Clinical Research: NIH and Pharmaceutical industry funding

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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 Addisons
  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
Total Testosterone (ng/dL)
500
400
300
200
100
0
Asymptomatic
ARC
AIDS
Dobs AS, et al. Am J Med. 198884611-616.
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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
BASIC RESEARCH
Infectious Agents Cell and Organ Systems
CLINICAL TRIALS
Translational Research
Pathways and Drug Discovery
Clinical Trials
Epidemiology
POPULATION SCIENCE
Behavioral Research
Groups at Risk
Outcomes and Health Services Research
Environmental Hazards
Adapted from David Nathan presented at
the Clinical Research Roundtable meeting, June 12
2002
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Realms of Clinical Research
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 US
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Pharmaceutical Industry
Pharmaceutical Industry
NIH
NIH
20
(Billion)
15
10
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Sources PhRMA, National Institutes of Health
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US Pharmaceutical Industry RD Expenditure NCE
Approvals, 1963-99
50
28
24
40
20
30
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RD (1999 billion)
NCEs
12
20
8
10
4
0
0
1963
1966
1969
1972
1975
1978
1981
1984
1987
1990
1993
1996
1999
NCEs
Inflation-adjusted RD 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 elses 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 elses grant
• Problems
• Multiple pressures to see patients, teach, do
  research
• Difficult to succeed alone

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A Balanced Research Portfolio
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
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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

• Health
• Services,
• Outcomes,
• Evaluative, and
• Comparative
• Research

Basic Scientific Research
Clinical Trials
Goal Improved Health
Block 1
Block 2
Translation from basic science to human studies
Translation of new 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 Asst 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
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 - Dont 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 Youre
  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