Driving the Efficiency and Cost-effectiveness of Cardiac Safety Trials

An Ask the Expert feature with Cardinal

How the efficiency and cost effectiveness of cardiac safety studies will be enhanced in the near future. By Tosja K. Zywietz, Director R&D at Cardinal Health Research Services Germany

“The cardiac safety market is at a turning point, with new technology and analysis methods looking to set to drive a significant efficiency gain”
-Tosja K. Zywietz, Cardinal Health Research Services

Recent examples of drugs withdrawn from the market due to their potential to cause life-threatening cardiac arrhythmias have driven the need for more careful cardiac safety studies to reach market approval by the FDA. However, drug development costs have reached a level which is hardly affordable for the pharmaceutical industry. It is therefore essential to reduce these costs, while increasing the accuracy of cardiac safety trials for the benefit of patients.

The cardiac safety market is at a turning point, with new technology and analysis methods looking set to drive a significant efficiency gain in the industry. Over the last three years we have invested a lot in new technology specifically designed for cardiac safety trials. We have not just developed specific hardware (ECG resting and Holter recorders), but have also spent a lot of time researching ways to improve the quality of our automatic, CRF21 Part 11 compliant analysis tools. On the software side, we have focused on the main cost drivers in the industry, and managed to achieve a significant cost reduction in cardiac safety ECG trials for our customers. This would not have been possible without significant investments in technology and efficient processes.

In order to look at the main cost drivers of cardiac safety studies, it is useful to consider a standard thorough QT (TQT) study. The technology applied is of course an important cost driver. For an ECG intense trial, this can make up a significant portion of the overall budget. Just think of a multi-center trial where hundreds of Holter-ECG-recorders and 12 lead ECG devices are needed, including the set-up, maintenance and the training of study nurses to use the equipment. Also, a lot of back-end technology is needed for data security, processing and storage.

However, the main cost driver is the manual over-reading of the recorded ECGs. Today, most of the over-reading is done by highly educated core lab staff, which takes a lot of time and is therefore expensive, especially for 24-48 hour Holter recordings. Usually, several thousand ECGs have to be evaluated. This is by far the most expensive part of any TQT or other cardiac safety stud ies. Interestingly, we see a lot of potential to reduce the cost with our new technology, optimized for clinical trials.

As mentioned above, our first step in enhancing the efficiency and effectiveness of cardiac safety trials was to develop new hardware to meet the specific needs of trials. So far, mostly standard equipment designed for hospital use is applied – this is sometimes difficult to handle, and does not meet trial requirements, such as enhanced usability, reduced set-up time and ‘above standard’ recording quality. Our new Holter and resting ECG machines meet these requirements, leading to lower cost while at the same time increasing reliability of results.

Second, we have made a big investment in automatic ECG analysis in our ECG core lab, and this will significantly enhance efficiency and cost effectiveness. Our automatic analysis has reached a level of sensitivity that is capable of supporting our cardiologists in a way that allows us to save a lot of time for over-reading and validation. In principle, we are already able to do a large part of the analysis fully automatically, instead of manually. Only the ‘critical ECGs’ will have to be analyzed fully manually in the future.

However, the sponsors will need to be convinced that our new method is even more accurate than the fully manual approach of ECG analysis. We will shortly apply our technology in a large pilot trial, to quantitatively prove the sensitivity of automatic ECG measurements and analysis.

We are sure the pharmaceutical industry will quickly adapt to our new technology – to the benefit of patients and significant cost savings.

Tosja K. Zywietz, Director R&D Cardinal Health Research Services, started his commercial career with The Boston Consulting Group as strategy consultant. He holds a PhD in theoretical physics from the Fritz-Haber-Institute in Berlin. Over the last few years, he has gained extensive experience in developing new technology and methods for cardiac safety trials.