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.