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In a move designed to both tout the importance of precision and to improve the sponsor experience in conducting cardiac safety assessment, iCardiac Technologies announced a full risk-sharing program for Thorough QT studies.
In a move designed to both tout the importance of precision and to improve the sponsor experience in conducting cardiac safety assessment, iCardiac Technologies announced a full risk-sharing program for Thorough QT studies. The program guarantees to sponsors that one of two desirable outcomes will be achieved: the results will (1) reflect a clean, negative study, in that the drug arm will show no prolongation above the regulatory threshold of concern, while the positive control arm will demonstrate assay sensitivity or (2) indicate that a positive result reflects an accurate one, in that the study will have QT measurements with standard deviations below specific levels, indicating a highly precise study. If neither of these two desirable outcomes is achieved, a sponsor will pay nothing to iCardiac.
Alex Zapesochny, CEO, and Tom Avery, Senior Vice President, of iCardiac Technologies explained to Applied Clinical Trials the multiple reasons for offering the guaranteed program. First, Zapesochny said that the company truly believes in its High Precision QT™ methodology for analyzing ECG waveforms and is backing this with the guarantee. Second, as Zapesochny and Avery analyzed contracts in other industries, and thought about the foundational theories of contract law, they noted that it is usually the party that is in the best position to control for risks and quality that is expected to bear the financial risks associated with those activities. To Zapesochny, that only makes sense. “But in our industry, we have the opposite. Core labs tell the sponsor we aren’t sure what the results will be, but we take no responsibility for inconclusive results based on poor precision. At iCardiac, we know we are in the best position to control the ECG measurement methodology and site training, so we will bear the financial risks if those activities turn out poorly.”
The FDA has previously reported that approximately 12% of all Thorough QT study results submitted between 2006 and 2013 were deemed to be “inconclusive.” Poor precision can cause inconclusive results, which sometimes occurs when an ECG core lab powers a study based on an expectation of achieving a precision level that it does not actually achieve when it runs the study. An even greater concern is the risk of a false positive QT result for a promising compound. Approximately 20% of all Thorough QT results submitted to the FDA from 2006-2013 were deemed to be “positive” for QT prolongation, though some of those positives might actually have been false positive results due to poor precision causing a widening of the confidence intervals pertaining to the study. (See Figure Below)
Early Phase, Late Phase Applicability
Avery noted that the enhanced precision used by iCardiac in TQT studies, which are usually conducted in parallel to Phase II or early in Phase III, can be highly useful when applied in ECG assessment during Phase I. “The trend is gaining information more efficiently in clinical development earlier and to shuffle the R&D spend more effectively. This provides that earlier actionable information,” said Avery.
Late phase is also benefitted from more precise ECG assessment, said Zapesochny. “Patients today are sometimes excluded from trials based on inaccurate ECG measurements. So applying better precision can speed up Phase III recruitment,” he explained. False continuation of patients can also occur in late phase trials, Zapesochny concluded, “We also see that imprecise ECG measurements in late phase trials can lead to financial waste due to inappropriate randomizations and false continuations of patients,” concluded Zapesochny.