Bioequivalence and Bioavailability Forum

Hi everyone,

Here is a slightly different but related scenario for an EMA study:

Regulatory has imposed some recruiting restrictions on our BE study which has forced us to dose in 2 groups due to an inability to recruit a sufficient number in a single group within the current timeframe.

Say we estimate we need to enroll 60 to complete 50 (~17% dropout rate) so we say in the protocol that Group 1 and Group 2 will have 30 subjects each. Can we do the following:

1. Dose Group 1 with 30 subjects.
   
2. Wait for Group 1 to complete Period 2 and assess the dropout rate. Let's say the dropout rate is higher than expected and 9 dropout during the study (ie: 30% dropout rate).
   
3. Amend the protocol at this point to enroll 45 more subjects for Group 2 to account for the higher than expected dropout rate and in hopes of meeting the final complete target of 50.

If this is even acceptable, do we need to state how many subjects are planned to be dosed in each group a priori in the protocol knowing that Group 2 size may need to change? I have doubts that we could say something like: 30 subjects will be dosed in Group 1 and a sufficient number dosed in Group 2 to complete with 50 subjects.

Thanks for your valuable opinions!