Bioequivalence and Bioavailability Forum

WinnieH
☆

Sweden,
2023-01-04 14:33
(856 d 05:50 ago)

Posting: # 23417
Views: 3,690

Questions on understanding the 4-way RSABE method SAS code [RSABE / ABEL]

Dear all,

I am a new learner and I am trying on understanding the 4-way RSABE method SAS code provided by FDA:

/*Intermediate analysis – ilat*/  

proc mixed data=scavbe;

  class seq;

  model ilat =seq/ddfm=satterth;

  estimate 'average' intercept 1 seq 0.5 0.5/e cl alpha=0.1; 

  ods output CovParms=iout1; 

  ods output Estimates=iout2;

  ods output NObs=iout3; 

run;

data ilat;

  set iout2;

  pointest=exp(estimate);

  x=estimate**2-stderr**2;

  boundx=(max((abs(lower)),(abs(upper))))**2;

/*Intermediate analysis – dlat*/  

proc mixed data=scavbe;

  class seq;

  model dlat=seq/ddfm=satterth; estimate 'average' intercept 1 seq 0.5 0.5/e cl alpha=0.1;

  ods output CovParms=dout1;

  ods output Estimates=dout2;

  ods output NObs=dout3; 

run;

data dlat;

  merge dout1(keep=estimate) dout2(keep=df);

  s2wr=estimate/2;

  dfd=df;

run;

/*Criterion Bound */  

data results;

  merge ilat(keep=pointest x boundx) dlat(keep=s2wr dfd);

  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;

I found some discussion about the S2wr and it is really helpful to me. About the ilat, my understanding is that the model is a simple linear model and the estimate is the least square mean. My R code example is as follows:


  mod<-lm(ilat~SEQ, dataset)

  result <- confint(emmeans(mod, specs=~1), level = 0.9)

  pointest <- exp(result$emmean)

  x <- (result$emmean)^2- (result$SE)^2

  boundx <-(max(c(abs(result$lower.CL), abs(result$upper.CL))))^2

My question is 1) how to interpret x and critbound=(x+y)+sqrt(((boundx-x)**2)+((boundy-y)**2))? Is there any related explanation about them? 2) Has anyone tried to reproduce this FDA code in R before? I would like to get some hints from you :-)

Thank you very much and wish you a happy new year!

Bests,
Winnie

Helmut
★★★

Vienna, Austria,
2023-01-04 15:02
(856 d 05:20 ago)

@ WinnieH
Posting: # 23418
Views: 2,990

Questions on understanding the 4-way RSABE method SAS code

Post reply

Hi Winnie,

❝ I am a new learner and I am trying on understanding the 4-way RSABE method SAS code provided by FDA: […]

❝ I found some discussion about the S2wr and it is really helpful to me. About the ilat, my understanding is that the model is a simple linear model and the estimate is the least square mean.

I don’t speak SAS but isn’t it a restricted maximum likelihood estimate?

❝ My R code example is as follows: […]

I’m short in time right now; compare it to Detlew’s script in base R.

❝ My question is 1) how to interpret x and critbound=(x+y)+sqrt(((boundx-x)**2)+((boundy-y)**2))? Is there any related explanation about them?

Haha, ‘the unknown x’. :-D

I’m aware of only one reference,* which is – regrettably – not in the public domain.

The statistical approach we use is very similar to that proposed by Tothfalusi,
Endrenyi, et al. 2001, with a minor difference (use of an unbiased estimator for
(μ_T–μ_R)²).

Schuirmann D. U.S. FDA Perspective: Statistical Aspects of OGD’s Approach to Bioequivalence (BE) Assessment for Highly Variable Drugs. Presentation at the 2^nd conference of The Global Harmonisation Initiative (GBHI). Rockville. September 15–16, 2016.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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

WinnieH ☆ Sweden, 2023-01-04 16:12 (856 d 04:10 ago) @ Helmut Posting: # 23419 Views: 2,933	Questions on understanding the 4-way RSABE method SAS code Post reply
	Hi Helmut, Thank you so much for your fast reply! They are very helpful! Best regards, Zhe

Questions on under­standing the 4-way RSABE method SAS code [RSABE / ABEL]

Questions on understanding the 4-way RSABE method SAS code

Questions on understanding the 4-way RSABE method SAS code

Questions on understanding the 4-way RSABE method SAS code [RSABE / ABEL]