zigzag [RSABE / ABEL]

posted by Mikalai  – Belarus, 2020-02-06 12:38 (1567 d 06:06 ago) – Posting: # 21152
Views: 17,825

Ok, guys let discuss a bit further. I am gonna describe two bad scenarios.

The first one, we assume that the CV of a drug is around 35%, so we are ready for the worst inflation TIE in our ABEL trial with 4-periods. Thus, we decided to increase our sample size to 42 subjects to compensate for the adjusted TIE and then added the 15% dropout rate that resulted in 49 subjects in our full sample size. We have done our trial. We have got the CV around 32% and big inflation TIE, but we passed because of safety measures.

The second is a bit worse. We assume that the CV of a drug is around 40-42%. We decided to recruit 40 subjects - with full compensation - to conduct a 4 periods ABEL trial. Then have suddenly got the CV 32% and massive inflation TIE. We failed the trail because of the lack of power. We did the second trial with 49 subjects and passed.

There are a couple of questions.
Are these scenarios are plausible?
How frequent can they be?
Could three-periods trials reduce the number of subjects?

In terms of the flat world and also as response to the remark from mittury. In Belarus, if you decided to conduct a crossover ABE trial in multiple groups and decided to drop the group factor and its interaction from the statistical model (3rd method of FDA) then you have to prove the groups are from the same population. You should statistically compare the demographics of groups. And you can only drop the group factor if there are no statistical differences between groups irrespectively of the fact that subjects have been randomized to the group before the first period of the first group. But how it is possible to have different populations if people have been recruited from the same places (Minsk and its surroundings for example) and according to the same inclusion and exclusion criteria. It is not like one group is from Belarus and the other is from China or Australia. Again, the design is the crossover.

Also, mittury, you should take into account that not all sections of the Euroasian guideline are applied in Belarus at this time. It is left at the discretion of experts. One example. If they decide that a drug is risky (I do not know how they do this), then a sponsor should measure analytes - if the FDA says that - irrespectively of what is written in the guideline and the fact that the parent drug can be perfectly measured. No analytes and only parent drug, no registration. They do not disclose what other sections can be applied differently.

Best regards

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