EMA: Method A or B [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2018-01-23 12:25 (2336 d 17:52 ago) – Posting: # 18263
Views: 4,171

Hi Mohamed,

❝ For Partial and full replicate studies, if we have some subjects with missing periods, i mean for example subjects who attended only 2 periods in partial replicate

First answering a question you didn’t ask. In partial replicate designs (TRR|RTR|RRT) I suggest to specify two analysis sets if data of the third period in sequence RRT is missing:
  1. Exclude subjects from the assessment of BE since the GL requires at least one treatment of T and R.
  2. Keep subjects for the estimation of CVwR.

❝ 1) Which method to use following the EMA guidelines; method A "GLM" or method B "Mixed"?.

❝ I want a clarified answer please with guideline reference if applicable.

Good question. The Q&A document states:

The analysis […] show that this approach (Method A) is feasible even for unbalanced replicate design studies. The advantage of this approach is that it is straightforward and that it appears to be software and software option independent. A simple linear mixed model, which assumes identical within-subject variability (Method B), may be acceptable as long as results obtained with the two methods do not lead to different regulatory decisions. However, in borderline cases and when there are many included subjects who only provide data for a subset of the treatment periods, additional analysis using Method A might be required.

My understanding and comments:From a purely statistical perspective my preferences are: Method C ≫ Method B > Method A. I don’t like the idea to treat subjects as a fixed effect. Given the observations from above, a sponsor probably would fair best with Method A only.

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