Do Lessons Learned Help Make New Drugs Safer?: Presented at ACCP


By Linda J. Little

PHOENIX, AZ -- October 8, 2004 -- The risk of new drugs coming on the market that cause irregular heart beats in patients who are treated with them remains a serious concern, but great strides in safety have been made, stated Jeffrey Barrett, MD, Research Associate and Professor of Pediatrics, Children's Hospital, Philadelphia, here on October 4^th at the American College of Clinical Pharmacology Annual Meeting.

The issue of QT prolongation first became a safety concern after patients taking the H₂ antagonist, Seldane (terfenadine), reported symptoms of irregular heartbeat. The drug was taken off the market in the mid-1990s, prompting federal regulatory agencies and drug manufacturers to question whether it could happen again.

"Because this wasn't part of the early drug development, the problem wasn't caught early on," said Dr. Jeffrey Barrett, Research Associate and Professor of Pediatrics, Children's Hospital, Philadelphia. "This lasted longer than it should have because it wasn't being looked at."

This prompted regulatory agencies and researchers to take an increased interest in QT prolongation and the clinical manifestation of Torsades de Points and the implications of these conditions in new drug development, he said.

Since then, the U.S. Food and Drug Administration has put out a white paper on the subject, the drug industry instituted more standardized approaches to drug development and clinical research organizations were formed to undertake testing.

Clearly, some drugs elicit QT prolongation, and many drug companies now perform QT tests routinely, Dr. Barrett said in an interview. " There are standard study designs to assess the potential for QT prolongation," he added.

Drug companies now perform early studies on new drugs to assess the extent of this problem, he said. "And some have stopped the development of agents for fear that QT prolongation might be an indication of Torsades de Pointes."

Dr. Barrett stressed the need to study the problem further and set even better standards for assessing possible problems in drugs that have not yet hit the marketplace.

"It's a catch 22," he said. "You want to protect patients and ensure that drugs that are put on the market are safe. But at the same time you don't want to prevent the development of a very important agent because of a biomarker or a measurement that doesn't correlate an outcome."

There still remain questions on how QT prolongation is measured, he said. "We understand the issue of QT prolongation with Seldene, where we know there was an issue. But can that [case] be generalized to all other drugs?" he asked.

Dr. Barrett called for further research to determine whether a general class of compounds generates this effect or whether structures of certain molecules are correlated.

While there is a more standardized approach to preventing QT prolongation in 2004 than in past years, there is a need to develop correct methodologies and to perform studies that will help avoid the problem, he said.


[Presentation title: " Conclusions: Lessons Learned and Interactive Panel Discussion."]