Interagency Registry for Mechanically Assisted Circulatory Support

Marissa A. Miller, DVM, MPH

National Heart, Lung, & Blood Institute

“Implantation of an MCSD is not a simple, time-limited treatment episode. Because of the patient’s total dependence on the device and because problems can occur at any time, clinical trial subjects should be followed closely during the trials: they and other MCSD patients should be followed, through a registry, for the remainder of their lives...

Maintaining a registry of MCSD recipients should be considered a routine aspect of this care…The committee recommends that NHLBI…support long term follow up studies of an adequate sample of MCSD patients.”

The Artificial Heart: Prototypes Policies and Patients; Institute of Medicine Report, 1991.

What does INTERAGENCY mean?

National Heart Lung and Blood Institute

Patrice Nickens, Tim Baldwin, Marissa Miller,

Karen UlisneyCenters for Medicare and Medicaid

Services

Marcel Salive, Joanna Baldwin

Food and Drug Administration

Wolf Sapirstein, Eric Chen, Tom Gross,

Bram Zuckerman

Objective

To advance the understanding and application of mechanical circulatory

support in order to improve the duration and quality of life of patients with

advanced heart failure.

Purpose

To collect and analyze clinical and laboratory data and tissue and blood

samples from patients who are receiving MCSDs for whom discharge from the hospital is feasible (including destination therapy for end stage heart

failure, bridge to transplantation and bridge to recovery patients).

To disseminate information that will refine:• Patient selection

• Establish best practices to improve clinical management

• Expedite new clinical trials

• Improve economic outcomes

• Evaluate function and quality of life of patients

• Guide next generation device development

• Promote research into heart failure and recovery

Goals of the Registry

NHLBI Contract #N01-HV-58198Data Coordinating Center

Site: Univ. of Alabama at Birmingham

PI James Kirklin, MD

Date: May 31, 2005

Duration: 5 years

Subcontracts: United Network of Organ Sharing

Robert L. Kormos, MD

Lynne W. Stevenson, MD

Study Chair: James B. Young, MD

NHLBI,FDACMS

Funding, regulation,reimbursement

Clinical sitesData collection

SteeringCommittee

Medicalexpertise

IndustryDevice expertise

DCCUAB

Data Analysis

UNOSWeb-basedData entry

Steering CommitteeOperations Committee

Marissa Miller, James Young, James Kirklin, Lynne Stevenson, Robert Kormos, Tim Baldwin, Patrice Nickens, David Naftel,

Leah Edwards, Eric Chen, Wolf Saperstein

Subcommitees

Data Access, Analysis and Publications

F Pagoni

Hospital Training and Standards

J Long

Adverse Events And Adjudication

R Kormos

Pediatrics

E Blume

Industry RelationsAnd

Device Development

E Rose

Focused Research and

Mission Activities

S Koenig

Coordinators Council

T CleetonK Chisholm

T MartinS Wissman

Protocol Development

INTERMACS Timeline

Contract Awarded to UAB06/01/05

Training101 Coord 35 PIs 84 Sites

02/28/06

Data Element Development

Refine WBDE

Hospital Enrollment

Patient Enrollment

Launch06/23/06

CMS Destination

Therapy03/27/07

Mea

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Good Clinical Trial

Typical Registry

The Major Task for the INTERMACS Registry

Mea

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of

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Good Clinical Trial

Typical Registry

Planned (thoughtful) Analyses

Complete Data

Adverse Event Definitions

All Cases

Audits

Complete Follow-up

Adjudication of Outcome EventsLocal PI Certification

Data Freeze

OSMB

Inclusion/Exclusion Criteria

Site enrollment and compliance• Number of enrolled, and trained sites• Number of enrolled patients• Timely and complete submission of data

Descriptive Statistics• Demographics and characteristics of patients• Type and number of devices-*ability to capture high

proportion of devices implanted in US

Outcomes and Risk Factors• Death, survival, adverse events, transplantation

Data Collection and Analysis

Inclusive ProcessInclusive Process• Engaged experts in specific areas: AEs, QOL, HF,

Bioengineering • Included academic, industry and government

Series of Steering Committee Meetings • 6 face-to-face meetings over 6 months to develop

and refine the data elements• Meetings with FDA and CMS to harmonize

Coordinators Training and Site Testing• Coordinators’ training January 27& 28, 2006• Over 100 sites sent representatives to participate• Dialogue and feedback process

Data Element & Adverse Event Definition Development

Standardized definitions & data elementsStandardized definitions & data elements• Adverse event definitions developed in conjunction with

FDA and Industry• Potential to use in pre-market and clinical trials

Direct reporting of adverse events/MDRs to FDA• Majority of data collected on MEDWATCH Form 3500A

available in INTERMACS.• Event adjudication process through INTERMACS

experts meeting quarterly

Web-based data entry• Ongoing, rapid and user-friendly• Future integration of ISHLT-MCSD data

Innovations

1. Fulfills CMS reporting requirements to a national registry for destination therapy.

2. Semi-annual site specific reports, including confidential comparisons to aggregate results.

3. Sites already contributing to ISHLT MCSD database will be “grandfathered in” if they desire.

Clinical Site Benefits

1. Provides CMS detailed data on sites placing MCSDs for destination therapy.

2. Has obviated the need for sites to report mechanical device failures to FDA.

3. Adverse event definitions are being utilized in pre and post-market device studies.

4. Industry is utilizing registry data for regulatory trials and studies.

Stakeholder Benefits

Device Strategy at Implant n % of 420

Bridge to Recovery 21 5%

Bridge to Transplant* 336 80%

Listed 179 43%

Likely to be listed 83 20%

Moderate likely to be listed 44 10%

Unlikely to be listed 30 7%

Destination Therapy 63 15%

Total 420 100%

*In all subsequent slides “Bridge to Transplant” will include the four subcategories.

June 2006 – December 2007 (n=420)

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June 2006 – December 2007Device Strategy: Bridge to Transplant, n=336

Months after Device Implant

Pro

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f P

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Alive (still waiting) 33%

Death (before transplant) 22%

Transplant 42%

Explanted (recovery) 3%

20%

24%

53%

3%

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June 2006 – December 2007Device Strategy: Destination Therapy, n=63

Months after Device Implant

Pro

po

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f P

atie

nts

Alive (still waiting)68%

Death (before transplant)

25%

Transplant5%

Explanted (recovery)2%

53%

37%

8%

2%

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June 2006 – December 2007 (n=420)Device Strategy at Implant

Months after Device Implant

% S

urv

ival

Destination Therapy n=63, deaths=19

Event: Death

Bridge to Recovery or Rescue Therapy n=21, deaths=11

Bridge to Transplant (includes BTT subcategories)n=336, deaths=74

p= .006

Summary92 Sites/969 Patients

• INTERMACS reflects extensive cooperation and collaboration

across government, academia and industry

• It is a national registry that fulfills CMS requirements for reporting of destination device placements

• FDA has optimized upon INTERMACS definitions for adverse events and considers the enterprise beneficial to their mission

• Utilization of INTERMACS platform can benefit Industry and advance the development of new devices, especially critical for ‘orphan’ products such as pediatric devices

• Challenge include extending into pediatric populations, premarket and international areas and sustainability.

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