Long Term Electrocardiographic Monitoring: It’s Role in Clinical Drug Development and Population Screening

Wednesday, December 2, 2015

Final agenda and links to presentations

8:00am-8:10am– Introduction and goals of the Think Tank: Philip Sager, MD (Stanford University) (10min)

8:10am-9:40am–Session 1: Approach- provocative talk & most of work accomplished during the roundtable.
Moderator: Richard Clark (Medtronic)

Technology- State of the Art- Novel Arrhythmia Monitoring Technologies What are the performance specifications, sensitivity, specificity, and positive predictive value? Suneet Mittal, M.D. (Valley Medical Group) (20min)

Novel Diagnostic Derived Big Data Applications; insights regarding arrhythmia prevalence, characterization, and applications to support clinical management and clinical research

Introduction and Real World Examples: Paul Ziegler, M.S. (Medtronic) (10min)
Future Considerations: Judy Lenane, R.N., M.H.A. (Rhythm Technologies, Inc.) (10min)

Round Table Discussion (50min)

9:55am-1:00pm–Session II: Potential roles of more intensive arrhythmia monitoring in the safety assessment of drug/device development- what areas are of greatest impact?
Moderator: Philip Sager, MD (Stanford University)

Afib detection during drug development

What is the evidence that drugs increase Afib? What is known and where are the knowledge gaps, with case examples? What is the role of the patient population regarding the background AF incidence? How does the substrate impact interpretation? Todd Rudo, M.D. (GSK) (10min)

What constitutes a “signal” and what constitutes a potential safety signal during drug
development? When is Afib of clinical importance? What are the issues that impact interpretation? (e.g., age of the study population) Peter Kowey, M.D. (Lankenau Medical Center) (10min)

When might monitoring for Afib using these technologies add value? What is the optimal duration of observation? Role of comparator cohorts? Implications for study design and sample size? Jonathan Piccini, M.D. M.H.S (Duke University) (10min)

Exacerbation of conduction disorders and sinus node function. What are examples and how might these technologies add value? Speaker should give an example where monitoring technologies may have been informative Case study of Harvoni & amiodarone recommended and to discuss patient characteristics, such as normal with high vagal tone? James Reiffel, M.D. (Columbia University) (15min)

Non-sustained VT signal detection and the potential clinical significance when there are no QT effects (please address examples). Importance of the baseline prevalence. Role of monitoring duration on signal detection. When might these technologies add value? Jay Mason, M.D. (University of Utah) (15min)

NSVT: Agency perspective: what is clinically relevant issue, when a drug that does not affect the QTc is possibly associated with NSVT? Potential role of more intensive monitoring. Preston Dunnmon,M.D. (FDA) (10min)

Can newer telemetry approaches assist in the evaluation of a safety signal when there is not a placebo/comparator group (e.g., oncology). Implications for study design-multiple baseline recordings, monitoring in a comparator group, etc (Pre-screening could add value to understand baseline arrhythmic burden. Ideally speaker would present case studies.). Robert Kleiman, M.D. (ERT) (10min)

Round Table Discussion Afib- 60min | Other topics 45 min
1:00 pm -1:30pm- Lunch

1:30pm-3:45pm– Session III: Focused topic: AF Detection- Screening to Prevent Strokes
Moderator: Jonathan Piccini, M.D. M.H.S (Duke University)

Stroke Prevention- primary and secondary stroke prevention

AF Screening-primary stroke prevention- What are practical and scientific issues associated with population screening of asymptomatic patients? What patient populations might be considered; all comers, biomarker directed, EP screening, risk factors? Mintu Turakhia, M.D., M.A.S. (Stanford University) (15min)

Debate: Population screening is important and we have sufficient data to advocate screening

Pro-advocate for screening: Dave Albert, M.D. (AliveCor) (15min)
Con-not worthwhile: Jonathan Piccini, M.D. M.H.S (Duke University) (15min)

Secondary Stroke Prevention- Current monitoring approach for detecting AF in strokes of unknown cause, data supporting post stroke monitoring, application of novel arrhythmia monitoring technology to post stroke monitoring. Alex Abou-Chebl, M.D. (Baptist East Medical Pavilion) (10min)

How new telemetry approaches can impact clinical trials of drugs to reduce AF? Fraz Ismat, M.D. (Bristol-Myers Squibb) (10min)

Using Telemetry approaches to determine who with PAF should be anticoagulated? Norman Stockbridge, M.D., Ph.D (FDA) (10min)

Round Table Discussion (75 min)

3:45pm- 4:00pm-Conclusions and next steps