lessons learned from cardiovascular trials - isctm · lessons learned from cardiovascular trials:...
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Adrian Hernandez, MD, MHS
Director, Health Services & Outcomes Research
Associate Director, Duke Clinical Research Institute
Lessons Learned from
Cardiovascular Trials:Getting to the Heart of the Matter in Uniting
Patients, Clinicians and Systems for Evidence
Generation
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Evolving Themes
Integration with the Real World
Informed patients grow as partners
•Participant-Partnered Research
“System-ness” of care
•Networked partnerships for research
Built in Quality (by Design)
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Real World?
1
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Looking Back at a Disruptive Technology
4
“It started with no funding and skepticism in some quarters
but today GISSI is recognized as an Italian achievement that
has changed cardiology treatment worldwide.”
http://eurheartj.oxfordjournals.org/content/31/9/1023.full
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5
1989
GUSTO
40,000+ pts
3-page faxed CRF
100’s of papers!1969
Duke Databank
1st and largest CV
clinical registry
2016
ADAPTABLE
Patient Centric RCT
20,000 pts; EHR driven
Mobile based pt follow-up
Evolving Technology!
5
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NATRECOR®
• FDA approved on Aug 10, 2001
– Intravenous treatment of
patients with acutely
decompensated congestive
heart failure who have
dyspnea at rest or with
minimal activity
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Real World Challenges- Equipoise?
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• Investigator independence in context of joint Executive Committee/large Steering Committee
• Large, pragmatic trial model
– Focused
– Efficient study design
– Streamlined procedures
– Simple follow-up
• Enroll clinical heart failure
• Meaningful outcomes
• ‘Real world’ treatment (standard of care)
• Feasible sub-studies to advance knowledge in acute heart failure
Design of ASCEND-HF: Guiding Principles
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ASCEND-HF North American Enrollment
Months
Patients
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XXXXXX
(>10,000)
ASCEND-HF
(n=7142)
Type of Trial Chronic CV Acute Heart
Failure
Traditionally
Reported SAEs
10,373 964
Triggered
Events
10,895 1480
Coded AEs 65,296 386
Concomitant
Therapies
332,677 <50,000
Visits 478,001 14,200
eCRF pages >2.5 million <200,000
Data Points >30 million <3 million
Costs +++++++++ ++
Benchmarking…
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Swedish Registry-Trial Hybrids
TASTE Trial: Thrombus-Aspiration in MI
Frobert O et al NEJM 2013
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HOW CAN WE ENGAGE
PATIENTS (PARTICIPANTS)?
2
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Post Approval
Studies
Create study
procedure
Implement the Study
Monitor the
study
Analyze data and
interpret results
Dissemi-nate study informatio
n
FDA Review
and Approva
l
Develop the
study concept
Secure Funding
Prepare the
Study Protocol
• Provide input on study design such as barriers to participation, study endpoints, and risk/benefit perception
• Recruit study participants
• Serve as a peer advocate during the informed consent procedure
• Provide feedback on how the patient community will view results
•Work with research team to ensure study participants get feedback from study
•Write newsletter articles or blog about results
• Co-present results with researcher at a conference or support group
•Serve on a Data Safety Monitoring Board
• Provide recommendations for revising study protocol if changes need to be made
•Work with researcher to
secure NIH, PCORI,
AHRQ funding
• DART & Halo Therapeutics, e.g. raise seed funding
•Fundraise for own research
• Help finalize eligibility criteria within the study protocol
• Assist in creating the informed consent form
• Advise study recruitment
Engaging participants Across the continuum?
• Provide information on unmet need aand therapeutic burden
• Interest of research question to patient community
• Serve on FDA advisory committees or post-market surveillance initiatves
Courtesy: Bray Patrick-Lake,
MFS
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Common problems with protocols from patient perspective
• Exclusion/inclusion criteria so stringent that no “real” patients meet criteria
• Study not feasible
– Procedural burden too high– Unmanageable dosing
regimen– Too many study
appointments– Location not convenient– Pediatric patients needing
to be seen during school hours
Courtesy: Bray Patrick-Lake, MFS
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Participant Engagement is Finally Recognized
as Crucial to Research and Regulatory Success
• NIH
• PCORI
• FDA
• Patient-focused drug
development
• Patient-preference risk-
benefit
• 21st Century Cures
• Precision Medicine
Initiative
• Common rule reform
CTTI PGCT Academic 2014
Interview Respondent
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CAN WE UNITE SYSTEMS
FOR THE GOOD OF THE
WORLD?
3
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Partners in a National Infrastructure
Health
Plan 2
Health
Plan 1
Health
Plan 5
Health
Plan 4
Health
Plan 7
Hospital
1
Health
Plan 3
Health
Plan 6
Health
Plan 8
Hospital
3
Health
Plan 9
Hospital
2
Hospital
4
Hospital
6
Hospital
5
Outpatien
t clinic 1
Outpatien
t clinic 3
Patient
network
1
Patient
network
3
Patient
network
2
Outpatien
t clinic 2
18
• Each network developing infrastructure, governance, data curation,
analytics, security and software
• Potential partners: disease or treatment-specific networks
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PCORnet: uniting people, clinicians, systems
19
20 Patient-Powered Research
Networks (PPRNs)
13 Clinical Data
Research Networks
(CDRNs)
PCORnetA national infrastructure
for people-centered clinical research
+ =
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PCORnet as a National Evidence System
20
For clinical trials
For observational studies
MissingWhite Non-White
Female Male
Mis
sin
g
22–64 65+0–4
42,545,341
83,131,450
5–14 15–21
Pool of patients
Race
Sex
Age
Number of people for participation in
clinical trials
in PCORnet to date:
~ Millions*Based on data from 57 DataMarts as of July 15, 2016
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Enabling Pragmatic Research: eScreening, eEnrollment and eFollowup
4 12 16 30
DCRI FOLLOW-UP • Patient Reported Outcomes
• Medication use
• Health outcomes
Baseline Data
ADAPTABLE
Enrollee8 20 ….
OR
CMS & Payer Virtual Data Warehouse FOLLOW-UP• Longitudinal health outcomes
Portal FOLLOW-UP • Patient Reported Outcomes
• Medication use
• Health outcomes
PCORNet Coordinating Center FOLLOW-UP • Via Common Data Model
• Longitudinal health outcomes
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ClinicalTrials.gov: NCT02697916
Adaptable.patient.com
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NIH CollaboratoryHealth Systems Research Demonstration Project Overview
Mission: Strengthen the
national capacity to implement
cost-effective large-scale
research studies that engage
healthcare delivery organizations
as research partners
• 10 Demonstration Projects
spanning 12 NIH institutes and
centers
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Large, high impact, cost effective studies are possible.Collaboratory: Health Care Systerms Research
Pragmatic Trial Target N Health Care Systems
Manage PTSD & Other
Conditions1,000 24 Level I Trauma Centers
Manage Chronic Pain 1,000 200 pract in 3 HCS
ESRD Care 6,400 400 HD Units
DM,HTN & CKD Care 12,000 80 Clinics in 4 HCS
Suicide Prevention 16,000 Primary Care in 3 HCS
Colon Ca Screening 20,000 26 Clinics in OCHIN
Nursing Home Care 152,160 230 NH in 2 NH Corp.
Back Pain Imaging 250,000 100 Sites in 4 HCS
Hospital Infections 285,000 50 Hospitals in HCA
~ Cost/Patient
Average = $1,500
Range = $25 - $7,300
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Final Thoughts
4
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QUALITY FIRST: What is A Quality Clinical Trial?
1. Relevant question being addressed
2. A protocol that is clear, practical, focused
3. Adequate number of events to answer question with confidence
4. In a general practice setting to make results generalizable
5. With proper randomization
6. With reasonable assurance that patients receive (and stay on)
assigned treatment
7. With reasonably complete follow-up and ascertainment of primary
outcome (and other key outcomes like death)
8. With a plan for ongoing measurement, feedback, improvement of
quality measures during trial conduct
9. With safeguards against bias in determining clinically relevant
outcomes
10. With protection of rights of research patients
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Conclusions
Conclusions• Real world matters & is relevant
– Right participant
– Right intervention
– Right outcome
• Build partnerships with patients, clinicians and
systems
• Take advantage of growing interest in population
health and “systemness” of care to do research
• Finally….Quality will always matter – By design
– Less ≠ More
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Thank You!