clinical research: nih and pharmaceutical industry funding adrian s. dobs, m.d., m.h.s. professor of...
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Clinical Research: NIH and Pharmaceutical industry funding
Adrian S. Dobs, M.D., M.H.S.Professor of Medicine
The Johns Hopkins University School of Medicine
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Outline
• Research questions
• Career paths in academic medicine
• Promotions
• Personal reflections of how to have a successful career
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Bedside Observation
• HIV-AIDS first recognized 1983
• 1985 cases of hypotension, electrolyte abnormalities
• Autopsies showing destruction of the adrenal gland
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Postulating a Research Question
• Question – Could these patients have Addison’s Disease (adrenal Insufficiency)?
• Original description by Addison – Invasions of the gland by TB or auto-immune destruction
• Hypothesis – Men with HIV disease commonly have adrenal insufficiency due to invasion of the adrenal gland by CMV or HIV or granulomatous infection (TB)
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Findings from our First Study of Endocrine Disorders in HIV
• Our primary hypothesis was wrong: Adrenal insufficiency was rare
• Our other measures showed significant findings: Low testosterone (hypogonadism) was common
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Total Testosterone in AIDS, ARC, and Asymptomatic Patients
900
800
700
600
500
400
300
200
100
0Asymptomatic ARC AIDS
To
tal T
esto
ster
on
e (n
g/d
L)
Dobs AS, et al. Am J Med. 1988;84:611-616.
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Outline
• Research questions
• Career paths in academic medicine
• Promotions
• Challenges faced by the clinical investigator
• Personal reflections of how to have a successful career
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Information Flow in Health Research
Infectious AgentsCell and Organ Systems
POPULATION SCIENCE
Translational Research
Clinical Trials
Epidemiology
Behavioral Research
Outcomes and Health Services Research
BASIC RESEARCH
Pathways and DrugDiscovery
Groups at Risk
Environmental Hazards
CLINICAL TRIALS
*Adapted from David Nathan; presented at theClinical Research Roundtable meeting, June 12 2002
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Realms of Clinical Research
Bedside Observation
Epidemiologic analysis
Patient-oriented Study
Health care services
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Examples of Clinical Trial Study Designs
• Phase I clinical trials– First time in humans, safety studies, dose finding,
pharmacokinetics
• Phase II clinical trials– Use in the diseased population, small sample size, intense
study
• Phase III clinical trials– Large scale studies, in diseased population, pre-FDA filing
• Phase IV clinical trials– Post-approval, new indications, new populations
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My Path
• Fellowship – Basic science lab– Mentor was not committed to me– Dropped too many test tubes
• Instructor – Didactic training and Pharmaceutical studies– MHS in Epidemiology– Began to learn the basics
• Assistant Professor – NIH collaborations– Epidemiology studies who needed MD input
• Associate Professor – NIH Principal Investigator• Professor – NIH Center grant
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Research Spending in the US25
NIH20
15
10
5
Pharmaceutical Industry
$ (
Bill
ion
)
Sources: PhRMA, National Institutes of Health
5,000
10,000
15,000
20,000
25,000
1993 1994 1995 1996 1997 1998 1999 2000 2001
Year
Pharmaceutical Industry
NIH
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US Pharmaceutical Industry R&D Expenditure & NCE Approvals, 1963-99
0
10
20
30
40
50
1963 1966 1969 1972 1975 1978 1981 1984 1987 1990 1993 1996 1999
NC
Es
0
4
8
12
16
20
24
28
R&
D (1999 $ b
illion
)
NCEs Inflation-adjusted R&D expenditure (in 1999$)NCE Trend
Source : Tufts CSDD Approved NCE database and PhRMA; Analysis by Joseph DiMasi, Ph.D.
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Types of Clinical Research Studies
• Case Reports
• Cross-sectional
• Case-control
• Observational cohort
• Clinical trial
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Building a Clinical Research Staff Team
• Staff support– Share resources: Access to someone else’s group– Research coordinator: Smart college grad– Research nurse– Technitian– Data manager– Budget administrator
• Trainees– Post-docs– Fellows– Students
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Building a Collaborative Clinical Research Investigator Team
• Content investigator
• Method investigator
• Biostatistician
• Outcome investigator
• Basic science investigator
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Logistics for Success
• Funding,– GCRC, R21
• Space– GCRC, 550 Brdwy, clinic area
• Staff support– Coordinator, recruiter, phlebotomist
• Equipment– Centrifuge, freeezers
• Data management
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Advantages of Pharmaceutical Studies
• Networking with other national leaders in a clinical field
• Expanded knowledge of the field
• Quality study design and quality assurance
• Unrestricted funds
• Opportunity to hire staff to help with non-funded studies
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Budgets in Industry-funded Studies
• Often given a set per-patient reimbursement
• Try to put as much as possible outside the patient, e.g IRB work, advertizing
• External budget – based on procedure done– Visit 1 – screening, PEx– Visit 2 – phlebotomy, specimen preparation
• Internal budget – based on %FTE
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Investigator-initiated studies
• A means of support for key opinion leaders
• Sometimes meritorious - sometimes not
• Sometimes at odds with product label
• Can provide novel insights
• Investigators enter into contracts with industry
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Career Progression as a Clinical Investigator
• Didactic training – MPH, MHS, GTPCI, short courses
• NIH progression – NRSA, K23, R21, R01, Program projects, U grants
• Know them, collaborate, start as a junior person on someone else’s grant
• Problems: – Multiple pressures to see patients, teach, do research– Difficult to succeed alone
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A Balanced Research Portfolio
National Institutes of Health
Pharmaceutical Industry
Co-investigator with others
Other Federal/Foundation Funding
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Disadvantages of Industry-funded Studies
• Budget is based on per-patient recruited, i.e. work without reimbursement
• More research is being done in private practices, free-standing research facilities and internationally
• Difficulty in identifying patients
• Major delays in the administration
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Common Contract Problems
• Publication rights
• Intellectual property
• Terms of payments
• Conflict of interest
• Low priority for ORA
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Problems for Clinical Research
Campbell, JAMA 286, 800-6, 2001
0
10
2030
4050
6070
8090
100
Issue
Pressure to seepatientsInsufficient clinicalrevenuesQuality researchers
External support
Competition fromCROsIRB process
Finding subjects
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Challenges to the Institution to Help the Clinical Investigator
• Streamlining of IRB and especially ORA• Consent process – video, instructions• Case Report Form management repository• Consistency in advertising of studies• Regulatory checklists for all studies – RO1• Certification programs which vary by personnel • Standing Data Safety and Monitoring Boards
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Health Research Continuum & the Two Translational Blocks
Basic Scientific Research
Clinical Trials
Health Services,
Outcomes, Evaluative,
and Comparative
Research
Goal:Improved
Health
Block 1
Block 2
Translation from basic science to
human studies
Translation ofnew knowledge
into clinical practice
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Delivering the Promise
Clinical Research could…
Be a powerful vehicle to deliver the promises of basic science to the public
OR
Emerge as the block limiting the translation of basic science to
benefit the greater public health
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How to Identify Industry Sources
• Persaverance
• Asking colleagues
• Searching on web sites
• Local people
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Outline
• Research questions
• Career paths in academic medicine
• Promotions
• Personal reflections of how to have a successful career
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Change in Ass’t and Associate Professors at Johns Hopkins SOM Based on Gender
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Change in Full Professors at Johns Hopkins SOM Based on Gender
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Faculty Representation and Attrition at Johns Hopkins
• The proportion of women at the ranks of Assistant and Associate Professor has remained roughly constant over the past six years.
• Women now constitute 15% of full professors, up from 7.5% in 1994.
• Women are less likely than men to be promoted to a higher rank.
• Women take longer to be promoted than men. • The attrition of women faculty is higher than that of
men. • There are currently 3 (out of 30) female department
directors
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Salary Discrepancies Between Men and Women at Johns Hopkins
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Ambivalence of the Clinical Investigator
No81%
Yes19%
Do you believe that clinical research receives the same support, recognition, and credit for promotion as more basic research?
UCSF - 2000
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Outline
• Research questions
• Career paths in academic medicine
• Promotions
• Personal reflections of how to have a successful career
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Some Facts Not on My CV
• Married for 27 years to a physician
• Four children
• Had children when chief resident, instructor, fellow, and assistant professor
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The Ten Top Things To Remember in Life
• #10 -You Can Do Anything, but Not Everything
• #9 - Everyone Has a Life
• #8 - Have Your Children
• #7 - There Are Lots of Childcare Options
• #6 - Compartmentalize Life
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The Ten Top Things To Remember in Life
• #5 - Keep Your Private Life Private
• #4 - Family Rituals
• #3 - Share Your Work With Family
• #2 - Don’t Let Your Spouse Off the Hook
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The Ten Top Things To Remember in Life
• #1 - No One at Work Will Remember You When You’re Dead and Gone
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Conclusion
• Working in science and medicine is a true privilege
• Academics provide opportunities for helping patients, teaching students and trainees and pursuing scientific questions
• Success is that winding path of finding mentors, sincere desire to help, and a balance with personal growth