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RegisterSignificance [Power / Sample Size]
Hi Outlaw,
a 90% CI that doesn't spanover 1.0 should generally be no problem. It means that Test and Ref differ but so be it; all products differ and sometimes we can even detect it as a significant treatment effect as in your case. The primary equivalence criterion is still just a 90% CI within the acceptance range. Statistically different isn't necessarily clinically relevant.
If there is a concern of this type from the assessor's side then
I support this view in principle. But of course one should note that a 90% CI within 0.8-1.25 is a general acceptance principle but not guaranteed to be applicable to each and every drug. If anyone -such as an assessor- would have considerations about two products being too different or the classical criterion for BE is inadequate for a specific product, then a much more obvious solution would be for the assessor to suggest a narrower 90% CI acceptance range.
Finally, as a curiosity note that in Denmark they still have an odd clause requiring 1.0 being part of the 90% CI. As mentioned above I doubt very much that they will be able to defend this principle in a referral.
a 90% CI that doesn't spanover 1.0 should generally be no problem. It means that Test and Ref differ but so be it; all products differ and sometimes we can even detect it as a significant treatment effect as in your case. The primary equivalence criterion is still just a 90% CI within the acceptance range. Statistically different isn't necessarily clinically relevant.
If there is a concern of this type from the assessor's side then
- I'd suggest to confront the assessor with your view. Keep your argumentation as 'quality-focused' as possible thus avoiding too much clinical justification.
- The assessor might not be very experienced.
- The assessor might be an MD.
- If this is a European submission then you will with quite some likelihood win with little effort if you enter a referral.
❝ Personally, I'm focusing on the study results being compliant with the guideline requirements (Cmax is within the confidence intervals). Since this is the case, whatever difference in Cmax between test and reference products are non-significant. Is this correct? Comments?
I support this view in principle. But of course one should note that a 90% CI within 0.8-1.25 is a general acceptance principle but not guaranteed to be applicable to each and every drug. If anyone -such as an assessor- would have considerations about two products being too different or the classical criterion for BE is inadequate for a specific product, then a much more obvious solution would be for the assessor to suggest a narrower 90% CI acceptance range.
Finally, as a curiosity note that in Denmark they still have an odd clause requiring 1.0 being part of the 90% CI. As mentioned above I doubt very much that they will be able to defend this principle in a referral.
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Pass or fail!
ElMaestro
Pass or fail!
ElMaestro
Complete thread:
- Significance The Outlaw Torn 2012-11-20 07:56 [Power / Sample Size]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- SignificanceElMaestro 2012-11-20 08:17
- Significance The Outlaw Torn 2012-11-20 08:55
- Quality vs. Clinical ElMaestro 2012-11-20 09:04
- Significance The Outlaw Torn 2012-11-20 08:55
- Sample size? Helmut 2012-11-20 20:10
- Sample size? The Outlaw Torn 2012-11-21 07:52
- Sample size? The Outlaw Torn 2012-11-22 10:55
- Sample size, ratio, CV ↔ power Helmut 2012-11-22 13:35
- Sample size, ratio, CV ↔ power The Outlaw Torn 2012-11-23 14:47
- Sample size, ratio, CV ↔ power BEQool 2025-01-31 13:12
- TOST != treatment effect mittyri 2025-02-20 13:13
- Sample size, ratio, CV ↔ power zizou 2025-02-21 13:40
- Not vice versa mittyri 2025-02-22 21:08
- Not vice versa? zizou 2025-02-24 11:02
- Not vice versa? mittyri 2025-02-25 06:12
- Not vice versa? zizou 2025-02-24 11:02
- Not vice versa mittyri 2025-02-22 21:08
- Sample size, ratio, CV ↔ power Helmut 2012-11-22 13:35
- Sample size calculation using Marzo and Balant method kumarnaidu 2013-01-31 07:48
- Marzo / Balant formula d_labes 2013-01-31 10:05
- Marzo / Balant formula kumarnaidu 2013-01-31 10:54
- Marzo / Balant formula kumarnaidu 2013-02-04 05:48
- Marzo / Balant formula for parallel groups d_labes 2013-02-04 08:44
- Marzo / Balant formula kumarnaidu 2013-02-04 05:48
- Marzo / Balant formula kumarnaidu 2013-01-31 10:54
- Marzo / Balant formula d_labes 2013-01-31 10:05
- SignificanceElMaestro 2012-11-20 08:17
Ing. Helmut Schütz