P1246990946hiRBn

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Interagency Registry for Mechanically Assisted
Circulatory Support Marissa A. Miller, DVM,
MPH National Heart, Lung, Blood Institute
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Implantation of an MCSD is not a simple,
time-limited treatment episode. Because of the
patients 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 careThe committee
recommends that NHLBIsupport long term follow up
studies of an adequate sample of MCSD
patients. The Artificial Heart Prototypes
Policies and Patients Institute of Medicine
Report, 1991.
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What does INTERAGENCY mean?
National Heart Lung and Blood Institute Patrice
Nickens, Tim Baldwin, Marissa Miller, Karen
Ulisney
Centers for Medicare and Medicaid
Services Marcel Salive, Joanna Baldwin
Food and Drug Administration Wolf Sapirstein,
Eric Chen, Tom Gross, Bram Zuckerman
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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.
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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).
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Goals of the Registry

• 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

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NHLBI Contract N01-HV-58198 Data 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
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NHLBI,FDA CMS Funding, regulation, reimbursement

Clinical sites Data collection
UNOS Web-based Data entry
Industry Device expertise
Steering Committee Medical expertise
DCC UAB Data Analysis
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INTERMACS Timeline
Data Element Development
Hospital Enrollment
Protocol Development
Refine WBDE
Patient Enrollment
Contract Awarded to UAB 06/01/05
Training 101 Coord 35 PIs 84 Sites 02/28/06
Launch 06/23/06
CMS Destination Therapy 03/27/07
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Good Clinical Trial
The Major Task for the INTERMACS Registry
Measure of Study Quality (Study Design, Data
Analysis)
Typical Registry
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Good Clinical Trial
Planned (thoughtful) Analyses
OSMB
Adjudication of Outcome Events
Local PI Certification
Data Freeze
Measure of Study Quality (Study Design, Data
Analysis)
Audits
Complete Follow-up
Complete Data
All Cases
Adverse Event Definitions
Inclusion/Exclusion Criteria
Typical Registry
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Data Collection and Analysis

• 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

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Data Element Adverse Event Definition
Development

• Inclusive 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

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Innovations

• Standardized 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

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Clinical Site Benefits

• Fulfills CMS reporting requirements to a national
  registry for destination therapy.
• Semi-annual site specific reports, including
  confidential comparisons to aggregate results.
• Sites already contributing to ISHLT MCSD database
  will be grandfathered in if they desire.

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Stakeholder Benefits

• Provides CMS detailed data on sites placing MCSDs
  for destination therapy.
• Has obviated the need for sites to report
  mechanical device failures to FDA.
• Adverse event definitions are being utilized in
  pre and post-market device studies.
• Industry is utilizing registry data for
  regulatory trials and studies.

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June 2006 December 2007 (n420)
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.
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June 2006 December 2007 Device Strategy Bridge
to Transplant, n336
Transplant 42
53
Proportion of Patients
Alive (still waiting) 33
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20
Death (before transplant) 22
Explanted (recovery) 3
3
Months after Device Implant
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June 2006 December 2007 Device Strategy
Destination Therapy, n63
Alive (still waiting)
68
53
Proportion of Patients
25
Death (before transplant)
37
5
Transplant
8
Explanted (recovery)
2
2
Months after Device Implant
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June 2006 December 2007 (n420) Device Strategy
at Implant
Bridge to Transplant (includes BTT
subcategories) n336, deaths74
Destination Therapy n63, deaths19
Survival
p .006
Bridge to Recovery or Rescue Therapy n21,
deaths11
Event Death
Months after Device Implant
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• Summary
• 92 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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