The Use of the Interagency Registry for Mechanically Assisted Circulatory

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The Use of the Interagency Registry for
Mechanically Assisted Circulatory Support
(INTERMACS) to Generate Objective Performance
Criteria (OPCs) for Use in MCSD Trials David C
Naftel, Joseph G Rogers, James B Young, Timothy
Baldwin, James K Kirklin, Eric Chen, Wolf
Sapirstein, Robert L Kormos, Deborah V Ascheim,
and Kathleen A Chisholm For the INTERMACS
Investigators
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Relevant Financial Relationship Disclosure
Statement

• The Use of the Interagency Registry for
  Mechanically Assisted Circulatory Support
  (INTERMACS) to Generate Objective Performance
  Criteria (OPCs) for Use in MCSD Trials
• David C. Naftel, PhD
• I will not discuss off label use and/or
  investigational use of the following
  drugs/devices
• The following relevant financial relationships
  exist related to this presentation
• Joseph Rogers Thoratec Consultant, Research
  Support
• Robert Kormos Ventrassist Scientific Advisory
  Board
• Deborah Ascheim Ventracor, Terumo Research
  Support

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• Purpose
• Define a possible use of INTERMACS in MCSD
  clinical trials for FDA approval
• Provide a data-based framework for a national
  dialogue to define appropriate outcome measures
  and study designs for MCSD trials

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• INTERMACS
• NHLBI funded U.S. Registry for FDA approved
  durable MCSDs
• Collaboration among NHLBI, FDA, CMS, industry,
  UNOS, UAB, 111 hospitals, physicians, scientists
• Audited Major events adjudicated
• 511 patients (420 prospective)
• Almost 2000 adverse events
• Quality of Life and Neurocognitive Testing
• 151.2 exposure years in the prospective patients

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FDA Approved Durable Devices AbioCor
TAH Novacor PC HeartMate IP Novacor
PCq HeartMate VE Syncardia Cardiowest HeartMate
XVE Thoratec IVAD MicroMed DeBakey
VAD-Child Thoratec PVAD
Investigational Durable Devices Arrow
Lionheart Jarvik 2000 Berlin Heart
EXCOR LVAD Technologies Berlin Heart
INCOR Medos CorAide MicroMed DeBakey
VAD Evaheart Terumo Duraheart HeartMate
II Toyobo Heartware Ventracor VentrAssist
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FDA Approved Durable Devices AbioCor
TAH Novacor PC HeartMate IP Novacor
PCq HeartMate VE Syncardia Cardiowest HeartMate
XVE Thoratec IVAD MicroMed DeBakey
VAD-Child Thoratec PVAD
INTERMACS Eligible Devices
Investigational Durable Devices Arrow
Lionheart Jarvik 2000 Berlin Heart
EXCOR LVAD Technologies Berlin Heart
INCOR Medos CorAide MicroMed DeBakey
VAD Evaheart Terumo Duraheart HeartMate
II Toyobo Heartware Ventracor VentrAssist
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• How can INTERMACS contribute to the complex
  process of approving new devices?
• Standardization of Adverse Event Definitions
• Template for Data Collection Structure
• Historical Control Patient Data
• Concurrent Control Patient Data
• Objective Performance Criteria

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OPC Background For some investigational devices,
notably prosthetic heart valves, the FDA has
allowed the approval process to include single
arm clinical studies where the control group has
been replaced by expected standard results known
as objective performance criteria (OPCs).
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Objective Performance Criteria OPCs are derived
from summarizing the major endpoints in published
studies with well defined patient populations and
definitions of events of similar devices.
Traditionally, OPCs have been presented as fixed
standards (i.e. no standard errors).
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Objective Performance Criteria (OPC) specified by
1994 FDA Heart Valve Guidance Document
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• OPCs for MCSDs
• Therefore, the concept of OPCs may be valid for
  MCSD trials but the structure will have to be
  quite different
• Results during the first 30 days post implant
  cannot be ignored. OPCs should be a function of
  time.
• Mortality must be central to the OPCs.
• Results are clearly a function of the MCSD
  position (LVAD, Bi-VAD, etc) with the
  understanding that the position of the VAD is a
  function of patient condition and clinical
  decision.

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• Should an OPC be
• a single number?
• a series of time related numbers?
• a number per LVAD, Bi-VAD, TAH?
• a number per DT, BTT, etc?
• a function of risk factors
• patient profile
• demographics
• hemodynamics
• etc.

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June 2006 December 2007
Device Strategy
Bridge to Transplant (includes BTT
subcategories) n336, deaths74
Destination Therapy n63, deaths19
Survival
Event Death (censored at transplant or recovery)
Months after Device Implant
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June 2006 December 2007
BTT LVAD n242
Alive (dev in place)
40
51
Proportion of Patients
25
Transplant
21
39
Death (before transplant) 18
Explanted (recovery) 3
3
Months after Device Implant
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June 2006 December 2007
BTT LVAD n242
Success Outcomes
Alive (dev in place)
40
51
Proportion of Patients
Transplant
25
39
21
Death (before transplant) 18
Explanted (recovery) 3
3
Months after Device Implant
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June 2006 December 2007
BTT LVAD n242
Failure Outcomes
Alive (dev in place)
40
51
Proportion of Patients
Transplant
25
39
21
Death (before transplant) 18
Explanted (recovery) 3
3
Months after Device Implant
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June 2006 December 2007
BTT LVAD n242
Failure Outcomes
Success Outcomes
Alive (dev in place)
40
51
Proportion of Patients
Transplant
25
39
21
Death (before transplant) 18
Explanted (recovery) 3
3
Months after Device Implant
18
MCSD Primary Outcomes
Success Outcome Alive Failure Outcome Dead
19
MCSD Primary Outcomes
Success Outcomes Transplantation Recovery
(explant) Alive (device in place) Failure
Outcome Death
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MCSD Primary Outcomes
Success Outcomes Transplantation (regardless of
survival post-tx) Recovery (explant) and alive
for at least 2 months Alive (device in place)
regardless of listing status Failure
Outcome Death while device in place Death
within 2 months post recovery
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MCSD Primary Outcomes
Status at 6 months BTT
LVAD DT (n242) (n63) Success
Outcomes Transplantation 39
8 Recovery (explant) 3 2 Alive
(device in place) 40 53 Failure
Outcome Death 18 37 Total
100 100
63
82
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Conclusions

• INTERMACS can provide the evidence- based
  substrate for a collaborative approach to the
  generation of OPCs.
• These OPCs should take into consideration the
  time related simultaneous occurrence of
  transplant, death and recovery.
• Investigation into risk adjusted OPCs should
  continue.