Transcript Protocol Submissions to UCI IRB

Human Subjects Research
Mariam Davtyan, MPH
UC Irvine
Department of Population Health & Disease Prevention
Program in Public Health
PhD Candidate/IRB Member & Ambassador
04.29.2015
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/
Pertinent Laws & Regulations
• 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"
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?
Case #2
• 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 ?
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 process
Sources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html
Types of Risks & Benefits
Risks:
• Physical
• Psychological
• Invasion of Privacy
• Social & Economic
• Community
Benefits:
• Personal
• Societal
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
Case #3
• 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?
Informed Consent
•
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
Components of Appropriate 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
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 & Confidentiality
•
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)
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
> Minimal Risk
Convened IRB Meeting
Full Committee
Expedited
Minimal Risk
Subcommittee
Exempt
Virtually No Risk
Chair or Administrator
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 Reputation
Source: http://www.research.vt.edu/research-integrity-office/brochure/misconduct-brochure.pdf
Hints & Suggestions
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
• Applications & Forms
• Human Research
Protections
• Click on “Consent
Forms”
Complete Informed Consent Documents 2nd !
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!
Source: http://www.xkcd.com/1390/
Thank you!
Questions? Comments?
References
1. 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