Bioequivalence and Bioavailability Forum • Highly variable long half life drug parallel reference scal

DAHK
☆

2011-10-11 09:27
(5372 d 15:37 ago)

Posting: # 7465
Views: 5,744

Highly variable long half life drug parallel reference scal [Design Issues]

A drug with a very long half life, gets retained in body for a very long period, thus it requires a parallel design for establishing Bioequivalence.
When a drug is having a very high variability, we prefer to conduct a partial replicate or a full replicate design (RTR or RTRT).
On the other hand if a drug is highly variable and with a very long half life can we go in for a parallel study design with three groups i.e. R T and R and do the reference scaled averaging.

else how do we design this study?

Dr_Dan
★★

Germany,
2011-10-11 12:05
(5372 d 12:58 ago)

@ DAHK
Posting: # 7468
Views: 4,815

Highly variable long half life drug parallel add on design?

Dear all
One question to Helmut:
Is it possible to conduct in case of a highly variable long half life drug a parallel group study with an add on design?
Rationale: widening of acceptance range not possible due to the fact that the replicate design is out of question but intention to be more on the safe side with the possibility to adapt sample size.
Kind regards
Dan

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Kind regards and have a nice day
Dr_Dan

Helmut
★★★

Vienna, Austria,
2011-10-11 16:34
(5372 d 08:29 ago)

@ Dr_Dan
Posting: # 7470
Views: 4,899

HVDs/HVDPs parallel add on design?

Post reply

Dear Dan!

❝ Is it possible to conduct in case of a highly variable long half life drug a parallel group study with an add on design?

Theoretically yes. Actually group sequential methods were developed for parallel designs (superiority case). It should be possible to adapt these methods even more easily to the equivalence case than in the recent work for cross-overs (Potvin et al. 2008, Montague et al. 2011). But since the Null-hypothesis is formulated differently we would need simulations to demonstrate no α-inflation. Maybe one of the forum’s members is already working on it? :cool:

❝ Rationale: widening of acceptance range not possible due to the fact that the replicate design is out of question but intention to be more on the safe side with the possibility to adapt sample size.

Right.

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

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Helmut
★★★

Vienna, Austria,
2011-10-11 16:54
(5372 d 08:09 ago)

@ DAHK
Posting: # 7471
Views: 5,029

Highly variable long half life drug parallel reference scal

Post reply

Dear DAHK!

I. Yes.

❝ II. When a drug is having a very high variability, we prefer to conduct a partial replicate or a full replicate design (RTR or RTRT).

What is the question?^*)
The selection between 4-period and 3-period replicate design depends on:

Ethical considerations (blood loss, AEs).
Sensitivity of the analytical method. In a 4-period design you may be forced to decrease the volume of blood samples.
Expected drop-out rate.
Power considerations. Although the same number of administrations will give the same power (sample size in a full replicate design 50% of a 2×2 cross-over and in a three-period 75%), you have to take into account the block size:
2 in TRT|RTR, TRR|RTR, TRR|RTT, RTRT|TRTR;
3 in TRR|RTR|RRT;
4 in TRT|RTR|TRR|RTT.
Interest in not only CV_WR (three period) but also CV_WT (four period) although not necessary for scaling? Note that there are some three period designs which also allow the estimation of CV_WT (e.g., TRT|RTR or TRT|RTR|TRR|RTT).

III) See this post.

^*) When it comes to fruits: I do prefer apples or oranges. :-D

—
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

navoday ☆ India, 2012-06-01 19:52 (5138 d 05:11 ago) @ DAHK Posting: # 8655 Views: 4,256	Highly variable long half life drug parallel reference scal Post reply
	Dear DAHK, I think you are talking about risedronate Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]