Bioequivalence and Bioavailability Forum

Dear Ioana,

❝ Do I have to calculate an average of readings from the sites in duplicate (for the same moment) and use it in the analysis?

Pilot dose duration response study

At least eight dose durations and four untreated control sites are randomly assigned among the 12 sites in each subject, maintaining two untreated control sites and four dosed sites on each arm (six sites per arm). In case more sites are dosed (duplicating of doses in the other arm) (ex: a total of 12 sites in each arm with 2 untreated sites in each arm) the averaging of AUEC values for the duplicate dose duration sites will be done.

AUECs for all the individual sites will be calculated after baseline and untreated site corrections. curve will be plotted and ED50 calculated. Using ED50 the D1, D2 will be calculated.


Pivotal study

AUECs for the individual sites will be calculated after baseline and untreated site corrections. Averaging of duplicate sites will be done folowing which subjects' data will be selected if they meet the criteria D1 & D2 both being negative and Ratio (D2/D1)>=1.25 (Detectors)

The data of these subjects will be subjected for T/R ratio calculation using Locke's method.

Please check appendix III & IV in the following link for specific details
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070234.pdf

Best wishes
Max