Medical Devices

How can the Internet of Things help to Design a Patient-oriented Clinical Trial? – Part II

Medical Devices

07:00, October 23 2017

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In the second part of this series, Francis Plat provides a case study exploring the effects of a self-administered drug designed to detect SVT

Is 48 Hours a Sufficient Period of Monitoring?

There is a large inter-patient and intra-patient variability in the frequency of SVT episodes. Therefore, the time between the randomization and the next episode of SVT (supraventricular tachycardia) can vary from days to weeks or months. The objective of the ambulatory cardiac monitoring is not to detect the SVT but to accurately document when a patient feels the symptoms. The recorded ECG (electrocardiogram) should be appropriate to confirm or reject the SVT identified by the patient, and the effect of the drug. The constraint of wearing the device for a very long period was judged inappropriate. Therefore, instead of using a loop recorder with a limited total loop memory, it was considered preferable to ask the patient to put the device on the chest and activate it immediately at the onset of symptoms.

The Holter is an acceptable option, but it necessitates good training and experience to place the electrodes on the chest; the available small size devices with integrated electrodes are much more user-friendly. We have considered that a 10-hour full recording of the ECG should be sufficient to document SVT, as well as the elapsed time between study drug administration and termination of the SVT converted to a sinus rhythm. Since the duration of action for the drug, its degradation, and elimination are rapid, we estimated that 10 hours of full monitoring would be long enough to detect and document potential SVT recurrences or new arrhythmia. The battery life and recording memory for most of the devices can cover this monitoring time.

Is It Necessary to Detect Asymptomatic Arrhythmias?

The episodes of SVT are most often symptomatic in patients suffering PSVT, contrasting with atrial fibrillation (AF). Therefore, implantable devices able to detect events during a very long period are not necessary for the study purpose and would not be ethically justified.

Is It Critical to Have Real-Time Access to the Transmitted Rhythms?

Patients randomized in the study are well aware of their diagnosis and do not need immediate assistance during SVT. In a case of prolonged resistant SVT, the patients are requested to seek medical assistance in a clinic or an emergency room where they will receive the IV therapy with adenosine or verapamil. The ECG will be recorded on the monitoring device that will stay in place for 10 hours.

How to Interpret the Data

The transmission, data analysis, and adjudication are the key success points for such a clinical trial. The available devices can recognize ECG anomalies like arrhythmia or various degrees of AV block. The algorithms used by the current devices and reading systems are very efficient, and their sensitivity and specificity exceed 90 percent in several AF studies. In the context of our SVT clinical research, the false positive, and even more importantly, the false negative, characteristics of the algorithm are not well known. For this reason, the transmission of data to a core laboratory is paramount.

Some devices like ELR can electronically transmit sequences of ECGs selected by the recognition algorithm. In this research, the entire 10-hour recording, i.e., the device or the memory card should be sent to the core laboratory due to the large size of the full ECG recording file. A specialized technician in the core laboratory should be able to identify the episode of SVT and the time of termination and conversion to a sinus rhythm. The endpoint needs to be adjudicated to comply with the requirements of a phase III trial.  

Two independent electrophysiologists will review the ECGs transmitted by the core laboratory technician. The first one will confirm the diagnosis of SVT without access to the conversion to the sinus rhythm. The second adjudicator will confirm the termination of the SVT and the conversion to the sinus rhythm for at least 30 seconds. Additionally, it should confirm the time between the study drug administration and the termination of the SVT positively adjudicated by the first electrophysiologist. Since the vagal maneuvers (VM) are recommended as the first-line intervention to terminate acute SVT, the patients will practice VM first and will take the drug if SVT is not terminated after two minutes.

Interestingly, the efficacy of the VM has never been assessed in a real world setting. The REVERT trial is the most recent study that tested an improved technique of VM versus the usual practice, all the patients in the study practiced the VM in an emergency clinic, under medical guidance and supervision. (1) The ambulatory cardiac monitoring will give a better evaluation of the VM practiced in real world conditions.

But crucially, as we move forward, clinical research is becoming more and more patient-oriented. As such, the rising influence of IoT provides the opportunity to fully involve consenting individuals in clinical trials designed to provide the best possible evidence of new drugs in real world conditions.

 

Francis Plat

Chief Medical Officer

Milestone Pharmaceuticals

 

References:

1) Appelboam A, Adam Reuben A, Clifford Mann C et al.Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. www.thelancet.com Published online August 25, 2015. DOI: http://dx.doi.org/10.1016/S0140-6736(15)61485-4

 

*To read Part I of this article, click here.

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