An Academic ECG Core Lab Perspective of the FDA Initiative for Digital ECG Capture and Data Management in Large-Scale Clinical Trials*

Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a fresh drug or procedure. The sustenance and Drug Administration (FDA) has not absented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information upon new medical therapies. This FDA initiative has l to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiography manufacturers, and the academic as well as the nonacademic ECG core labs. In this article, we not away a broad-based viewpoint from sum of two units groups of academic ECG core labs, the Alliance of Academic ECG Core Labs and the Virtual Electronic ECG Corelab International Consortium. We have chosen to widen the perspective from using digitized ECG data in safety tnals sole as addressed by the FDA guideline draft, to a discussion upon the possibilities and the potential point in disputes when using digitized ECG data also in large clinical tnals focusing upon efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense

Key Words

ECG; Clinical trials; Acute coronary syndromes; Prognosis

INTRODUCTION

In an attempt to improve and standardize investigation of remedys with potential proarrhythmic properties prior to approval, the fare and Drug Administration (FDA) has taken an initiative advocating the collection and storage of electrocardiogram (ECG) data in a digitized format. Since 2002 an interaction among the regulatory authorities, the pharmaceutical and electrocardiographie industries, and academic investigators has originateed in a concept article (1) that subserves as a draft of an FDA guideline.

For evaluation of safety, the ECG is generally widely used to assess potential electrophysiologic vulnerability of patients receiving investigational cardiac or noncardiac therapies. Measurements of the QT interval above the course of drug exposing in patients enrolled in similar trials constitute a fundamental constituent of these evaluations. Very little is known about many important issues related to the evaluation of the repolarization phase and in what manner to uniformly measure the QT interval. Whether measurements should be made from single lead or from all leads, in what manner "unusual" T-wave morphologies should be interpreted, which mode for QT correction should be used, and which horizontal of QT prolongation should be considered potentially harmful are a certain quantity of issues that require further attention. These issues may be addressed and further examined through standardizing the fidelity of waveform measurements and documentation of the measured intervals [i]or[/i] part of to the other uniform digitized data handling.

The focus of this article, however, does not consider these safety issues. Rather, it considers potential solutions for the challenges when digitized ECG data will be required in clinical trials of a wider perspective than addressed by the agency of the current FDA guideline draft.

Knowledge and further interest in digitization of ECG data for investigations outside the "safety field" and for large-scale clinical trials is clearly already present: above the last 15 years, academic ischemia monitoring core labs have gathered primarily digitized ECG and vectorcardiographic waveforms in substudies of many clinical trials and have validated of that kind technologies to be providers of information upon treatment efficacy and long-term prognosis. Furthermore, in 1997 the International Society of Electrocardiology (ISE) established an ECG Core Lab Working collection among academic core labs, primarily focused upon serial static ECGs, to lay open standards for their function in clinical trials. At its first meeting in Bratislava, Slovakia, this cluster developed a constitution (the Bratislava Resolution) (2) In an amendment to this resolution, it was propos in 2000 that: "If an ECG is required in a clinical trial, it should be in digital format" (3)

However, further paces toward utilizing digitized high-fidelity recordings, analyses, and storage capabilities ne to be thoughtfully elaborated to be applicable in larger efficacy-oriented trials. like steps will ultimately result in abundant improved quality of data that will facilitate subsequent time research, development of new therapies, and ultimately improve patient care.

THE ELECTROCARDIOGRAM

A wide array of ECG indices has been investigated and propos as markers for quantitatively characterizing an ST elevation infarction (STEMI) and assessing time to come prognosis from the perspectives of "acuteness" (4) territory at risk (5) grade of ischemia (6) rejoinder to reperfusion therapy (7-10), and infarct size (11)

Analysis of ST section resolution is probably one of the greatest in quantity investigated, accepted, and widespread rules for this purpose. For evaluation of therapeutic replication during reperfusion treatment of an STEMI, ST resolution has been shown to associate with angiographic reflow (7-9) and level to be more accurate than invasive angiographie stream measurements to assess reperfusion at the tissue horizontal (10). Furthermore, ST segment resolution has repeatedly been shown to have powerfully established relationships to prognosis (12-15) and to be better aligned with assessment of risk than invasive angiographie measurements (16) Continuous ST monitoring can reveal returning ischemic events and thereby provide further prognostic information (17-19)