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NIH Review and Funding of

Clinical Research

Norka Ruiz Bravo, PhD

Deputy Director for Extramural Research

NIH/DHHS

Clinical Research Forum

26 April 2006

Today’s conversation

• Part I

– Starting from the same page…

• Part II

– Hypothesis

– Definitions and methods

– Presentation order for data

– Data

• Part III

– Conclusions

The Basics

• NIH separates the technical and scientific

merit review of applications from funding

• Peer review panels conduct reviews

• Funding decisions are made by Institutes

and Centers

• CSR reviews ~70-75% of NIH applications;

~ 50% of dollars

• Trans-NIH peer review policy – OER

responsibility

Part II

Review and Award of NIH Grants

for Clinical Research

• Hypothesis

– Clinical research grant applications have

lower success rates* than basic research

applications

– Success rate correlates with locus of review







* SR = Number of applications funded

Number of unique applications reviewed

Definitions (1)

• Clinical Research:

– 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 (or colleague) directly interacts

with human subjects. Excluded from this definition

are in vitro studies that utilize human tissues that

cannot be linked to a living individual. Patient-

oriented research includes: (a) mechanisms of

human disease, (b) therapeutic interventions, (c)

clinical trials, or (d) development of new

technologies.

– Epidemiologic and behavioral studies.

– Outcomes research and health services research.

Definitions (2)

Research Grants: Research grant mechanisms employed in

FY 2005 (Distributed to Budget Categories and Reporting

Groups)

• Research Project Grants

• Research Project Grants: DP1, P01, P42, PN1, R01, R03,

R15, R21, R29, R33, R34, R36, R37, R55, R56, U01, U19, UC1

• Small Business Grants: R43, R44, U43, U44, R41, R42

• R01 Equivalent Grants: R01, R23, R29, R37

• Research Centers

– Research Center Grants: G12, M01, P20, P30, P40, P41, P50,

P51, P60, U41, U42, U54

• Research Careers (Mentored and Other)

• Other Research (excluding research careers)

– Other Research Grants

R&D Contracts

Definitions (3)

• Human subjects (HS+) applications

– For the analyses shown, involvement of human

subjects (HS+) is used as a surrogate for clinical

research.

– Records employing coded human specimens and

information (Exemption 4) are included in the non-

human subjects research category

• How good a surrogate for clinical research is

HS+?

– $8.7 Billion is NIH Office of Budget estimate for

clinical research (FY2005)

– $9.6 Billion is HS+ (FY2005)

Presentation order for data

#

Number Applications

HS+

reviewed HS- HS+ HS-



Success rt. Success rt.

CSR # Awards # Awards

$ Awarded $ Awarded

CSR Locus IC

Review Review

of Success rt. Success rt.

review IC # Awards # Awards

$ Awarded $ Awarded





HS+

HS- HS+ HS-







Success rate

Research Grants (FY 2005)



RG Applications

Total

55,546 Applications

21.32 HS+ (38%)

34,244 HS- (62%)





Locus of Review



CSR IC

42,124 Applications 13,422 Applications

13,926 HS+ (33%) 7,376 HS+ (55%)

28,198 HS- (67%) 6,046 HS- (45%)





Awards



HS+ HS- HS+ HS-

2,624 Awards 6,705 Awards 1,912 Awards 2,128 Awards

Success Rate 19% Success Rate 24% Success Rate 26% Success Rate 35%

Human Subjects Research Grant Applications Reviewed in CSR and ICs with Success

Rates



16,000 CSR HS+ Applications 50%



CSR HS+ Awards



14,000 IC HS+ Applications

IC HS+ Awards

CSR HS+ Success Rate 40%

12,000 IC HS+ Success Rate





10,000

30%









Success Rate

Number









8,000





20%

6,000







4,000

10%



2,000







- 0%

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Number of Research Grant Awards involving or not involving Human Subjects by Locus

of Review Compared to NIH Appropriations (FY 1996 to 2005)

8,000 $30.0

CSR HS+ Awards

CSR HS- Awards

7,000 IC HS+ Awards

IC HS- Awards $25.0

Approprations (Billions)

6,000









NIH Appropriations (billions)

$20.0

5,000

Number of Awards









4,000 $15.0







3,000

$10.0



2,000



$5.0

1,000







- $-

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Dollars Awarded for Competing and non-Competing Research Grants with and without

Human Subjects by Locus of review Compared to NIH Appropriations (Fiscal Years 1996

to 2005)

$8.00 30.000

CSR HS+

CSR HS-

$7.00

I/C Review HS+

25.000

I/C Review HS-

$6.00 NIH Appropriations









NIH Appropriations (Billions)

Dollars Awarded (Billions)









20.000

$5.00







$4.00 15.000







$3.00

10.000



$2.00



5.000

$1.00







$- -

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Research Project Grants (FY 2005)



RPG Applications

RPG

43,268 Applications

16,603 HS+ (38%)

26,665 HS- (62%)





Locus of Review



CSR IC

35,208 Applications 8,060 Applications

11.955 HS+ (34%) 4,648 HS+ (58%)

23,253 HS- (66%) 3,412 HS- (42%)





Awards



HS+ HS- HS+ HS-

2,177 Awards 5,530 Awards 1,041 Awards 900 Awards

Success Rate 18% Success Rate 24% Success Rate 22% Success Rate 26%

Human Subjects Research Project Grant Applications Reviewed in CSR and ICs with

Success Rates

14,000 50%

CSR HS+ Applications

CSR HS+ Awards

IC HS+ Applications

12,000

IC HS+ Awards

CSR HS+ Success Rate 40%

IC HS+ Success Rate

10,000





30%









Success Rate

8,000

Number









6,000

20%





4,000



10%

2,000







- 0%

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Number of Research Project Grant Awards involving or not involving Human Subjects by

Locus of Review Compared to NIH Appropriations

6,000 $30.0

CSR HS+ Awards

CSR HS- Awards

IC HS+ Awards

5,000 IC HS- Awards $25.0

Approprations (Billions)









NIH Appropriations (billions)

4,000 $20.0

Number of Awards









3,000 $15.0









2,000 $10.0









1,000 $5.0









- $-

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Dollars Awarded for Competing and non-Competing Research Project Grants with and

without Human Subjects by Locus of Review Compared to NIH Appropriations

(Fiscal Years 1996 to 2005)

$8.00 30.000





$7.00 CSR HS+

CSR HS- 25.000

I/C Review HS+

$6.00

I/C Review HS-









NIH Appropriations (Billions)

Dollars Awarded (Billions)









NIH Appropriations 20.000

$5.00





$4.00 15.000





$3.00

10.000



$2.00



5.000

$1.00





$- -

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

R01 and Equivalent Grants (FY 2005)



R01 Equivalent Applications

R01 Equiv.

28,423 Applications

10,199 HS+ (36%)

18,224 HS- (64%)





Locus of Review



CSR IC

26,243 Applications 2,180 Applications

8,687 HS+ (33%) 1,512 HS+ (69%)

17,556 HS- (67%) 668 HS- (31%)





Awards



HS+ HS- HS+ HS-

1,627 Awards 4,298 Awards 298 Awards 240 Awards

Success Rate 19% Success Rate 24% Success Rate 20% Success Rate 36%

Human Subjects R01 Equivalent Applications Reviewed in CSR and ICs with Success

Rates



10,000 CSR HS+ Applications 50%



CSR HS+ Awards

9,000 IC HS+ Applications

IC HS+ Awards

8,000 CSR HS+ Success Rate 40%

IC HS+ Success Rate

7,000





6,000 30%









Success Rate

Number









5,000





4,000 20%





3,000





2,000 10%





1,000





- 0%

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

R01 Equivalent Awards involving or not involving Human Subjects by Locus of Review

Compared to NIH Appropriations

6,000 $30.0

CSR HS+ Awards

CSR HS- Awards

IC HS+ Awards

5,000 IC HS- Awards $25.0

Approprations (Billions)









NIH Appropriations (billions)

4,000 $20.0

Number of Awards









3,000 $15.0









2,000 $10.0









1,000 $5.0









- $-

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Dollars Awarded for Competing and non-Competing R01 Equivalent Grants with and

without Human Subjects by Locus of review Compared to NIH Appropriations

(Fiscal Years 1996 to 2005)



$7.00 30.000

CSR HS+

CSR HS-

$6.00 I/C Review HS+

25.000

I/C Review HS-

NIH Appropriations









NIH Appropriations (Billions0

$5.00

Dollars Awarded (Billions)









20.000



$4.00



15.000



$3.00



10.000

$2.00





5.000

$1.00







$- -

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Center Grants (FY 2005)



Center Applications

Center

818 Applications

481 HS+ (59%)

337 HS- (41%)





Locus of Review



CSR IC

39 Applications 779 Applications

14 HS+ (36%) 467 HS+ (60%)

25 HS- (64%) 312 HS- (40%)





Awards



HS+ HS- HS+ HS-

10 Awards 18 Awards 153 Awards 121 Awards

Success Rate 71% Success Rate 72% Success Rate 35% Success Rate 39%

Human Subjects Research Center Grant Applications Reviewed in CSR and ICs with

Success Rates

700 100%

CSR HS+ Applications

CSR HS+ Awards

90%

IC HS+ Applications

600

IC HS+ Awards

CSR HS+ Success Rate 80%

IC HS+ Success Rate

500

70%





60%









Success Rate

400

Number









50%



300

40%





30%

200



20%

100

10%





- 0%

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Number of Center Grant Awards involving or not involving Human Subjects by Locus of

Review Compared to NIH Appropriations

250 $30.0

CSR HS+ Awards

CSR HS- Awards

IC HS+ Awards

IC HS- Awards $25.0

200 Approprations (Billions)









NIH Appropriations (billions)

$20.0

Number of Awards









150





$15.0





100



$10.0







50

$5.0









- $-

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Dollars Awarded for Competing and non-Competing Center Grants with and without

Human Subjects by Locus of Review Compared to NIH Appropriations

(Fiscal Year 1996 to 2005)

$2.00 30.000

CSR HS+

$1.80 CSR HS-

I/C Review HS+

25.000

$1.60 I/C Review HS-

NIH Appropriations









NIH Appropriations (Billions)

$1.40

Dollars Awarded (Billions)









20.000



$1.20





$1.00 15.000





$0.80



10.000

$0.60





$0.40

5.000



$0.20





$- -

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Fiscal Year

Part III

Conclusions

• Hypothesis

– Clinical research grant applications have

lower success rates* than basic research

applications.

• True for RGs, RPGs, R01s, and Centers

– Success rate correlates with locus of review

• True for RGs, RPGs, R01s, and Centers





But the devil is in the details…

Conclusions

Success Number of Dollars

rate awards awarded

RGs CSR CSR CSR

IC IC IC

RPGs CSR CSR CSR

IC IC IC

R01 CSR CSR CSR

equivalents IC IC IC

Centers CSR CSR CSR

IC IC IC

Key questions



Why?

What interventions

work?



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