Ethical Issues for Human Subjects Research
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Transcript Ethical Issues for Human Subjects Research
Ethical Issues for Human
Subjects Research
Role of IRBs
I. Purpose of Human Subjects
Research
Understand Disease
Validate New Therapies
Understand Physiological Processes
Study Human Behavior
Evaluate Curricular Changes
Evaluate New Teaching Methods
Ethical Issues in Research
When using humans or animals for
research, important ethical issues must be
addressed
Historically,
these issues were addressed by the
professional code of ethics
Codes of conduct have evolved and now have
been codified into law.
Ethical Issues in Research
World War II—The Nuremburg Trial
Joseph
Mengele and unethical experiments
performed by Nazi doctors
Ethical Issues in Research
World War II-The Nuremburg Trial
20
doctors were charged with War Crimes and
Crimes against humanity
Joseph Mengele fled and was not tried
Lead to Nuremburg Code of 10 Principles
Nuremburg Code
Requires voluntary consent
Experiments must be rational
Experiments must be based on animal studies and
knowledge of the disease
Experiments should avoid suffering
No experiment should involve excessive risks,
except in those studies where physical
experimental physicians also serve as subjects
Nuremburg Code
Degree of risks should be determined by importance of the
problem
Precautions should be taken to avoid against even remote
possibilities of injury, disability, or death
Experiment should be conducted only by scientifically
qualified persons
Subjects should be able to end experiment at any time
The scientist in charge must be prepared to terminate the
experiment at any stage, if they believe the experiment is
likely to result in injury, disability, or death to the subject
Ethical Issues in Research
Unfortunately, codes were not always
followed:
Tuskegee
Not treated even after penicillin discovered
Jewish
Syphilis Study-USPHS-1930’s
Chronic Disease Hospital
Patients injected with cancer cells
Midgeville State
Hospital
Investigational drugs used without consent
Ethical Issues in Research
Willowbrook State Hospital-1970
Retarded injected with viral hepatitis
US Department of Energy-1950s-60s
Studies on radioactive fallout
University of Iowa-1940s
Research on stuttering in orphans home
Johns Hopkins-2001
Asthma study with hexamethonium
National Research Act
Increased Public concern led to congressional action and
National Research Act of 1974
President Nixon then established National Commission for the
Protection of Human Subjects of Biomedical and Behavioral
research
Commission charged to consider:
Boundaries between practice and research
Assessment of role of risk vs. benefit in research
Guidelines for selection of subjects
Informed Consent
Belmont Report
National Commission submitted the Belmont
Report to President in 1979
Led to 1981 revision of 1974 guidance (45 CFR 46) for
human research committees
45 CFR 46-has become the bible for reviewing research
funded by DHHS
Required appointment of Institutional Review Boards or IRB’s
to review human subject studies
Provided standards for appointment of IRBs, record-keeping
and oversight in research
45 CFR 46
Revised in 1983 and 1991
In
1991 revisions referred to as Common Rule
Adopted by 15 federal agencies, not just DHHS
Institutions with
NIH funding must submit
assurance of compliance to OHRP, DHHS
After February 28, 2001-assurances must cover all
research at institution, not just NIH
II. Institutional Review Boards
Makeup of IRB
At
least 5 members
Male/Female
Professionals/laypersons
External “non-affiliated” member
Must represent community
Lay person must be at meeting for reviews
II. Institutional Review Boards
IRB’S must be guided by principles
outlined in Belmont Report:
Respect
for persons: respect for patient
autonomy
Beneficence: maximize benefits and minimize
harm
Justice: Equitable distribution of research
burdens and benefits
III. IRB Review of Research
Three categories of Review:
Exempt
Expedited
Full
Review
IRB Review of Research
Exempt-by Chair or Administrator
Research
in educational settings involving
normal educational practices
Instructional strategies
Effectiveness of instructional techniques
Comparison of techniques or curricula, etc.
IRB Review of Research
Exempt-by Chair or Administrator
Research
involving educational tests (cognitive,
diagnostic, aptitude)
Unless
– Names or identifiers are recorded and
– Disclosure could put subject at risk of criminal liability or
affect employability
IRB Review of Research
Exempt-by Chair or Administrator
Survey
research without identifiers; interviews,
observation of public behavior
Unless
– Names or identifiers are recorded and
– Disclosure could put subject at risk of criminal liability or
affect employability
IRB Review of Research
Exempt-by Chair or Administrator
Collection
or study of existing data, documents,
records, pathological or diagnostic specimens
If the sources are publicly available, or
If information is recorded so that the subject cannot
be identified, directly or indirectly
IRB Review of Research
Exempt-by Chair or Administrator
Research and demonstration projects conducted
by or subject to approval by DHHS to study,
evaluate or examine:
Public benefit or service programs
Procedures for obtaining benefits or services from
these programs
Other changes in these programs
– Taste and food quality evaluation and consumer
acceptance studies
IRB Review of Research
Expedited Review
Research activities reviewed by Chair or designee
Two cautions however:
Only for activities involving minimal risk-i.e., no more risks
than those in everyday life
Cannot be used if subject responses might pose civil or
criminal risk to subject, unless
– Reasonable protections can be implemented so that risks related
to invasion of privacy and breach of confidentiality are minimal
IRB Review of Research
Expedited Review-Categories eligible
Some
studies of approved drugs or devices
Collection of blood from adults
Not to exceed 550mL in 8 weeks
Not more often than 2 times per week
Collection
of specimens by non-invasive
means: sweat, excreta, amniotic fluid, hair,
teeth, plaque
IRB Review of Research
Expedited Review-Categories eligible
Collection of data through non-invasive means,
excluding X-ray and microwave
EKG, ECG, MRI, weighing, thermography, ultrasound,
doppler blood flow, exercise, flexibility testing, etc.
Research involving data, records, specimens collected,
or that will be collected solely for non-research
purposes
Collection of voice, video, digital, or images made for
research purposes
IRB Review of Research
Expedited Review-Categories eligible
Research on individual or group characteristics or behavior
including:
Perception, cognition, motivation, identity, language,
communication, beliefs or practices, etc.
Research involving surveys, interview focus groups,
program evaluations, or quality assurance methods
Continuing reviews for previously approved projects
Minor changes in previously approved research
IRB Review of Research
Full Review-Full Committee
Investigational
drugs, devices, invasive
techniques (PET scan), implants, etc.
Higher risk research
NOTE-research not approved by IRB cannot be
approved by higher authorities, however
approved research may be disapproved by
higher authorities
IV. IRB Approval
To be approved:
Risks
must be minimized by sound research
design
Risks must be reasonable in relation to benefits
Selection of subjects must be equitable
Informed consent will be sought from each
subject
IRB Approval
To be approved-continued:
Informed consent will be appropriately
documented
When appropriate, research plan must ensure
continued safety of subjects
Where appropriate, provisions made to protect
privacy of subjects and data
When working with subjects vulnerable to
coercion, must consider added safeguards
Continuing Review
For research continuing more than one year,
an annual review is required
New standards under review:
Will
probably require IRB monitoring of some
clinical trials
Constant assessment of conflict of interest of
the investigators
Informed Consent
Not needed for exempt studies
Required for Expedited Review-but may be
simplified for low risk studies
Rigorous consent for Full Review projects
May be waived by IRB for emergency
Medicine research-controversial issue
Informed Consent
Consent must address critical elements or
points outlined by Federal Law
Consent signed by subject or legal
representative and investigator
Subject must be given copy of consent
No exculpatory language may be used in the
written consent
Basic Elements of Consent
Explanation of purpose and duration
Description of risks
Description of benefits
Disclosure of alternatives to participation
Basic Elements of Consent
Explanation of Confidentiality of Records
Who to contact regarding patient rights
For
research with more than minimal risks,
comment on compensation and care for injury
Right to withdraw without prejudice
Statement regarding unforeseen risks,
especially to unborn child
Additional Elements for Consent
Statement that investigator may terminate
patient participation
Information regarding any costs
Statement regarding consequences of
withdrawing-especially for drug studies
Number of subjects in study
Special Populations-Children
Special Considerations
Children
are persons who have not attained the
legal age for consent to treatments or
procedures involved in research
Research not involving greater than
minimal risk may be approved:
With
assent of the child and permission of
parents
Special Populations-Children
Special Considerations
Research
involving greater than minimal risk
and the prospect of direct benefit to the child
may be approved:
If the risk is justified by the anticipated benefit
The relation of the benefit to risk is at least as
favorable to subjects as the alternative approaches
With assent of the child and permission of parents
Special Populations-Children
Special Considerations
Research involving greater than minimal risk and no
prospect of direct benefit to the child may be approved:
If the risk represents a minor risk over minimal risk
If the intervention presents experiences that are reasonably
similar to those in actual medical, dental, social, psychological,
or educational situations
If the intervention is likely to yield generalizeable knowledge
about the disorder or condition
With assent of the child and permission of parents
Special Populations-Children
Special Considerations
Assent of the child
Usually
verbal-confirmed by parents
“Assent” cam usually be provided by children
over six years of age-but varies based on
maturity and psychological state
Failure to object should not, absent affirmative
agreement, be construed as assent
Special Populations-Prisoners
Special Considerations
IRB membership
Majority
of members must have no association
with the prison
Must include a prisoner, or prisoner
representative with experience to serve in this
capacity
Special Populations-Prisoners
Special Considerations
The
research may be approved if:
The advantages of participation are not “enticing” or
prohibit good judgment
Risks are similar to those for non-prisoner research
Consent is understandable to prison population
Decision to participate will not affect parole
Special Populations-Prisoners
Special Considerations
Permitted
Research:
Study of causes, effects, or processes involving
incarceration
Study of prisons as institutional structures or of
prisoners as incarcerated persons
Study of conditions affecting prisoners as a class
– Vaccine trials for diseases prevalent in prisons
– Study of social behavior of prison population
VI. Federal Oversight
FDA spot checks IRBs to monitor
compliance with drug and device studies
Recent problems at Rush, Duke, UIC, U of
Colorado, U of Oklahoma, and Hopkins
have prompted calls for greater scrutiny of
IRBs
VI. Federal Oversight
New 2000/2001 DHHS guidelines require:
Training
of investigators and “key” personnel
in human research protection
Certification by investigators that they have
received training (NIH offers on web)
Certification that investigator has no conflict of
interest
Monitoring of clinical trials by IRB
VI. Federal Oversight
Education on “Responsible Conduct of
Research”
Nine
Areas:
Data acquisition, management, sharing, ownership
Mentor, trainee practices and responsibilities
Publication practices and responsible ownership
Peer review
VI. Federal Oversight
Education on “Responsible Conduct of
Research”
Nine
Areas:
Collaborative science
Human subjects
Research involving animals
Research misconduct
Conflict of interest and commitment
VII. New HIPAA regulations
Health Insurance Portability and
Accountability Act of 1996
Privacy
Rules effective April 14th, 2001
Health insurers must safeguard personal health
information
May not disclose to employers for employmentrelated decisions
However, information can be used for research
approved by a properly convened IRB
– http://www.hipadvisory.com/regs/finaladvisory/gresearch.htm
HIPAA allows research with
conditions
If material has been or can be de-identified,
no conflict with HIPAA regulations
Appropriate
if records custodian uses data
Often not practical to disclose since records
custodian may simply state this is too difficult
HIPAA allows research with
conditions
To use or disclose data without patient
authorization:
Discloser (records custodian) must document that
waiver (of consent) has been obtained from an IRB
or
Researcher must represent in writing or orally, that
disclosure is preparatory to research, and no records
will be removed
or
Researcher must represent in writing or orally that the
disclosure is for research on decedents
Document of death may be required by disclosure
Laboratory Research Animals
Laboratory Research Animals
All NIH funded research with animals
requires IACUC approval
IACUC
or Institutional Animal Care and Use
Committee must meet NIH standards
Scientist
Non-scientist
Non-affiliated member
Veterinarian
Laboratory Research Animals
Functions of the IACUC
Review animal care and use program every six months
Inspect facilities for housing animals every six months
Prepare reports o reviews for Institutional Official
Review concerns involving animals at institution
Make recommendations regarding program to Official
Laboratory Research Animals
Functions of the IACUC
Review,
approve, require modifications in
applications for animal use
Review, approve, require modifications of
proposed changes in approved animal projects
Suspend activities not adhering to approved
uses
Laboratory Research Animals
To approve animal use:
Procedures
must avoid pain or discomfort and
have sound research design
Procedures involving minor discomfort or pain
must include sedation, analgesia, or anesthesia
Animals that would experience chronic pain
must be euthanized at the end of the procedure
Laboratory Research Animals
To approve animal use:
Living conditions must be appropriate for species
Medical care must be available from veterinarian
Personnel conducting procedures must be qualified
Methods of euthanasia must abide by AVMA rules
Studies approved by IACUC may be disapproved by
Institutional offices, however, unapproved studies may
not be approved by higher officials
Laboratory Research Animals
USDA and NIH have oversight
NIH
does not have inspection arm
USDA makes periodic, unannounced visits to
assess compliance for “covered” species
Case Number 1
Social scientist
Observing 1st
grade play activities
What level of review?
Exempt
Expedited
Full Review
Case Number 2
Psychologist
Interviewing 1st
Benign questions: no names or identifiers
What
level of review
Exempt
Expedited
Full Review
graders
Case Number 3
Behavioral Scientist
Interviewing 3rd
Questions regarding sexual behavior, parental
handling of bad behavior, etc.
What
level of review?
Exempt
Expedited
Full Review
graders
Nuremburg Code
The voluntary consent of the human subject is absolutely essential
The experiment should be such as to yield fruitful results for the
good of society, unprocurable by other methods or means of study,
and not random and unnecessary in nature.
The experiment should be so designed and based on the results of
animal experimentation and a knowledge of the natural history of
the disease or other problem under study, that the anticipated results
will justify the performance of the experiment.
The experiment should be so conducted as to avoid all unnecessary
physical and mental suffering and injury.
Nuremburg Code
No experiment should be conducted, where there is an a priori
reason to believe that death or disabling injury will occur; except,
perhaps, in those experiments where the experimental physicians
also serve as subjects.
The degree of risk to be taken should never exceed that determined
by the humanitarian importance of the problem to be solved by the
experiment.
Proper preparations should be made and adequate facilities provided
to protect the experimental subject against even remote possibilities
of injury, disability, or death.
Nuremburg Code
The experiment should be conducted only by scientifically qualified
persons. The highest degree of skill and care should be required through all
stages of the experiment of those who conduct or engage in the experiment.
During the course of the experiment, the human subject should be at liberty
to bring the experiment to an end, if he has reached the physical or mental
state, where continuation of the experiment seemed to him to be impossible.
During the course of the experiment, the scientist in charge must be
prepared to terminate the experiment at any stage, if he has probable cause
to believe, in the exercise of the good faith, superior skill and careful
judgment required of him, that a continuation of the experiment is likely to
result in injury, disability, or death to the experimental subject.