Bioequivalence and Bioavailability Forum

Hi VP!

I'm confused. You dispensed IPs to subjects one week before dosing, five subjects were withdrawn from the study, and now you want to administer the 'same IPs' to another five subjects? Will you ask the noncompliers to return IPs and hope nothing will have happened to these IPs? Using the same subject IDs for new subjects is a very bad idea - troubles approaching. Most guidelines discourage inclusion of new subjects in a study - you should plan your study for an anticipated dropout-rate (i.e. include reserves). The study should be large enough to have suitable power after eventual dropouts. In our protocols we mandate recruitment of additional subjects only if we would face a sample size of <12 after dropouts. A study with less than 12 subjects is not acceptable in many regulations, even for formulations with a small CV.

Please check FDA's guidances yourself the next time!
You would have found Section V.B. Sample Size and Dropouts:

Sponsors should enter a sufficient number of subjects in the study to allow for dropouts. Because replacement of subjects during the study could complicate the statistical model and analysis, dropouts generally should not be replaced. Sponsors who wish to replace dropouts during the study should indicate this intention in the protocol. The protocol should also state whether samples from replacement subjects, if not used, will be assayed. If the dropout rate is high and sponsors wish to add more subjects, a modification of the statistical analysis may be recommended.