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

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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