Transcript HeartStart Home OTC Defibrillator FDA Panel Presentation

HeartStart Home OTC Defibrillator
FDA Panel Presentation
Introduction
• Carl Morgan
– Company Co-Founder and Scientist
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Introduction to today’s discussion
We propose to remove the
prescription requirement for the
Philips HeartStart Home
Defibrillator.
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HeartStart Home Rx cleared in 2002
Rx requirement:
“CAUTION: FEDERAL LAW
RESTRICTS THIS DEVICE TO
SALE BY OR ON THE ORDER OF
A PHYSICIAN.”
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Improving access to help save lives
• Mission
– Prevent unnecessary deaths due to sudden cardiac
arrest.
• Focus
– Improving access by developing and deploying
automated external defibrillators (AEDs) that can
be used by virtually anyone to help save a life.
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Timeline
• Heartstream founded
1992
• ForeRunner launched
1996
• First save on American Airlines
1998
• Initial discussions with the FDA re: OTC
1999
• FR2 launched
2000
• Filed pre-IDE
2001
• HeartStart Home Defibrillator launched 2002
• Filed 510(k) for OTC clearance
2004
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Medical device labeling
The Food, Drug and Cosmetic Act requires that medical device
labeling must bear “adequate directions for use…”
(502
(f)(1))
“directions under which the
layman can use a device safely and
for the purposes for which it is
intended.” (21CFR§801.5)
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The prescription caution
A prescription caution must be included in labeling if
a device:
“…is not safe except under the supervision of
a practitioner licensed by law to direct the use
of such device, and hence for which ‘adequate
directions for use’ cannot be prepared.”
(21CFR§801.109)
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Basis for removing the Rx requirement for
the HeartStart Home Defibrillator
• Demonstrate established history of safe
use.
• Demonstrate that the HeartStart Home
Defibrillator can be used safely and for its
intended purpose based upon its labeling
alone.
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Presenters
• David Snyder
– Director of Research, Philips
• Dr. Lance Becker
– Professor of Medicine
– Director, Emergency Resuscitation Center, University of
Chicago
• Dr. Jeremy Ruskin
– Founder and Director, Cardiac Arrhythmia Service and
Clinical Electrophysiology Laboratory, Massachusetts
General Hospital
– Arrhythmia research
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Product overview
• David Snyder
– Director of Research, Philips
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Philips HeartStart Home Defibrillator
• Received FDA clearance in
November 2002.
• Indications for use:
– Unresponsive or not breathing
normally.
– If in doubt, apply pads.
• Safety and effectiveness
already established.
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Demonstration
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Designed as safety equipment
• “If you have concerns about your health or an existing
medical condition, talk to your doctor. A defibrillator is
not a replacement for seeking medical care.”
• Cannot predict who might need it, or when.
• Equipment may be used once in a lifetime.
• Key characteristics:
– Safe for all
– Ready when needed
– Easy in the moment
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History of Philips AED technology
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Sophisticated arrhythmia detection
• No single parameter can lead
to “shock advised.”
• Multiple parameters required.
Rapidity of
signal conduction
ECG
amplitude
Heart rate
Stability of ECG
complexes
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Field-demonstrated sensitivity/specificity
• Biphasic waveform study
– 1st generation AED--ForeRunner
– 286 out-of-hospital patients (1st 100 VF)
– 100% sensitivity, 100% specificity
• American Airlines study
–
–
–
–
1st generation AED--ForeRunner
200 consecutive uses; 15 VF patients
100% sensitivity, 100% specificity
Includes use as a rhythm monitor
• Tens of thousands of analyses
• One known inappropriate shock.
– Successful defibrillation, followed by AF with no ventricular activity;
indistinguishable from fine VF. Patient survived with normal neurological
function.
Gliner et al., Biomed Instrum Technol. 1998;32(6):631-643.
Page et al., N Eng J Med. 2000;343:1210-1216.
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Philips AED use estimates
Through 12/31/2003
• Over 150,000 AEDs deployed since 1996.
• > 1,000,000 total patient applications.
– ~ 200,000 patients required shocks.
– ~ 800,000 patients did not require shocks.
• Non-random sampling based on ForeRunner
AEDs.
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Field performance
• Six confirmed AED emergency use failures
across Philips installed base (> 1,000,000
patient applications).
– 4 no patient impact
– 1 patient impact indeterminate
– 1 possible patient impact
• No complaints about shock effectiveness.
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MDR summary—ForeRunner and FR2
Top 3 issues and predominant causes, confirmed & unconfirmed
Issue
n
No voice
prompts
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Poor patient- 11
pads
connection
Algorithm
6
sensitivity
Patient Impact
No patient
involvement
Predominant
Cause
Open speaker
circuit
Indeterminate
Suspected pads
damage
Indeterminate
ECG did not
meet rate criteria
(too low)
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HeartStart Home Defibrillator
Design features relevant to top 3 ForeRunner and FR2 MDR issues
ForeRunner/ FR2
HeartStart Home Defibrillator
issue
design feature
No voice prompts Weekly speaker self-test.
Poor patient-pads
connection
Pads enclosed in rigid cartridge.
Pads self-test every 24 hours.
Algorithm
sensitivity
No change to (cautious) design.
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First-year annualized failure rate for
Philips defibrillators (all causes)
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Automated self-test
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Iterative design process
Problem
Solution
Delayed device activation
Added fire alarm-style handle with the word
“PULL.”
Put pads on top of clothes
Added emergency scissors.Voice instruction:
“Begin by removing all clothing from the
patient’s chest. Cut clothing if needed.”
Failed to remove liner from
pads
Contrasting liner color.Voice instruction: “Peel
one pad from the yellow plastic liner.”
Poor pad position
Explicit graphics on each pad.Voice instructions:
“Look carefully at the picture on the white
adhesive pad… Place pad exactly as shown in
the picture.”
Accidental device turn-off
Must hold power button down for 2 seconds.
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HeartStart Home life-cycle support
Purchase
Product
Packaging
Sales
Materials
Product
Website
•Resources
Set-Up
Training
Storage &
Maintenance
Use
Post-Use
HeartStart Home Defibrillator
Primary labeling—Voice Prompts, Device Icons, Self-Test
HeartStart Home Defibrillator
Secondary labeling—Quick Reference, Owner’s Manual, Training
Video, Quick Start, Training Coupons, Product Registration Card
•FAQs
Philips Customer Service
Product Information, Training Resources, Consumables, Data Retrieval,
Counseling, Physician Access
Grief
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Philips HeartStart Home Defibrillator
• Designed as safety equipment.
• History of safety and
readiness.
• Designed for ease of use.
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Clinical overview
Safety and usability study
• Dr. Lance Becker
– Professor of Medicine, University of Chicago
• Disclosures
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Sudden Cardiac Arrest:
A leading killer in the United States
• Majority have no prior
symptoms.
• Nearly 80% happen in
the home.
• More than 50% of home
arrests witnessed.
American Heart Association. Heart Disease and Stroke Statistics — 2004 Update. Dallas, Tex.: American Heart Association; 2003.
Litwin et al., Ann Emerg Med. 1987;16:787-791.
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American Heart Association. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Dallas, Texas: American Heart Association, 2000.
Cummins et al., Circulation. 1991;83:1832-1847.
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Time is key to survival
Response curve (exponential decay rate) is after: De Maio et al., Ann Emerg Med. 2003;42:242-250.
Time intervals after Herlitz et al., Eur Heart J 2003;24:1750-5. Blackwell et al., Academic Emerg Med. 2002;9:288-295., Braun et al., Ann Emerg Med.
1990;19:1058-64., White et al., Resuscitation. 2002Oct;55(1):17-23., Myerburg et al., Circulation. 2002;106:1058-1064.
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Early access can help save more lives
Response curve (exponential decay rate) after: De Maio, et al. Ann Emerg Med. 2003;42:242-250.
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Early defibrillation programs
American Airlines program
(Philips AEDs)
Chicago O’Hare & Midway
Airport programs
(Philips AEDs)
Casino security officers program
(Various manufacturers’ AEDs)
Page et al., N Eng J Med. 2000;343:1210-1216.
Caffrey et al., N Eng J Med. 2002;347:1242-1247.
Valenzuela et al., N Eng J Med. 2000;343:1206-1209.
•191 uses in aircraft, 9 in terminal
•15 VF patients; 40% (6/15) survived
to discharge
•No adverse events
•21 cardiac patients in 2 years
•18 VF patients; 61% (11/18) survived to
discharge
•No adverse events
•148 cases in 32 months
•90 VF patients; 59% (53/90) survived to
discharge, 74% for those shocked <3
minutes
•No adverse events
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NHLBI-sponsored Public Access Defibrillation
(PAD) trial: Will AEDs improve survival?
• Study objective — Will AEDs improve cardiac arrest survival
compared with CPR alone?
– 20,000 lay responders in facilities with a pre-defined risk of an event.
• Results
– Survival in CPR+AED group doubled (n=29) compared with
CPR alone (n=15).
– No serious adverse events associated with AED use.
– 89.3% of evaluated responders (n = 3,671) demonstrated “adequate”
AED skills 3 months after training.*
• Conclusion
– Laypersons can use AEDs safely to provide early defibrillation.
Ornato J. AHA Scientific Sessions 2003.
*Sehra et al., (Abstract 2002);Suppl to Circulation, Vol 106, No 19, pg II-403.
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Rapid response saves lives
• Time is critical — Early defibrillation is highly
effective.
• Primary question — Can the HeartStart
Home Defibrillator be used safely by lay
people?
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Safety and usability study
• Hypothesis #1
– The Philips HeartStart Home Defibrillator and FR2 are
safe – even in the absence of training.
• Hypothesis #2
– The HeartStart Home and FR2 have high usability when
used with primary labeling components (voice
prompts, product graphics) plus training video.
• Study method
– Mock cardiac arrest scenario with a fully dressed manikin
and AED.
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Enrollment and randomization
FR2
HeartStart Home
Randomization
Randomization
FR2 Naïve
n = 69
FR2 Video
n = 63
HeartStart Naïve
Naïve
n
=
61
n 62
8 minute training
video
Simulated Use
Simulated
Test
Simulated Use
Use Test
Test
HeartStart Video
n = 63
3 minute training
video
Simulated Use
Simulated
Test
Powered to detect a 20% difference between naïve and video trained for
each device with power = 0.80 and alpha = 0.05 (approx. 62 per group).
Simulated Use
Use Test
Test
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Primary and secondary endpoints
• Primary endpoints
– Safe: no touching of patient in a manner that could result
in a shock across the rescuer’s chest.
– Successful: shock delivered with pads positioned in a
manner likely to defibrillate (includes power on, attach
pads with appropriate pad placement, analyze, and
defibrillate within 5 min).
• Secondary endpoints (based on starting time from
when participant entered the room).
– Time-to-pads on
– Time-to-shock
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FR2 results:
Simulated-use test
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FR2 results: Time-to-shock
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HeartStart Home results:
Simulated-use test
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HeartStart Home results: Time-to-shock
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Study limitations
• Simulated use vs. reality
• Demographics
• Human anatomy more varied
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Conclusions
• The HeartStart Home Defibrillator and the FR2
were used safely in all cases (n = 132, 124
respectively).
• FR2 success rate significantly improved by video
training from 48% to 86% (p < 0.001).
• HeartStart Home Defibrillator successfully
used by both naïve and video trained
volunteers at 87% (79% LCL, n = 61) and 89%
(81% LCL, n = 63) with no difference detected
between naïve and video trained.
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Labeling evaluation and simulated use
Lay user survey
Post-market study
• David Snyder
– Director of Research, Philips
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Labeling evaluation and simulated use
Purpose
• Labeling evaluation: Test comprehension of secondary
labeling materials for the Philips HeartStart Home
OTC Defibrillator.
–
–
–
–
Owner’s Manual
Quick Reference
Training Video
Quick Start Poster
• Simulated use: Demonstrate safe and successful use
after review of only one component of labeling.
– Owner’s Manual
– Quick Reference
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Secondary labeling materials
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Methods
• Recruitment in 3 geographically diverse shopping
malls.
• No medical or defibrillator training, no CPR training
within 2 years.
• Age range 21-74.
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Methods
• Hypothesis for comprehension test:
– The written labeling materials are well understood.
– Approximately 90% passing grade (LCL > 80%).
• Hypotheses for simulated use:
– The HeartStart Home Defibrillator is safe.
– The HeartStart Home Defibrillator can be successfully
used by laypersons to deliver a defibrillation shock.
– Non-inferiority vs. 90% (10% margin).
• Study method
– Mock cardiac arrest scenario with a fully dressed manikin
and AED
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Enrollment and randomization
Stratified
30 min
15 min
Randomized
Randomized
Owner’s Manual
n = 89
Quick Reference
n = 89
Training Video
n = 79
Quick Start
n = 73
Written
comprehension
Test
Written
comprehension
Test
Written
comprehension
Test
Written
comprehension
Test
Simulated Use
Simulated Use
Simulated
Use
Test
Test
Test
Comprehension
sample size
determined to
establish 95% LCL of
80% for presumed
success rate
(C grade or better)
of 90%.
Simulated use
powered for a noninferiority delta of 10%
versus presumed
success rate of 90%
with power = 0.80 and
alpha = 0.05.
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Primary and secondary endpoints
• Primary endpoints
– Safe: no touching of patient in a manner that could result
in a shock across the rescuer’s chest.
– Successful: shock delivered with pads positioned in a
manner likely to defibrillate (includes power on, attach
pads with appropriate pad placement, analyze, and
defibrillate within 5 min).
• Secondary endpoints (based on starting time from
when participant entered the room).
– Time-to-pads on
– Time-to-shock
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Comprehension test
•
•
Written labeling materials at a 6th grade
reading level or lower (Flesch-Kincaid).
Test topics included:
–
–
–
–
–
–
–
–
–
Definition of SCA (vs. MI, stroke, etc.)
Set-up
Training
Storage
Maintenance
When to use defibrillator
Rescue steps
Post-shock care
Infant/child use
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Results: Median comprehension scores
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Results: Simulated-use test
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Results: Median time-to-shock
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Limitations and conclusions
• Study limitations same as safety and usability study.
• All labeling well understood with at least 90%
receiving a “passing” grade. Passing grade LCL ≥ 88% for
all tests.
• Defibrillator used safely in all cases (n = 178).
• Successful use 97% (92% LCL, n = 89) with Quick
Reference.
– Recommended labeling for emergency response.
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Follow-up
• Added information to training video and
Quick Start poster regarding intended use of
various labeling materials.
• Cover of Owner’s Manual modified to clarify
its purpose as a guide to set up,
maintenance, and accessories.
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Lay user survey–Purpose
• Determine if lay use of Philips AEDs results in
any previously unreported problems.
Jorgenson et al., Resuscitation. 2003;59:225-233.
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Lay user survey–Methods
Owned AED at
least 1 year
Medical professionals
excluded
Lay users identified
145 homes
businesses and public facilities
2,683
Initial contact by phone center
(at least 7 contact attempts)
Brief interview
Use by layperson?
Yes—Use by a layperson
Detailed interview with medical
professional
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Lay user survey–Results
• Surveyed 78 homes and 1,645 businesses.
– No problems reported.
– 209 businesses (13%) had used an AED at least once.
– 9 uses in homes/home offices.
• Conducted 11 detailed interviews regarding pads
applied to unresponsive patients.
– EMS called in all cases.
– 3 patients appropriately received no shocks.
– 8 patients received shocks.
• 6 survived to hospital admission.
• 4 received shocks solely from lay responders, and all survived to
hospital admission.
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Lay user survey–Limitations and
conclusions
• Limitations—Survey and interview participation was
voluntary.
• Conclusions
–
–
–
–
No harm or injury to users, bystanders or patients.
No malfunctions or problems.
All users willing to use defibrillator again.
No safety or effectiveness issues reported.
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Ongoing HeartStart Home
post-market study
Purpose
• Evaluate lay uses of HeartStart Home
Defibrillator for safe and appropriate
application.
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Methods
Contact lists generated:
HeartStart Home owned > 1 year
or 1 year since last surveyed
Pads re-ordered or use
reported to Philips
AED
used?
Contact owner
Detailed interview
with medical professional
Yes
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Proposed extension to HeartStart Home
post-market study
• Extend ongoing post-market study to 200 home
uses total or 4 years from HeartStart Home OTC
Defibrillator clearance.
• Results to be reviewed by DSMB and reported
annually to FDA.
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Clinical perspective
• Dr. Jeremy Ruskin
– Director, Cardiac Arrhythmia Service,
Massachusetts General Hospital
• Disclosures
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Sudden death - Risk stratification
"High-Risk" Pts
Prior MI
LV Dysfxn
CHF
VEA
+EPS
Ruskin et al., NEJM. 1980;303:607-613.
Wilber et al., NEJM. 1988;318:19-24.
VT-VF
Survivors
50%
65%
50%
50%
65%
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Sudden death–Risk stratification
"High Risk" Pts
VT-VF
Prior MI
LV Dysfxn
CHF
VEA
+EPS
Survivors
50%
65%
50%
50%
65%
Undetected
High-Risk
Patient Pool
Ruskin et al., NEJM. 1980;303:607-613.
Wilber et al., NEJM. 1988;318:19-24.
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Evolving role of defibrillation
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Safety equipment
Air bags
Smoke alarm
HeartStart Home
Defibrillator
Fire extinguisher
Seat belt
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Benefits and limitations
Smoke Alarms
Benefits
Seat Belts
Airbags
Reduces chance of dying
in a fire by 40%.
• 11,000 lives saved
each year.
• Reduces risk of
death in car crashes
by 45%.
• Reduces risk of
death in frontal car
crashes by 31%.
• 4,758 total lives
saved through 1999.
Limitations Nuisance alarms result in
alarm deactivation.
Not used 30% of the
time.
May cause injury or
death for children and
small adults—approx.
140 deaths through
1999.
Ahrens, M. U.S. experience with smoke alarms and other alarm devices, Nov 2003, National Fire Protection Association, Fire Analysis and Research Division, 1 Batterymarch Park,
Quincy, MA 02169-7471
National Highway Safety Administration, Air Bag Facts, Safety Fact Sheet, 11/02/1999 http://www.nhtsa.dot.gov/airbags/factsheets/numbers.html
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SCA and motor vehicle injury deaths in US
(1999)
State-Specific Mortality from Sudden Cardiac Death--- United States, 1999. CDC, MMWR, February 15, 2002/ 51(06); 123-6
10 Leading Causes of Unintentional Injury Deaths, United States, 1999, All Races, Both Sexes. CDC Website
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10-year expectations for emergency events
• U.S. Experience with Smoke Alarms and other Fire Alarms, Ahrens, Fire Analysis and Research Division, National Fire Protection Association, Nov 2003.
• Projections of the Number of Households and Families in the United States: 1995 to 2010, P25-1129, US Dept of Commerce, Bureau of the Census, April 1996.
• How Many Homes Are There? US Census Bureau, American Housing Survey, http://www.census.gov/hhes/www/housing/ahs/01dtchrt/tab2-1.html.
• Safety Fact Sheet, National Highway Traffic Safety Administration, 11/2/99, http://www.nhtsa.dot.gov/airbags/factsheets/numbers.html.
• ZJ Zheng, et al, State-Specific Mortality from Sudden Cardiac Death-- United States, 1999. MMWR Weekly, CDC, Feb 15, 2002/ 51(06); 123-6.
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Benefits of removing the Rx requirement
• Broader access to a safe and effective technology
that is the only definitive treatment for SCA.
• Provide an opportunity to save some of the
lives that would otherwise be lost to SCA.
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Risks—Can the AED cause harm?
• HeartStart Home OTC is the same intended
user and patient population as Rx.
• Robust safety features.
– ECG analysis system
– Artifact detection
– No manual override
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Philips AED field performance
• > 1,000,000 total patient applications.
– ~ 200,000 patients required shocks.
– ~ 800,000 patients did not require shocks.
• One known inappropriate shock.
• No complaints about shock effectiveness.
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Summary
• Safe design and established history of safe
use.
• The HeartStart Home Defibrillator can be
used safely and for its intended purpose
based upon its labeling alone.
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Theoretical risks
• Will OTC AEDs interfere with medical care?
–
–
–
–
–
Not a substitute for medical care.
Risk factors still need to be addressed.
Care and prescribed therapies for pre-existing conditions need to continue.
Physicians retain option to prescribe AEDs in cases of medical necessity.
Target populations are different.
• Will OTC defibrillators interfere with EMS response?
– SCA survival rate is <5% because defibrillators do not arrive in time.
– Philips supports calling EMS in labeling.
• Early defibrillation one part of emergency response.
– Rx requirement does not enhance EMS response.
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HeartStart Home Defibrillator:
Realistic expectations
• SCA is an epidemic and a major public health
problem; the most common cause of death in
adults.
– Survival rates are abysmally low (<5%).
• A defibrillator is not a “cure” for the problem of
SCA.
– Unwitnessed arrests, devices used incorrectly, device
failure, other human and logistical factors.
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HeartStart Home Defibrillator:
Realistic expectations
• OTC defibrillators represent a paradigm shift
and a step toward wider access.
– Potential to save some lives that would otherwise
be lost.
• Long term: even a small impact could double
current survival rates.
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Strategies for addressing SCA
• Prevention of coronary artery disease.
• Revascularization and ICDs in high-risk patients.
• Availability of on-site rapid defibrillation.
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“Successful defibrillation depends on
immediate recognition of the
emergency and prompt application of
the external defibrillator.”
Paul M. Zoll, M.D. 1956
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