Deficiencies [Power / Sample Size]

posted by d_labes  – Berlin, Germany, 2018-02-01 19:57 (2327 d 07:56 ago) – Posting: # 18326
Views: 20,689

Dear Helmut,

Point 1.: IMHO the deficiency is not correct. To show dose linearity the equivalence test for both dose levels have to be fullfilled. Combination of both tests with AND.
That's similar to the BE decision for AUC and Cmax. Both have to be a positive outcome. Otherwise dose linearity would be rejected. No alpha-adjustment at all. As always stated by me in statistical analysis plans for that cases under the heading "Multiplicity".

Point 2. In the light of the combination of two BE statements (tablet vs. reference or capsule vs. reference) this is combination with OR. If, and only if a global statement is here appropriate. IMHO here both hypotheses are standing for it's own.
As a friend of mine told me quite recently: Since only tablets or capsules came to market, only for that formulation a patient risk exists ;-). Means no alpha-adjustment for multiple testing necssary.
This case is what my former company's boss always told the sponsors: Be aware that the regulatory bodies may ask you for 95% CIs as BE test if you submit "pilot" studies in which one of the two used Test formulations showed BE and the other not.
Regulators acted different. Sometimes accepted the study without deficiencies, sometimes asked really for 95% CIs. Fortunately in all cases I remember 90% CI's and 95% CI's gave the same answer: BE proven. That's because such cases, pilot BE studies with sample sizes around 12 with positive outcome, only occure for very small variabilities, CV around 10%.

Thus in contrast to nobody it would be reasonable to start a discussion with the authority concerning your point 1. But I know of course that discussing with regulatory authorities is NIL.
Answer their questions without question their questions.



Complete thread:

UA Flag
 Admin contact
23,057 posts in 4,840 threads, 1,641 registered users;
108 visitors (0 registered, 108 guests [including 89 identified bots]).
Forum time: 04:54 CEST (Europe/Vienna)

If you tell the truth you don’t have to remember anything.    Mark Twain

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