To Err is Human d_labes 2010-07-16 10:42
        
        To Err is Human preyes323 2010-07-17 11:14
        
        Regulatory constants d_labes 2010-07-19 10:00
        
        Data format ElMaestro 2011-02-06 11:54
        
        SAS System Viewer Helmut 2011-02-06 13:02

To Err is Human [General Sta­tis­tics]

Complete thread:

To Err is Human [General Statistics]