Partial replicate design: reference(s)? [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2020-08-13 16:22 (1298 d 10:42 ago) – Posting: # 21868
Views: 6,710

Dear all,

I try to figure out when – and hopefully why – the partial replicate design TRR|RTR|RRT entered the scene.

I must confess that I never heard about it till I was asked at a workshop in Ahmedabad in 2008. I knew only another partial replicate, the so-called extra-reference design TRR|RTR 1 (which should be avoided since it is biased in the presence of period effects).
The first paper 2 of the ‘Two Lászlós’ dealt solely with the two-sequence, three-period full replicate design TRT|RTR. It laid the foundations of reference-scaled ABE.
The FDA’s guidance of 2001 stated in Appendix B.2.:

… the two-sequence, three-period design TRR|RTT is thought
to be optimal among three-period replicated crossover designs.

Fine with me. Same design characteristics, balanced like the TRT|RTR. Not a single word about the partial replicate.

The partial replicate is given in the FDA’s progesterone guidance of April 2010 and by the EMA in Annex I of September 2016 (appeared first in Rev. 3 of the Q&A document in January 2011) though regulatory documents  scientific justification.

If you know any publication (preferrably prior to 2010), please let me know.

  1. Chen KW, Chow SC, Li G. A Note on Sample Size Determination for Bioequivalence Studies with Higher-order Crossover Designs. J Pharmacokin Biopharm. 1997;25(6):753–65. doi:10.1023/a:1025738019069.
  2. Endrényi L, Tóthfalusi L. Regulatory Conditions for the Determination of Bioequivalence of Highly Variable Drugs. J. Pharm Pharmaceut Sci. 2009;12(1):138–49. [image] Open access.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz

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

Complete thread:

UA Flag
 Admin contact
22,919 posts in 4,807 threads, 1,641 registered users;
19 visitors (0 registered, 19 guests [including 5 identified bots]).
Forum time: 02:04 CET (Europe/Vienna)

The analysis of variance is not a mathematical theorem,
but rather a convenient method of arranging the arithmetic.    R.A. Fisher

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz