The multiple benefits of centralized ECG data collection.
Cardiac safety concerns are cited as a particularly prevalent reason for withdrawing drugs from the market, making changes to labelling and postponing, or refusing, regulatory approval. If one or more of these occur, it can result in significant cost for a company in the short run and reduced revenue in the long run. To monitor accurately the cardiac safety of new compounds, sponsors require precise and high quality ECG data, which is sometimes unavailable through a decentralized model. Using a decentralized model can often produce fragmented and inconsistent ECG data collection and analysis, because it is done across multiple investigator sites using local ECG machines. Inconsistent results can frequently occur because of the variation in instrument models using different algorithms for calculations that are then evaluated by multiple clinical personnel of varying experience.
Pharmaceutical companies worldwide, therefore, are increasingly recognizing the important benefits associated with centralized ECG collection. In February 2010, the Tufts CSDD published research results regarding the industry adoption of centralized cardiac safety laboratories and perceptions from key stakeholders.1 According to the report, 97% of the respondents rated central laboratories as being accurate and 90% rated them as being efficient. Looking ahead, 89% of respondents expected the use of centralized ECG to increase in 5 years. The increasing adoption of centralized cardiac safety laboratories has been triggered to a high extent by the latest regulatory developments and pressure on the biopharmaceutical companies to reduce cost.
FDA, the European Medicines Agency (EMA), Health Canada and the Japanese Ministry of Health have adopted the current ICH E14 guidance for industry, which provides recommendations to sponsors concerning the design, conduct, analysis and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization.2 This assessment should include testing the effects of new agents on the QT/QTc interval, and collecting cardiovascular adverse events. The investigational approach used for a particular drug should be individualized, depending on the pharmacodynamics, pharmacokinetic and safety characteristics of the product, as well as on its proposed clinical use.
The guidance recommends performing a thorough ECG trial (TET) and if any cardiac safety concerns are raised, later phase trials will require more robust or intense ECG collection. A key requirement of the ICH E14 guidance is that a proof of concept, providing evidence that a centralized ECG system can be successfully used, must be done prior to commencing a TET trial. The guidance also stipulates the use of centralization in cases where cardiac safety concerns are raised.
The 2010 Tufts research revealed that only 33% of all ECGs are collected using a core laboratory. This low percentage reflects sponsors' and CROs' misconception that collecting ECGs locally is cheaper than the centralized approach. In reality, the 'hidden costs' of data capture at site and associated data cleansing result in higher total costs than using a core laboratory. The findings of the research showed that it could cost up to $245 for a single decentralized ECG to be collected. This fee excludes the internal costs to the sponsor for data cleaning and reconciliation associated with a decentralized, paper approach.
When using a decentralized model, the majority of collection, transcription, cleaning and interpretation of ECG data are conducted by the sponsor and the individual monitoring site. As a consequence, sponsors must pay a considerable ECG acquisition fee, which includes charges for technician time and the use of ECG machines at the investigator site. Additional fees for cardiac specialists to provide over read of the ECGs are also incurred based on the experience of the specific study Investigator. By following a centralized approach, this fee is substantially reduced as all work is outsourced to a single provider. In addition, the digital collection equipment supplied by leading core laboratories provides an easy-to-use interface to reduce data entry errors and collect, transfer and store data electronically.
Accelerated Analysis Time
When using a decentralized model, ECG studies are conducted within a variety of investigator sites using local ECG machines. Combining all collected ECG data from the different sites can be time-consuming, as each site will need to manually transcribe data from paper printouts and data reconciliation, which negatively affects the decision-making process. Using a centralized model can dramatically accelerate analysis time as it employs standardized ECG data collection processes. This promotes early detection of cardiac risk and so reduces the risks of wasted time and cost of a potentially unviable drug compound. There are many case studies demonstrating that the collection of digital data improves quality and timeliness of data ... and ECG data are no exception.
When relying on local ECG analysis, there are many factors that may influence the interpretation of ECG data and introduce variability and inconsistency of results. Centralized cardiac safety services minimize potential bias and facilitate confidence in the quality and consistency of results. All ECG data are collected digitally using high resolution, validated systems, thereby eliminating common transcription and misinterpretation errors. Many core laboratories also use systems that can automatically check for missing visits or demographic changes, further improving data quality, integrity and consistency.
Qualified individuals assess all interval duration measurements (IDMs) and a qualified cardiologist--who is trained to follow standardized procedures, which are continually validated through a quality control programme--evaluate every ECG. These standardized processes provide cleaner and more accurate and reliable data. The improved confidence in the accuracy and quality of ECG data enables sponsors to make more informed internal decisions regarding the compounds under investigation.
Access to Innovation
Pharmaceutical companies rely heavily on the use of innovative technologies to facilitate continued success. A centralized cardiac safety approach enables sponsors to implement the latest technological advancements, including lightweight and compact ECG machines, which have a significantly smaller footprint than their predecessors. As a result, the challenges associated with more traditional heavy and expensive instrumentation are removed. New ECG systems are easier to maneuver and are cheaper to ship and store. In addition, the compact size of the state-of-the-art instruments provides a better 'technical' service, offering more consistency and improved accuracy whilst effortlessly and seamlessly integrating with computer systems through a web application. Furthermore, enhancements in the collection of data to provide real-time data integrity checks to obtain clean data as early as possible are also provided.
Pharmaceutical companies worldwide are increasingly recognizing the value and advantages of centralized ECG data collection for cardiac safety purposes. The centralized approach promotes compliance with current legislation, and benefits sponsors by offering improved data accuracy and reliability, significant time and cost savings and access to the most advanced ECG technology.
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|Title Annotation:||CLINICAL TRIALS|
|Date:||Mar 1, 2012|
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