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Human Subjects Research
Mariam Davtyan, MPHUC Irvine
Department of Population Health & Disease PreventionProgram in Public Health
PhD Candidate/IRB Member & Ambassador04.29.2015
What is Research?• A systematic investigation,
including research development,
testing and evaluation, designed
to develop or contribute to
generalizable knowledge
• Definition applies to quantitative
research studies
• May need to be enhanced for
qualitative research protocols
Source: US Department of Health & Human Services, Code of Federal Regulations (45CFR 46.102)
Definition of Human Subject
• A living individual about whom an
investigator (whether professional or
student) conducting research obtains:
• Data through intervention or interaction
with the individual, or
• Identifiable private information
Source: US Department of Health & Human Services, Code of Federal Regulations (45CFR 46.102)
Unethical Human Experimentation
• Nazi medical experiments (1939-
1945)
• Tuskegee Syphilis Study (1932-1972)
• Willowbrook Study (1963-1966)
• Milgram “electric shock” experiments
(1961)
• Stanford Prison Experiment (1971)
• U. Penn gene therapy study (1999)
Source: http://www.niehs.nih.gov/research/resources/bioethics/timeline/
• National Research Act (1974)
• Development of guidelines for human subjects research
• Regulation of human experimentation in medicine
• Title 45 Code of Federal Regulations Part 46
• Research conducted, supported, or otherwise subject to regulation by any
federal department or agency
• Policies pertaining to human subjects research for investigators and IRBs
• Declaration of Helsinki (1964)
• Medical research involving human subjects
• Protect health/welfare, sound design, respect, appropriate qualifications,
expectation of some benefit
• Nuremberg Code (1948)
"The voluntary consent of the human participant is absolutely essential"
Pertinent Laws & Regulations
Source: http://history.nih.gov/about/timelines_laws_human.html
Ethical Principles in Human Research
• Belmont Report (1979):
– Respect
• Understanding the study
• Making an autonomous decision to participate or not
• Those with diminished autonomy require special
protection
– Beneficence
• Expectation of benefit in research
• Minimizing risk
• Sound experimental design and rigorous review by IRBs
– Justice
• Equitable selection of participants
• Protecting vulnerable groups (ex. prisoners, children,
mentally ill) from coercion Source: http://videocast.nih.gov/pdf/ohrp_appendix_belmont_report_vol_2.pdf
Case #1
• An instructor wants to have
all students in a class
interview each other to
practice interviewing skills.
The results will not be written
up or distributed outside the
classroom in any way.
– Is this research?
• You will be analyzing data
from an existing dataset on
the dietary habits of elderly
individuals living in the
Southern US. The dataset
does not contain any personal
identifiers?
• Human subjects research?
• IRB approval ?
Case #2
Defining Risk & Benefit
• Risk: the probability and magnitude of harm or
discomfort anticipated in the research are not
greater in and of themselves than those ordinarily
encountered in daily life or during the performance
of routine physical or psychological examinations or
tests
• Benefit: A valued or desired outcome; an advantage
Sources: US Department of Health & Human Services, Code of Federal Regulations (45CFR 46.102(i)http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html#assessment
Risk/Benefit Assessment
• Identify risks associated with research
• Assure that the risks will be minimized to
the extent possible
• Identify benefits to be derived from the
research
• Assure that the risks are reasonable in
relation to benefits to subjects
• Make certain that prospective subjects
will be provided with an accurate
description of study risks and benefits
during consent processSources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html
Types of Risks & Benefits
Benefits:
• Personal
• Societal
Risks:
• Physical
• Psychological
• Invasion of Privacy
• Social & Economic
• Community
Sources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html
Minimizing Risks
• Provide information on experimental design and the
scientific rationale
• Assemble a research team expertise and experience
• Determine if sample size is sufficient to yield useful results
• Collect data from standard-of-care procedures to avoid
unnecessary risk
• Appropriate data safety monitoring plan, trained
personnel, and procedures to protect the confidentiality
of the data (e.g. encryption, codes, and passwords).
Sources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html
• Stigma is a significant stressor for
people living with HIV and often leads to
poor health outcomes. In your study,
you will be interviewing people living
with HIV and asking them to share their
experiences with Stigma. You will also
look at their medical charts and abstract
information about drug use and mental
health pathologies.”– Potential Risks? Benefits?
– Strategies for minimizing risks?
Case #3
• Based on concepts of Autonomy,
Beneficence, Justice
• More than a signature
• Process by which researchers inform
potential participants about all aspects of
research
• Prospective participants not subjected to
undue influence, fraud, duress, and
coercion
• Prospective participants agree to
participate voluntarily and with informed
choice
• Your duty as researchers to protect and
inform
Informed Consent
• Full Disclosure
– Inform about all study constructs
– Risks/Benefits
– Alternatives to participation
• Understanding
– Must understand what is being explained
– Lay Language
– Translated to other languages
• Voluntariness
– Voluntary
– Withdrawal at any point
• Competence: prospective participant must be competent to provide consent
• Consent: signature or verbal understanding
• Exculpatory Language:
– Consent must be free of language by which participant waives legal rights or releases
investigator from liability for negligence
Components of Appropriate Informed Consent
Case #4
• After having completed a study that
involved the collection of tissue from
the subjects, an investigator wishes
to perform additional analysis of the
archived tissue samples. This nature
of this analysis was not explicitly
stated in the original consent form.
• Should the investigator be required to
obtain explicit consent for the new
research?
Source: https://depts.washington.edu/bioethx/topics/resrchc3.html
• Privacy:
– About people
– A sense of being in control of access that others
have to ourselves
– A right to be protected
– Is in the eye of the participant, not the researcher
or the IRB
• Confidentiality:
– Is about identifiable data
– Is an extension of privacy
– Is an agreement about maintenance and who has
access to identifiable data
– In regards to HIPAA, protects patients from
inappropriate disclosures of "Protected Health
Information" (PHI)
Privacy & Confidentiality
Source: http://www.research.uci.edu/compliance/human-research-protections/researchers/privacy-and-confidentiality.html
Ethics Committees & IRBs
• Appropriately constituted group designated to review
and monitor research involving human subjects
• IRB has the authority to:
– approve
– require modifications in (to secure approval)
– disapprove research.
• Group review serves an important role in the protection
of the rights and welfare of human research subjects
• Assure (in advance and periodically) that appropriate
steps are taken to protect human subjects
• Group process to review research protocols and
materials to ensure protection of human subjects
Source: http://www.fda.gov/RegulatoryInformation/Guidances/ucm126420.htm
Levels of Review
• Exempt:
– Anonymous surveys or interviews
– Passive observation of public behavior without collection of identifiers
– Analyses of discarded pathological specimens without patient identifiers
• Expedited:
– Studies involving collection of hair, saliva or dental plaque samples
– Studies of blood samples from healthy volunteers
– Analyses of voice recordings
– Studies of existing pathological specimens with patient identifiers
• Full Committee:
– Proposed human subject research which does not fall into either the
exempt or expedited review categories must be submitted for full
committee review
Level of Risk Generally Determines Level of Review
ExemptChair or Administrator
ExpeditedSubcommittee
Convened IRB MeetingFull Committee
Minimal Risk
RISK
Virtually No Risk
> Minimal Risk
Source: Valerie Sanchez & Beverley Williams, UCI Office of Research
Case #5
A patient with a rare form of
incurable cancer is offered a clinical
trial opportunity at the
Comprehensive Cancer Center by
his treating physician. The clinical
trial is testing whether two
medications that are FDA-approved
for other forms of cancer, are
effective in this rare form of cancer.
– Level of review? (e.g. exempt,
expedited, full committee)
Designing Ethical Research Studies
• Participant Protection
• Rights & Interests
• Health & Welfare
• Risks & Benefits
• Participants & Society
• Maximizing benefits
• Non-maleficence
• Informed Consent
• Written
• Verbal
• Protection of Privacy & Confidentiality
• Privacy involves individual
• Confidentiality involves data
Research Misconduct
• Fabrication, falsification, plagiarism in
proposing, performing, reviewing research, or
reporting research results
• Pressure to “publish or perish”, the desire to
“get ahead”, personal issues or character
issues, and other reason
• Impact:
– Retraction of published work
– Restitution of funds to the granting agency
– Ineligibility to apply for federal grants/contracts
– Tarnished science
– Ruined ReputationSource: http://www.research.vt.edu/research-integrity-office/brochure/misconduct-brochure.pdf
UCI IRB Application: Protocol Narrative
• Applications & Forms
• Human Research
Protections
• Click on “Other Forms”
http://www.research.uci.edu/
Protocol Narrative
•Purpose & Background
•Role & Expertise of Study Team
•Study Methods & Procedures
•Description of Participants
•Recruitment Methods & Process
•Informed Consent Process
•Risks & Benefits
•Reporting Adverse Events
•Compensation & Reimbursement
•Confidentiality of Data
•Etc. etc. etc.
Complete Protocol Narrative First !!!!!
Informed Consent Forms
Complete Informed Consent Documents 2nd !
• Applications & Forms
• Human Research
Protections
• Click on “Consent
Forms”
Tips for IRB Approval
• Research staff CITI Training & Certification
• Navigate the UCI Office of Research website
• Use brief and concise language in narratives and consent forms
• Address risks & benefits adequately
• Address privacy & confidentiality adequately
• Don’t forget to submit supplemental documents
• Recruitment Materials (ex. fliers, scripts)
• Instruments
– Surveys
– Interview questions
• My office hours (Mondays, 12:30-1:30, AIRB 2020B)
• When in doubt ask the IRB!
References1. Cassell, E. J. (2000). The principles of the Belmont report revisited: How have respect for persons, beneficence, and justice been applied to clinical medicine?. Hastings Center Report, 30(4), 12-21.2. World Medical Association. (2001). World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bulletin of the World Health Organization, 79(4), 373.3. Shuster, E. (1997). Fifty years later: the significance of the Nuremberg Code. New England Journal of Medicine, 337(20), 1436-1440.4. US Department of Health and Human Services. (2009). Code of federal regulations: title 45 public welfare; Department of Health and Human Services: part 46 protection of human subjects.5. Sieber, J. E. (2007). Privacy and Confidentiality: As Related to Human Research in Social and Behavioral Science (Research Involving Human Participants V2). Online Ethics Center for Engineering, 5(25), 2007.6. Adams,R. (2013). Research Ethics. Retrieved on January 25, 2015 from: https://depts.washington.edu/bioethx/topics/resrch.html