Bioequivalence and Bioavailability Forum

New Zealand [RSABE / ABEL]

posted by Helmut  – Vienna, Austria, 2015-02-02 00:54 (3754 d 11:43 ago) – Posting: # 14342
Views: 22,795

Hi nobody,

❝ What was the exact wording for this "40-volunteers is too much" thing in the 5th edtition of this guideline?

The entire paragraph of the 6^th ed, p20 was exactly the same in the 5^th (section 15.5.5 p143).

If the calculated number of subjects appears to be higher than is ethically justifiable, it may be necessary to accept a statistical power which is less than desirable. Normally it is not practical to use more than about 40 subjects in a bioavailability study. Where calcu­la­­tions suggest that an excessive number of subjects is required, clinical efficacy and/or safety studies are an alternative. The use of a co-administered active ingredient labelled with non-radioactive isotope as a reference, or studies in which treatments are replicated within each subject, may improve discriminatory power for highly variable medicines.

In the 6^th ed. you find also

If the calculated number of subjects appears to be higher than is ethically justifiable, it may be necessary to accept a statistical power which is less than desirable. It is usually not ethically justifiable to use more than about 40 subjects.

on p32. Same text in the 5^th, p153.

Personal remark: If >40 subjects in a PK study are not ethical, I don’t comprehend how “clinical efficacy and/or safety studies“ (with extreme sample sizes!) could be “an alternative”.
There are very few examples of PD endpoints having less variability than PK. A surrogate – or even more a true – clinical endpoint? Wellington, show me an example!

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


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