Maximizing Comparative Effectiveness

Research The DECIDE CV Consortia

Eric D. Peterson, MD, MPHEric D. Peterson, MD, MPH

Professor of MedicineProfessor of Medicine

Vice Chair for Quality, Duke DOMVice Chair for Quality, Duke DOM

Associate Director, Duke Clinical Research Associate Director, Duke Clinical Research Institute (DCRI)Institute (DCRI)

David Magid, MD, MPHDavid Magid, MD, MPHDirector of Research, Colorado Permanente Director of Research, Colorado Permanente

Medical GroupMedical GroupAssociate Professor, University of Colorado Associate Professor, University of Colorado

Comparative Effectiveness Research

Wilensky G Health Affairs Nov 2006:w572-w588

"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.”

Elements Stimulating Comparative Effectiveness Research

As part of ARRA: $1.1 billion set aside for comparative effectiveness research (CER)

IOM CER Priorities 2009

Leading Causes of Death in US

Htttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm5539a9.htm

Lack of Evidence in Guidelines: Recommendation Based on RCT Data

11.7%11.7%

26.4%26.4%

15.3%15.3%

13.5%13.5%

12.0%12.0%

22.9%22.9%

6.4%6.4%

6.1%6.1%

23.6%23.6%

0.3%0.3%

9.7%9.7%

11.0%11.0%

19.0%19.0%

3.5%3.5%

4.8%4.8%

0%0% 10%10% 20%20% 30%30%

AFAF

Heart failureHeart failure

PADPAD

STEMISTEMI

PerioperativePerioperative

Secondary preventionSecondary prevention

Stable anginaStable angina

SV arrhythmiasSV arrhythmias

UA/NSTEMIUA/NSTEMI

Valvular diseaseValvular disease

VA/SCDVA/SCD

PCIPCI

CABGCABG

PacemakerPacemaker

Radionuclide imagingRadionuclide imaging

Tricoci P et al JAMA 2009

ConceptConcept

OutcomesOutcomes

Clinical EvidenceClinical

Evidence

GuidelinesGuidelines

PerformanceIndicators

PerformanceIndicators

MeasurementMeasurement+ Feedback+ Feedback

MeasurementMeasurement+ Feedback+ Feedback

Cycle of Evidence Development and Dissemination

Large CV Large CV RegistriesRegistriesLarge CV Large CV RegistriesRegistries

Adapted from Califf RM, Peterson ED et al. JACC 2002;40:1895-901

QI InitiativesQI Initiatives

Role of Clinical Registries for Evidence Development:E. 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

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

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)

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

CV Registries across the Care Spectrum

Primary Prevention

Admitting Event

Post-Event:Cardiac rehabilitationSecondary PreventionD/C

In pt CareAdmit

HF/Stroke AMI/Care

ACTION GWTG HF, CVAACC-PCI, ICD

PVD, CongenitalSTS-CABG,

Valve

ACC IC3 GWTG OutpatientTRANSLATE ACS

ORBIT-AF

AHA H360

In-hospitalRegistry

Claims Data

In-hospitalRegistry

In-hospitalRegistry

LongitudinalOutcomesDevice/Drug

Information

In-hospitalRegistry

LongitudinalOutcomes

BiomarkerGentics Samples

Cross sectional studies

Longitudinal studies

Comparative Effectiveness

Translational Discovery

Clinical Registries as Engines for Evidence Development

Clinical Registries as Engines for Evidence Development

Duke DEcIDE and FDA CV Work(to Date)

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

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

Diffusion of TMR into Clinical PracticeDiffusion of TMR into Clinical Practice

0

5

10

15

20

25

30

35

40

1998 1999 2000

Cum

ula

tive

pro

port

ion o

f STS s

ites

per

form

ing T

MR

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

% T

MR

of

tota

l pro

cedure

s

% Sites performing TMR % Total TMR procedures

% TMR+CABG procedures % TMR only

Peterson E. JACC 2003;42:1611-6.

NCDR DES vs BMS Longitudinal Analysis Methods

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

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 5;53(18):1629-41.

ACC 2009 LBCT: NCDR DES vs BMS 30-Month Event Rates

ACC 2009 LBCT: NCDR DES vs BMS 30-Month Event Rates

0

5

10

15

20

25

Death MI Revasc Bleeding Stroke

BMS

DES

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)

Rat

e /

100

pat

ien

ts

HMORNHMORNHMORNHMORN

Consortium of 15 Health PlansConsortium of 15 Health Plans

Collectively provide community-based healthcare to Collectively provide community-based healthcare to ~11 million persons~11 million persons

Broad age, gender, and racial/ethnic diversity Broad age, gender, and racial/ethnic diversity across sitesacross sites

High patient retention ratesHigh patient retention rates

Consortium of 15 Health PlansConsortium of 15 Health Plans

Collectively provide community-based healthcare to Collectively provide community-based healthcare to ~11 million persons~11 million persons

Broad age, gender, and racial/ethnic diversity Broad age, gender, and racial/ethnic diversity across sitesacross sites

High patient retention ratesHigh patient retention rates

HMORN CentersHMORN Centers

HMORN Health PlansHMORN Health PlansHMORN Health PlansHMORN Health Plans

Established Research Centers Established Research Centers

Diverse delivery settings (e.g. inpatient, outpatient) Diverse delivery settings (e.g. inpatient, outpatient) and care modelsand care models

Provide longitudinal care (including prevention, Provide longitudinal care (including prevention, diagnosis, and treatment)diagnosis, and treatment)

Linked lab, pharmacy, ambulatory care and hospital Linked lab, pharmacy, ambulatory care and hospital datadata

14/15 sites have implemented an electronic medical 14/15 sites have implemented an electronic medical record (EMR)record (EMR)

Established Research Centers Established Research Centers

Diverse delivery settings (e.g. inpatient, outpatient) Diverse delivery settings (e.g. inpatient, outpatient) and care modelsand care models

Provide longitudinal care (including prevention, Provide longitudinal care (including prevention, diagnosis, and treatment)diagnosis, and treatment)

Linked lab, pharmacy, ambulatory care and hospital Linked lab, pharmacy, ambulatory care and hospital datadata

14/15 sites have implemented an electronic medical 14/15 sites have implemented an electronic medical record (EMR)record (EMR)

Registry Data StandardizationRegistry Data Standardization Virtual Data Warehouse (VDW) Virtual Data Warehouse (VDW) Registry Data StandardizationRegistry Data Standardization

Virtual Data Warehouse (VDW) Virtual Data Warehouse (VDW) Common data dictionaryCommon data dictionary Data arrayed using identical names, formats, and Data arrayed using identical names, formats, and

specificationsspecifications

SAS program written at one site can be run at SAS program written at one site can be run at other sites other sites

Increases efficiency of multi-site studiesIncreases efficiency of multi-site studies

NOT a Data Coordinating Center or Centralized NOT a Data Coordinating Center or Centralized Data WarehouseData Warehouse

Common data dictionaryCommon data dictionary Data arrayed using identical names, formats, and Data arrayed using identical names, formats, and

specificationsspecifications

SAS program written at one site can be run at SAS program written at one site can be run at other sites other sites

Increases efficiency of multi-site studiesIncreases efficiency of multi-site studies

NOT a Data Coordinating Center or Centralized NOT a Data Coordinating Center or Centralized Data WarehouseData Warehouse

HMORN VDW Registry HMORN VDW Registry Standardized Data TablesStandardized Data TablesHMORN VDW Registry HMORN VDW Registry

Standardized Data TablesStandardized Data Tables

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

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

AHRQ Sponsored CV Research Projects - AHRQ Sponsored CV Research Projects - HMORNHMORN

AHRQ Sponsored CV Research Projects - AHRQ Sponsored CV Research Projects - HMORNHMORN

Comparative Effectiveness ResearchComparative Effectiveness Research

2nd-line Anti-hypertensive therapy2nd-line Anti-hypertensive therapy

β-blockers in patients with heart failure

Benefit/Harms of Medications in Routine PracticeBenefit/Harms of Medications in Routine Practice

Clopidogrel duration vs MI, Death, and BleedingClopidogrel duration vs MI, Death, and Bleeding

Interaction of Clopidogrel and PPIsInteraction of Clopidogrel and PPIs

Outcomes of Medical Devices in Routine PracticeOutcomes of Medical Devices in Routine Practice

Use of DES in off-label indicationsUse of DES in off-label indications

Safety and Effectiveness of of ICDs Safety and Effectiveness of of ICDs

Comparative Effectiveness ResearchComparative Effectiveness Research

2nd-line Anti-hypertensive therapy2nd-line Anti-hypertensive therapy

β-blockers in patients with heart failure

Benefit/Harms of Medications in Routine PracticeBenefit/Harms of Medications in Routine Practice

Clopidogrel duration vs MI, Death, and BleedingClopidogrel duration vs MI, Death, and Bleeding

Interaction of Clopidogrel and PPIsInteraction of Clopidogrel and PPIs

Outcomes of Medical Devices in Routine PracticeOutcomes of Medical Devices in Routine Practice

Use of DES in off-label indicationsUse of DES in off-label indications

Safety and Effectiveness of of ICDs Safety and Effectiveness of of ICDs

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

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

BP Control usually requires > 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. β-blockers (BB) for HTN patients who are started on a thiazide but whose BP is inadequately controlled on a thiazide alone

BP Control usually requires > 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. β-blockers (BB) for HTN patients who are started on a thiazide but whose BP is inadequately controlled on a thiazide alone

HMORN HTN Registry HMORN HTN Registry Unique CharacteristicsUnique CharacteristicsHMORN HTN Registry HMORN HTN Registry Unique CharacteristicsUnique Characteristics

Size – Over 1 million patientsSize – Over 1 million patients

Exposure Assessment – properly identified and Exposure Assessment – properly identified and excluded patients receiving ACE or BB for reasons other excluded patients receiving ACE or BB for reasons other than HTNthan HTN

Ability to control for baseline BP (higher in patient Ability to control for baseline BP (higher in patient receiving BB as 2receiving BB as 2ndnd-line therapy-line therapy

Control for confounding bias using both diagnostic and Control for confounding bias using both diagnostic and lab data (e.g. renal function)lab data (e.g. renal function)

Assess BP controlAssess BP control

Assess progression to renal diseaseAssess progression to renal disease

Size – Over 1 million patientsSize – Over 1 million patients

Exposure Assessment – properly identified and Exposure Assessment – properly identified and excluded patients receiving ACE or BB for reasons other excluded patients receiving ACE or BB for reasons other than HTNthan HTN

Ability to control for baseline BP (higher in patient Ability to control for baseline BP (higher in patient receiving BB as 2receiving BB as 2ndnd-line therapy-line therapy

Control for confounding bias using both diagnostic and Control for confounding bias using both diagnostic and lab data (e.g. renal function)lab data (e.g. renal function)

Assess BP controlAssess BP control

Assess progression to renal diseaseAssess progression to renal disease

BP control at 1 year(adjusted model results)

BP control at 1 year(adjusted model results)

• Control Rates• ACE 70.5%

• β-blocker 69.0% (p=0.09 for comparison)

• Results consistent in subgroup analysis by site, gender and year

• Control Rates• ACE 70.5%

• β-blocker 69.0% (p=0.09 for comparison)

• Results consistent in subgroup analysis by site, gender and year

Hypertension Sequelae:Cox proportional hazards models

Hypertension Sequelae:Cox proportional hazards models

Outcome # events Hazard ratio

ACE vs. BB

95% CI

MI 96 1.05 (0.69-1.58)

Stroke 101 1.01 (0.68, 1.52)

CKD*

(stage 3)

1,446 1.02 (0.91, 1.13)

* Additionally adjusted for eGFR

DEcIDE CV ConsortiumVision

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

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

CV Consortium – Guiding PrincipalsCV Consortium – Guiding PrincipalsCV Consortium – Guiding PrincipalsCV 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 Work collaboratively to leverage our joint data resources and expertise resources and expertise

Actively and transparently communicate with external audiences to allow accountability

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 Work collaboratively to leverage our joint data resources and expertise resources and expertise

Actively and transparently communicate with external audiences to allow accountability

2008 Kick-off Meeting 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

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

Future of CV ConsortiumFuture 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

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

Future of CV ConsortiumFuture 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

Broaden Stakeholders American College of Physicians American Association of Family Physicians Patients

Strengthen Collaborations DEcIDE Network Professional Societies Other Non-governmental agencies

Proposed CV Consortium Organization

Proposed CV Consortium Organization

At the End of the Day…At the End of the Day…

The CV DEcIDE Consortium and Collaboration can:The CV DEcIDE Consortium and Collaboration can:

capture high quality clinical data efficientlycapture high quality clinical data efficiently

be used for scientific discoverybe used for scientific discovery track patients’ longitudinal caretrack patients’ longitudinal care track drugs/devisestrack drugs/devises be linked to biological/imaging databe linked to biological/imaging data

complement/support traditional and practical RCTscomplement/support traditional and practical RCTs

helps drive new evidence into routine practicehelps drive new evidence into routine practice

Thank youThank you

Questions?Questions?