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ICH revises regulatory path in TQT clinical studies

Monday, January 4, 2016

Rochester, N.Y.-based iCardiac Technologies, a provider of cardiac safety assessments, has voiced support of the official release of a regulatory revision enacted by the International Council for Harmonization (ICH) that defines and enables an alternative path to the conduct of a Thorough QT (TQT) study in clinical drug development.

Possibly the most significant regulatory shift in cardiac safety since the original E14 Guidance was adopted by the ICH in 2005, the new revision emerged following the successful conduct of a prospective validation study in 2014 that was sponsored by iCardiac and which utilized iCardiac’s personnel and technology to perform the critical data analysis.

The FDA and other regulators currently expect nearly all new drugs to be tested using a costly, stand-alone TQT study to assess a drug’s effect on the QT interval before market approval, since a prolonged QT interval is associated with a heightened risk for arrhythmias and possible sudden cardiac death. The revision adopted by the ICH, an international forum for regulators to harmonize drug approval practices, describes how data from ECGs collected during routine phase I or other early clinical trials may be used to conclusively demonstrate a drug’s QT effect.

The approach relies on intensive, high-quality ECG analysis and the use of exposure response modeling. A sponsor that submits QT data to a regulator meeting certain defined standards, as described in the ICH revision document, may seek a waiver from having to conduct a TQT study. The FDA granted the first TQT waiver based on the alternative approach earlier in 2015. In addition to representatives from the FDA, the ICH includes regulatory representatives from the European Union, Japan, Canada and Switzerland.

iCardiac has been at the forefront of championing the alternative approach for several years. Its proprietary High Precision QT methodology, which was optimized over many years to provide conclusive results from smaller studies, provided iCardiac with early confidence in the feasibility of gaining actionable QT data from phase I studies. In addition to serving as the only ECG core laboratory involved in the conduct of the definitive 2014 validation study, iCardiac has developed a Certified Site network of phase I sites that are trained and tested in the conduct of capturing high-quality ECG data that is optimally suited for the alternative approach.

Given its unique experience with the type of study, iCardiac is conducting two free public webinars to explain the new ICH guidance and the standards it establishes for receiving a waiver from the TQT study. The public webinars will be held Jan. 12 and Jan. 20.

“The significance of the change in regulations is that it gives sponsors a choice. You can either perform a careful assessment of the drug’s effect on ECG parameters as part of your standard early clinical trials, or you can later on conduct a formal TQT study. Both options are now viable alternatives, provided you do things right,” said Dr. Borje Darpo, a cardiologist and chief scientific officer at iCardiac.

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