Transcript Clinical Research - Federation of American Societies for

Clinical Research
Bridging the Gap
between Basic Science and
Improved Human Health
FASEB
Clinical Research Subcommittee
What Is Clinical Research?
• Research conducted on humans or human
tissues that makes use of patient data.
• Includes study of disease mechanisms,
therapeutic interventions, epidemiology, and
clinical trials.
• Aimed at understanding human disease and
improving human health.
• Interaction between researchers and patient
data is a key feature.
Definitions of Clinical Research
Why is Clinical Research Important?
• Enhances our understanding of human physiology
and pathophysiology.
• Translates basic research into medical care.
• Informs and drives basic research.
• Improves diagnostic tools and preventive care.
• Improves human health!
What Can Clinical Research Accomplish?
• Research in human physiology and pathophysiology
translates basic research into knowledge of disease
mechanisms and medical therapeutics.
• Clinical trials establish safety and efficacy of new
interventions.
• Epidemiological and behavioral research identify high risk
populations with potential to benefit from prevention, early
detection, or therapeutic intervention.
• Outcomes and health services research assess the health
impact and cost-effectiveness of interventions.
Physiological Research
• Carefully controlled studies in patients or normal
subjects that are intended to understand basic
physiologic mechanisms and their disruption in
human disease.
• Translation of basic research findings (in vitro and preclinical
animal investigation) to human subjects to confirm the human
relevance of proposed disease mechanisms, which will inform
scientifically targeted medical therapeutics.
• This work is usually done through General
Clinical Research Centers (GCRC) and informs
clinical trials.
Clinical Trials
• Research that prospectively assigns human subjects to
intervention and concurrent comparison/control groups to
study the cause-and-effect relationship between a medical
intervention and a health outcome (International Committee of
Medical Journal Editors).
http://clinicaltrials.gov/ct/info/whatis#types
Clinical Trial Phases
• Phase I trials: First-time test of intervention in a small group of
people (20-80) to evaluate safety, determine appropriate
dosage, and identify side effects.
• Phase II trials: Intervention given to a larger group (100-300) to
evaluate effectiveness and safety.
• Phase III trials: Intervention given to large groups (1,000-3,000)
to confirm effectiveness, monitor side effects, compare to other
treatments, and collect information that will allow it to be used
safely.
• Phase IV trials: Post marketing studies determine additional
information including risks, benefits, and optimal use of an
intervention.
Population Research
• Epidemiology and behavioral research to identify
high risk populations with potential to benefit from
prevention, early detection, or intervention of
established disease processes.
• Outcomes and health services research to assess
the health impact and cost-effectiveness of an
effective intervention in a population or community
setting.
Basic and Clinical Research are
Interdependent
Basic
Research
Clinical
Research
Translation from
basic science to
human studies
Improved
Health
Translation of
new knowledge
into clinical practice
Adapted from Sung et al. (2003) JAMA, 289, 1278-89.
Copyright © (2003) American Medical Association. All Rights reserved.
Linking HIV to AIDS
• Basic research into DNA, viruses, and retroviruses paved the
way for the identification of the first human retrovirus in
cancer patients.
• Clinical studies showed that cancer-causing retroviruses
exert similar effects to AIDS on the human immune system.
• This helped scientists to identify HIV, a retrovirus in the same
family as the cancer-causing retroviruses,
as the one responsible for the development
of AIDS.
http://opa.faseb.org/pdf/Finding_Chinks.pdf
Helping Newborns Breathe
• Tens of thousands of babies died annually from a mysterious
respiratory ailment.
• Clinical investigators characterized the patients and
studied infant respiration and human lung physiology.
• Separately, basic studies of surface tension and pulmonary
physiology allowed researchers to identify and characterize
pulmonary surfactant.
• With this information in mind, clinical and basic scientists determined
that the deaths were due to a lack of surfactant, which caused the
alveoli, or air sacs in the lungs, to collapse.
• Treatments were then developed in the lab and tested in
and applied to patients with great clinical success.
http://opa.faseb.org/pdf/babies_bubbles.pdf
Combating Breast Cancer
• Basic research findings demonstrated the anti-tumor
effects of tamoxifen in lab animals.
• Clinical researchers showed that tamoxifen shrank breast
tumors in afflicted women and reduced the risk of tumor
recurrence.
• Clinical researchers also demonstrated that healthy women
treated with tamoxifen were less likely to develop breast cancer.
• Tamoxifen is now widely used as a breast cancer treatment and
preventive.
http://opa.faseb.org/pdf/Breast_Cancer_Breakthru.pdf
Who Funds Clinical Research?
• Federal Government
–
–
–
–
–
National Institutes of Health
Department of Veterans Affairs
Centers for Disease Control and Prevention
Agency for Health Care Research and Quality
Department of Defense
• State and Local Governments
• Private Organizations
– Foundations and other not-for-profits
– Industry
Sponsors of Biomedical Research
(Basic and Clinical)
Moses et al. (2005) JAMA, 294, 1333-42
Copyright © (2003) American Medical Association. All Rights reserved
National Institutes of Health
• NIH Mission: Science in pursuit of
fundamental knowledge about the nature
and behavior of living systems and the
application of that knowledge to extend
healthy life and reduce the burdens of illness
and disability.
• NIH is a major sponsor of clinical research.
Former NIH Director,
• Clinical Research Initiatives:
Dr. Elias Zerhouni
– NIH Roadmap: Reengineering the Clinical Research Enterprise
– Clinical and Translational Science Awards
NIH Spending on Clinical Research
NIH Budget
FY 2004-2008
Spending ($ Billions)
Clinical Trials
Other Clinical Research
Non-Clinical Research
2005
2007
30
25
20
15
10
5
0
2004
2006
2008
Fiscal Year
*Estimated funding
http://officeofbudget.od.nih.gov/ui/2008/tabular%20data.pdf
http://www.nih.gov/news/fundingresearchareas.htm#content
NIH Spending on Clinical Research
Total NIH Budget
FY 2008
$29.5 Billion
Non-Clinical Research
$19.8 Billion
(67.3%)
Other Clinical Research
$6.1 Billion
(20.6%)
Clinical Trials
$3.6 Billion
(12.1%)
http://officeofbudget.od.nih.gov/ui/2008/tabular%20data.pdf
http://www.nih.gov/news/fundingresearchareas.htm#content
Reengineering the
Clinical Research Enterprise
• Improve medical diagnostics and
treatment.
• Enhance access to and sharing of data
through integrated clinical research
networks.
• Enhance clinical outcomes assessment by developing a
computerized system to collect and store
patient-reported outcomes data.
http://nihroadmap.nih.gov/clinicalresearch/
Reengineering the
Clinical Research Enterprise
• Expand and diversify the clinical research workforce by
optimizing training and career development programs.
• Harmonize federal requirements regarding conduct of
clinical research to facilitate compliance with regulations
and policies.
• Promote translational research by improving clinical
research infrastructure (Clinical and Translational Science
Award program).
http://nihroadmap.nih.gov/clinicalresearch/
Funding for the NIH Roadmap
FY 2008
Total NIH Budget
FY 2008
$29.5 Billion
2%
Non-Roadmap
$29.0 Billion
(98.3%)
Roadmap
$495.6 Million
(1.7%)
98%
http://officeofbudget.od.nih.gov/ui/2008/tabular%20data.pdf
Clinical and Translational Science Awards
• Transforms academic health centers into definable academic
homes for clinical and translational science, which work
together to improve the conduct of clinical research.
• Subsumes some General Clinical Research Centers (GCRC).
• 38 academic health centers currently participating.
• Funded from existing clinical research programs and
Roadmap dollars.
• No funds are taken from basic research.
http://ctsaweb.org/about.html
Department of Veterans Affairs
• Medical and Prosthetics Research Program—Core of the VA
research and development program.
• VA has four major R&D areas:
–
–
–
–
Clinical Science Research and Development Service
Health Services Research and Development Service
Rehabilitation Research and Development Service Biomedical
Laboratory Research and Development Service
• 75% of supported researchers are clinician scientists.
• More than half of all VA research is for investigator-initiated
projects.
• All R&D investment is intramural.
http://www.aaas.org/spp/rd/va08p.htm
Department of Veterans Affairs
• Total FY 2009 R&D budget = $952M
– Medical and Prosthetics Research Program
• Clinical Science Research and Development Service = $87M
• Health Services Research and Development Service = $81M
• Rehabilitation Research and Development Service = $65M
• Biomedical Laboratory Research and Development Service =
$297M
• Research Support = $442
http://www.aaas.org/spp/rd/va09p.htm
Other Federal Sponsors of
Clinical Research
• Agency for Healthcare Research and Quality
– Clinical practice, patient safety, health IT, primary and priority
populations care, and evidence-based medicine.
• Centers for Disease Control and Prevention
– Infectious disease, disability, environmental health, health statistics.
• Department of Defense
– Congressional Special Interest Research Programs: Includes research
on breast, prostate, and ovarian cancer and other diseases.
– Deployment Health-Related Research: Research on conditions
affecting deployed or previously deployed military (e.g., PTSD).
– Defense Advanced Research Projects Agency: Includes funding for
applied biological research (e.g., effects of bioagent exposure).
Private Sponsors of Clinical Research
• Not-for-profits
– Foundations, voluntary health organizations, and research institutes.
– Examples: Bill and Melinda Gates Foundation,
Burroughs-Wellcome Foundation, Juvenile Diabetes Research
Foundation.
• Industry
– Pharmaceutical, biotechnology, and medical device firms.
• Pharmaceutical Research and Manufacturers of America (PhRMA).
• Biotechnology Industry Organization (BIO).
– Total R&D spending by industry in 2006 estimated at $56.1 B billion
– Total PhRMA spending on R&D in 2006 estimated at $43.4 billion
PhRMA Spending on Research in 2006
Research area
Dollars (in billions)
Percent of total
spending
Pre-human and
Pre-clinical
11.8
27.2
Phase I
2.9
6.7
Phase II
5.7
13.1
Phase III
12.2
28.1
Phase IV
5.6
6.1
Uncategorized
2.6
12.9
Total R&D
43.4
100
http://www.phrma.org/files/2008%20Profile.pdf
How is Clinical Research Regulated?
• Office of Human Research Protections
– Protects the rights, welfare, and well-being of subjects involved in
research conducted or supported by the Department of Health and
Human Services.
• Food and Drug Administration
– Regulates the approval process and assures the safety, efficacy, and
security of drugs, biological products, medical devices.
• Local Institutional Review Boards
– Conducts initial review of research proposals.
– Ensures participants are not exposed to unreasonable risks and that
they give informed consent.
– Conducts continuing review of approved research to ensure that
human-subjects protections remain in force.
Challenges Faced By
Clinical Researchers
• Difficulty balancing patient care and research responsibilities.
• Expensive medical training; lower salaries compared to private
clinicians.
• Long training time compared to medical
school peers.
• Burdensome regulations and paperwork.
• Insufficient mentoring due to competing pressures.
• Low success rate for clinical R01s.
Addressing the Challenges
• Assess clinical research career development awards to
optimize retention of clinical researchers.
• Promote effective mentoring by senior clinical researchers.
• Implement loan forgiveness programs to boost retention in the
research track.
• Streamline, standardize, and simplify regulatory requirements.
• Include reasonable “protected time” requirements in grants to
ensure sufficient time for research.
• Ensure adequate representation of clinical researchers on
review panels for clinical research grants.
For additional information: Kotchen et al. (2006) J. Investigative Medicine;
Murillo et al. (2006) Academic Medicine; Sung et al. (2003) JAMA.
Why Improve the Landscape for Clinical
Research?
• Enhance recruitment and retention of clinical
researchers.
• Prevent future shortage of clinical researchers.
• Optimize bench to bedside translation of research.
• Drive basic science discoveries.
• Improve human health!
Resources: Clinical Research
Organizations
• Association of American Medical Colleges
• Association for Patient-Oriented Research
• Clinical Research Forum
• Health Research Alliance
• Institute of Medicine: Clinical Research Roundtable
• National Institutes of Health
Resources: Clinical Research Reports
•
The NIH Director’s Panel on Clinical Research Report to the Advisory Committee to
the NIH Director (The Nathan Report,1997, NIH).
•
The Physician Scientist: Career Issues and Challenges at the Year 2000 (Zemlo et
al., 2000, FASEB Journal).
•
Central Challenges Facing the Clinical Research Enterprise (Sung et al., 2005,
JAMA).
•
Meeting the Challenges Facing Clinical Research: Solutions Proposed by Leaders
of Medical Specialty and Clinical Research Societies (Murillo et al., 2006, Academic
Medicine)
•
Outcomes of National Institutes of Health Peer Review of Clinical Grant
Applications (Kotchen et al., 2006, J. Investigative Medicine).
•
Promoting Translational and Clinical Science: The Critical Role of Medical Schools
and Teaching Hospitals (2006, AAMC).
•
New Physician-Investigators Receiving National Institutes of Health Research
Project Grants (Dickler et al., 2007, JAMA).
Resources:
FASEB’s NIH Advocacy Tool
• FASEB has created a
customizable slide
presentation for scientists,
university deans, and
professors to use locally to
demonstrate NIH's impact on
human health.
For more information:
http://opa.faseb.org/pages/Publications/NIH_PPT.htm
Interested in Learning More?
Please visit FASEB’s Office of Public Affairs at:
http://opa.faseb.org
The Federation of American Societies for Experimental Biology