IRB & Regulatory Agencies

Institutional Review Board for
Human Research (IRB)
Human Subject Protections
Susan Sonne, PharmD, BCPP
Nuremberg Code
 first major control on research in any
 prescribed 1948 as part of trial of a
Nazi Physician
 willfully harmful research on unwilling
human subjects
Jewish Chronic Disease Hospital
• July 1963
• Injection of live cancer cells into 22 patients
• No written consent
• Some verbally informed – “involved in
Never told being given live cancer cells
• Guilty of fraud, deceit, unprofessional
The Declaration of Helsinki
 Produced 1961, adapted 1964
 Informed consent = ethical research
 Basis for FDA policy
Willowbrook State School
Study began 1956
Institution for “mentally defective” children
Study designed to contribute to
understanding etiology of infectious
hepatitis and test effects of gamma
globulin in preventing disease.
First subjects fed extracts of infected
Public attention 1971
National Research Act of 1974
Created National commission for the
protection of Human Subjects of Biomedical
and Behavioral research.
Charge was to:
Identify basic ethical principles that should
underlie conduct of biomedical and behavioral
research involving human subjects
More specifically, consider
Boundaries between research and practice
Role of assessment of risk-benefit
Selection of subjects
Nature and definition of informed consent
Result was 1976 Belmont report
Good Clinical Practice
Why have this training?
The Tuskegee Syphilis Study
 1932 to 1972
 399 African American
Males were denied
treatment for syphilis
 Study conducted by
U.S. Public Health
From President Clinton
 "Although these regulations [Protection of Human Subjects, Code
of Federal Regulations, Title 45, Part 46} provide the framework
for protecting human subjects in research, we must exercise
constant care and ensure that these regulations are strictly
enforced by departments and agencies. Therefore, I direct each
department and agency of Government to review present
practices to assure compliance with the Federal Policy for the
Protection of Human Subjects and to cease immediately
sponsoring or conducting any experiments involving humans that
do not fully comply with the Federal Policy." -Bill Clinton, 1994
 “The people who ran the study at Tuskegee diminished the
stature of man by abandoning the most basic ethical precepts.
They forgot their pledge to heal and repair. They had the power to
heal the survivors and all the others and they did not. Today, all
we can do is apologize….” – Bill Clinton, 1997
OHRP Suspensions
 During the last 6-7 years, OHRP has
suspended all human research at the
following institutions:
– University of Illinois, Chicago Campus
– University of Colorado
– Duke University
– Johns Hopkins
– University of Pennsylvania
– And others
General Rule for Human Subject
Any element of research?
Undergo review
IRB Purpose
 To protect the rights and welfare of human
research subjects
 Authority to approve, require modification
and disapprove any research involving
human subjects
Institutional Review Board
responsible to verify
1. Safety
2. Integrity
3. Human rights
4. Public reassurance
5. Scientific content
The Belmont Report
 3 Basic Principles for Protection of Human Subjects:
– Respect
 voluntary informed consent
 privacy
 protections for vulnerable populations
– Beneficence
– Justice
Persons treated in an ethical
 Protecting them from harm
 Helping to secure their well
• Who ought to receive the benefits of
research and bear the burden of research?
• Equals ought to be treated equally
• Fairness in distribution
• What is deserved
Criteria for Approval
Risks are minimized
Reasonable risk:benefit ratio
Equitable selection of subjects
Informed consent obtained appropriately
Informed consent adequately documented
Monitor data to insure safety
Protect confidentiality
No coercion
Informed Consent
• Essential to ethical conduct of clinical
• Potential subject chooses whether or not they will
• Obtained after full information is given and
• Explanation of study objective, potential benefits,
risks, inconveniences, subject’s rights and
Informed Consent
–Purpose of the Study
–Potential Risks and Discomforts
–Anticipated Benefits to Subjects
–Anticipated Benefits to Society
–Alternative to Participation
–Emergency Care and Compensation for Injury
–Payment for Participation
–Financial Obligation
–Privacy and Confidentiality
–Participation and Withdrawal
–Rights of Research Subjects
The Mountain of Responsibility
•Protecting Participants
•Implementing Study
•Reporting Accurately
Investigator Obligations
• Conducts a clinical investigation
• Responsible for
All procedures conducted
All data collected
• May delegate work in conducting
study but they retain responsibility
Investigators – and by delegation
all study staff responsibilities
• To protect the rights of participants
• To obtain informed consent from each
• To keep specific records and issue
specific orders
• To assure that the IRB is provided
information for initial and continuing
review of the study
Useful Regulatory/Policy Material
Office for Human Research Protections
Food & Drug Administration