Rules acc. to Health Canada [Outliers]
I'm just thinking about another slightly related issue.
Assume that there is an outlier in the study for Health Canada.
If the outlier wasn't removed, we would get GMR1, intra-subject CV1 and corresponding 90% CI.
However the outlier is removed according to the study protocol and the results are different:
- GMR T/R can be higher or lower than GMR1 randomly.
- intra-subject CV will be always lower than intra-subject CV1.
Assume the border case with true GMR 0.8 and intra-subject CV e.g. 30%. The TIE (in the border case equal to power) in standard 2x2 BE is 5%. However I am not sure if it is the same with exclusion of outlier. So do we get some bonus power as intra-subject CV will be always lower after exclusion? I just imagine the simulation - individual simulated cases with:
- observed GMR lower or equal to 0.8 - the same as standard 2x2, i.e. not bioequivalent cases.
- observed GMR is higher than 0.8 - as observed intra-subject CV is lower in cases with the exclusion of outlier(s) - there will be slightly more bioequivalent cases than in standard 2x2 without exclusion of outlier(s).
Maybe someone could try to simulate it - TIE with the exclusion of outlier(s) for BE in 2x2.
I am not familiar with outliers and complicated simulations - simulate data (true GMR 0.8 and intra-subject CV 30%), look for outliers and exclude them (it could end with lowering the intra-subject CV), calculate 90% CI, and do it million times. The result will be probably close to 5%, but still higher?
- Rules acc. to Health Canada Helmut 2019-02-05 15:04 [Outliers]
- Rules acc. to Health Canada ElMaestro 2019-02-05 15:30
- Rules acc. to Health Canada Ohlbe 2019-02-05 15:54
- Rules acc. to Health Canada Helmut 2019-02-05 17:52
- for either the test or reference product? mittyri 2019-02-05 15:58
- Discordant outliers Helmut 2019-02-05 17:42
- Rules acc. to Health Canada Shuanghe 2019-02-06 11:48
- Rules acc. to Health Canada zizou 2019-02-06 20:52
- Great post! Helmut 2019-02-07 10:37