HeartStart Home OTC DefibrillatorFDA Panel Presentation

Introduction

• Carl Morgan– Company Co-Founder and Scientist

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We propose to remove the prescription requirement for the Philips HeartStart Home

Defibrillator.

Introduction to today’s discussion

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Rx requirement:“CAUTION: FEDERAL LAW RESTRICTS THIS DEVICE TO SALE BY OR ON THE ORDER

OF A PHYSICIAN.”

HeartStart Home Rx cleared in 2002

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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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The Food, Drug and Cosmetic Act requires that medical device labeling must bear “adequate directions for use…” (502 (f)(1))

Medical device labeling

“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) P

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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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• Received FDA clearance in November 2002.

• Indications for use:– Unresponsive or not

breathing normally.– If in doubt, apply pads.

• Safety and effectiveness already established.

Philips HeartStart Home Defibrillator

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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

Heart rate

Stability of ECG complexes

Rapidity of signal conduction

ECG amplitude

• No single parameter can lead to “shock advised.” • Multiple parameters required.

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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 Patient Impact

PredominantCause

No voice prompts

35 No patient involvement

Open speaker circuit

Poor patient-pads connection

11 Indeterminate

Suspected pads damage

Algorithm sensitivity

6 Indeterminate

ECG did not meet rate criteria (too low)

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HeartStart Home DefibrillatorDesign features relevant to top 3 ForeRunner and FR2 MDR issues

ForeRunner/ FR2 issue

HeartStart Home Defibrillator 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 SolutionDelayed 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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Philips Customer ServiceProduct Information, Training Resources, Consumables, Data

Retrieval, Grief Counseling, Physician Access

HeartStart Home life-cycle supportSet-Up

Training

Storage & Maintenance Use Post-

Use

Purchase

HeartStart Home DefibrillatorPrimary labeling—Voice Prompts, Device Icons, Self-

Test

Product Packagin

gSales

Materials

Product Website•Resource

s•FAQs

HeartStart Home DefibrillatorSecondary labeling—Quick Reference, Owner’s

Manual, Training Video, Quick Start, Training Coupons, Product Registration Card

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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

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.

• Majority have no prior symptoms.

• Nearly 80% happen in the home.

• More than 50% of home arrests witnessed.

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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. P 31

Early defibrillation programsAmerican Airlines program(Philips AEDs)

•191 uses in aircraft, 9 in terminal•15 VF patients; 40% (6/15) survived to discharge•No adverse events

Chicago O’Hare & Midway Airport programs(Philips AEDs)

•21 cardiac patients in 2 years•18 VF patients; 61% (11/18) survived to discharge•No adverse events

Casino security officers program(Various manufacturers’ AEDs)

•148 cases in 32 months•90 VF patients; 59% (53/90) survived to discharge, 74% for those shocked <3 minutes•No adverse events

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.

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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

Randomization RandomizationFR2 HeartStart Home

FR2 Naïven = 69

Simulated UseTest

FR2 Videon = 63

8 minute trainingvideo

Simulated UseTest

HeartStart Naïven = 61

HeartStart Videon = 63

3 minute trainingvideo

Simulated UseTest

Simulated UseTestSimulated Use Test Simulated Use 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). P

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HeartStart Naïven = 62

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 surveyPost-market study

• David Snyder– Director of Research, Philips

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Labeling evaluation and simulated usePurpose• 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

Owner’s Manualn = 89

Writtencomprehension

Test

Simulated UseTest

Quick Referencen = 89

Writtencomprehension

Test

Simulated UseTest

Training Videon = 79

Writtencomprehension

Test

Quick Startn = 73

Writtencomprehension

Test

Randomized Randomized30 min 15 min

Stratified

Simulated Use TestComprehension sample size determined to establish 95% LCL of 80% for presumed success rate (C grade or better) of 90%.

Simulated use powered for a non-inferiority delta of 10% versus presumed success rate of 90% with power = 0.80 and alpha = 0.05. P

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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.

P 57Jorgenson et al., Resuscitation. 2003;59:225-233.

Lay user survey–MethodsOwned AED at least 1 year

Medical professionals

excluded

Lay users identified145 homes

2,683 businesses and public facilities

Initial contact by phone center (at least 7 contact

attempts)

Yes—Use by a layperson Detailed interview with medical

professional

Brief interview Use by layperson?

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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 studyPurpose

• 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

Detailed interviewwith medical professional

Pads re-ordered or use reported to Philips

AEDused?Contact owner

Yes P 62

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 VT-VF SurvivorsPrior MILV DysfxnCHFVEA+EPS

50%65%50%50%65%

P 65Ruskin et al., NEJM. 1980;303:607-613.

Wilber et al., NEJM. 1988;318:19-24.

Sudden death–Risk stratification

"High Risk" Pts VT-VF SurvivorsPrior MILV DysfxnCHFVEA+EPS

50%65%50%50%65%

UndetectedHigh-Risk

Patient Pool P 66Ruskin et al., NEJM. 1980;303:607-613.

Wilber et al., NEJM. 1988;318:19-24.

Evolving role of defibrillation

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Safety equipment

Air bags

Seat beltFire extinguisher

Smoke alarm

HeartStart HomeDefibrillator

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Benefits and limitationsSmoke Alarms Seat Belts Airbags

Benefits 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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State-Specific Mortality from Sudden Cardiac Death--- United States, 1999. CDC, MMWR, February 15, 2002/ 51(06); 123-610 Leading Causes of Unintentional Injury Deaths, United States, 1999, All Races, Both Sexes. CDC Website

SCA and motor vehicle injury deaths in US (1999)

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• 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.

10-year expectations for emergency events

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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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• 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.

HeartStart Home Defibrillator: Realistic expectations

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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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• Prevention of coronary artery disease.

• Revascularization and ICDs in high-risk patients.

• Availability of on-site rapid defibrillation.

Strategies for addressing SCA

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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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