Transcript Presentation Goals

Human Subjects
Research 101
Revised January 2008
Presentation Goals

Discuss Human Subjects Research
– Definitions

Historical Background

Identify Ethical and Legal Requirements
– Belmont Report
– 45 CFR 46 – “The Common Rule”

Describe Institutional Review Board
– Structure & Policies

Implications For Student Research
Why Discuss
Human Subjects Research?

Federal guidelines

Messiah College policy regarding all
research involving human subjects

Preparation for graduate studies
What Is Human Subjects
Research? – Part I
Federal definition of research
A systematic investigation, including
research development, testing, and
evaluation designed to develop or
contribute to generalizable knowledge.
What Is Human Subjects
Research? – Part II
Federal definition of human subject
A living individual about whom an
investigator (professional or student)
conducting research obtains


Data through intervention or
interaction with the individual, or
Identifiable private information.
Definitions Continued

Intervention includes both physical
procedures by which data are gathered
and manipulations of subject or
subject’s environment that are
performed for research purposes.

Interaction includes communication or
interpersonal contact between
investigator and subject.
Definitions Continued

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.
Historical
Background
The Nuremberg Trial

Trial of Nazi doctors who experimented
on 300 Dachau concentration camp
prisoner-subjects, of whom 30% died.

Held from December 9, 1946 to August
20, 1947.

23 defendants charged with murder,
torture, and other atrocities committed
in the name of medical science. 15
found guilty.
Nuremberg Code - 1947

Written as part of the judgment of the
Nazi trials.

Became the “ethical yardstick” by which
the defendants had been measured and
guilt determined.

Essential reading for everybody
involved in human subject research.
Principles of Nuremberg Code

Voluntary informed consent is essential

Research should yield useful results

Risk must be outweighed by importance
of research

Base research on prior animal
experiments

Avoid physical and mental suffering
Principles of Nuremberg Code
(continued)

Only qualified scientists may conduct
research

Subjects may withdraw from study

Investigators must be willing to withdraw
subjects

No expectation of death or disabling
injury
Effect of Nuremberg Code

Code largely ignored until 1964
because researchers did not see the
relevancy to their own work
– Hippocratic oath

Missed a lot of important aspects of
research
– Children and informed consent
– People with diminished mental capacity and
informed consent
Declaration of Helsinki - 1964

Rules developed by researchers and
physicians

Reinterpretation of Nuremberg

Became required for publication in
scientific journals to state that the
research abided by the Declaration of
Helsinki
Public Health Service Policy

1966: All PHS supported research must
undergo prior review to:
– Protect the rights and welfare of subjects
– Assure appropriate informed consent
– Determine acceptable risk/benefit balance
Beginnings of the IRB
(Institutional Review Board)
Era of Standards
 Standards
accepted by researchers
 Standards accepted by the media
 Standards became the accepted
principles for judgment of research
– Thalidomide Trial
– Jewish Chronic Disease Study
– Willowbrook Hepatitis Study
– Hidden Recorder Studies
– Milgram Study
– Tuskegee Study
The Tuskegee Study
Purpose: identify the natural history of
untreated syphilis
 Began in 1932
 Involved 300 black males with syphilis
 1933 – added 300 controls
 Was initially supposed to last 1 year
 Study stopped in March of 1973 after
government investigations and public
pressure

Syphilis Study Problems

Lack of respect for persons
– No informed consent
– Deception
– Coercion

Lack of good will to subjects
– Withholding effective treatment (penicillin)
– No continuing review of the research

Unjust
– Used an extremely vulnerable population: illiterate,
poor farmers in rural Alabama
Response to Research Abuses

1974 – Congress passes the National
Research Act
– Requirements for informed consent
– Necessary review of research by IRB
May 1974 – First version of 45 CFR 46
 April 1979 – The Belmont Report
 1981 – Revision of 45 CFR 46
 1991 – Common Rule: 56 FR 28003
 2001 – Latest revision of 45 CFR 46
incorporates Common Rule

The Belmont Principles:
How They Came About
1974 – establishment of the National
Commission by the federal government
 Task

– “Identify basic ethical principles that underlie the
conduct of human research.”
– Develop guidelines to ensure that human research
follows these principles

1979 – The Belmont Report: current set
of federal regulations
The Belmont Principles
 Respect
for persons
 Beneficence
 Justice
Respect for Persons

Treat individual as autonomous agents

Do not use people as a means to an
end

Allow people to choose for themselves

Give extra protection to those with
limited autonomy and have an inability
to choose for themselves
Beneficence

Do no harm

Prevent harm

Prevent evil

Promote good

Maximize possible benefits and
minimize risk
– Benefits to individual and/or to society
– Risk: consider physical, social, legal, economic,
psychological
Justice

Fair sharing of burdens and benefits of
research
– Selection of subjects should not systematically
draw from certain classes simply because of their
easy availability
– Inclusion of diverse populations/groups
– Subjects should have a future chance of benefiting
personally from the subsequent applications of
research findings
Rules Derived From Principles

Respect for persons
– Informed Consent
– Respect for privacy
• Confidentiality
• Anonymity

Beneficence
– Good research design
– Competent investigators
– Favorable risk/benefit analysis

Justice
– Equitable selection of research subjects
Conflict in Belmont Principles

Conflict is expected
– Sometimes decisions that are made utilizing the
principles may yield different outcomes,
depending on which principle is being considered:
one decision is to approve the research, one to
limit the research, one to deny the research

Remember: all 3 principles are on
equal footing with equal moral force.
– Consider each situation individually
– Carefully review the principles
– Avoid the tendency to always put one principle
above another
Code of Federal
Regulations
45 CFR 46
Title 45 of CFR Part 46

Codified by the government in 1991
– Based on Belmont Principles, 56 FR 28003
– Title 45: Public Welfare and Human Services
– Part 46: Protection of Human Subjects

Last revised in November 2001

Supporting agencies
– Department of Health & Human Services
– National Institutes of Health
– Office for Human Research Protections
Title 45 of CFR Part 46

Subpart A – Basic DHHS Policy for the
Protection of Human Research Subjects

Subpart B – Pregnant Women, Human
Fetuses and Neonates Involved in
Research

Subpart C – Prisoners

Subpart D - Children
Institutional Review
Board
(IRB)
Institutional Review Board

DHHS requirement for all human
subjects research sponsored by federal
agencies

Regulations for IRB found in 45 CFR
46.107-123
IRB Structure

Minimum of 5 members with varying
academic backgrounds

Every nondiscriminatory effort will be
made to ensure diversity (e.g., race,
gender, cultural)

One member who primary training is in
nonscientific areas

One member whose primary training is in
scientific areas

One member from the community
Primary Duties of IRB

Protect human subjects from undue risk &
deprivation of human rights and dignity

Ensure confidentiality and voluntary
participation of subjects

Balance potential benefits with risks

Determine appropriateness of research
design & study methods

Assist researcher through peer review and
institutional approval

Ensure research compliance with DHHS
regulations & other funding agencies
Is Any Research Exempt From
Review?
Yes, if the research involves no more
than minimal risk to subjects, no ethical
concerns, does not involve vulnerable
subjects, and meets at least one of the
exempt research categories established
by the government regulations. IRB
chair can make this determination.
Expedited Review

Nine governmentally designated
research categories that allow for
expedited review

Proposal distributed to all IRB members
and all must agree on expedited review

Approval by one designated reviewer
– Reviewer cannot disapprove research. Must go to
full IRB for rejection.

Decision reported to IRB at next
meeting
Informed Consent
Informed Consent

“Informed consent is a process of
information exchange that takes place
between the prospective subject and
the investigator, before, during, and
sometimes after the study.”
Dunn & Chadwick (1999), Protecting Study Volunteers in Research
Information
 Comprehension
 Voluntariness

Essential Basic Elements

Research
– Purpose/Duration
– Procedures
– Experimental

Compensation for
injury

Whom to contact
re:
Risks

Benefits

Alternatives


Confidentiality
– Study, subject’s
rights, event of
injury

Right to refuse or
withdrawn
Additional Elements

Currently unforeseeable risks

Termination of participation

Additional costs to subjects

Consequence of withdrawal

Informing of new findings

Number of subjects
Other Considerations

There are situations where DHHS
regulations allow for waiver of informed
consent.

There are also situations where DHHS
regulations allow for exception to
providing written documentation of
informed consent.
Informed Consent Process

Sufficient time to make decision

Sufficient opportunity to ask questions

Strategies to minimize coercion

Avoid overstating benefits

Ensure an understanding of
risks/benefits

Be sensitive to subject’s needs
Informed Consent Process

Train individuals obtaining consent

Fully explain use of technology or
innovative approaches

Make adjustments in process, as
necessary

Obtain IRB approval for changes
Implications For
Faculty and Student
Research
What Does This Mean For Me?

MC policy applies only to research in certain cases;
determination can be made by IRB in consultation
with IRB chair.
 Approval must be obtained from the IRB prior to
beginning research, including any research that will
be disseminated beyond the classroom, including
public presentations and publications.
 Student projects that will not be disseminated beyond
the classroom are considered course assignments
and not subject to regulations.
 However, all research must be done with due
consideration of Messiah’s ethical and legal
responsibility to protect subjects.
Research Likely Exempt From
Review - #1
Educational tests (cognitive, diagnostic,
aptitude, achievement), survey
procedures, interview procedures, or
observation of public behavior, if
minimal risk, no correlation between
subjects/responses, and no vulnerable
population included. (Category #2)
Anonymous Versus
Confidential


Anonymous: No way to trace
responses to an individual person. Will
not use any coding system or be able
to trace responses to a person (e.g.,
ethnicity, gender, etc.)
Confidential: Can trace responses to
an individual, even though this may not
be revealed beyond the investigative
team.
Research Likely Exempt From
Review - #2
Research involving the collection or
study of existing data, documents,
records, or specimens if these sources
are publicly available or the information is
recorded in such a way that subjects
cannot be identified, indirectly or through
identifiers linked to the subjects.
(Category #4)
Research Likely Exempt From
Review - #3
Taste and food quality evaluation and
consumer acceptance studies if
wholesome foods without additives are
consumed or food contains ingredients
approved by FDA, EPA, or USDA.
(Category #6)
If You Plan on Conducting a
Research Study

Complete Form 100 – Request for
Review of Faculty Project

If a student: Work with course
professor to complete Form 050 –
Request for Review of Student Project

Submit application and proposal to
Provost’s Office, Box 3016.

If you have questions, contact Jenny
Dose, IRB Chair (ext. 2320).