## bootstrap [Study As­sess­ment]

Hi Samaya,

» Can you please explain in some more detail how to use bootstrap data set to get a sense of the data and bootstrap with larger sample size?

Many program can perform bootstrap. If you use SAS, try PROC SURVEYSELECT. Use METHOD=URS for sampling with replacement. You can specify the sample size (say 28) with SAMPSIZE=28* and and repeated number (say 1000 times) with REPS=1000. Use subject as selection unit with SAMPLINGUNIT subject; .

* Note that you can have sample size which is greater than your original data since this is sampling with replacement.

now you have a data set with 1000 sets of data with each set having 28 subjects. You can do BE analyse as usual (add BY replicate statement in your sas code) so for each replicate you'll have T/R ratio and 90% CI and ISCV etc. So you'll have 1000 of those now. Obvious BE result of each replicate will be slightly different. Now you can see how they vary.

However, there are some drawbacks such as repeated subject number, sometimes sequence is extremely unbalanced (e.g., for certain replicate you might have 20 subject with TR and 8 with RT) etc.

You can generate dummy subject number to replace with the original ones and to remove certain replicates with extremely unbalanced sequence (what you think is unlikely occur in real life. for example, for BE study with 100 subjects (50TR+50RT), after 15 drop out, 45TR +40RT might be likely but 50TR +35RT might not) before doing BE analysis.

Also, you can try adding some random number to your logPK data based on the intra-subject variability of the formulation before analysis. But I'll leave it to you to try them.

All the best,
Shuanghe