Post on 15-Dec-2015
Leveraging Operational Cardiovascular Registries: An ACC View
Plenary Session:Novel Infrastructure for Clinical Trials & Innovation
CSRC Transradial Thinktank MeetingFDA White Oak , Silver Spring
July 29, 2013
Ralph Brindis, MD, MPH, MACCSenior 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!
1998 2004 2005 2006 2007 2008 2010 2012
PVI
2500 hospitals> 2000 cardiologists
16 million clinical records
2500 hospitals> 2000 cardiologists
16 million clinical records
Science and QualityEducationAdvocacyChapters
Data Quality
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– Upto 650 records are audited annually.
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%.
JACC June, 2012
ACC/Duke Partnership: Develop a ACC/Duke Partnership: Develop a National Cardiovascular ResearchNational Cardiovascular Research
Infrastructure (NCRI)Infrastructure (NCRI)
NCRI’s Infrastructure Opens Doors
Outcomes to CER toRCTs to Post Market to IDE
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: Prospective, Observational Study: DAPT Among AMI-PCI Patients DAPT Among AMI-PCI Patients
11MonthsMonths
33 66 1212 1515Index AMIIndex AMIHospitalizationHospitalization
DischargeDischarge
FOLLOW-UP FOLLOW-UP – – Validated events, medications, costsValidated events, medications, costs
ClopidogrelClopidogrel
or or
PrasugrelPrasugrel
oror
(Ticagrelor)(Ticagrelor)
ObjectivesObjectives: to evaluate: to evaluate
• long-term effectiveness and safetylong-term effectiveness and safety• adoption of novel antiplatelet medsadoption of novel antiplatelet meds• short- and long-term Rx patternsshort- and long-term Rx patterns• antiplatelet medication switchingantiplatelet medication switching• patient adherencepatient adherence• economic cost implicationseconomic cost implications
www.translate-acs.orgwww.translate-acs.org
SAFE-PCI for Women Study
Pilot study for the National Cardiovascular Research Infrastructure (NCRI) grant
Study of
Access Site
For
Enhancement of
Percutaneous
Coronary
Intervention for Women
ww
w.c
vrn
.org
CVRN Longitudinal CVRN Longitudinal Study of ICDsStudy of ICDs
Circ Cardiovasc Qual Outcomes. 2012;5:e78-85.
CVRN ICD Study AimsCVRN 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 & National & international international device registriesdevice registries
• Modernize adverse event reporting
• New methods for New methods for evidence evidence generation, generation, synthesis and synthesis and appraisalappraisal
TVT Collaborative PartnershipsTVT Collaborative Partnerships
• Clinical Registry Program• Quality/Outcomes Research• Device Surveillance• Post-Approval Studies• IDE Studies• Network for RCTs
• 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
Nat
iona
l Res
earc
h In
fras
truc
ture
Nat
iona
l Res
earc
h In
fras
truc
ture
Phase 1 Phase 2 Phase 3Post-
Approval
Phase 4
• Safety is primary endpoint
• Highly selected population (must meet several selection criteria)
• Short duration
• Safety and efficacy are primary endpoints
• Highly selected population
• Short duration
• Safety and efficacy are primary endpoints
• Selected population
• Pivotal studies (randomized controlled trial, RCT)
• Longer duration
• FDA driven and negotiated
• Centers defined
• Generally a Phase 3 continuance
• Sample size pre-determined
• Study interval defined
• Sponsor driven• Generally RCT
or Claims based• Direct product
comparisons• Costs collected• Sample size
pre-determined• Study interval
defined
Pre-Market Post-Market
Post-Market
• 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
TraditionalRegistries
Role for New Generation of Clinical Registries
Clinical registries provide a platform for phase 3 & 4 research
Highest PriorityShort 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.Participant Subscription2.NCD/CED Mandates3.Payer/Health Plan Support4.Industry Grants5.Government/Non-profit Grants
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