Transcript GEARING UP FOR AAHRPP

GEARING UP
FOR AAHRPP
A Presentation for IRB Members – March 2011
Beverley Esparza, CIP
Assistant Director, Human Research Protections
Learning Objectives – March 2011

Principles, regulations, and statutes

What is Human subject research

Level of risk to subjects determines review
process

IRB requirements, composition and authority

Coming in April: Considerations during the IRB
review process
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Principles, Regulations, & Statutes
Response to Research Abuses

Nazi atrocities in World War II drew attention to the lack of
international standards on research with human participants and
led to the formulation of the Nuremburg Code (1947).

The thalidomide disaster led to the adoption of the "Kefauver
Amendment" (1962) to the Food, Drug and Cosmetic Act,
requiring drug manufacturers to prove to the FDA the safety and
effectiveness of their products and physicians to obtain informed
consent from potential subjects before administering
investigational medications.

The Declaration of Helsinki drafted by the world Medical
Association in 1964 (most recently updated in 2000) builds on the
Nuremberg Code and is the basis for Good Clinical Practices used
today.
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Research Tragedies in the U.S.A.
Tuskegee Syphilis Study
(1932-72)
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Tuskegee Syphilis Study

The U.S. Public Health Service (now the Center for Disease
Control) conducted a study in Alabama to record natural history
of syphilis to justify treatment programs for blacks.

The study involved 600 black men--399 with syphilis and control
group.

Researchers told the men they were being treated for "bad
blood," a local term used to describe several ailments, including
syphilis, anemia, and fatigue.

Compensation: free medical exams, free meals, and burial
insurance

Study projected to last 6 months, actually went on for 40 years.
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Tuskegee Syphilis Study & The
National Research Act of 1974
What went wrong?

No informed consent - Although the men had freely agreed to be examined and treated there
is no evidence that researchers had informed them of the study or its real purpose.

Withheld treatment - The men were never given adequate treatment for their disease. Even
when penicillin became the drug of choice for syphilis in 1947, researchers did not offer it to
the participants.

Participants were never given the choice of quitting the study - even when penicillin
became widely used.

In 1973, a class-action lawsuit ended in a settlement that gave more
than $9 million to the study participants. As part of the settlement, the
government promised to give free medical and burial services to all living
participants, including wives, widows, and children who had been
infected because of the study.

The National Research Act (1974) passed primarily in response to the
syphilis study, codified the requirement that human participants in
research must be protected and set the stage for the issuance of the
Belmont Report.
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Belmont Principles (1979)

Respect for Persons (Be Respectful)
 Individuals
should be treated as autonomous
agents
 Individuals with limited autonomy are entitled to
protection

Beneficence (Be Nice)
 Do
no harm
 Minimize risk/maximize benefits

Justice (Be Fair)
 Fair
distribution of risks and benefits of research
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Regulations & Statutes
Protecting Human Subjects in
Research
Federal





45 CFR Part 46 – OHRP
21 CFR Parts 50 and 56 – FDA
Health Insurance Portability and Accountability Act – HIPAA
Family Educational Rights and Privacy Act – FERPA
Protection of Pupil Rights Amendment – PPRA
State

Health and Safety Code: Protection of Human Subjects in
Medical Experimentation Act

Health and Safety Code: Consent for Minors

Health and Safety Code: Use of Death Data Records
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Subpart
A: “The Common Rule”
The Common Rule is a federal policy regarding Human Subjects
Protection that applies to 17 Federal agencies and offices.
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DHHS Federal Policy for the
Protection of Human Subjects
45 CFR Part 46
(enforced by the Office of Human Research Protections)

Subpart A: Basic HHS Policy “Common Rule”

Subpart B: Pregnant Women, Fetuses and
Neonates

Subpart C: Prisoners

Subpart D: Minors (shared by FDA)
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What is
Human Subject
Research?
When accessing if an activity is human subject
research, BOTH DHHS and FDA
regulations must be considered.
First, lets look at DHHS…
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Human Subject Research - DHHS
IS THE ACTIVITY RESEARCH?

DHHS regulations define research at 45 CFR 46.102(d) as
follows:

Research means a systematic investigation, including research
development, testing and evaluation, designed to develop or
contribute to generalizable knowledge. Activities which meet this
definition constitute research for purposes of this policy, whether or
not they are conducted or supported under a program which is
considered research for other purposes. For example, some
demonstration and service programs may include research activities.
ARE HUMAN SUBJECTS INVOLVED?

DHHS regulations define a human subject as follows:

A Human Subject is a living individual about whom an investigator
conducting research obtains (1) data through intervention or
interaction with the individual; or (2) identifiable private
information. (DHHS)
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Human Subject Research - DHHS
Definitions…

Intervention includes both physical procedures by which data are
gathered (e.g., venipuncture) and manipulations of the subject or the
subject's environment that are performed for research purposes.

Interaction includes communication or interpersonal contact between
investigator and subject.

Private information includes information about behavior that occurs in a
context in which an individual can reasonably expect that no observation
or recording is taking place, and information which has been provided for
specific purposes by an individual and which the individual can reasonably
expect will not be made public (for example, a medical record). Private
information must be individually identifiable (i.e., the identity of the
subject is or may readily be ascertained by the investigator or associated
with the information) in order for obtaining the information to constitute
research involving human subjects.
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Human Subject Research - FDA
IS THE ACTIVITY RESEARCH?

The FDA defines a clinical investigation at 21 CFR 50.3 as
follows:

Any experiment that involves a test article and one or more human
subjects and that either is subject to requirements for prior
submission to the Food and Drug Administration under section 505(i) or
520(g) of the act, or is not subject to requirements for prior
submission to the Food and Drug Administration under these sections
of the act, but the results of which are intended to be submitted later
to, or held for inspection by, the Food and Drug Administration as part
of an application for a research or marketing permit…
ARE HUMAN SUBJECTS INVOLVED?

The FDA defines a human subject as follows:
Human subject means an individual who is or becomes a participant in
research, either as a recipient of the test article or as a control. A
subject may be either a healthy human or a patient.
 WHEN TESTING THE EFFICACY OF IN-VITRO DEVICES: FDA definition of
a human subject includes an individual on whose specimen a device is
to be used. This includes those specimens that are anonymous.

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Human Subject Research

Refer to this checklist: Determining Whether a
Proposed Activity is Human Research
According to DHHS or FDA Regulatory
Definitions

Remember: publication does not equal research
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Level of Risk Generally
Determines Level of Review
Convened IRB Meeting-
> Minimal Risk
Full Committee
Expedited*
Minimal Risk
Subcommittee
Virtually No Risk
Exempt*
Chair Confirmation
RISK
*defined by lists in regulations
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UCI’s Definition of Minimal Risk
•
Risk: The probability of harm or
injury (physical, psychological,
social, or economic) occurring as a
result of participation in a research
study. Both the probability and
magnitude of possible harm may vary
from minimal to significant.
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IRB Process
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Composition of the IRB
Per federal regulations each IRB is required to have:
•
Five members, with varying backgrounds to promote
complete and adequate review of research activities.
•
One member whose primary concerns are in
nonscientific areas.
•
One member not otherwise affiliated with the
institution and not part of the immediate family of a
person who is affiliated with the institution.
•
No IRB member may participate in initial or continuing
review of any research if the member has a conflicting
interest. (See Purple Laminated Sheet)
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IRB Members Must
Disclose Conflict of Interest

Subcommittee and Full Committee: Have on hand IRB Member Conflict of
Interest Disclosure laminated sheets (Purple Sheet)

Disclosure requirements

All members disclose annually

HRP Staff create spreadsheet to track conflicts for reviewer assignment
purposes

Reviewer Checklist has IRB Member address COI

IRB members leave the room for discussion and vote if they have a conflict
(IRB members recuse themselves)
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UCI’s IRB

UCI has three IRB Committees:
 IRBs “A” and “B” review biomedical research
 IRB “C” reviews social/behavioral research

UCI IRB Members and Alternates are appointed
to a three-year renewable term

UCI IRB Chairs & Vice Chairs are appointed to a
two-year renewable term (with term limits)
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IRB “C” – Social / Behavioral

In general, a protocol’s hypothesis or research
question determines whether a protocol is
reviewed by a biomedical Committee or the
social/behavioral Committee.

Social/behavioral research may include
prospective collection of biological specimens
and/or collection of data via non-invasive
measures that customarily may be considered
clinical in nature, and involve no greater than
minimal risk.
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IRB “A” & IRB “B” – Biomedical
Research that does not qualify for review
by the social/behavioral IRB requires
review by one of the biomedical IRB
committees.
 Research that involves testing the safety
and effectiveness of an investigational
drug, biologic or medical device always
requires review by a biomedical IRB.

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IRB Authority

Protocol Review of all human subjects research covered
by the regulations. IRB must notify the institution and
the investigator in writing of its decision




Approved as is (A).
Require minor changes to secure approval (M). Revisions can
be reviewed and approved by the Chair outside of the Full
Committee.
Require substantial revisions and tabled for re-review by
Committee (T). Resubmit revised documents to Full
Committee/Subcommittee.
Disapproved (D). Rarely occurs only after multiple attempts by
IRB to resolve issues. Can only occur at a convened IRB
meeting.
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IRB Authority


Conduct Continuing Review Research (annually)
 Review progress report of study and subject accruals
to reassess actual risks/discomforts to subjects
Research Oversight
 May observe or have a third party observe the
consent process and/or the research
 May embargo of publications/presentations or
disqualification of thesis/dissertation
 May suspend or terminate approval of research
 not conducted in accordance with the regulations
 associated with unexpected serious harm to
subjects
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IRB Authority – Informed Consent


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
Verify that consent process will be conducted in
accordance with the regulations
Ensure all elements of consent are included in
consent document
Review and approve consent document or verify
that request for waiver or alteration (use of
information sheet, short form) is in accordance
with the regulations
When involving children, if 45 CFR 46.404 or 45
CRF 46.405, indicate if 1 signature is acceptable
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Learning Objectives – Scheduled for April 2011

Considerations During IRB Review

Conflict of interest

Devices

Drugs

Quality improvement
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