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RegisterReplicate vs. 2×2×2 [Regulatives / Guidelines]
Hi Helmut,
Thanks for your comprehensive reply and explanation,
Can i get the link or the name of the paper when the authors submit it ?
In General, if a drug isn't known to be HVDP and by definition of HVDP that, they have wide therapeutic index yet the CRO/Sponsor went with replicate design.
How the assessor would consider that? mean if the published literature or pilot study suggest low CV of the reference /test product yet the cro/sponsor went with replicate design?
Like abusing the use of scABE ?
Agree, yet i read an ANDA submission -can't find the link now- where the sponsor detected outliers based on T/R ratio of each subject and redosing of such subjects along with other subjects who exhibited normal pkp profile; though it was after reviewing with FDA regulator.
Another published paper about ibandronic acid https://www.ncbi.nlm.nih.gov/pubmed/24756462 the sponsor/CRO stated the definition of outliers using studentized residuals and boxplot to eliminate subjects with values away from the boxplot by more than 3 IQR.
My point is, as your kindly said, it's best to state in the protocol how to deal with outliers especially regarding variability estimation and proving/showing to the assessor the reasons for excluding such outlier(s) from study or reviewing it with the regulator before submission of the data?
Thanks and Best Regards.
P.S:
Apologies for being information/knowledge leecher atm, will try to get my seed/leech ratio up ^^
Thanks for your comprehensive reply and explanation,
❝ while ago I reviewed a manuscript exploring the pros and cons of TSDs vs. ABEL. Was very interesting and I hope that the authors submit a revised MS soon.
Can i get the link or the name of the paper when the authors submit it ?
In General, if a drug isn't known to be HVDP and by definition of HVDP that, they have wide therapeutic index yet the CRO/Sponsor went with replicate design.
How the assessor would consider that? mean if the published literature or pilot study suggest low CV of the reference /test product yet the cro/sponsor went with replicate design?
Like abusing the use of scABE ?
❝ Nobody knows how to deal with this story. 
Regulations ≠ science. Not required by the FDA…
Agree, yet i read an ANDA submission -can't find the link now- where the sponsor detected outliers based on T/R ratio of each subject and redosing of such subjects along with other subjects who exhibited normal pkp profile; though it was after reviewing with FDA regulator.
Another published paper about ibandronic acid https://www.ncbi.nlm.nih.gov/pubmed/24756462 the sponsor/CRO stated the definition of outliers using studentized residuals and boxplot to eliminate subjects with values away from the boxplot by more than 3 IQR.
My point is, as your kindly said, it's best to state in the protocol how to deal with outliers especially regarding variability estimation and proving/showing to the assessor the reasons for excluding such outlier(s) from study or reviewing it with the regulator before submission of the data?
Thanks and Best Regards.
P.S:
Apologies for being information/knowledge leecher atm, will try to get my seed/leech ratio up ^^
Complete thread:
- Highly Variable Drug BE Justification jag009 2017-03-20 04:42 [Regulatives / Guidelines]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Highly Variable Drug BE Justification ElMaestro 2017-03-20 06:55
- Study costs: Replicate vs. 2×2×2 Helmut 2017-03-20 13:12
- Study costs: Replicate seems to be cheaper VStus 2017-03-21 12:49
- Study costs: Replicate seems to be cheaper Dr_Dan 2017-03-21 13:06
- Study costs: Replicate seems to be cheaper Helmut 2017-03-21 14:50
- expected power d_labes 2017-03-21 15:16
- Doesn't hurt! VStus 2017-03-23 14:24
- Study costs: Replicate seems to be cheaper Helmut 2017-03-21 14:50
- Study costs: Replicate seems to be cheaper Dr_Dan 2017-03-21 13:06
- Study costs: Replicate vs. 2×2×2 mahmoud-teaima 2017-03-23 08:17
- Study costs: Replicate vs. 2×2×2 M.tareq 2017-05-07 21:21
- Replicate vs. 2×2×2 (ethics?) Helmut 2017-05-08 14:21
- Replicate vs. 2×2×2 (ethics?) nobody 2017-05-08 14:52
- Applicability of reference-scaling Helmut 2017-05-10 14:10
- Replicate vs. 2×2×2M.tareq 2017-05-14 23:04
- Replicate vs. 2×2×2 Helmut 2017-05-15 19:07
- Replicate vs. 2×2×2 M.tareq 2017-05-15 21:02
- Regulators view of HVD drugs DavidManteigas 2017-05-16 12:41
- Regulators view of HVD drugs Helmut 2017-05-16 15:01
- What's the problem? ElMaestro 2017-05-17 03:30
- What's the problem? nobody 2017-05-17 07:48
- What's the problem? nobody 2017-05-17 09:31
- What's the problem? DavidManteigas 2017-05-17 11:25
- What's the problem? ElMaestro 2017-05-17 12:07
- What's the problem? kumarnaidu 2017-07-11 14:43
- What's the problem? ElMaestro 2017-07-11 14:56
- What's the problem? kumarnaidu 2017-07-11 14:43
- What's the problem? ElMaestro 2017-05-17 12:07
- What's the problem? DavidManteigas 2017-05-17 11:25
- What's the problem? nobody 2017-05-17 09:31
- What's the problem? nobody 2017-05-17 07:48
- Replicate vs. 2×2×2 Helmut 2017-05-15 19:07
- Replicate vs. 2×2×2 (ethics?) nobody 2017-05-08 14:52
- Replicate vs. 2×2×2 (ethics?) Helmut 2017-05-08 14:21
- Study costs: Replicate seems to be cheaper VStus 2017-03-21 12:49
- Study costs: Replicate vs. 2×2×2 Helmut 2017-03-20 13:12
- Highly Variable Drug BE Justification ElMaestro 2017-03-20 06:55
Ing. Helmut Schütz