T-32: Baseline Adjustment in Concentration-QTc Modeling: Impact on Assay Sensitivity
Poster Presenter
Dalong Patrick Huang
Lead Mathematical Statistician, CDER
FDA United States
Objectives
To evaluate and assess impacts of different baseline adjustments using C-QTc modeling in assay sensitivity analysis
Method
The data was selected from TQT studies submitted to FDA’s QT Interdisciplinary Review Team from July 2006 to September 2016. The pre-selected C-QTc model from the Scientific White Paper was used in our evaluation (Garnett et al 2017).
Results
Results of Two Key Research Questions:
How does the C-QTc modeling with different baseline adjustments compare with the classical E14 analysis regarding assay sensitivity?
Excellent agreement between C-QTc and E14 under crossover design;
High agreement between C-QTc and E14 under parallel design (except time-matched baseline).
Does baseline adjustment have an impact on C-QTc modeling in showing assay sensitivity?
Impact depends on study design;
Impact depends on sample size.
Conclusion
Sample size planning:
Start with sufficiently large number of subjects on moxifloxacin arm (e.g. at least 20).
Baseline choice:
Choose appropriate baseline to use in C-QTc analysis according to study design.
