Transcript Predictors of Academic Success at a Historically Black

The Institutional Review Board (IRB) and
its functions
Theresa M Boyd
Associate Professor of Pathology
Howard University College of Medicine
Director Transfusion Medicine
Howard University Hospital
Howard University IRB
Information
IRB Review Process
The government mandated purpose of
IRBs
The singular purpose of the Howard University
IRB, as mandated by Federal Law, is to protect
the rights and welfare of human research
participants recruited to participate in research
activities conducted under the auspices of
Howard University.
 This purpose can not be outweighed by any
other consideration (i.e. time, money, research
publications, graduation, etc.)
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Why were/are IRBs needed?
Tuskegee Syphilis Study (Alabama, 1932-1972)
 Nazi Experiments (1930s-1940s)
 Stanley Milgram's experiment ."Obedience and
Individual Responsibility" (Yale, 1961-1963)
 Willowbrook Study (New York, 1963-1966)
 Tearoom sex (Washington Univ., 1960s)
 Zimbardo Stanford Prison Experiment 1971
 Research conducted in prisoners, children and
other vulnerable populations
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Guiding Ethical Principles
Nuremberg Code of 1947
 Declaration of Helsinki, 1964 (last
updated in 2004)
 Belmont Report 1979
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Nuremberg Code
Voluntary consent of subject must be
obtained.
 Prior animal experimentation is needed
to assess risks.
 Human experimentation must be
performed by qualified individuals.
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Belmont Report
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Respect for persons
◦ People are autonomous and have the right to self
determination
◦ Obtain informed consent, protect privacy and
confidentiality
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Beneficence
◦ Do no harm, provide benefit when possible, limit
risks
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Justice
◦ Equitable selection of subjects
◦ Equal distribution of risks and benefits
The Belmont Report
The principles of the Belmont Report
govern all research supported by the U.S.
Government. The ethical principles
outlined in the report are the basis for
subsequent regulations designed to ensure
protection of human subjects in research.
The Basic Principles of the
Belmont Report
1. Respect for Persons
2. Beneficence
3. Justice
IRB Decision Matrix
BENEFICENCE
Favorable Risk/Benefit Analysis
Good Experimental Design
Competent &Qualified PI
JUSTICE
Subject selection - equitable
Inclusion/exclusion
Recruitment
RESPECT FOR PERSONS
Informed consent
Surrogate consent
Assent
J. Cooper, Albany Medical Center
Privacy & Confidentiality
Protection of subjects (especially
vulnerable populations)
Respect for Persons
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Treat individuals as autonomous agents
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Do not use people as a means to an end
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Allow people to choose for themselves
o
Provide extra protections to those with diminished
autonomy (i.e., Prisoners, Children, Cognitively Impaired, etc.)
Beneficence
The two general rules formulated from the
principle of beneficence are:
o First, do no harm
o Second, maximize possible benefits and
minimize risks
Justice
o Treat people fairly
o Fair sharing of burdens and benefits of
the research
An injustice occurs when:
1. benefits to which a person is entitled are
denied without good reason, or
2. when burdens are imposed unduly.
The Common Rule
The “Common Rule” is the set of regulations which
were developed to ensure compliance with the
principles of the Belmont Report. The regulations fall
under the Department of Health and Human Services.
These regulations have been adopted by many other
federal departments which regulate human research.
There are many other regulations with which
UVM/FAHC are required to comply, such as the Food
and Drug Administration, but these are all in addition to
the “Common Rule”.
Historical Overview
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The protection of the rights and privacy of human
participants involved in research activities is mandated by
federal law.
The National Research Act Public Law 99-158, The Health
Research Extension Act of 1985, and the National
Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research provide guidelines for
research with human participants to ensure their protection
in the design and conduct of research.
These federal regulations require that any institution
requesting and receiving funds from a federal department or
agency for research involving human participants must
assure that such research is reviewed and approved by the
institution's institutional review board (IRB).
Federal Regulations and Policy
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45 CFR 46 - Basic DHHS Policy for Protection of
Human Research Subjects
Originally adopted May, 1974, Revised January 13, 1981,
Revised June 18, 1991
◦ Additional protections for vulnerable populations
in Subparts B-D
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Federal Policy for the Protection of Human Subjects “The Common Rule” June 18, 1991
◦ Departments of Agriculture, Energy, Commerce, HUD, Justice,
Defense, Education,Veterans Affairs, Transportation, and HHS.
NSF, NASA, EPA, AID, Social Security Administration, CIA, and
the Consumer Product Safety Commission.
Regulations and Guidelines
DHHS: CFR 45 Part 46 (4CFR$^)
 FDA: CFR 21 Parts 50, 56, 312, 812
 National Research Act of 1974
 ICH Good Clinical Practice
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◦ The regulations are open to interpretation
◦ 45 CFR 46, OHRP is the interpreter
◦ 21 CFR and it subparts are interpreted by the
FDA
Regulatory Requirements for IRB
Approval
Risks to subjects are minimized.
 Risks are reasonable in relation to
anticipated benefits – if any.
 Selection of subjects is equitable.
 Informed consent will be sought and
appropriately documented.
 When appropriate, the research plan
makes adequate provision for monitoring
the data collected to ensure the safety of
subjects.
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Regulatory Requirements for IRB
Approval
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When appropriate, there are adequate
provisions to protect the privacy of subjects
and to maintain the confidentiality of data.
When some or all of the subjects are likely
to be vulnerable to coercion or undue
influence, such as children, prisoners,
pregnant women, mentally disabled persons,
or economically or educationally
disadvantaged persons, additional safeguards
have been included to protect the rights and
welfare of these subjects.
More Recent Violations
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In a totally unprecedented flurry of enforcement activity, the National
Institutes of Health (NIH) Office for Protection from Research Risks
(OPRR) stopped research at Rush-Presbyterian-St. Luke's Medical
Center (AP 1998), the West Los Angeles Veterans Affairs Medical
Center (Monmaney 1999; Hilts 1999a), Duke University (Stout 1999;
Weiss 1999), the University of Illinois at Chicago (Guerrero and
Herguth 1999; Grahnke and Ritter 1999), the University of Colorado
(Hubler 1999),Virginia Commonwealth University (Mathews 2000),
and most recently, the University of Alabama at Birmingham (Hansen
and Spencer 2000; Hilts 2000).
While there have been some substantive concerns relating to subject
enrollment and informed consent, most of these sanctions have been
levied because of sloppy and inadequate operation of institutional
review boards (IRBs) and slow or inadequate response to OPRR's
concerns.
Violations
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Researchers at Stanford University were permitted by the state in 1997
to test the use of Depakote in incarcerated adolescent males to see if
the drug would reduce aggressive behavior (Weber 1999).
Researchers at the New York State Psychiatric Institute, the Mount Sinai
School of Medicine, and the Research Foundation of the City University
of New York came under fire for giving fenfluramine to young children,
many of whom were Hispanic or African American. The children were
at-risk younger siblings of child offenders identified by the researchers
through court records (Hilts 1998a; Waldman 1999; Bernstein 1999).
In the early 1990s, plastic surgeons at the Manhattan Eye, Ear, and Throat
Hospital performed a study in which different surgical face-lift
techniques were used on the opposite sides of patients' faces without
securing IRB approval and without express patient consent (Hilts
1998b).
Jesse Gelsinger and Gene
Therapy (U. of Penn.)
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In 1999-2000 the Food and Drug Administration stopped all gene
therapy trials at the University of Pennsylvania, because of alleged
shortcomings and violations of protocols, revealed in an audit .prompted
by the death of Jesse Gelsinger
Gelsinger suffered from Ornithine transcarbamylase (OTC) deficiency, a
rare metabolic disorder.
Gelsinger's death also prompted a revelation of at least six deaths in
other gene therapy trials that had not been reported to the NIH, in
violation of the law, because the investigators determined the deaths
were caused by the subjects' disease and not the experimental therapy.
Several institutions and foundations sponsoring genetic therapy research
halted trials because of concerns about patient safety. The public
hearings also spurred the reporting to NIH of 652 adverse events in
trials using modified adenoviruses (as used in the Penn trial), compared
to only 39 that had been reported promptly as required by law.
Issues - Conflict of interest, did not meet the inclusion criteria, consent
forms did not adequately discuss risks.
Research Regulations
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In 1979, the federal government developed regulations of ethical
principals underlying the current regulations and standards that are
contained in the Belmont Report.
It was the capstone of the National Commission for the Protection
of Human participants of Biomedical and Behavioral Research. It
outlines the ethical principals upon which the ethics of a research
study are evaluated in the United States.
The Belmont Report embodies the moral consensus upon which
stand our present US Federal regulations governing the ethics of
human participants research conduct with Federal funds from the
majority of Federal agencies.
Our present regulations formulize The Belmont Report's
requirements for informed consent and establish another
Commission recommendation that formalized and extended the
existing peer review system of that time, which has matured into the
Institutional Review Board (IRB) system that we have today.
Definitions
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Research - a systematic investigation designed to
develop or contribute to generalizable knowledge.
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Human Subject - a living individual about whom an
investigator conducting research obtains
◦ data through intervention or interaction with the individual, or
◦ identifiable private information
IRB Review of Research
All research projects are categorized into one of three categories
for the IRB review process. Each category is different in the
level of scrutiny and submission procedures. The IRB is
responsible for making the final decision of which category a
research project falls under.
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Full
Expedited
Exempt
Research Not Involving Human Subjects
Types of Review
Initial
 Continuing Review
 Amendments
 Safety Information or Unanticipated
Problems to Subjects or Others
 Noncompliance
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Purpose of the IRB at Howard
University
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Review research proposals, projects, and
activities that involve human participants;
Determine for each activity or proposed
activity if human participants will be placed at
risk;
if risk is involved, determine if the importance
of the knowledge to be gained warrants
allowing the participant to accept the risks;
Oversee protection of rights and welfare of
participants.
Assess whether the researcher(s) is/are
qualified to conduct research involving human
participants.
In General
Applies to funded and unfunded research
 Submission of a protocol and approval by the
IRB is mandatory for any faculty, staff or
student who will interact with a human being
for purposes of conducting research
 Research may not begin before approval from
the IRB is given
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IRB Membership
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Each IRB shall have at least five members, with varying backgrounds to
promote complete and adequate review of research activities commonly
conducted by the institution.
Each IRB shall include at least one member whose primary concerns are in
the scientific area and at least one member whose primary concerns are in
nonscientific areas.
Each IRB shall include at least one member who is not otherwise affiliated
with the institution and who is not part of the immediate family of a person
who is affiliated with the institution.
No IRB may have a member participate in the IRB's initial or continuing
review of any project in which the member has a conflicting interest, except
to provide information requested by the IRB.
Every nondiscriminatory effort will be made to ensure that no IRB consists
entirely of men or entirely of women, including the institution's
consideration of qualified persons of both sexes, so long as no selection is
made to the IRB on the basis of gender. No IRB may consist entirely of
members of one profession.
What type of research requires
review?
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Research which involves the administration of drugs or other
substances to participants
Research involving pregnant women and/or fetuses in utero
Research involving participants with life-threatening physical
conditions
Research involving physically intrusive procedures
Research which previous experience (by the particular investigator
or other investigators) has shown to create a potential of risk to
participants
Research which potentially could put the participant at risk for legal
or civil liability or invade a participant's privacy in regard to
sensitive aspects of his/her behavior (e.g., illegal conduct, drug use,
sexual behavior, alcohol use).
Full Review
One or more Committee member(s) are assigned to review the
complete protocol or amendment, consent form, Investigational
Drug/Device Brochure and any other protocol materials.
 These Primary & Secondary Reviewers summarize the protocol
or amendment to the Full Committee at a convened meeting
and answer questions during the discussion.
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Expedited Review
Protocols, amendments, or continuing reviews that
meet specific federal criteria qualify for an expedited
review.
 The complete protocol, consent form, and any other
protocol materials receive review and approval by a
Committee Chair.
 Expedited does not mean “fast” it is a federal term
used for research that must meet specific criteria
(DHHS 45 CFR 46.110)
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Some Common
Expedited Review Categories
Blood collection – within limits.
 Collection of other biological specimens.
 Collection of data through non invasive
procedures such as MRI, EKG.
 Research on existing data, specimens,
materials collected for NON research
purposes.
 Surveys, questionnaires.
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Some Common
Expedited Review Categories
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Continuing Review when: the research is
permanently closed to the enrollment of new
subjects; (ii) all subjects have completed all
research-related interventions; and (iii) the
research remains active only for long-term
follow-up of subjects; or
(b) where no subjects have been enrolled and
no additional risks have been identified;
where the remaining research activities are
limited to data analysis.
Exempt from IRB Review
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Committee review is not required for certain
categories of research activities that involve little or
no risk to human subjects.
To determine if your research qualifies for exemption
from formal committee review, complete the
“Protocol Exemption Review and Determination
Checklist.”
 Only the IRB can make the determination of
Exempt, this cannot be determined by
researchers!
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Some research can not be
exempted!!!!
IRB Review and Determination of “Research
Not Involving Human Subjects”
There is some research that involves coded private information
or specimens that do not involve human subjects.
 When conducting research using data or specimens, the level of
review by the IRB depends primarily on one factor: whether the
data or specimens are identifiable to the principal investigator
or key personnel.
 Determinations of whether research involving coded
private information or biological specimens is
considered to be “human subjects research” must be
made by the IRB, not the investigator.
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Criteria for IRB Approval
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Risks are Minimized (Consistent with a sound research design and does not
unnecessarily expose subjects to risk)
Risks are Reasonable in Relation to Benefits
Selection of Subjects is Equitable
Informed Consent will be Sought for Each Prospective Subject
Informed Consent will Be Documented
Research Plan Adequately Provides for Monitoring the Data Collected to
Ensure Safety of the Subjects
Research Plan Adequately Protects the Privacy of Subjects and Maintains
Confidentiality
When some or all of the subjects are likely to be vulnerable to coercion or undue
influence, additional safeguards need to be included in the protocol to protect
the rights and welfare of these subjects.
The IRB has the authority to:
o Approve
o Require modifications prior to
approval
o Table
o Disapprove all research activities
including proposed changes in
previously approved human subject
research.
Determining an Action
Approval – the criteria for approval are met.
 Approve with Administrative Review– IRB stipulates
specific revisions requiring simple concurrence by the
investigator, then the IRB Chair or another IRB member
designated by the Chair subsequently approve the
revised research protocol on behalf of the IRB.
 Deferral - substantive clarifications or modifications
required that are directly relevant to the criteria for
approval.
 Disapproval – major ethical or scientific issues – PI can
respond to the IRB or start over.
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Informed Consent
Beyond the
Consent Form
The Consent Process
Informed consent is not a single event or just a
form to be signed -- rather, it is an educational
process that takes place between the
investigator and the prospective subject.
The basic elements of the consent process include:
 full disclosure of the nature of the research and the
subject's participation,
 adequate comprehension on the part of the potential
subjects, and
 the subject's voluntary choice to participate.
Informed Consent
• Information – includes research
procedure, purpose, risks, benefits,
alternatives, etc.
• Comprehension – function of intelligence,
rationality, maturity and language,
presentation of information must be
adapted to the subject’s capacity
• Voluntariness –requires conditions free of
coercion and undue influence
Consent Form Required
Elements
Statement that the study involves research
 Research is described
 Description of Risks
 Description of Benefits
 Disclosure of Alternatives
 Confidentiality
 If more than minimal risk, compensation and/or medical
treatment
 Participation is voluntary
 Whom to Contact
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Additional Elements of
Informed Consent
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Unforeseeable risks
Early termination
Additional costs to subjects
Consequences of a subject's decision to withdraw
from study participation
Disclosing new findings which may impact a subject's
willingness to continue participation
Number of subjects involved
Informed Consent Process
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Informed Consent is
more than just the IRBapproved document
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Initial
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Ongoing
Initial Informed Consent
Take the time at the initial discussion with subjects so that they
have a thorough understanding of what they are making a
commitment towards
 Test subject comprehension
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Research versus standard of care procedures
Time commitment
Randomization
Alternatives
Potential costs
Risks and Benefits
Taking time upfront with potential subjects most likely will
improve subject understanding and improve retention
Ongoing Consent
Every time you have an encounter with a subject
gives researchers an opportunity to continue the
informed consent process
 Discuss new information that may impact a subject’s
willingness to continue study participation (i.e., new
known risks, benefits, alternatives, changes in study
design, etc.)
 Remind subject of study goals and objectives this will
improve subject compliance with the protocol and
improve retention of subjects
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Documentation of Consent
Articles in most popular magazines are at the 8th grade
level. Factors that improve readability include the
following:
 Technical terms should be replaced with ordinary
language;
 Use active tense rather than passive tense verbs ("We
did" rather than "It was done");
 Write shorter sentences in general; and
 Make clear the links of logical sequences and of
cause-and-effect, even if doing so makes the sentence
much longer. ("We will do this, because that
happened".)
Research
Approved
Most faculty regarded the new streamlined
IRB Process as an improvement
Summary…Take home message
The IRB is a key element in the conduct of
human participant research at the University.
 But, it is the primary responsibility of the IRB
to safeguard the rights and safety of human
participants. It is not necessarily the role of
the IRB to expedite research at the University
at the expense of safety and human rights.
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OHRP Electronic Access
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E-mail: [email protected]
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Web Site: http://ohrp.osophs.dhhs.gov
Last Words
Welcome and thank you.
 Please don’t be afraid to communicate
with our office.
 Please don’t be afraid to ask for advice at
the meetings.
 Please don’t be afraid to contact Senior
Administrators and the IRB Chair for
assistance.
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