Data analysis and sample size for replicate study designs as per recent FDA guidance [Regulatives / Guidelines]

posted by balakotu – India, 2023-05-23 14:16 (417 d 13:43 ago) – Posting: # 23564
Views: 1,322

Dear All,

Please give me your valuable inputs.

Q) As per Recent FDA Draft Guidance they introduced 3-period, 2 -sequence full replicate study design.

Replicated crossover designs:

Other fully replicated crossover designs are also possible. For example, a three-period design, as shown below, could be used. A fully replicated design can estimate the subject-by-formulation interaction variance components.

I am unable to calculate Estimates as per the below SAS code for Reference variability and Scaled average bioequivalence.

/*TRT and RTR*/ /*Reference Variability*/

%macro Analysis(Par,Code);
proc Mixed data=scavbe;
class seq;
model &Par =seq/ddfm=satterth;
estimate "&Par" intercept 1 seq 0.5 0.5/e cl alpha=0.1;
ods output CovParms=dout1&Code;
ods output Estimates=dout2&Code;
ods output NObs=dout3&Code;
title1 ‘Intra subject variability of Reference';
title2 "&Par-Analysis";
run;
%mend Analysis;
%Analysis(Cmax,1);
%Analysis(AUCt,2);
%Analysis(AUCi,3);

/* Scaled average BE'*/

%macro Analysis(Par,Code);
proc Mixed data=scavbe1;
class seq;
model Ln&Par =seq/ddfm=satterth;
estimate "&Par" intercept 1 seq 0.5 0.5/e cl alpha=0.1;
ods output CovParms=iout1&Code;
ods output Estimates=iout2&Code;
ods output NObs=iout3&Code;
title1 'SCALED Average BE';
title2 "&Par-Analysis";
run;
%mend Analysis;

%Analysis(Cmax,1);
%Analysis(AUCt,2);
%Analysis(AUCi,3);

Please let me know if any idea or thoughts?

Q) Two-Period Replicated Crossover Designs

For this Two-Period Replicated Crossover Designs i.e. the modified Balaam design (TR, RT, RR) -----How to calculate Sample size using R-Software.

Regards
Kotu

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