A new early-phase research center opened this month in Kansas by Vince & Associates Clinical Research includes a specialized QT safety assessment unit, which reflects recent regulatory changes to cardiac safety assessments that could bring more drugs to the pipeline and cost savings to sponsors.

“Clinical trials are getting more complex, and that means we have to keep up with the technological and innovative approaches in order to be able to conduct these ever-changing studies,” said Brad Vince, DO, CEO and medical director of Vince & Associates, an Altasciences company. The new four-story building also includes a controlled ventilation smoking area, a limited access specialty unit to sequester special populations, a state-of-the-art pharmacy and an expanded recruitment center.

The facility’s QT safety assessment unit has been specially designed to minimize 60hz cardiac monitoring interference and allow for enhanced data collection. The unit has been engineered for traditional electrocardiogram (ECG) collection as well as Holter monitoring. “This cutting-edge QT safety assessment unit positions us to support the new ICH E14 guideline,” Vince said. “It allows us to obtain the highest quality ECG data and potentially eliminates the need for a full Thorough QT (TQT) study.”

While ICH E14, the document sanctioned in 2005 by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, has been successful in that no compounds that have gone through TQT studies have been withdrawn from the market due to QT prolongation—an indication of risk of producing Torsade de Pointes (TdP), a potentially lethal arrhythmia—efforts have been ongoing for some time to explore ways to perform cardiac safety assessments in a more cost-effective and time-efficient manner.

The traditional TQT approach is expensive, at a typical cost of $2 to $5 million to run such studies. In addition, an unintended consequence of ICH E14 is that a number of drugs, some of which may have been safe and effective, were dropped in development due to minor QT concerns or unclear preclinical signals. 

In 2012, members of the Cardiac Safety Research Consortium (CSRC), including the FDA and other partners, began discussions around E14 and initiated a study two years later to explore options to replace TQTs with intense ECG collection during phase I single ascending dose or multiple ascending dose studies.

iCardiac Technologies, a centralized core laboratory for cardiac safety and respiratory services, signed on to sponsor, manage and analyze the data from the study. “We wanted to confirm if ECG data collected from routinely conducted phase I studies, with a little additional data collection and precise analysis, could result in definitive QT results for regulatory and decision-making purposes,” said iCardiac CEO, President and Co-Founder Alex Zapesochny.

The findings led to an ICH E14 guidance revision in December 2015 indicating that in the right circumstances, regulatory bodies will accept phase I ECG and pharmacokinetic-pharmacodynamic data to replace a TQT study for regulatory submission and review.

Vince said his company’s new facility was planned to optimize this new approach to cardiac safety assessments. “The FDA has begun to issue the first waivers for TQT trials,” Vince said. “This allows pharmaceutical companies to not only save money, but more importantly to de-risk their program much earlier in the development process. This is especially important for small biotech and virtual pharma companies, especially when it comes to obtaining funding for development.”

Vince & Associates was the first company to become a certified iCardiac partner, and a number of other partners have since joined. “There are many subtle factors that can disturb and effect electrocardiogram data, such as having too many people in the room or too much noise or external stimulation,” Zapesochny said. “Vince & Associates sought to address the environmental and other factors that can cause small and not-so-small differences that could affect the data, and designed their facility to minimize them.”

As the industry moves away from mandatory later-stage TQT studies, observers say steps toward the new guidance revision are becoming more common. A number of CRUs have invested in centralized ECG platforms that include the capture of telemetry and other ECG collection methodology and technology, said Boaz Mendzelevski, M.D., vice president of cardiology at Bioclinica, a cardiac safety core laboratory that has been involved in the ongoing evolution within the cardiac safety and TQT arena.

“With these changes in the regulatory paradigm, the clinical research industry is realigning to serve the new cardiac safety approach and intensive QT study by acquiring advanced ECG technologies and partnering with cardiac safety providers at core ECG laboratories,” Mendzelevski said.

“Part of what’s very effective in doing QT analysis this way,” Zapesochny pointed out, “is that it does not significantly alter the way phase I trials are already done at the site. That’s the beauty of it. For the most part, you can design and run a phase I trial exactly the way you would have. The only thing you need to make sure of is that the QT data are being collected very carefully, and that you are collecting it enough times throughout the study so that you are getting the relevant information at the right time.” 

This article was reprinted from Volume 20, Issue 20, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »