#2: Two Part Hybrid Design
Two part refers to
- initial randomization + prospectively defined observational cohort
- direct assessment of antiviral effect during first 10 d then indirect dose response via correlation with baseline PT
Assumes that lead-in period is brief enough that:
- pts on OLD + Drug X don’t develop resistance
- pts continuing OLD regimens won’t have adverse consequences due to not changing therapies
However, lead-in period needs to be long enough to assess antiviral effect
May provide supportive evidence in NDA package