misunderstanding [RSABE / ABEL]

posted by Mikalai  – Belarus, 2020-02-06 14:41 (1529 d 22:17 ago) – Posting: # 21153
Views: 17,593

(edited by Mikalai on 2020-02-06 16:18)

Hi Mitturi,
My remarks

❝ Republic of what?

This is from the Star Wars.

❝ I think the reason of that words is the misunderstanding of arguments given above...

I think there is no misunderstanding. I never said that in ABEL/RABE trials TIE should not be controlled. What I worry is the control TIE may invalidate the whole method, because in a big number studies the reduction in sample size can be negligible but risks can double for subjects. I also afraid that this can be assesd only post-hoc. Do we have a decisicion tree for ethic committees?

❝ There's no science in p value = 0.05. Or could you do me a favour and give some link where the contrary arguments exist? That's just a convention (given in GLs too). Rules of game. If you go there, please use it.

It probably deserves a separate topic. Who set up rules of the game in this case? Moreover TIE as consumer protection metric is very controversial. Have we asked people about this convention? Do we have good feedback mechanisms with consumers? Do we incorporate qulitative studies in our regulatory documetns. How can we represent consumers if we do not speak with them? It seems that people tolerate much higher risks than we use currently. Look at alternative medicine. They have millions customers and don't bother with any statistics.

❝ It should be controlled everywhere, not only in ABEL

It is Utopia, and good luck with this. See my comments above. But I can give another argument.

At the heart of bioequivalence lie the concept that products are different. But what does this mean. Is the fact that they are manufactured by different companies is enough to make this conclusion? Have manufacturing processes of different manufactures have ever been compared. And what about TIE deflating factors like industrial statisticians, industrial spies, angry sacked employees from original producers, the same equipment and the same supppliers. Might be that the TIE inflation risk is a bit overestimated This is why if something is widely used and is a reason to rejection, it should be mentioned in regulatory documents.

❝ Please define 'win'. You didn't win until null hypothesis(es) is rejected.

If somebody shot all alpha level and passed the bioequivalence at the first stage.

❝ Are the arguments regarding TIE inflation not clear? WE are living in the real world where »the precedence does not rule everywhere. And the experts also err. Maybe they didn't »realize here the problem of TIE inflation. Remember that the problem is rather new.

It seems that the issue is still not clear for most regualtors.It also seems that this issue is afloat for more 7 years. Also, where are results of the inflated TIE? Where are unsafe and ineffecient drugs.

❝ what are the benefits of replicate design for that CV value (30%)?

We never know our final CV. See my comments below.

❝ Have you read Helmut's calucations for the sample sizes?

See my comments below

❝ I think it is a good reason not to read the end of that paragraph, sorry...

There are no stupid questions there are either not good answers or ignorance. Sorry ...

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