Embracing innovative technology to make a centralized approach to ECG data collection more accessible

By Amy Furlong, EVP Cardiac Safety Operations

Over recent years the use of a centralized electrocardiogram (ECG) process has become key to the detection of cardiac risk in clinical trials. The increased adoption of this approach for the management and analysis of ECG data can be attributed to its ability to provide clinical sponsors with real-time collection of consistent, quality information, a vital element in the accurate assessment of a new drug's cardiac effect. The application of this model offers substantial advantages all of which have been widely acknowledged, however one common misconception has limited its uptake: that it is not cost-effective.

The demand from trial sponsors for the improved accuracy and reliability that the centralized process offers is steadily increasing, and now there is a need for innovative new instruments to help sponsors achieve their goals and make this model more economical. Clinical technology providers have been looking for ways to make centralization a more accessible solution and as a result the pharmaceutical industry is currently seeing the emergence of new highly compact instrumentation being introduced in a bid to overcome the issues of larger ECG equipment.

Legislative outlook

Drugs in clinical development that potentially have effects on the cardiac health of patients require systematic cardiac safety assessments throughout phases II and III. While there is no legislative mandate in relation to ECG assessment across clinical trials, the requirement to conduct a Thorough ECG Trial (TET) for new compounds has been mandated by the US Food and Drug Administration (FDA) with limited exceptions. This is as a result of the introduction of the ICH E14 guideline which was developed to assess QT/QTc prolongation in new drugs to determine cardiac safety risks. The ICH E14 guideline advocates that a TET should be performed to establish any cardiac concerns that may be raised by a drug. If any cardiac issues are found, Phase III trials will then require further intense ECG collection.

What is centralization?

Using a centralized approach to ECG data collection and interpretation allows for the detection of cardiac issues in the early stages of a drug's development. This avoids waiting until post-marketing safety studies to ascertain any issues and the risk of having to withdraw a product from the market. A centralized approach uses digital ECGs and a core laboratory which handles the majority of the work done by clinical trial sponsors, CROs and individual monitoring sites. The core laboratory typically provides investigator sites with all standard ECG equipment having first ensured that it has been tested to full functionality and is programmed for the correct demography capture for the particular study.

The use of digital ECG data collection at the core laboratory accelerates the analysis process and generates much cleaner data by using a high resolution digital methodology eliminating common transcription and misinterpretation errors. In addition, many core laboratories also employ systems that are able to automatically check for missing visits or any changes in demography. Each ECG is evaluated by a qualified cardiologist at the core laboratory to ensure maximum data quality, integrity and consistency. The ICH E14 document recommends centralization in cases where cardiac safety concerns are raised. As such, the guideline further highlights the superior results generated by this approach.

Cost implications

There is a perception, within the clinical trials industry, that the true cost of standardizing on a centralized ECG system is difficult to estimate. There are concerns that quantifying the number of ECGs that will be necessary in advance of a study program is hard to do and makes it challenging to estimate the true expense that will be incurred by using this model. Staffing costs, the number of investigator sites and the number of ECG machines needed are also unknown and will vary based on the specific study design.

Centralized ECG trials involve the rental, storage and shipping of the ECG machines to each investigator site. A typical ECG device can weigh anything between seven to 10lbs and can be of substantial size, which means they can be expensive to transport and store. Furthermore, the maneuvering and preparing of the instruments ready for use can be time consuming and difficult for inexperienced users. The average rental cost of such a machine generally varies between $100 and $150 per month. Reducing the acquisition fee, which includes the amount of rental paid for the ECG instrumentation, is one way of lowering costs.

The future of centralization

The cost implications of a centralized approach demonstrate a clear need for innovative new instruments to help sponsors achieve their goals and increase accuracy, reliability and cost-effectiveness. The issue of large, heavy and expensive instrumentation could be overcome with the introduction of highly compact ECG machines that have a much smaller footprint than existing systems. Revolutionary new highly-compact instruments that will substantially reduce costs yet provide full ECG functionality are being developed. These small hand-held devices will make it easier for companies to adopt a centralized system as it is not only easier to maneuver but is also significantly less expensive to ship and store. Utilization of such devices and technology incorporated with the process enhancements and reduced site and sponsor burden will result in significant measurable cost savings.

Traditional ECG machines produce a paper printout of all key ECG data, which is then transcribed and the results analyzed. Errors are common during transcription, which leads to inaccurate results and has a detrimental effect on the validity of the findings of a trial. Introduction of such new instrumentation will provide an on-line workflow solution for point-and-click demographic selection with real-time edit checks avoiding data entry errors while saving staff time and costs. Transmission of data is performed using secure internet transmission thus reducing the burden of analog/digital methods by utilizing existing solutions at the site. Further, a live electronic inventory for immediate access to ECG waveforms which can be generated in hard copy as required for audit purposes.

Regulators are increasingly requesting that studies submit ECG data to a central digital system to assist with regulatory inspections. All data stored on the system can then be accessed by regulators to efficiently analyze the quality of the data. Although this is not a mandatory requirement as yet, most clinical trial sponsors are now complying with this request. A centralized ECG system makes this requirement simple to comply with, as all data is already stored centrally and simply has to be transferred to the database as required.

Conclusion

ICH E14 guidance highlights centralization as a more vigorous means of ECG data collection and while there are no plans to enforce it as an industry standard at the present time, the substantial advantages that this method offers to clinical sponsors are clear. The introduction of new instrumentation will make it easier and less costly for trial sponsors to adopt a centralized model that will allow them to reduce site burden, increase accuracy, reliability and usability and accessibility to quality results. This in turn will enable them to safeguard patient health and ensure future regulatory compliance. Such developments in technology will assist organizations to further streamline their ECG collection and analysis methods and overcome the perceived challenges that are widely associated with the use of a centralized approach.

Amy Furlong, Executive Vice President, Cardiac Safety Operations - Amy has been Executive Vice President of Cardiac Safety at ERT since December 2005 and previously served as Senior Vice President of Regulatory Compliance. She holds a Bachelor of Science degree in Biology and a Master of Science degree in Quality Assurance and Regulatory Affairs from Temple University's School of Pharmacy. Amy has more than 10 years of clinical research experience specializing in regulatory compliance and computer system validation.

For further information on ERT and its technology and services please email info@ERT.com, call +1 215 972 0420 or visit www.ERT.com.

For further press information please contact Fiona Robinson, The Scott Partnership, 1 Whiteside, Station Road, Holmes Chapel, Cheshire CW4 8AA, United Kingdom. Phone +44 1477 539539, Fax +44 1477 539540, Email ert@scottpr.co.uk

About ERT

Based in Philadelphia, PA, ERT (www.ERT.com) is a provider of technology and services to the global biopharmaceutical and medical device industries. The company is a market leader in providing centralized core-diagnostic electrocardiographic (ECG) technology and services to evaluate cardiac safety in clinical development. The company is also a leader in providing technology and services to streamline the clinical trials process by enabling its customers to automate the collection, analysis and distribution of clinical data in all phases of clinical development.

Statements included in this release may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements, including, but not limited to, 2009 financial guidance, involve a number of risks and uncertainties such as the Company's ability to obtain new contracts and accurately estimate net revenues due to uncertain regulatory guidance, variability in size, scope and duration of projects, and internal issues at the sponsoring client, integration of acquisitions, competitive factors, technological development, and market demand. As a result, actual results may differ materially from any financial outlooks stated herein. Further information on potential factors that could affect the Company's financial results can be found in the Company's Reports on Form 10-K and 10-Q filed with the Securities and Exchange Commission. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.