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Related Experiment Videos

Assay sensitivity in "Hybrid thorough QT/QTc (TQT)" study.

Dalong Patrick Huang1, Janell Chen1, Qianyu Dang1

  • 1a Office of Biostatistics, Office of Translational Sciences, CDER, FDA.

Journal of Biopharmaceutical Statistics
|October 23, 2018
PubMed
Summary

Hybrid TQT studies use concentration-QTc analysis for QTc clinical trials. Assay sensitivity with moxifloxacin in these trials depends on sample size, design, and model, impacting regulatory compliance.

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Area of Science:

  • Clinical pharmacology
  • Regulatory science
  • Biostatistics

Background:

  • ICH E14 guidance mandates concurrent positive controls in QTc clinical trials.
  • Hybrid TQT studies offer a reduced sample size alternative to traditional TQT studies, utilizing concentration-QTc (C-QTc) analysis.

Purpose of the Study:

  • To evaluate the statistical characteristics of assay sensitivity using moxifloxacin as a positive control in hybrid TQT studies.
  • To understand the impact of data subsampling on assay sensitivity in hybrid TQT study designs.

Main Methods:

  • Analysis of original and subsampled moxifloxacin and placebo data from over 100 TQT studies submitted to the FDA.
  • Comparison of assay sensitivity results between classical ICH E14 analysis and C-QTc analysis.
  • Investigation of factors influencing assay sensitivity in subsampled hybrid TQT data, including sample size, study design (crossover vs. parallel), and C-QTc model.
Keywords:
Assay sensitivityMoxifloxacinTQTconcentration-QTc modelinghybrid TQT

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Main Results:

  • Assay sensitivity results were consistent between classical E14 and C-QTc analyses using original datasets.
  • The performance of assay sensitivity in hybrid TQT studies with subsampled data is influenced by the number of moxifloxacin subjects, study design, and the C-QTc model used.

Conclusions:

  • The findings support the use of hybrid TQT studies for meeting ICH E14 requirements.
  • Results provide guidance for optimizing the design of future hybrid TQT studies to ensure robust assay sensitivity.