1. "What is your involvement with the Apple Heart Study?"
That’s a question I would love to answer, because we (BioTel Research) were really involved in this fascinating study. More than 500,000 participants signed up for this study. We were working very closely with Stanford University and Apple. Our ePatch holter monitor was utilized as a gold standard to compare how well the Apple Watch algorithm performs. All the participants who were recognized by the Apple Watch with episodes of potential arrhythmia were provided our ePatch. They then had to wear it for seven days, along with the Apple Watch. We were providing very thoroughly designed reports by two independent cardiologists, based on the review of the seven days of continuous Holter monitoring data. The data was later compared for concordance with the Apple Watch algorithm. In case there was a disagreement in reporting, a senior panel would come up with a final conclusion in term of the finding. The focus was on arrhythmia and AFib in particular. The study was very successful and the Apple Watch algorithm was FDA cleared for both EKG and irregular rhythm notification functions.
2. "Does the FDA allow Apple Watch to be used for clinical study endpoints, in addition to being a screening tool?"
It is not about what the FDA allows, but more about what you as a drug developer require. The decision is yours. How thoroughly would you like to evaluate the potential arrhythmias? If you are talking just about quick detection of potential arrhythmic episodes, then Apple Watch could be used as a screening tool. But when you think about the quality of the data that is informative, that is clinically and statistically relevant in term of number of events, duration of those events, the clear validity of those events confirmed by the cardiologists - then you certainly need something that is more sophisticated with a better algorithm - more in-depth analysis of the data. So I would say that certainly as a clinic tool, absolutely this is a great tool. But, as a monitor that is highly recommended for sole evaluation of arrhythmia or tachycardia events or blocks, for evaluation of your study you need some more sophisticated tools that are also available.
3. "What are the factors behind the increasing prevalence of Atrial Fibrillation (AFib) expected in the future? Are they due to metabolic factors or something else?"
Well a major factor, which is good news, is that the worldwide population especially in developed countries and highly developed countries live longer. This is confirmed by looking at AFib statistics - the highest rate of AFib is in well-developed countries. That's because the lifespan is much longer and the quality of life of people is definitely different. They are living longer with more active lives. When you are in your 50's the rate of AFib is 0.5 percent. When you reach your 80's the rate of AFib is 25 percent, which is a shocking, stunning difference - right? Stress contributes to AFib in younger people. Metabolic, diet related, and substance related issues also play a role. The two major drivers are increased lifespans and higher stress levels.
4. "Is AFib more prevalent in heart failure patients with preserved or reduced ejection fraction, or equally with both?"
I would say from the data we have seen so far, it is more prevalent with a reduced ejection fraction.
5. "Is the GIRK assay helpful to predict bradycardia potential of drugs in development?"
I would say that we do not have enough scientifically confirmed data. We're in the process of collecting this data right now and I cannot tell you with confidence because the data is not sufficient. But I would say that from what we've seen so far there is some level of predictability, some trend that could be a sign of predictability of this assay. More to come, the more data we collect the better answers we will have.
6. "For anti-arrhythmic drug trials in patients with ICDs, what are the challenges in monitoring beyond triggering of the ICD?"
I would say that the major challenge is in fact triggering ICD. We do run quite a lot of studies where ICD patients are enrolled and I don't really believe we have come across challenges that were so obvious in the past with the traditional Holter design and available algorithm then. Even detecting the ICD was not possible with some arrhythmia algorithms we had then. It's so much better right now, the algorithms are so much better that I couldn’t cite big challenges that differentiate the analysis for patients with ICD versus known ICD patients.
7. "Is the MCOT device waterproof, and what is the average wear time?"
Both patches, MCOT and ePatch are water-resistant. So patients can shower with them on. The battery time that is available right now, with a single charge, is roughly up to 10 days - which is great. Not a long time ago it was five to seven days. As you can see, we're making lots of progress. I certainly believe that the technology team will be able to come up with an even longer battery lifetime for these devices.
8. "Are there apps available to monitor AFib via smartphones?"
I might not be so up to date on this, because new devices literally come out on daily basis. One of the applications that I am aware of is AliveCor. It's a little device that you use as more of an event monitor. When you put your fingers on it, it runs a 30-second strip on your via your application on a smartphone. That device is available and being used by patients who are aware of their episodes, and who wants to see when they need to take their medication or maybe visit the doctor.
9. "Does the Apple Watch provide waveform of EKG, and if so, why does it need ePatch to verify?"
Well it does provide the strip on your Apple Watch, so you can see the strip. As I already mentioned, this device is very good for screening for the alert to the patient and to potential patient and to the doctor that there must be something going on with the patient's heart. When we are talking about clinical drug development and clinical trials that need to be conducted, my opinion and the opinion of many of my colleagues is you really need something that provides a much better algorithm in term of ability to customize it to your specific clinical, statistical endpoints. I am talking about the statistics such as minimal heart rate, maximal heart rate, average heart, mean heart rate. Same with AFib, the shortest, longest duration, attributes of AFib. There are so many things, so many points you need to evaluate while you are collecting the data in clinical trials that makes professional clinical monitors absolutely necessary to be utilized during your drug development.
10. "In the environment of phase one clinical trials, where subjects are compliant in a clinical pharmacology unit, typical devices used for cardiac safety are 12-lead Holters and 12-lead telemetry systems. Do you think there is a place for the new devices you just described? Perhaps as a screening tool?"
Well I would say that if patients are compliant, which is very correctly said - there is a solid, sophisticated telemetry monitoring system available - preferably 12 lead. It is a perfect setting to run this as described here. You may wish to consider utilizing an ePatch or MCOT device, or even one of the wearables. If one of the inclusion/exclusion criteria in your study includes episodes of arrhythmia, you may want to recommend that participating subject wear this device for two weeks or three weeks or a four week period of time to eliminate patients with certain types of arrhythmias from inclusion into the project. That's one thing I can think of. Another scenario would be an early-phase study design where patients are going to stay in for certain periods of time. But then go home for two or three weeks or ten days, and then come back for another inpatient kind of session. Here consider some device, for example MCOT, that will report real time the episodes of arrhythmia or other clinically potentially significant episodes. Or even using ePatch to collect date while the patient is out of the phase one unit. This way you collect data more economically than keeping the patient in house for three or four weeks just to monitor the arrhythmia.