Josephine Briggs, MD Director National Center for Complementary and Alternative Medicine National Institutes of Health Opening Keynote "Research in an IT Connected World: Building Better Partnerships – NIH and Health Care Systems" The era of ‘Big Data’ has arrived for biomedical research, bringing with it immense challenges as well as spectacular opportunities. NIH is establishing major programs with the potential to transform the future of US biomedical research by building the capacities necessary for these challenges. These programs will strengthen research partnerships with health care systems and the IT networks that support them. The Big Data to Knowledge (BD2K) initiative, to be launched in 2014, will implement a set of recommendations from the Data and Informatics Working Group to the Advisory Committee to the Director. Investments are planned to meet scientific needs to manage and utilize large complex datasets, including strengthening training, and investing in improved analysis methods and software development and dissemination. NIH is also evaluating strengthening data and software sharing policies, and the potential creation of catalogs of research data, and data/metadata standards. The Common Fund’s Health Care Systems (HCS) Research Collaboratory program has the goal to strengthen the national capacity to implement cost-effective large-scale research studies by engaging major health care delivery organizations as research partners. The aim of the program is to provide a framework of implementation methods and best practices that will enable the participation of many health care systems in clinical research. Research conducted in partnership with health care systems is essential to strengthen the relevance of research results to health practice. Seven demonstration projects, currently in a feasibility phase, are developing detailed methods to implement rigorous randomized studies of questions of major public health impact. These studies, and the IT infrastructure that will make them possible, will be described in detail.

1. Research in an IT
Connected World:
Building Better
Partnerships – NIH and
Health Care Systems
August 21, 2013

2. Building Partnerships
1. Why? The urgent need
2. Concrete examples of partnerships – the Health Care
System Collaboratory Demonstration Projects
3. Preliminary thoughts about IT capacities, methods,
rules

3.  Cost: personal, institutional, and
national
 Outcomes

5. IOM: The Imperative for Action
Drivers of the Problem
 Scientific uncertainty
 Perverse economic and practice incentives
 System fragmentation
 Opacity as to cost, quality and outcomes
 Lack of patient involvement
 Underinvestment in population health
Clinical evidence development is not
keeping pace with the emergence of
new diagnostics, treatments and insights
into individual variation.
IOM- Learning Health Care System

7. Mayo Clinic Proceedings: A
Breakdown of NEJM Articles
Concerning a Medical Practice

8. Reversals
 Examples:
 Mortality was higher with recommended glycemic targets as
opposed to more permissive standards (ACCORD, NEJM
2008)
 Routine use of pulmonary artery catheters worsened ICU
outcomes (NEJM, 2009)
 Breast cancer survival was not improved by autologous stem
cell transplant and intensified chemo compared with
standard chemo (Tallman et al NEJM 2005)
 Impermeable bedcovers have no benefit for adults with
asthma, in spite reduced dust mite exposure (Woodcock,
2003 NEJM

9. Take home lesson:
We don’t always know what we think we know.
(hence the need to continue to examine standards
of care)

10. What is a Practical Trial?
 Defined Practical (pragmatic) Trials as those in which “the
hypothesis and study design are developed specifically to
answer the questions faced by decision makers”
 Decision makers include patients, clinicians, payers,
 & health care system policy makers

11. Pragmatic vs. Explanatory
 Broad eligibility
 Flexible interventions
 Typical practitioners
 No follow-up visits
 Objective clinical outcome
 Usual compliance
 Intent-to-treat
 Narrow eligibility
 Strict instructions
 Expert practitioners
 Frequent follow-up visits
 Surrogate outcomes
 Close monitoring
 ITT plus per protocol
Thorpe KE et al. J Clin Epidemiol 2009;62:464-75

12. What is a Pragmatic/Practical Trial?
The PRECIS Tool is Developed
Thorpe KE et al. CMAJ 2009;180:E47

13. Pragmatic Study Elements
Broad eligibility criteria
Flexible interventions
Typical practitioners
No follow-up visits
Clinical outcomes
Usual compliance
Intent-to-treat
Thorpe KE et al. CMAJ 2009;180:E47

14. The Urgent Need
 We need continual improvement in standards of care
 To achieve that we need pragmatic trials
 We cannot maintain an artificial distinction between
research and quality improvement

15. Building a Partnership
1. Why? The urgent need
2. Concrete examples of partnerships –
the Health Care System Collaboratory
Demonstration Projects
3. Preliminary thoughts about IT capacities, methods, rules

16. The overall goal of the Commons Fund’s
Health Care System (HCS) Collaboratory is to
strengthen the national capacity to
implement cost-effective large-scale research
studies that engage health care delivery
organizations as research partners.

17. Pragmatic Trial Demonstration Projects
1. Preventing hospital acquired infections: (PI Huang) Do
intensified antibacterial bathing measures reduce hospital-
acquired infections? Cluster randomized trial - HCA
randomizing 50 hospitals – 375,000 patients

18. “The implications of this study are highly important. The lack of effectiveness of
active detection and isolation should prompt hospitals to discontinue the
practice for control of endemic MRSA in ICUs….”

19. Pragmatic Trial Demonstration Projects
1. Preventing hospital acquired infections: (PI Huang) Do intensified
antibacterial bathing measures reduce hospital-acquired infections?
Cluster randomized trial - HCA randomizing 50 hospitals – 375,000
patients.
2. Colorectal cancer screening: (PI Coronado) Does a simple intervention
implemented through Federally Qualified Health Centers improve colorectal
cancer screening? Cluster randomized trial 18 OCHIN Clinics – 10,000
patients.
3. Suicide prevention: (PI Simon) A pragmatic trial comparing suicide
prevention programs. Can patients who admit to suicidal thoughts in a
health care encounter be successfully randomized to one of two
management strategies and do interventions reduce subsequent suicide
attempts? Group Health, Kaiser Colorado – 16,000 patients.

20. Pragmatic Trial Demonstration Projects
4. Lumbar Spine imaging: (PI Jarvik) Does insertion of epidemiological
information into imaging reports reduce subsequent diagnostic and
therapeutic interventions? Kaiser, N Ca; Group Health, Mayo, Henry
Ford. Cluster randomized 128 clinics,135,000 imaging reports.
5. Nocturnal blood pressure control: (PI Rosenthal) Does taking anti-
hypertensive medications at night reduce CV events? U of Iowa and Duke
primary care clinics, 6,000 patients.
6. Collaborative care pain management model: (PI Debar) Study impact of
integration of psycho-social supports for patients with chronic pain on pain
measures and opioid use. 3 Kaiser regions, Georgia, Hawaii, Northwest.
Cluster randomized by practice. Several hundred practices, 6,000
patients.
7. Longer dialysis duration: (PI Dember) Does increasing dialysis duration
reduce mortality? Partners Fresenius, da Vita, Cluster randomized trial
of 402 dialysis units. 7000 patients.

21. Test and Strengthen Models for Clinical
Research in Partnership with Health Care
Delivery Systems
 Develop capacity to leverage resources of major
integrated health care systems for large scale clinical
research studies
 Test and improve methods to extract research quality
data from electronic health information systems
 Strengthen relevance and translatability of research
results to ‘real world’ health practice
 Develop and test more cost-effective models for large
scale randomized clinical trials

22. Building a Partnership
1. Why? The urgent need
2. Concrete examples of partnerships – the Health Care
System Collaboratory Demonstration Projects
3. Preliminary thoughts about Health IT
capacities, methods, rules to facilitate a
learning health care system

23. Myriad Data Types
Other ‘Omic
Imaging Phenotypic
EHR
Genomic
Administrative

25. Data Steward #1
Authorized user
NIH DRN Secure Network
Portal
1
52
Data
tables
Review &
Run Query
3
Review &
Return
Results
4
6
Data
tables
Review &
Run Query
3
Review &
Return
Results
4
1- User creates and
submits query
(a computer program)
2- Data partners
retrieve query
3- Data partners
review and run query
against their local data
4- Data partners
review results
5- Data partners
return results via
secure network
6 Results are
aggregated
Data Steward #2
ONC
Query Health Compliant

26. Send the question to the data!

27. The Goal of the IT Approach
 Creating secure networking capabilities and
analysis tools
 Build networking capacity, not a network
 Insure that access to data occurs only with
data stewards’ permission and active
engagement

28.  Leverages existing networks’ data and analysis tools
 Can use many data types, e.g., EHR, claims, registries
 Can use many data models, e.g., Mini-Sentinel, i2b2,
OMOP
 Can use existing querying tools, e.g., Mini-Sentinel modular
programs
 Every use requires the agreement of the data steward
Health
Plan 1
Health
Plan 2
CTSA 1
Research
Dataset 1
NIH Distributed Research Network Secure
Portal
Research
Dataset 2
CTSA 2 Registry

29. NIH DRN Secure Portal
Mini-Sentinel
Site A
Registry 1
Mini-Sentinel
Site B
Medical
Practice 1
PBRN 1
CTSA 1
Hospital
1
Research
dataset 1
NIH Distributed Research Network Coordinating Center
CTSA 2
Health
Plan 2
Health
Plan 1
Network
Managemen
t
Research
Support
Query
Support
Query Tool
Developmen
t
Knowledge
Database
Software
Developmen
t
Project
Managemen
t
Data Models
& Standards
Consultation
Health System
Expertise
Knowledge Management System
Cross project lessons learned, query tracking, meta-data capture, search functions, etc
AdministrationQuery Tools
SAS, SQL,
menu-drivenModular Programs
Summary Tables
Project 1
PROJECTS
LIRE study
Analytic ToolsFeasibility study
Query Interface Reporting Tools
Security Access Control
File Query Repository
User Administration
Workflow Management

30. Thorny issues
 Defining the right questions
 Ethical issues surrounding research on standards of
care: eg. when is waiver of consent appropriate
 Optimum trial design for group or cluster randomized
trials
 Preserving effective public-private partnerships
https://www.nihcollaboratory.org/

31. National Center for
Complementary and
Alternative Medicine
Clearinghouse: 1-888-644-6226
Web site: nccam.nih.gov
Twitter: @NCCAM
31

32. Pragmatic Trials
 Pragmatic trials should test an intervention, or compare
several interventions.
 The question should be important – to patients, payers
and with health care delivery systems.
 The intervention should be reasonable simple and not
require a complex structure for implementation. System
level interventions may be particularly suitable.
 The trial design should incorporate rigorous controls,
prospectively identified, preferable by randomization.
 The monitoring and outcome assessment should be as
simple as possible – and potentially utilize electronic
health records.