Partial replicate ≠ Reference scaling [RSABE / ABEL]
Hi heaven sent,
interesting nick.
No, you don’t.
2 period (full) replicate 3 period (full) replicates 3 period (partial) replicates Notes:Only for jurisdictions which have adopted ABEL and the Gulf States / Mexico you have to provide a clinical justification that expanding the acceptance limits imposes no risk (safety/efficacy) on patients.
Conventional sample size estimation is not possible – you need to perform simulations. I recommend the package
interesting nick.

❝ Do I understand correctly that Reference scaling is the same design as Partial Replicate:
❝ RRT, RTR, TRR ?
No, you don’t.
- Reference-scaling is a method assessing bioequivalence.
- The partial replicate is a design for it.
- 4 period (full) replicates
- TRTR | RTRT
- TRRT | RTTR
- TTRR | RRTT
- TRTR | RTRT | TRRT | RTTR 1
- TRRT | RTTR | TTRR | RRTT 1
- TR | RT | TT | RR 2
- TRT | RTR
- TRR | RTT
- TRR | RTR | RRT
- TRR | RTR 3
- The FDA requires at least 24 dosed subjects if the study is intended for reference-scaling.
The EMA requires at least 12 eligible subjects in the sequence repeating R of the 3 period full replicate designs.
- In any of the designs conventional (unscaled) average bioequivalence ABE can be evaluated as well (e.g., if CVwR <30% or reference-scaling for a particular PK metric is not acceptable).
- The statistical models differ between regulations.
- FDA (model RSABE: reference-scaled average bioequivalence).
- EMA (model ABEL: average bioequivalence with expanding limits) – also adopted by the WHO, Eurasian Economic Union, Australia, New Zealand, Brazil, Egypt, South Africa, ASEAN States.
Cmax and some PK metrics of MR-products. WHO: pilot phase for AUC; full replicate design mandatory.
- Health Canada (ABEL but potentially wider limits). Only AUC.
- Gulf States, Mexico: ABE but wider acceptance limits for Cmax (75–133%).
PowerTOST
for the statistical software R (open-source and free of costs).- Confounded effects (design not recommended).
- Balaam’s design (not recommended due to poor power characteristics).
- Extra-reference design (biased in the presence of period effects; design not recommended).
—
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Helmut Schütz
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Partial replicate or Reference scaling heaven sent 2017-12-29 17:24 [RSABE / ABEL]
- Partial replicate ≠ Reference scalingHelmut 2017-12-29 18:36