CDER established the Interdisciplinary Review Team (IRT) for QT studies in 2006 to provide expert and consistent review advice to sponsors and review divisions within the FDA on the design and interpretation of thorough QT studies. In addition, the IRT evaluates the potential for drugs to cause torsade de pointes using an integrated approach of nonclinical assays as described by the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative, and clinical ECG data.
In 2018 the FDA issued a draft guidance on the assessment of the pressor effects of drugs. The scope of the IRT was subsequently expanded to include providing consistent review advice on the design and interpretation of safety blood pressure studies, including ambulatory blood pressure monitoring (ABPM) studies.
The IRT is a consulting review team within the Division of Cardiology and Nephrology (DCN) that consists of clinical reviewers and analysts, clinical pharmacologists, statisticians, safety pharmacologists, project manager, data specialists and representatives from the Division of Applied Regulatory Science (DARS).
The IRT can answer general and scientific questions related to proarrhythmia and blood pressure evaluation. However, all drug product-specific questions should be directed to the appropriate Clinical Review Division.
Current Advice *
Proarrhythmic Risk Assessment
- QT Evaluation Report Submission Checklist updated 6/21/21 (DOC - 31 KB)
- Clinical Pharmacology and Cardiac Safety Table updated 6/21/21 (DOC - 95 KB)
- Submitting Clinical Trial Datasets for Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential of Drugs – Technical Specifications Document and Proarrhythmic Potential of Drugs – Technical Specifications Document updated 6/21/19 (PDF - 581 KB)
- Submitting ECG Waveform Data (Frequently Asked Questions) updated 10/08/21 (PDF- 168 KB)
- In Vitro Ion Channel Protocols updated 8/11/21 (PDF - 152 KB)
- MaPP 6020.14 Interdisciplinary Review Team for QT Studies updated 11/20/18 (PDF - 136 KB)
- ICH E14: The Clinical Evaluation of QT/QTc Interval Prolongation
- ICH E14: Questions and Answers Revision 3
- ICH S7B: The Non-Clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals
Ambulatory Blood Pressure Monitoring Studies
* Content is subject to change without notice
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- Vicente J, et al. Assessment of Multi-Ion Channel Block in a Phase I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study. Clin Pharmacol Ther 2019;105(4):943-953
- Garnett C, et al. Scientific white paper on concentration-QTc modeling. J Pharmacokinet Pharmacodyn 2018;45(3):383-97
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- Malik M, et al. Universal Correction for QT/RR Hysteresis. Drug Saf 2016;39(6):577-88
- Darpo B, et al. Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase. Clin Pharmacol Ther 2015;97(4):326-35
- Johannesen L, et al. Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil. Clin Pharmacol Ther 2014;96(5):549-58
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- Garnett C, et al. Methodologies to characterize the QT/corrected QT interval in the presence of drug-induced heart rate changes or other autonomic effects. Am Heart J 2012;163(6):912-30
- Zhang J, et al. Statistical issues including design and sample size calculation in thorough QT/QTc studies. J Biopharm Stat 2008;18(3):451-67