Bioequivalence and Bioavailability Forum • Issue with PBE Calculation when Stage = 1

weiguo2122
☆

2025-01-13 21:19
(116 d 18:03 ago)

Posting: # 24339
Views: 1,216

Issue with PBE Calculation when Stage = 1 [Regulatives / Guidelines]

FDA “Draft Guidance on Budesonide” part 5, provides Recommendation Related to the Population Bioequivalence (PBE) Statistical Analysis Procedure (Step 3):

a. If SigmaR is greater than 0.1, the reference-scaled procedure should be used.
b. If SigmaR is less or equal to 0.1, then the constant-scaled procedure should be used.

However, when stage (m) is 1, SigmaR cannot be defined because the calculation for MSWk cannot proceed when m = 1 (see formula for MSWk in the guidance).
[image]

What approach should be used to calculate PBE when m = 1? Are there any alternative methods or approaches recommended in this scenario?

I have attached formula from Draft Guidance on Budesonide for reference.

Thanks for replying and suggesting!

ElMaestro
★★★

Denmark,
2025-01-13 22:08
(116 d 17:14 ago)

@ weiguo2122
Posting: # 24340
Views: 1,054

Issue with PBE Calculation when Stage = 1

Post reply

Hello Weiguo2122,

❝ What approach should be used to calculate PBE when m = 1? Are there any alternative methods or approaches recommended in this scenario?

When m=1 you have a between units variation (MSB = Mean Square Between) but you do not have a within-unit-variation (MSW = Mean Square Within). A mean square is a variance. The square root of a variance is a standard deviation. You see, at m=1 the entire right-hand side of whatever is under the square root sign disappears.
So, at m=1 the stdev for ref is the square root of MSB for that formulation. :-)

—
Pass or fail!
ElMaestro

weiguo2122 ☆ 2025-01-15 21:45 (114 d 17:37 ago) @ ElMaestro Posting: # 24341 Views: 924	Issue with PBE Calculation when Stage = 1 Post reply
	Hi ElMaestro, Thank you for your reply. Based on your suggestion, I have been working with a set of code Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Ohlbe]