Replicate vs. 2×2×2 [Regulatives / Guidelines]

posted by M.tareq  – 2017-05-14 23:04  – Posting: # 17353
Views: 18,154

Hi Helmut,

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 ? :confused:

» 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 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.

Apologies for being information/knowledge leecher atm, will try to get my seed/leech ratio up ^^

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