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RegisterCounterintuitive? [Design Issues]
Hi Nobody,
The BE studies I have seen (I am quite junior), the drugs follow dose-linearity. One convenient result is that the shape of the PK curve generally stays the same under test conditions. That means the tests aren't required to be sensitive for changes in shape.
This drug doesn't follow that assumption for reasons previously discussed. The PK shape changes under small formulation changes (e.g. REL). There is definitely a need for non traditional parameters, as it is conceivable that AUCinf and Cmax may pass, but with wildly (and clinically relevant) differences in shape.
I agree that the test applied should be invariant to T/R or R/T. Perhaps run a test on Tmax - which based on the above image, appears to be sensitive to changes in REL. Or require passing all the tests together.
Cheers,
BF
❝ Why should the ratio of REL influence the appropriate metric for BE? Switching T and R should not influence the test in my opinion...
The BE studies I have seen (I am quite junior), the drugs follow dose-linearity. One convenient result is that the shape of the PK curve generally stays the same under test conditions. That means the tests aren't required to be sensitive for changes in shape.
This drug doesn't follow that assumption for reasons previously discussed. The PK shape changes under small formulation changes (e.g. REL). There is definitely a need for non traditional parameters, as it is conceivable that AUCinf and Cmax may pass, but with wildly (and clinically relevant) differences in shape.
I agree that the test applied should be invariant to T/R or R/T. Perhaps run a test on Tmax - which based on the above image, appears to be sensitive to changes in REL. Or require passing all the tests together.
Cheers,
BF
Complete thread:
- Counterintuitive? nobody 2018-04-03 11:16 [Design Issues]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Counterintuitive? bebac_fan 2018-04-03 18:20
- Counterintuitive? nobody 2018-04-03 23:25
- Counterintuitive?bebac_fan 2018-04-04 00:43
- Counterintuitive? nobody 2018-04-04 11:03
- Counterintuitive?bebac_fan 2018-04-04 00:43
- What is clinically relevant? Helmut 2018-04-04 16:49
- What is clinically relevant? nobody 2018-04-05 10:04
- What is clinically relevant? bebac_fan 2018-04-05 14:19
- What is clinically relevant? nobody 2018-04-06 09:22
- What is clinically relevant? Helmut 2018-04-06 16:10
- What is clinically relevant? bebac_fan 2018-04-06 20:53
- What is clinically relevant? Helmut 2018-04-06 22:05
- Korsmeyer–Peppas’ model mittyri 2018-04-06 23:36
- What is clinically relevant? Helmut 2018-04-06 22:05
- What is clinically relevant? bebac_fan 2018-04-06 20:53
- Counterintuitive? nobody 2018-04-03 23:25
- Counterintuitive? bebac_fan 2018-04-03 18:20
Ing. Helmut Schütz