Centralized Cardiac Safety

Research demonstrates that some drugs have the potential to pose a significantly increased risk of arrhythmias or other serious cardiac conditions. As a consequence, cardiac safety is cited as one of the primary reasons for withdrawal; postponement; or refusal of new drugs entering the market, all of which incur significant cost to the sponsor. Accurate collection, analysis, and interpretation of ECG data are therefore essential.

In order to bring safe and effective therapies to patients, pharmaceutical companies are increasingly recognizing the need to standardize processes to ensure clean, accurate, and reliable health outcomes research data.

Why centralize?

When a decentralized model is used, ECG studies are carried out across multiple investigator sites using local ECG machines. The use of different instrument types at different sites leads to inconsistent results due to varying instruments using different algorithms for calculations.

A centralized approach enables companies to overcome the shortcomings associated with traditional methods by allowing high quality data to be collected digitally in a standardized format for evaluation that uses consistent and validated systems. Every interval duration measurement is measured by a qualified person and each ECG is evaluated by a qualified cardiologist. In addition, the use of digital ECG data collection at a centralized laboratory generates much cleaner data by using a high resolution digital methodology, eliminating common transcription and misinterpretation errors. Many core laboratories also employ systems that are able to automatically check for missing visits or any changes in demography.

Case study

The pharmaceutical company in this case study regularly uses centralized cardiac safety services for clinical trials across multiple therapy areas, in order to streamline processes and ensure consistently accurate and high quality data. More specifically, the company has used centralized services for lab analysis; biopsy reading; and MRI reading, in order to ensure less variability in interpretation and cleaner overall data. In the fall of 2010 the company selected ERT to provide centralized cardiac safety services for a Phase II study into the development of a new compound for allergic rhinitis. Due to the nature of this therapy area, there was a small window of time in which to screen and randomize over 500 patients. As a result, the company required reliable and accurate screening and interpretation of a large amount of data within a very short time period. The company selected ERT for its large "central" laboratory, with facilities that could efficiently process high volumes of sample data within a pressured timeframe.

Implementation and benefits

Prior to the implementation of ERT's services, the company had a list of key benefits that it expected to receive as a result of the centralized service. These expectations included: confidence in data quality, the ability to make go/no go decisions regarding the cardiac safety of new compounds, more global data regarding the safety of compounds, improvement of overall accuracy, and more objective interpretation.

Since implementation, ERT has enabled the company to eradicate issues associated with decentralized studies such as data-variability stemming from inconsistent ECG collection and evaluation methods. As a result, the company has benefited from reliable data that offers a high level of quality and integrity. Efficiency of processes and data accuracy were two of the other standout benefits gained as a result of implementing ERT's centralized cardiac safety services. The confidence gained by the consistent high data quality has enabled the company to make key internal decisions regarding the compound, improving time and cost efficiencies.

At the beginning of the year long study, the company had a regulatory uncertainty as to whether or not holter monitoring would be required. In order to prepare for the acknowledged risk that the company's health authority may demand holter monitoring at a later stage in the study, ERT provided the company with the opportunity to progress with the monitoring rapidly and at short notice, if and when required. The central lab's flexibility to adapt the service and processes at short notice was a key benefit for the company, enabling it to comply with any regulatory demands that may have arisen.

Site performance has also been positively impacted through the use of ERT's services. The ability to transfer analysis to a core lab with dedicated, trained staff has alleviated staff burden and enhanced overall trial performance.

Cost implications

The use of a centralized cardiac safety core lab is often thought to be more costly than the use of a decentralized system. Contrary to this perception, the use of a core lab may be more cost-effective than having multiple individual sites perform ECG evaluations. Contracting with a core lab reduces fees paid to each site for technical support and ECG reading (often by unskilled readers). Additionally, by eliminating errors in collection and transcription of ECG data, sponsors can minimize the amount of retesting that must be carried out. In a recent comparison of cost compiled by The Tufts Center for the Study of Drug Development, it was shown that the use of centralized ECG provides an overall cost reduction of 34.6%.¹

Conclusion

The pharmaceutical company implemented ERT's central cardiac safety services for a one year clinical trial on the development of a new compound for allergic rhinitis. Since implementation, the company has benefited from digital collection of high quality health reported outcomes data in a standardized format for evaluation, using consistent and validated systems. As a result, the integrity and quality of data is extremely high and has contributed to overall time and cost-efficiencies by accelerating the process of identifying no-go compounds at early stages.

In line with benefits experienced by the company, recent statistics indicate an increasing recognition of centralized cardiac safety services within the drug development and healthcare industry. More than 60% of all data submitted in an NDA in the past 15 years was produced by central laboratories, with that number expected to increase to 80% in the next five years.

John Blakeley, is Executive Vice President and Chief Commercial Officer at ERT, e-mail: jblakeley@ert.com.

References

1. Tufts Center for the Study of Drug Development, "Mapping Adoption of Centralized Cardiac Safety Assessment," (2010), http://www.ert.com/knowledge-series/.