Interagency Registry for Mechanically Assisted Circulatory Support (Text Version)

Slide Presentation from the AHRQ 2008 Annual Conference

On September 9, 2008, Marissa A. Miller, DVM, MPH, made this presentation at the 2008 Annual Conference. Select to access the PowerPoint® presentation (436 KB).

Slide 1

Interagency Registry for Mechanically Assisted Circulatory Support

Marissa A. Miller, DVM, MPH
National Heart, Lung, & Blood Institute (NHLBI)

Slide 2

• "Implantation of an MCSD [Mechanical Circulatory Support Device] 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."

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

Slide 3

What does INTERAGENCY mean?

• National Heart Lung and Blood Institute:
  • Patrice Nickens, Tim Baldwin, Marissa Miller, Karen Ulisney
• Centers for Medicare and Medicaid Services (CMS):
  • Marcel Salive, Joanna Baldwin
• Food and Drug Administration (FDA):
  • Wolf Sapirstein, Eric Chen, Tom Gross, Bram Zuckerman

Slide 4

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.

Slide 5

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).

Slide 6

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

Slide 7

NHLBI Contract #N01-HV-58198: Data Coordinating Center (DCC)

• Site:
  • Univ. of Alabama at Birmingham (UAB)
    Principal Investigator (PI): James Kirklin, MD
• Date:
  • May 31, 2005
• Duration:
  • 5 years
• Subcontracts:
  • United Network of Organ Sharing (UNOS)
    Robert L. Kormos, MD
    Lynne W. Stevenson, MD
• Study Chair:
  • James B. Young, MD

Slide 8

The diagram shows "intermacs" with arrows pointing towards it from six surrounding ovals. The six ovals read as follows:

• NHLBI, FDA, CMS: Funding, regulation, reimbursement
• UNOS: Web-based data entry (WBDE)
• Industry: Device expertise
• DCC UAB: Data analysis
• Steering Committee: Medical expertise
• Clinical Sites: Data collection

Slide 9

Steering Committee

• Operations Committee:
  • Marissa Miller, James Young, James Kirklin, Lynne Stevenson, Robert Kormos, Tim Baldwin, Patrice Nickens, David Naftel, Leah Edwards, Eric Chen, Wolf Saperstein
• Subcommittees:
  • Data Access, Analysis and Publications:
    • F. Pagoni
  • Hospital Training and Standards:
    • J. Long
  • Adverse Events and Adjudication:
    • R. Kormos
  • Pediatrics:
    • E. Blume
  • Industry Relations and Device Development:
    • E. Rose
  • Focused Research and Mission Activities:
    • S. Koenig
  • Coordinators Council:
    • T. Cleeton, K. Chisholm, T. Martin, S. Wissman

Slide 10

INTERMACS Timeline

• Data Element Development:
  • Protocol Development:
    • Contract Awarded to UAB 06/01/05
  • Refine WBDE:
    • Training: 101 Coord 35 Pls; 84 Sites 02/28/06
• Hospital Enrollment:
  • Patient Enrollment:
    • Launch 06/23/06
    • CMS Destination Therapy 03/27/07

Slide 11

The Major Task for the INTERMACS Registry

The bar graph shows "Typical Registry" needing to grow in order to become a "Good Clinical Trial."

Slide 12

What makes a "Good Clinical Trial?" From top to bottom:

• Planned (thoughtful) Analyses
• Observational Study Monitoring Board (OSMB)
• Adjudication of Outcome Events
• Local PI Certification
• Data Freeze
• Audits
• Complete Follow-up
• Complete Data
• All Cases
• Adverse Event Definitions
• Inclusion/Exclusion Criteria
• Typical Registry

Slide 13

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 U.S.
• Outcomes and Risk Factors:
  • Death, survival, adverse events, transplantation

Slide 14

Data Element & Adverse Event Definition Development

• Inclusive Process:
  • Engaged experts in specific areas: adverse events (AEs), quality of life (QOL), heart failure (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

Slide 15

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/medical device reporting (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

Slide 16

Clinical Site Benefits

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.

Slide 17

Stakeholder 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.

Slide 18

June 2006-December 2007 (n=420)

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%

• Note: *In all subsequent slides "Bridge to Transplant" will include the four subcategories.

Slide 19

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

The line graph's vertical axis, "Proportion of Patients," goes from 0.0 to 1.0 and the horizontal axis, "Months after Device Implant," goes from 0 to 12. The results show at 6 months:

• Transplant: 42%
• Alive-still waiting: 33%
• Death-before transplant: 22%
• Explanted-recovery: 3%

Slide 20

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

The line graph's vertical axis, "Proportion of Patients," goes from 0.0 to 1.0 and the horizontal axis, "Months after Device Implant," goes from 0 to 12. The results show at 6 months:

• Alive-still waiting: 68%
• Death-before transplant: 25%
• Transplant: 5%
• Explanted-recovery: 2%

Slide 21

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

The line graph's vertical axis, "Percent Survival," goes from 0 to 100 and the horizontal axis, "Months after Device Implant," goes from 0 to 12. The results show:

• Bridge to Transplant (includes BTT subcategories) n=336, deaths=74
• Destination Therapy n=63, deaths=19
• Bridge to Recovery or Rescue Therapy n=21, deaths=11
• Event: Death

Slide 22

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.

Slide 23

• www.intermacs.org