Maximizing Comparative Effectiveness Research The DECIDE CV Consortia

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Maximizing Comparative Effectiveness Research
The DECIDE CV Consortia

• Eric D. Peterson, MD, MPH
• Professor of Medicine
• Vice Chair for Quality, Duke DOM
• Associate Director, Duke Clinical Research
  Institute (DCRI)
• David Magid, MD, MPH
• Director of Research, Colorado Permanente Medical
  Group
• Associate Professor, University of Colorado

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Comparative Effectiveness Research
"There is a wealth of data available from large
databases that enable us to research important
clinical questions," "Robust methodology exists
for comparing different therapies through
observational database analysis.
Wilensky G Health Affairs Nov 2006w572-w588
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Elements Stimulating Comparative Effectiveness
Research
As part of ARRA 1.1 billion set aside for
comparative effectiveness research (CER)
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IOM CER Priorities 2009
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Leading Causes of Death in US
Htttp//www.cdc.gov/mmwr/preview/mmwrhtml/mm5539a9
.htm
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Lack of Evidence in Guidelines Recommendation
Based on RCT Data
11.7
26.4
15.3
13.5
12.0
22.9
6.4
6.1
23.6
0.3
9.7
11.0
19.0
3.5
4.8
0
10
20
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Tricoci P et al JAMA 2009
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Cycle of Evidence Development and Dissemination
Clinical Evidence
Concept
Guidelines
Large CV Registries
Outcomes
Performance Indicators
QI Initiatives
Measurement Feedback
Adapted from Califf RM, Peterson ED et al. JACC
2002401895-901
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Role of Clinical Registries for Evidence
DevelopmentE. Stead Using the Past to Guide
the Future

• Chronic diseases can be studied, but not by the
  methods of the past. If one wishes to create
  useful data computer technology must be
  exploited. Eugene Stead, MD
• Led to the concept of computerized textbook of
  medicine
• Formed foundation of the Duke Databank for CV
  Diseases
• Spurred a generation of clinical and quantitative
  researchers

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Types of Multicenter Registries

• Claims eg. CMS
• Advantages Comprehensive, longitudinal, cover
  in out-pt services
• Disadvantages Limited clinical data, age 65
• Managed Care/EHR eg. Kaiser/VA
• Advantages longitudinal, meds, labs, other
  clinical info
• Disadvantages select pts, miss out of coverage
  care
• Clinical Registries eg. ACC/STS/AHA
• Advantages targeted in-depth clinical data
• Disadvantages selective participation,
  traditionally in-patient focus

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CV Provider Led Clinical Registries

• Society of Thoracic Surgery 900 centers
• Coronary artery bypass surgery
• Valve surgery
• Congenital heart surgery
• Thoracic surgery
• National Cardiovascular Data Registry 1600
  Hospitals
• Cath/Percutaneous coronary intervention
• Implantable cardiac defibrillators (ICD)
• Acute coronary syndromes (ACS)
• Carotid stenting
• Ambulatory CV disease (launching)
• AHA-Get With The Guideline Program 1500
  hospitals
• Coronary artery disease (CAD)
• Heart failure
• Stroke
• Ambulatory module (launching)

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These CV Clinical Registries are

• large and growing more representative
• of US patients, providers, settings
• detailed...with rich clinical data
• presenting features, treatments, acute outcomes
• use standardized data elements
• With and among registries
• are high quality
• complete, accurate
• audited

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CV Registries across the Care Spectrum
HF/Stroke AMI/Care
Post-Event Cardiac rehabilitation Secondary
Prevention
Admitting Event
Primary Prevention
D/C
In pt Care
Admit
ACC IC3 GWTG Outpatient TRANSLATE ACS ORBIT-AF
AHA H360
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Clinical Registries as Engines for Evidence
Development
In-hospital Registry
Cross sectional studies
Claims Data
In-hospital Registry
Longitudinal studies
In-hospital Registry
Longitudinal Outcomes
Comparative Effectiveness
Device/Drug Information
In-hospital Registry
Longitudinal Outcomes
Translational Discovery
BiomarkerGentics Samples
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Duke DEcIDE and FDA CV Work(to Date)

• TMR Evaluation (2003)
• STS
• DES vs BMS Comparative Effectiveness (2008)
• ACC NCDR CMS part A
• DES vs BMS Subgroups Imaging (2009)
• ACC NCDR CMS part A B
• Aortic Valves (2009)
• STS CMS part A

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Diffusion of TMR into Clinical Practice
Peterson E. JACC 2003421611-6.
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NCDR DES vs BMS Longitudinal Analysis Methods

• Objective To examine comparative effectiveness
  and safety of DES vs BMS in a national PCI cohort
  
• Population All NCDR PCI pts 1/04-12/06
• Follow up Linkage to CMS inpatient claims data
  using indirect identifiers 76 matched
• Final cohort 262,700 pts
• 83 DES 46 Cypher, 55 Taxus
• Analysis Inverse propensity weighted model
• 102 covariates Cox PH to verify mortality

Douglas P JACC. 2009 May 553(18)1629-41.
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ACC 2009 LBCT NCDR DES vs BMS 30-Month Event
Rates
Rate / 100 patients
HR 0.91 (0.85,0.98)
HR 0.96 (0.88,1.04)
HR 0.75 (0.73,0.77)
HR 0.76 (0.72,0.80)
HR 0.91 (0.89,0.94)
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HMORN

• Consortium of 15 Health Plans
• Collectively provide community-based healthcare
  to 11 million persons
• Broad age, gender, and racial/ethnic diversity
  across sites
• High patient retention rates

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HMORN Centers
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HMORN Health Plans

• Established Research Centers
• Diverse delivery settings (e.g. inpatient,
  outpatient) and care models
• Provide longitudinal care (including prevention,
  diagnosis, and treatment)
• Linked lab, pharmacy, ambulatory care and
  hospital data
• 14/15 sites have implemented an electronic
  medical record (EMR)

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Registry Data Standardization Virtual Data
Warehouse (VDW)

• Common data dictionary
• Data arrayed using identical names, formats, and
  specifications
• SAS program written at one site can be run at
  other sites
• Increases efficiency of multi-site studies
• NOT a Data Coordinating Center or Centralized
  Data Warehouse

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HMORN VDW Registry Standardized Data Tables

• Patient Identification - Unique patient ID
• Membership - Enrollment status
• Demographics - Age, gender, race/ethnicity
• Laboratory - Lab tests and results
• Medications - Name, dose, route, date, pills
• Ambulatory - Diagnoses, tests, and procedures
• Hospital - Diagnoses and procedures
• Benefits - co-payments, co-insurance, deductibles
• Vital Signs BP, HR, BMI
• Mortality

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AHRQ Sponsored CV Research Projects - HMORN

• Comparative Effectiveness Research
• 2nd-line Anti-hypertensive therapy
• ß-blockers in patients with heart failure
• Benefit/Harms of Medications in Routine Practice
• Clopidogrel duration vs MI, Death, and Bleeding
• Interaction of Clopidogrel and PPIs
• Outcomes of Medical Devices in Routine Practice
• Use of DES in off-label indications
• Safety and Effectiveness of of ICDs

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CER of BB vs ACE as 2nd-line Anti-Hypertensive
Agents

• BP Control usually requires gt 1 med
• Optimal 2nd-line agent for pts whose BP is not
  controlled on a thiazide is unknown
• Objective To compare the effectiveness of
  ACE-inhibitors (ACE) vs. ß-blockers (BB) for HTN
  patients who are started on a thiazide but whose
  BP is inadequately controlled on a thiazide alone
  

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HMORN HTN Registry Unique Characteristics

• Size Over 1 million patients
• Exposure Assessment properly identified and
  excluded patients receiving ACE or BB for reasons
  other than HTN
• Ability to control for baseline BP (higher in
  patient receiving BB as 2nd-line therapy
• Control for confounding bias using both
  diagnostic and lab data (e.g. renal function)
• Assess BP control
• Assess progression to renal disease

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BP control at 1 year(adjusted model results)

• Control Rates
• ACE 70.5
• ß-blocker 69.0 (p0.09 for
  comparison)
• Results consistent in subgroup analysis by site,
  gender and year

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Hypertension SequelaeCox proportional hazards
models
Additionally adjusted for eGFR
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DEcIDE CV ConsortiumVision

• Created as part of the Effective Health Care
  program with the Duke University and the HMO
  Research Network DEcIDE Centers
• Bring expertise in multiple scientific areas to
  provide comparative effectiveness research
• Develop a framework that aligns interests from
  the clinical community, governmental agencies,
  payers, professional societies

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CV Consortium Guiding Principals

• Conduct and disseminate high-quality CV
  research with potential to improve health
  outcomes and care delivery
• Engage with Stakeholders group in setting
  research priorities
• Work collaboratively to leverage our joint data
  resources and expertise
• Actively and transparently communicate with
  external audiences to allow accountability

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2008 Kick-off Meeting

• CVC Stakeholder Committee had this initial
  meeting in October 14, 2008
• Project Investigators HMORN, Duke
• Governmental Agencies AHRQ, FDA, NIH, CMS
• Professional Socities ACC, AHA, STS
• Other Observers Major payors
• Topics Coronary stenting, antiplatelet therapy
  and aortic valve disease

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Future of CV Consortium

• Define and Prioritize Topic Areas
• Many existing and emerging CV therapies and
  diagnostic technologies, including
• Heart Failure
• Coronary Artery Disease
• Sudden Cardiac Death
• Valvular Heart Disease
• Atrial Fibrillation
• Hypertension and other risk factor control
• Peripheral Vascular Disease
• Stroke

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Future of CV Consortium

• Broaden Stakeholders
• American College of Physicians
• American Association of Family Physicians
• Patients
• Strengthen Collaborations
• DEcIDE Network
• Professional Societies
• Other Non-governmental agencies

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Proposed CV Consortium Organization
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At the End of the Day

• The CV DEcIDE Consortium and Collaboration can
• capture high quality clinical data efficiently
• be used for scientific discovery
• track patients longitudinal care
• track drugs/devises
• be linked to biological/imaging data
• complement/support traditional and practical RCTs
• helps drive new evidence into routine practice

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Thank you

• Questions?