Transcript Ralph Brindis, MD - Cardiac Safety Research Consortium

Leveraging Operational Cardiovascular
Registries: An ACC View
Plenary Session:
Novel Infrastructure for Clinical Trials & Innovation
CSRC Transradial Thinktank Meeting
FDA White Oak , Silver Spring
July 29, 2013
Ralph Brindis, MD, MPH, MACC
Senior Medical Officer, External Affairs, NCDR
Clinical Professor of Medicine, UCSF
Past President, American College of Cardiology
Background Overview of
Issue Under Discussion
• Harnessing the potential power of national
registries to be a seamless infrastructure
for RCTs.
– Leveraging 2500 hospitals and >1000 office
based physicians in the NCDR
– Casting a fishing rod into the Mississippi River
of NCDR patient data streams
• Rapid RCT study recruitment
• Marked reduction in RCT costs
• Comparative Effectiveness Research and more
What Works Well Today!
2500 hospitals
> 2000 cardiologists
16 million clinical records
PVI
1998
2004
2005
2006
2007
2008
2010
2012
Science and Quality
Education
Advocacy
Chapters
Data Quality
• Standardized
definitions
• Field ranges
values
• Skip/jump
patterns
• Blind abstraction
• On site
• Remote
• Initial training
• Ongoing site
support
• Annual/regional
conferences
Rigorous
field edit
checks
Coordinator
training and
support
On-Site /
Remote Audit
Data
completeness
requirements
• Online data
quality reports
NCDR’s Data Quality Program
• Training and Clinical Support
Team
–
–
–
–
–
–
Orientation webinars
Online FAQs
Live customer support
Email
Monthly webinars
Annual meeting with case reviews, etc.
• Data Entry Integrity
–
–
–
Software value checks
Field level range parameters
Parent:Child fields
• Data Completeness
–
–
Sites receive completeness reports to resubmit
with missing fields completed
predetermined levels of completeness and
consistency required for data to be included in
national and comparison group averages
• Data Accuracy
–
In the 2010 audits, the overall
accuracy of data abstraction
for the CathPCI, ICD, and
ACTION-GWTG registries
were, respectively, 93.1%,
91.2%,
and 90.0%.
Upto 650 records are audited annually.
JACC June, 2012
ACC/Duke Partnership: Develop a
National Cardiovascular Research
Infrastructure (NCRI)
NCRI’s Infrastructure Opens Doors
Site Descriptor
Database
Data Transfer System
Randomization
SDTM Output
Data Standards
Enhance Site
Research Readiness
Future Research
• Database of research ready sites within the NCDR
• An approach for targeted recruitment
• Connects CathPCI with an EDC System
• Provides mechanism for modified CRFs, additional data collection
• Connection with EDC system allows us to track randomized
patients within the registry
• Data Collection tool/ EDC system that can export data in SDTM
compliant structure (ready for FDA submission)
• Create CV standards in CDISC and HL7
• Load all standards in NCI repository for future uses in trials
• Employ educational webinars/ training to NCDR sites to become
research ready
• Ready for large randomized clinical trials
• Post approval studies and CER
Outcomes to CER to
RCTs to Post Market to IDE
ASCERT SYNTAX Study
60 CathPCI sites
TRANSLATE
300 CathPCI sites
SAFE PCI for Women
50 high volume radial CathPCI sites
ICD Longitudinal Study
10 ICD sites
Edwards PAS II ; IDE (alternative access) approved
STS/ACC TVT sites
BSC
Use data captured via the ICD Registry
Major Advances of CV Registries
as Novel Infrastructure for
Clinical Trials & Innovation
• Efficiency
–Due to vast data banks, data quality
structures RCTs more efficient than
ever imagined
• Decreased Cost
–Both quicker and less expensive
Prospective, Observational Study:
DAPT Among AMI-PCI Patients
Objectives: to evaluate
•
•
•
•
•
•
Clopidogrel
or
Prasugrel
or
(Ticagrelor)
long-term effectiveness and safety
adoption of novel antiplatelet meds
short- and long-term Rx patterns
antiplatelet medication switching
patient adherence
economic cost implications
FOLLOW-UP – Validated events, medications, costs
Months
Index AMI
Hospitalization
1
3
6
12
15
Discharge
www.translate-acs.org
SAFE-PCI for Women Study
DCRI
Study of
Access Site
• Study
Coordinating
For
Center
Enhancement of
Percutaneous
Coronary
Intervention for Women
ACC
• Registry
Platform
Pilot study for the National
Cardiovascular Research
Infrastructure (NCRI) grant
www.cvrn.org
CVRN Longitudinal
Study of ICDs
Circ Cardiovasc Qual Outcomes. 2012;5:e78-85.
CVRN ICD Study Aims
• Rates and determinants of adverse
outcomes over 3 years
• Rates of appropriate and inappropriate
shock in cohort and subgroups
• CER of single vs. dual chamber ICD
• UDI system
incorporated into EHR
• National &
international
device registries
• Modernize adverse
event reporting
• New methods for
evidence
generation,
synthesis and
appraisal
TVT Collaborative Partnerships
STS
ACC
FDA
AROs
TVT
Registry
CMS
Industry
NHLBI
• Clinical Registry
Program
• Quality/Outcomes
Research
• Device
Surveillance
• Post-Approval
Studies
• IDE Studies
• Network for RCTs
What is Missing…..
Does not Work Well Today
• “Opportunities for improvement”:
– Facilitating smoothing the interface between
registries, FDA, CMS and industry for
streamlining RCT study designs, IRB
requirements, data collection needs
– Variable funding mechanisms and associated
challenges
An Underused Opportunity for Using
National Registries for RCTs and Innovation
Research ready sites
Existing NCDR data capture system
Site recruitment
Data standards
Physician thought leadership
Customized site training
Ability to sync with additional EDC
Randomization and added
monitoring when needed
PMS - Collaborative Research
Clinical registries provide a platform for phase 3 & 4 research
Pre-Market
Post-Market
Role for New Generation
of Clinical Registries
Phase 4
Phase 1
• Safety is
primary
endpoint
• Highly selected
population (must
meet several
selection
criteria)
• Short duration
Phase 2
• Safety and
efficacy are
primary
endpoints
• Highly
selected
population
• Short duration
Phase 3
• Safety and
efficacy are
primary endpoints
• Selected
population
• Pivotal studies
(randomized
controlled trial,
RCT)
• Longer duration
PostApproval
• FDA driven and
negotiated
• Centers
defined
• Generally a
Phase 3
continuance
• Sample size
pre-determined
• Study interval
defined
PostMarket
• Sponsor driven
• Generally RCT
or Claims based
• Direct product
comparisons
• Costs collected
• Sample size
pre-determined
• Study interval
defined
Traditional
Registries
• Product performance
and safety data
• Effectiveness is the
primary endpoint
• Hypothesis
generating
• Large and usually
undefined sample
size
• Real world
population
• Continuous duration
• Treatment not
assigned
Highest Priority
Short Term 1-3 Years
• Increased collaboration building on recent
“Templates” using national registries:
– FDA
– CMS and private payers
– Industry
– Academia
– Professional Societies
• Developing new templates
Sustainability is reliant
on stakeholders
commitment to using
registries for needed
purposes
Sustainability is
reliant on financial
support:
1.
2.
3.
4.
5.
Participant Subscription
NCD/CED Mandates
Payer/Health Plan Support
Industry Grants
Government/Non-profit
Grants
Government
•Measurement
•Research
•PMA/PAS
•Post Market
Consumers
Health Plans
• Decision
support
•Measurement
•Payment
Registries
Clinicians
• QI
• Reporting
• Public
Industry
•Research
•Market analysis
Highest Priority
Long Term 3-5 years
• National Consortium- advisory body for registry
derived RCTs with all potential stakeholders
– NHLBI, FDA, CMS, PCORI, patient groups,
Industry, academia, etc.
• Transparent and full external RCT data access
• Stable funding and sustainable registry RCT
model