1. Clinical Applications and Prevention Branch
Division of Prevention and Population Science
Clinical Applications and Prevention Branch
Lawrence J Fine, M.D. ,Dr.P.H.
Branch Chief

2. Blood Lung Us!! Heart Division of Applications Of Research
Office of
Biostatistics
Research (OBR)
Division of
Applications
Of Research
Discoveries (DARD)
Blood
Lung
Us!!
Heart
Division of
Cardiovascular
Diseases (DCVD)
Division of
Prevention and
Population
Sciences (DPPS)

3. Investigator-initiated Studies R01 and R21
70% of NHLBI funding is investigator-initiated research ( < M DC )
Some examples of studies (titles):
Improving Self-Care Behavior and Outcomes in Rural Patients with Heart Failure
Telemonitoring to Improve Heart Failure Outcomes
Improving Coronary Prevention in a County Health System
NHLBI also has numerous investigator-initiated studies in QOC and Outcomes research. It should be remembered that the large majority of NIH funding is investigator initiated – the RFAs shown before were to address identified gaps needing additional research not already covered by investigator-initiated studies.
Here are some examples of our funded studies.
[These are just some titles I pulled off our portfolio as representative – there are a lot more]
[“Telemonitoring” = long-distance patient monitoring where measurements are sent electronically, e.g., body weight for HF management.]

4. Conceptualization of Causal Influences for Cardiovascular Disease
Type and quantity of food available
Physical activity opportunities
Tobacco availability
Social/cultural issues: SES, family, workplace
Community Environmental Factors
Atherosclerosis
Thrombotic vascular autonomic serotonergic inflammatory immunologic function
Mechanisms Subclinical Disease
Lifestyle Factors
Psychosocial factors
Behavioral Factors
Blood pressure
Blood lipids
Diabetes/insulin resistance
Obesity
Biological Risk Factors
CAD/CHD
Heart failure
Arrhythmias
Sudden cardiac death
Valvular heart disease
Stroke
Clinical Disease
Morbidity
Mortality
Life expectancy
Functioning & quality of life
Health Outcomes
Health care system, treatment delivery, access to care
ACCORD
GEMS
Door to Balloon
TAAG
HTN control
PROMIS
Worksite obesity
POWER
HF-ACTION
(DSM, 4/06)

5. Topics Being Addressed in NHLBI QOC and Outcomes Studies
AMI, CHD, and CVD treatment
HF management
Hypertension control
Dyslipidemia treatment
Anticoagulation in atrial fibrillation
Blood transfusion guidelines
Obesity control
Lifestyle (diet and physical activity)
If one looks across the NHLBI portfolio in QOC and Outcomes research, one can see the wide range of topics covered – ranging from disease treatment, to risk factor treatment, to lifestyle. All of these areas – from primary prevention to treatment – are important for high quality CVD care.

6. Determinants and Interventions for QOC &Outcomes: Multi-level Model
Insurance & Government
Performance measures (e.g.,HEDIS)
Accreditation (JCAHO)
Insurance reimbursement (p4p)
Clinical guidelines
Interventions
Clinical Institutions
CME, academic detailing
Services & appointments
Patient monitoring & feedback
Reminders, charting cues
Provider incentives
The approach to improving patient health through quality clinical care is a complex one. Here is a simplified schematic of a complex set of relationships, illustrating the various types of influences to consider. At NHLBI, we have used this model to conceptualize research in this area.
[This slide comes in a piece at a time, from right to left – bolded text below matches each piece. The boxes have examples – it’s not comprehensive].
To improve patient health, the patients themselves must have knowledge of their health status, adhere to treatments, and take action (such as lifestyle changes) to reduce risk factors. Clinicians directly interact with patients by conducting tests and making diagnoses, providing treatment and procedures, giving advice and counseling, and referring to other care when appropriate. However, clinician and patient actions are not in a vacuum. Clinicians and patients are both influenced by the environment of the clinical institution, which can provide education, foster certain types of care by the kinds of services offered and appointment scheduling (e.g., duration of appointments), monitor and provide feedback to clinicians and patients, and provide reminders, charting cues and incentives to clinicians. The institution does also not work in a vacuum, as insurance and government entities have influence through performance measures (HEDIS measures for HMOs), accreditation requirements, and development and dissemination of clinical guidelines.
Understanding the myriad of influences can help identify interventions to target them – hopefully to ultimately improve patients’ health. It should be noted that, although these arrows are in one direction, the influences are bi-directional.
Patient Health
Clinicians
Testing & diagnosis
Treatments & procedures
Advice & counseling
Referrals
Patients
Knowledge
Tx Adherence
↓Risk Factors
(Simons-Morton unpublished, 2005)

7. Types of Interventions Tested
Interventions targeting clinicians and systems
Clinician and staff training
Academic detailing
Patient chart audit and feedback to physicians
Decision-support tools
Clinician incentives
Nurse case management
Pharmacy-based approaches
Telemonitoring
This slide shows types of interventions being tested at the clinician and healthcare system levels – as in the hierarchical model shown earlier.
Clinicians and their staffs are being trained on implementation of evidence-based guidelines and are being “detailed” for delivery of quality of care (much as pharma “details” on specific drugs). They are being given feedback about their own patients and are being provided decision support tools (e.g., PDA for ATP III guidelines), as well as incentives. Nurse case management approaches are being tested, as are approaches delivered by pharmacists. Systems such as telemonitoring [long-distance monitoring, with data delivered to the clinic electronically] are being evaluated, as are practice support and facilitation tools, such as computerized integrated databases. Some studies are testing multiple approaches in combination.
These approaches are all being tested in randomized controlled trials, to provide the highest quality of evidence about how well they work.
[I think our “niche” in this area is the high-quality randomized trial design that is not required by other funding entities.]

8. Examples of NHLBI-initiated QOC & Outcomes Research
Trials to improve clinical practice through guidelines (RFA )
11 RCTs testing approaches to improve provider adherence to evidence-based guidelines (HTN, CVD secondary prevention
Weight Loss in Obese Adults with CV RFs: Clinical Interventions (RFA )
3 RCTs testing interventions delivered in routine clinical practice to reduce weight
Self-explanatory

9. Types of Interventions Tested – Chronic Care Model
Interventions addressing patients or patient-provider relationships
Home visits with assessment & counseling
Self-monitoring (e.g., BP monitoring)
Patient education & counseling
Interpersonal, e.g., motivational interviewing
Media-based, e.g., automated telephone counseling, patient motivational and educational videos
“Patient activation” approaches (e.g., waiting room materials)
Types of interventions being tested at the individual level are illustrated on this slide. Many and various approaches are being evaluated, including home visits, self-monitoring, patient education/counseling, and patient activation.

10. NHLBI Strategic Plan: Future Opportunities for Translation Research.
June , 2008
[I provided a title – I did not see a talk title on the agenda, only the session title]

11. Goals – embraces Quality and Outcome Research
Goal 3 Generate an improved understanding of the processes involved in translating research into practice and use that understanding to enable improvements in public health and to stimulate further scientific discovery Cause → Cures

12. Challenges Relevance to Outcomes Research – the Tent is large
Challenge 3.1.c. Develop and evaluate interventions to improve patient, provider, and health-care system behavior and performance to enhance quality of care & health outcomes
Challenge 3.2. Identify cost-effective approaches for prevention, diagnosis, and treatment
Several challenges within goal 3 are of particular relevance to the theme of this meeting and to Quality of Care and Outcomes research. [I selected some particularly relevant ones. These are quoted but with some reduction in number of words.]

13. Strategic Plan Impact
Research examining delivery of clinical care, and testing approaches to improve the quality of care, is extremely important for ultimately improving the public’s health
Pending results from NHLBI studies will have strong implications for future clinical practice
NHLBI has a strong, and increasing, portfolio in CVD QOC & Outcomes research
The NHLBI Strategic Plan provides a blueprint for additional future research
Self-evident

14. Program Directors Their goal is to help you Lawton Cooper
Paula Einhorn
Barbara Wells
with specific aims
Go over the summary statement with them
All questions are welcome

15. Awards For Young Investigators
Mentored Clinical Scientist Development Award (K08)
Mentored Patient-Oriented Research Career Development Award (K23)
Independent Scientist Award (K02)
NIH Pathway to Independence Award (K99/R00)
The goal of all these programs is to increase the numbers and capabilities of scientists engaged in biomedical and behavioral research and to offer scientists the opportunity to receive full_time training in areas that reflect a national need. The programs also provide postdoctoral individuals and new independent researchers the opportunity to establish their research careers.
The above awards provide both part_time and full_time support for 2 to 5 years.

16. Looking forward to our discussion

17. all slides after this are extra

18. Office of Research Training and Career Development Division of Cardiovascular Diseases (DCVD), NHLBI, NIH
Jane D. Scott, ScD, MSN
Michael Commarato, PhD
Jamie Varghese-Skipper, PhD
Tawanna Meadows, BS
DCVD Training

19. Independent Scientist Award (K02)
Investigators at non-federal public or profit U.S. institutions engaged and funded in health-related research.
Application deadlines: February 12, June 12, October 12 (new).
Support: 3-5 years
Salary support only: Up to $75,000 per year plus benefits. No other research development support funds are provided.
This award is a salary only grant whose function is to increase the time junior investigators may devote to research project(s). Candidates for this award must have demonstrated outstanding potential as independent investigators and be able to benefit from having a greater amount of time to devote to an on-going peer reviewed research project(s). Selection is by national competition.
Persons who receive this award are expected to devote at least a 75 percent effort to their research project(s). The institution is expected to reduced or defer the extra duties such as teaching, committee, and clinical work to enable the awardees to devote greater time to their on-going research.
Applicants must be U.S. citizens, noncitizen nationals, or legal permanent residents of the U.S. They must have a doctoral degree and must have demonstrated independent research accomplishments. Typically, applicants should have 5 years of postdoctoral research experience, including 2 years as an independent investigator with independent peer-reviewed grant support. Applicants who do not meet these criteria can qualify if they demonstrate an equivalent level of experience and independence. Researchers who have achieved tenure or the equivalent or have publication records indicating that they are well established in their fields are ineligible.

20. New NIH Pathway to Independence Award (K99/R00) PA-06-133
Applicants: Postdoctoral candidates who have clinical or research doctorates (Ph.D, M.D., D.O., etc.) with no more than 5 years of research training.
Requirements: at least 75% effort.
Support: 2 years (K99); 3 years (R00); need tenure track faculty position. IC review.
Salary:
K99--up to $90,000 per year plus benefits; up to $20,000 per year for research support; salary limited to $50,000; F & A is 8%.
R00– up to $249,000 per year plus benefits; full F&A costs
This program enables candidates holding professional degrees (e.g., M.D., D.O., D.V.M., or equivalent degrees) to undertake 3 to 5 years of special study and supervised research with the goal of becoming independent investigators. The program also allows awardees to pursue a research career development program suited to their experience and capabilities under a mentor who is competent to provide guidance in the chosen research area.
At least 2 years must have elapsed since the M.D. or D.O. degree was granted. Candidates can have varying levels of clinical training and research experience.
All candidates must be U.S. citizens, noncitizen nationals, or legal permanent residents of the U.S. The grantee institution must have a strong, well-established research and research training program in the chosen area, accomplished faculty in the basic and clinical sciences, and a commitment to the candidate's research development.
The proposed program should include an appropriate mentor.

21. NIH Pathway to Independence Award (K99/R00)
Eligible:
Clinical or research doctorate
No more than 5 years of postdoctoral research training
Former principal investigator on R03s, R21s and SBIRs/STTRs
US citizen or non-US citizen
Not Eligible:
Currently or previously held a research faculty position
More than 5 years of postdoctoral research training
Have been a principal investigator on NIH research grants or non-NIH research grants over $100,000 in direct costs per year
This program enables candidates holding professional degrees (e.g., M.D., D.O., D.V.M., or equivalent degrees) to undertake 3 to 5 years of special study and supervised research with the goal of becoming independent investigators. The program also allows awardees to pursue a research career development program suited to their experience and capabilities under a mentor who is competent to provide guidance in the chosen research area.
At least 2 years must have elapsed since the M.D. or D.O. degree was granted. Candidates can have varying levels of clinical training and research experience.
All candidates must be U.S. citizens, noncitizen nationals, or legal permanent residents of the U.S. The grantee institution must have a strong, well-established research and research training program in the chosen area, accomplished faculty in the basic and clinical sciences, and a commitment to the candidate's research development.
The proposed program should include an appropriate mentor.

22. NHLBI Research Training Contacts
K08 – Mentored Clinical Scientist Development Award
Ms. Lorraine Silsbee (301)
K23 – Mentored Patient-Oriented Research Career Development Award
Ms. Ann Rothgeb (301)
K02 – Independent Scientist Award
Dr. Traci H. Mondoro (301)
K99/R00 – Pathway to Independence Award
Dr. Jane Scott (301)
K24 – Patient-Oriented Research Award
Dr. Ellen Werner (301)
F33 – National Research Service Award for Senior Fellows
Dr. Jared Jobe (301)
F32– NRSA Individual Fellowship
Ms. Tawanna Meadows (301)

23. New Grant Submission Dates
Notice Number: NOT-OD
Starts January 2007

24. NIH Pathway to Independence (PI) Award K99/R00

25. NIH Pathway to Independence (PI) Award (K99/R00)
Up to 5 years support, two phases
Phase I Mentored research, 1-2 years (K99)
Phase II Independent research support (R00) 1-3 years, contingent on securing an independent research position
Each phase provides funds for salary & research costs

26. K99/R00 Applicant Requirements
Outstanding postdoctoral candidates
No more than 5 years postdoctoral research training
US citizens & non-US citizens
May submit only one PI Award application
May not simultaneously submit applications or have pending awards for any other PHS career development award (no K awards)

27. Eligible
Eligible: Individuals who were PIs on NIH R03, R21, & Phase I SBIR/STTR grants
Not Eligible: Those who have served as PI on peer-reviewed non-NIH research grants over $100K in direct costs per year (awards intended for faculty).

28. Ineligible
Individuals with current or prior “research faculty” positions or other professorships in academia, industry
More than five years of post-doctoral training at time of initial application or resubmissions
PI on NIH R01, P01, or subprojects of such grants
PI on an NIH career development award (K award)

29. K99 (Up to 2 years)
Total costs/yr may not exceed $90K including salary, fringe, and up to $20K in “research support costs”
Research support includes tuition and fees related to career development, supplies equipment, technical personnel, travel to research meetings, statistical services and computer time
Salary is limited to $50K
Minimum percent effort is 75%
K activities include research, publication, and searching for an independent research position

30. R00 (up to 3 years) Total costs per year not to exceed $249,000/yr
Includes salary, fringe, research support allowance and applicable F&A costs
R00 contingent on awardee securing an independent tenure-track, full-time assistant professor position at an eligible institution
Salary based on 12 month full-time appointment
Candidates must devote a minimum of 75% time to their research
Remaining time “devoted to activities related to the development of a successful research career”

31. Current Status First study section review November 2006
78 grants received first 2 cycles, 36 scored, 42 streamlined
First awards made December 2006
NHLBI funded 19 (11 DCVD)
Review & approval procedures for transition from K to R being developed.
K99 grants are assigned to training program officers, R00 grants will transition to appropriate DCVD branches
Screening for eligible candidates has been difficult
Screening by committee

32. K99/R00 Links
PA :
Questions and Answers
Backgrounder

33. DCVD Office of Research Training & Career Development
Jane D. Scott, ScD, MSN
Michael Commarato, PhD
Drew Carlson, PhD
Tawanna Meadows, BS

34. Types of Studies Funded/sponsored
Focus on obtaining evidence base for clinical and public-health practice
Research questions – continuums from
prevention to treatment
efficacy (“ideal settings”) to effectiveness (“real world” settings)
Intervention studies – RCTs, the most valid approach to determine effects of interventions
Large studies often needed to answer questions
Portfolio of smaller studies – investigator-initiated and targeted topics

35. Goals, Challenges & Strategies
NHLBI Strategic Plan has Three Goals, each Goal further defined by Challenges
To guide implementation, the Strategic plan has Eight Strategies, which will change as Challenges are met and new Challenges emerge

36. Phase 2 Translation Research: Rationale
Efficacy of certain treatment and prevention approaches has been established.
What we know is not always translated into clinical practice; there are many disparities.
Traditional approaches to translation are only partially effective (e.g., CME, publications).
Additional research is needed examining factors that affect care delivery and testing interventions to improve quality of care across a broad spectrum of delivery settings and populations.
Why do we need Phase 2 translation research? Scientific discoveries are not automatically implemented in practice. Many reports, including those from the AHA and the National Committee for Quality Assurance, have identified gaps between what we know works and what is actually delivered in practice. Traditional approaches are only partially effective. Improvements to this situation will occur best by developing an evidence base for practice, through additional observational and intervention research.

37. NHLBI “Working Group on CVD Outcomes Research” (Jan 2004)
Working Group Recommendations
National surveillance of CV care and outcomes
Focus on patient-centered care (e.g., QOL, patient decision-making)
Study patient adherence and self-management
Evaluate efficacy and effectiveness of therapies in “real-world” settings
Test interventions to improve provider delivery of effective therapies
Conduct economic evaluations
In addition to the just-released NHLBI Strategic Plan, the NHLBI held a working group in 2004 to advise the Institute on future directions in CVD Outcomes Research. These 6 recommendations are the major recommendations from that workshop. [see list on slide]
Krumholz et al, Circulation, 2005

38. Examples of NHLBI-initiated QOC & Outcomes Research
Improving Hypertension Control Among Inner City Minorities (RFA )
Feasibility, acceptability, and effectiveness of programs to detect & control HTN in inner-city minority groups
Overcoming Barriers to Tx Adherence in minorities & persons living in poverty (RFA )
13 RCTs testing innovative, practical interventions to improve adherence in disadvantaged groups
The NHLBI has released several RFAs over the past years for QOC and Outcomes research. The next few slides briefly summarize those activities. Many of these RFAs were for studies testing interventions at multiple levels, not just the patient level. All of these RFAs were for randomized clinical trials (RCTs).
[the rest of the information is self-explanatory.]

39. Examples of NHLBI-initiated QOC & Outcomes Research
Cardiovascular Research Network (CVRN) (RFA )
Infrastructure for CVD research in community-based healthcare – clinical epidemiology, health services research, etc.
Improving HF Disease Management (PA 2007)
Research to address unanswered questions about Dz management approaches for HF
[Content self-explanatory]
The Network will be funded this year.
The HF disease management PA was just released. [“Disease management” refers to systematic approaches for close patient monitoring and therapy adjustment, e.g., closely monitoring patients’ weight to catch early signs of fluid retention.]

40. Strategic Plan Challenge 3.3
To promote the development and implementation of evidence-based guidelines in partnership with individuals, professional and patient communities, and health care systems and to communicate research advances effectively to the public.
Self-evident

41. Division of Prevention and Population Sciences
Office of the Director
Michael Lauer, M.D., Director
Diane Bild, M.D., M.P.H., Deputy Director
Denise Simons-Morton, M.D., Ph.D., Senior Advisor
Clinical Applications and
Prevention Branch (CAPP)
Lawrence Fine, M.D., Dr.P.H.
Chief
Epidemiology Branch (EBP)
Paul Sorlie, Ph.D.
Women’s Health Initiative Branch
Jacques Rossouw, M.D.
DPPS supports and provides leadership for population- and clinic-based research:
on the causes, prevention, and clinical care of cardiovascular, lung, and blood diseases and sleep disorders.
epidemiological studies to describe disease and risk factor patterns in populations and to identify risk factors for disease;
clinical trials of interventions to prevent disease;
studies of genetic, behavioral, sociocultural, and environmental influences on disease risk and outcomes; and
studies of strategies to improve clinical care and public health.

42. Age-Adjusted Death Rates for Coronary Heart Disease, U.S., 1950-2004
Deaths/100,000 Population
600
500
400
300
U.S. Actual
200
Slide 7
I like the font size and colors and the absence of the white lines in slide 2; please apply this format to slide 6 and 7.
100
U.S. "Could Be"
(Based on Japan Actual)
1950
1960
1970
1980
1990
2000
2010
Year

43. The proposed SPRINT trial is designed to determine whether treating systolic blood pressure to the lower goal of less than 120 mm of Hg rather than the currently recommended goal of less than 140 mm of Hg reduces CVD morbidity/mortality in high risk adults. The trial will have 7500 participants who have an initial systolic blood pressure of 130 mm of Hg or above.

44. NHLBI Many Partnerships
Researchers
International Organizations
Professional Societies .
Voluntary Health Organizations
Federal-State-Local Agencies
Patient Advocacy Groups
Corporations
Community Organizations
Foundations

45. NHLBI K08 and K23 Applications
Fiscal Years *

46. Trends in Number of Individual K Awards by Institute or Center Fiscal Years 1995 - 2005
Excludes K12, K16, and K17.

47. Research Training & Career Development Opportunities, NHLBI, DCVDHS
&
College
Graduate &
Medical School
Post graduate Fellowships
Transition to
Established Investigator
Established
Investigator
MARC U*STAR
Undergrads
BRTPUG
Program
Undergrads, post-bac, &
graduates
T35
BRTPUG Prgm.
T32 Institutional
Award
T32
Minority Institutions
F31
Minority students & individuals with disabilities
Minority students
Institutional Award
Minority Institution Award
F32
Individual award
K08
K23
K25
K02
K01 Minority
Faculty
Institution
K99/R00
F33
K24

48. Number of NIH K Awards Fiscal Years 1995 - 2005
“Patient-Oriented Research” awards begin

49. Purpose
T32 Program Update
Discussion
Suggestions
Questions

50. Mentored Clinical Scientist Development Award (K08)
Applicants: Clinicians who are interested in developing independent research careers.
Requirements: at least 75% effort.
Support: 3-5 years.
Salary: Up to $75,000 per year plus benefits and up to $25,000 per year for research development support.
This program enables candidates holding professional degrees (e.g., M.D., D.O., D.V.M., or equivalent degrees) to undertake 3 to 5 years of special study and supervised research with the goal of becoming independent investigators. The program also allows awardees to pursue a research career development program suited to their experience and capabilities under a mentor who is competent to provide guidance in the chosen research area.
At least 2 years must have elapsed since the M.D. or D.O. degree was granted. Candidates can have varying levels of clinical training and research experience.
All candidates must be U.S. citizens, noncitizen nationals, or legal permanent residents of the U.S. The grantee institution must have a strong, well-established research and research training program in the chosen area, accomplished faculty in the basic and clinical sciences, and a commitment to the candidate's research development.
The proposed program should include an appropriate mentor.

51. Mentored Patient-Oriented Research Career Development Award (K23)
Applicants: Scientists who are committed to developing careers in patient-oriented research.
Requirements: at least 75% effort.
Support: 3-5 years.
Salary: Up to $75,000 per year plus benefits and up to $50,000 per year for research development support.
This award provides support for supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators focusing on patient-oriented research.
This program provides research development opportunities for clinicians with varying levels of research experience. Support is provided for a minimum of years.
All candidates must be U.S. citizens, noncitizen nationals, or legal permanent residents of the U.S.
Persons with temporary or student visas are not eligible.
Certification by an authorized individual at the degree-granting institution that all degree requirements have been met is acceptable. Candidates must have completed their clinical training, including specialty and, if applicable, subspecialty training prior to receiving an award.

52. Similarities between K08 & K23 Awards
Mentored research awards
Faculty appointment not required
Require > 75% effort
3 – 5 years of support
Budgets similar
Salary levels vary by NIH institute

53. Differences between K08 & K23
Research Development Support -
$25,000/year for K08
Up to $50,000/year for K23
K23 candidates:
must take courses such as study design, biostatistics, epidemiology, data management, hypothesis development, drug development, etc.
must complete courses on the legal and ethical issues associated with the safe conduct of human subjects research

54. K08 & K23 Pilot Program K Awards have required 75% effort, 3-5 years
Starting 2006, a new trial will permit 50% research effort for the duration of a K grant for selected sub-specialists including: cardiothoracic surgeons, vascular surgeons, and interventional cardiologists

55. What is “Patient-Oriented Research”?
Research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator directly interacts with human subjects.
mechanisms of human disease
therapeutic interventions
clinical trials
development of new technologies

56. What Doesn’t Count as Patient-Oriented Research?
Analysis of existing databases
Brief interaction with human subjects (such as one blood draw)
Candidate designs a questionnaire that will be administered by other staff
These projects are appropriate for K08 mechanism