"Predictions are always risky, particularly about the future." Dan Quayle

1
National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) Public
Health Service Act The general purpose of the
National Institute of Diabetes and Digestive and
Kidney Diseases...is the conduct and support of
research, training, health information
dissemination, and other programs with respect to
diabetes mellitus and endocrine and metabolic
diseases, digestive diseases and nutritional
disorders, and kidney, urologic, and hematologic
diseases.
NIDDK Scientific Programs
Diabetes Endocrinology Metabolic and Genetic
Diseases
Digestive Nutritional Obesity
Kidney Urologic Hematologic
Intramural Basic Clinical
2
Challenges to Large Scale Clinical Investigation

• Coordination is difficult and expensive
• Generally large unmet clinical need required
• Concept must survive preclinical, pilot trial
  hurdles
• Clinical trials take years
• Even the best of studies/outcomes are scrutinized
  and criticized
• Translation of study criteria to clinic is
  difficult
• Rapid adoption of even very successful new
  treatments not a given

3
NIDDK-Supported Major Multi-Center Clinical
Trials

• FY99
• DPP
• DPT-1
• AASK
• MTOPS
• HEMO
• EDIC

• FY02
• DPP Type 2 DM in kids
• DPT-1 LOOK AHEAD
• AASK CRIC
• MTOPS phytoRx for BPH
• HEMO homocysteine lowering
• EDIC HALT-C VIRAHEP-C

post-trial follow-up study
4
Trial Networks

• NASH
• Biliary Atresia
• FSGS
• PKD
• Urinary Incontinence Rx
• Chronic Prostatitis
• Vascular Access in Hemodialysis

5
Mechanisms to Enhance Clinical Research

• Ancillary studies
• RO3 applications for pilot clinical trials
• R18 applications for diabetes prevention and
  control projects
• Trans-NIH solicitation for environmental
  approaches to obesity prevention
• NIDDK Central Repository

6
Aspects of Prevention Research that Uniquely
Benefit from NIH Investment, Including
Partnerships with Private Sector

• Supporting research on basic disease mechanisms
• Identifying modifiable risk factors
• Characterizing natural history
• Validating surrogate markers
• Testing clinical interventions of limited
  interest to for-profit private sector, e.g.
  vaccines, or behavioral and other non-proprietary
  interventions

7
Even Among Clinical Trials,Prevention Trials are
Expensive, Often Requiring Large Numbers of
Subjects Followed for Long Periods

• Scientific discovery has created a dramatically
  increasing number of opportunities for prevention
  research based upon
• Basic biological findings
• Epidemiologic risk factors
• Interventions may have components that are
• Biological
• Behavioral
• Direct or surrogate markers for pre-clinical
  stages of disease or disability will be critical
  to diagnosis and evaluation of
• interventions.
• Translation of effective prevention to achieve
  public health impact will be a critical step.
  

8
Stages in the Natural History of Diabetes
Prevention Is Possible
Pre-Diabetes
Normal
IGT
Disability Death
Diabetes
Complications
Primary Secondary
Tertiary prevention prevention
prevention
9
Diabetes Incidence Rates by Age by
Age (years)
The DPP Research Group, NEJM 346393-403, 2002
10
Clinical Research to be Supported by Type 1
Diabetes Special Funds

• Long-term epidemiology study of environmental
  causes(s) of type 1 DM
• Population-based registry for childhood DM
• TrialNet
• Islet transplant studies and islet harvesting
  centers
• Clinical studies of prevention of diabetes
  complications (eye kidney)
• Prevention of hypoglycemia and evaluation of new
  glucose-monitoring devices in kids
• Bench to Bedside applications

11
You can observe a lot by just watching
Yogi Berra
12
Epidemiology and Outcomes ResearchExamples

• USRDS
• Urology in America
• Endoscopy Database
• TRIAD
• Health Disparities Strategic Plan

13
Effect of the Use or Nonuse of Long-Term Dialysis
on the Subsequent Survival of Renal Transplants
from Living DonorsKevin C. Mange, Marshall M.
Joffe, Harold I. FeldmanNEnglJMed 344(10)
726-731, 2001Using data from the U.S. Renal
Data System, we performed a retrospective cohort
study of 8481 patients
14
When is endoscopy used ?
- Diagnosis - Treatment - Prognosis
10 million procedures performed annually in
United States
15
National Endoscopic Database
Clinical Outcomes Research Initiative
16
CORI Research Goals

• Endoscopic use patterns
• Natural history of chronic conditions
• Effectiveness of endoscopic therapy
• Impact of endoscopy on patient outcomes
• Monitor complications
• Patient registries for clinical trials

17
National Weight Control Registry

• Eligibility Lose 30 lbs / keep it off one year
• Results
• Lost 66 lbs
• Kept it off 6 years
• Report eating 1381 kcal/d--24 from fat
• Report 2826 kcals/wk in physical activity

18
Behavior Change
Health Outcomes

• Long-term health impact of weight loss
  intervention
• Cardiovascular morbidity and mortality
• Diabetes, CVD risk factors, hospitalizations
• Opportunity for other studies-e.g. genetic studies

19
NIDDK Support for Surgery-Related Clinical
ResearchExamples

• Adult to Adult LDLT
• MIST
• Bariatric Surgery

20
Number and Types of Liver Transplants Performed
at 83 U.S. Centers
Total Cadaveric
3369
3786
3878
3576
21
Living Donor Liver TransplantationResearch Needs

• Studies on liver regeneration.
• Optimization of the procedure, including minimal
  liver size.
• Steatosis (fat) and liver function.
• Better understanding of short and long term
  complications, including mortality, and their
  predictive factors.
• LDLT Cohort Study.

22
Adult-to-Adult Living Donor Liver Transplantation
Cohort Study

• Examples of Possible Studies
• Outcomes of transplantation for hepatitis C
  comparing living donor and cadaveric LT
• Assess approaches to management of liver cancer
  using LDLT vs cadaveric LT (chemotherapy, effect
  of tumor size, effects on waiting time)
• Assess optimal means of informed consent for
  living donors including standardization across
  centers use of video technology

23
The Future

• Genome/proteome/informatics
• Genotype/phenotype
• Translational research

24
Complex Genetic Disease Consortia

• Type 2 Diabetes
• Type 1 Diabetes
• FIND
• ADImap
• Hepatotoxicity Network
• IBD

25
Balancing Life-Style and Genomics Research for
Disease PreventionWalter C. WillettScience
296 695-698, 2002