All dosed subjects have to be analyzed [General Sta­tis­tics]

posted by Helmut Homepage – Vienna, Austria, 2020-06-30 12:19  – Posting: # 21615
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Hi Sveta,

» In a 5-way BE crossover trial, is there a methodology available that allows one to analyze 3 out of 5 sequences for BE in an interim fashion, and contingent upon results complete the remaining 2 sequences and analyze all 5 sequences at the conclusion?

Once you dosed subjects (i.e., in all 5 sequences), you have to analyze them. Anything else is not ethical. Along these lines the EMA’s BE-GL, section Subject accountability:

Ideally, all treated subjects should be included in the statistical analysis. […]
The data from all treated subjects should be treated equally. It is not acceptable to have a protocol which specifies that ‘spare’ subjects will be included in the analysis only if needed as replacements for other subjects who have been excluded. It should be planned that all treated subjects should be included in the analysis, even if there are no drop-outs.

(my emphasis)

Even if your protocol would be accepted by the IEC/IRB and agency (I hope not), your approach might lead to an inflated type I error (if you fail with 3 sequences and continue with the other 2) because at the end you will use 60% of the data twice. Calls for some kind of α-adjustment (narrower CI) due to multiplicity issues.

» Could you please provide references on this subject.

IMHO, nothing published – and for a reason. Don’t even think about the ‘magic’ α 0.0294. In short: Forget it.

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Helmut Schütz
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