By Deb Bortifz
March 16, 2009 | Pfizer is the first and to date the only major pharmaceutical company to publicly share anonymous data from one of its drug safety trials, including data about the drug that was being evaluated. Trial sponsors have been inclined to share data only on the placebo, baseline, and control arm portions of their studies.
The Pfizer data came from a failed drug that had an adverse effect on cardiac ventricular repolarization, as monitored via the cardiac QT interval (the split-second period between the heart’s contraction and recovery phase), which is associated with heightened risk for adverse cardiac events. The recipient was the Telemetric and Holter ECG Warehouse (THEW), a national repository of data being developed by the University of Rochester Medical Center (URMC) and the FDA to aid researchers studying the electrical activity of the heart, says Jean-Philippe Couderc, director of the THEW drug safety initiative.
The FDA’s regulatory review process routinely requires evidence of a drug’s impact on the QT interval. QT prolongation is associated with fatal arrhythmias and is a leading cause of removal of several popular drugs. According to the Arizona Center for Education and Research on Therapeutics, more than 100 drugs on the market prolong the QT interval. The problem however, says Couderc, is that “QT prolongation is an imperfect surrogate marker of drug cardiotoxicity. So we need new ECG markers to complement QT prolongation and help companies better assess if a drug is dangerous for the heart or not. To do that, we need a central repository in which people can find relevant data to develop and validate new technologies.” International collaborations, including THEW, are developing studies to monitor the QT prolongation effects of new drugs.
Pfizer’s Sandwich Laboratory in the U.K. recently released a large set of continuous electrocardiographic (ECG) recordings to URMC, from which more than 1.5 million individual ECG datasets can be extracted, says Couderc. He expects more industry sponsors will supply similar types of data now that the “legal framework” has been accepted by two major pharma companies.
THEW began in December 2007 based on an idea by Norman Stockbridge, acting director for the division of cardiovascular and renal products in the FDA’s Center for Drug Evaluation and Research. The project officially launched in the middle of 2008 and has since received ECGs from 11 organizations, including Pfizer and Roche. Data from five studies are currently in the warehouse and three others are being integrated. Most recently, the University of Munich sent THEW trial data that includes a significant number of ECG recordings, including drug-induced arrhythmias, Couderc notes.
Strong History
URMC’s Heart Research Follow-Up Program, which hosts THEW, has a 35-year history, says Couderc, so it had plenty of clinical trial experience, data management expertise, and infrastructure with which to build the warehouse. It is intended to be a central place for researchers to connect, find information, and ultimately to “help improve the field of quantitative electrocardiography.”
Pharmaceutical companies, clinical research organizations, and ECG technology companies can access THEW after paying a membership fee, says Couderc. Not-for-profits can gain free access after their research project is accepted by a committee jointly headed by an FDA and URMC representative. The software allows for viewing and downloading selected portions of continuous ECG readings.
Five companies and two academic medical centers currently have right of entry to THEW, says Couderc, but today the data is being used primarily by academic researchers. For example, the Academy of Science of Czech Republic reports that it will study the static and dynamic QT/rate interval coupling based on ECG readings of healthy individuals in the THEW database. Similar collaborations with research centers in several European nations are underway that will generate an exchange of doctorate students.
Five years out, Couderc says he hopes to see THEW extend research activities “not only to drug safety but to cardiac safety in general.”