CPHS: The Cliff
Notes
Robert Nobles, MPH
Assistant Director
Office of Research
Whitney, et al. Article Overview
• Qualitative e-mail survey with 14% response rate
• Population: federally funded principal investigators
• Comments were analyzed to show underlying
themes
• In general, there was consensus that it is important
to protect human subjects from research abuse, but
disagreement over how well the IRB system is
functioning
Whitney, et al. Article Overview (2)
• Six primary questions in survey:
1. What has been your experience with the human subjects
protection system in general? What do you like? What would
you change?
2. What has been your experience with the informed consent
process with potential subjects? Is there anything you would
change?
3. Do you feel your IRB does its job well? If so, what helps you
the most? If not, how could it improve?
Whitney, et al. Article Overview (2)
• Six survey questions continued:
4. Do you feel that your IRB usually understands your protocols
adequately?
5. Have you ever served on an IRB?
6. What other thoughts do you have on informed consent and
the human subjects protection system?
Whitney, et al. Article Overview (3)
• Positive Comments:
– IRB functions as a safeguard against overoptimistic
investigators; protects subjects against both nonphysical
and physical harms; and promotes “social justice.”
• Negative Comments:
• The constraints placed upon investigators and indeed
research subjects by OHRP and so-called ethicists
approaches the absurd.
Whitney, et al. Article Overview (4)
• Negative Comments Continued
– Getting protocols approved gets worse each year
because you have to document more and more and more
USELESS stuff.
– For most of my work I receive coded samples devoid of
patient identifiers, yet I have to fill in all sorts of crap and
repeat over and over again that I couldn't track down
these subjects if I tried.
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January 15, 2009 – Presentation
Outline
Research Quiz
IRB Overview
HIPAA Documents
Research Misconduct
Obtaining Informed Consent
Questions and Answers
Research Quiz
• Question #1:
– What is the purpose of an IRB?
• Question #2:
– What is the definition of research and how does
research differ from standard practice?
Research Quiz (2)
• Question #3:
– What are quality improvement projects and when
do they qualify as research projects?
• Question #4:
– How long does it take for studies to get
approved? Why?
IRB Overview
• Mission:
– To protect the rights and welfare of human
research participants.
• Definition of Research:
– Systematic investigation, including research
development, testing and evaluation, designed to
develop or contribute to generalizable
knowledge.
Key Features Of Research
• Intent: generate new knowledge, principles,
or theories that revises or improves existing
knowledge, programs or processes.
• Systematic collection and/or analysis of
data.
• Anticipated results that are valid and
generalizable
Functions of the IRB
• Reviewing research to ensure:
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Risks are minimized
Risks are reasonable vs. benefits
Selection is equitable
Informed Consent is obtained
Data and Safety are protected/monitored
Privacy and confidentiality are upheld
Vulnerable population protections are enhanced
CPHS Logic Model
Protect
Human
Subjects in
Research
1Federal Regulations
2Investigators
(faculty/staff/students)
3Committee Members
(faculty and community
volunteers)
4CPHS Staff
5Research Participants
6Research Sponsors
(funding entities)
7Expert Consultants
8IRIS (electronic reporting
system)
9Space Resources
1Monitoring Program
1Research Intermediary
1Collaborating agencies
1UT Legal Affairs
Protocol submission
Comply, critique
Protocol review
Approve, disapprove, or
alter submission
Modify consent forms
Simplify, correct
Consultation
Appropriateness
confirmed
Notification
Fully informed
Monitoring/ enforcement
Compliance
Open Communication
Trust, efficiency
Training
Competency
gained
Documentation
Record keeping,
verification
Research Intermediary
Verification, reduce
coercion
1Science and
logistics enhanced
2Consent is
representative
3 Cultural norms
enforced
4Transparent
review process
5Protection of
subjects through
record review
6Trained/ethical
investigators
7QA and QI
8Subject consent
verified/ rights
reiterated
9 Quality IRB
program
implemented
Materials Submitted for Review
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Application
Protocol
Consent Forms
Letters of
Approval/Cooperation
• Recruitment Flyers
• HIPAA Forms
• Investigator Brochure
• Pediatric Risk
Assessment
• Grant Application
• Data Collection
Forms
(questionnaires)
• Translations
• *Change Request
• *Continuing Review
Protocol Elements
• literature review/current
state of knowledge
• justification for the
study
• potential use of study
findings
• study design and
locations
• hypothesis
• Methodology
• Description and source
of study population
• Inclusion and exclusion
criteria
• Number of participants
• Sampling and
participant selection
Protocol Elements (2)
• Recruitment/enrollment
activities
• Consenting process;
• Confidentiality/privacy
• Data monitoring
• Explanation of study
instruments
• Data analysis plan.
Types of Review
• Exempt Research
– Case studies and retrospective chart reviews
• Expedited Review
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Minimal Risk Protocols and minor changes to approved research
Collection of blood samples
Prospective collection of biological specimens by noninvasive means
Collection of data through noninvasive procedures routinely
employed in clinical practice
– Research on individual or group characteristics or behavior
– Research employing survey, interview, oral history, focus group,
program evaluation, human factors evaluation, or quality assurance
methodologies
Types of Review
• Full Committee Review
– Protocols that have risks that are unknown or more than
minimal
– Clinical trials
• Including studies on drugs, devices, and procedures
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Cohort Studies
Case Control Studies
Cross-sectional study techniques in certain settings
Bio-banking and sample repositories
HIPAA Documents and the IRB
• HIPAA Exempt
• HIPAA Waivers subject to approval
– Retrospective Chart Review
– Screening and Recruitment
– Decedent Data
• HIPAA Authorization for PHI
Misconduct Defined
• (1) Fabrication, falsification, plagiarism and other forms of
misappropriation of ideas, or additional practices that
seriously deviate from those that are commonly accepted in
the research community for proposing, conducting, or
reporting research.
• (2) Material failure to comply with federal and University
requirements for the protection of researchers, human
subjects, or the general public or for ensuring the welfare of
laboratory animals.
Misconduct Defined (2)
• (3) Failure to adhere to other material legal requirements
governing the field of research.
• (4) Failure to comply with established standards regarding
author names on publications.
• (5) Retaliation of any kind against a person who reported or
provided information about suspected or alleged misconduct
and who has not acted in bad faith.
Additional Definitions
• Plagiarism – appropriation of another person’s ideas,
processes, results, or words without giving appropriate credit
• Fabrication – making up data or results and recording or
reporting them.
• Falsification – manipulating research materials, equipment,
or processes, or changing or omitting data or results such
that the research is not accurately represented in the
research record.
Additional Definitions (2)
• Noncompliance: Noncompliance is a failure by an
investigator to abide by research related requirements, good
clinical practice requirements, CPHS requirements and
applicable regulatory requirements. :
– Failure to obtain approval for research prior to initiating the research
activities,
– Continuing research activities beyond the expiration date without
obtaining continuing review approval,
– Failure to obtain informed consent when required,
– Failure to file an adverse event report,
– Implementing changes to the protocol without prior approval.
Examples of Violated Research Ethics
• 1945-1946 - Nuremburg Trials
– Included studies on hypothermia, infectious disease,
altitude, pharmacologics, sterilization, surgery and traumatic
injuries
• 1950’s – Willowbrook Hepatitis Study (New York)
– Intentionally infected healthy “retarded” children by feeding
them feces from children with active hepatitis (with food)
• 1955 – The Wichita Jury Study (Kansas)
– Audiotaped jurors to analyze decision-making without
consent
• 1962 – The Thalidomide Experience (nationwide)
– Investigational treatment given to pregnant women to
alleviate “unpleasant symptoms”
Examples of Violated Research Ethics
Cont….
• 1966 – “Ethics of Clinical Research” published by Dr. Beecher
(Harvard Medical School), NE Journal of Medicine
– Cited ethical violations in 22 published articles
• 1960’s – Jewish Chronic Disease Hospital Studies (New York)
– Injected live cancer cells in demented patients with
weakened immune systems
• 1960’s – Milgram Studies of Obedience to Authority (Yale
University)
– Participants deceived into thinking the study was evaluating
the role of negative reinforcement on learning
• 1970’s – San Antonio Contraception Study
– Clinic randomized patients to active birth control or placebo
Examples of Violated Research Ethics
Cont….
• 1970’s – Tearoom Trade Study
– PhD Dissertation of Laud Humphrey’s from Washington
University
– Observed men participating in sexual activities, served as a
“watch queen”, copied license plates, and followed up with
men one year later in disguise to gather additional
information (i.e. marital status, employment, etc.)
• 1932 – 1972 – Tuskegee Syphilis Study (Alabama)
– Evaluated the natural history of untreated syphilis
– Led to the creation of NIH Office for the Protection
– from Research Risks (now OHRP) and IRB’s
Oversight Of Human Subject Research
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1949 – Nuremberg Code
1964 – WMA Declaration of Helsinki
1966 – PHS policy leading to IRBs
1974 – National Research Act of 1974
established 45 CFR 46
• 1978 – The Belmont Report
• 1991 – Common rule
Overview of Informed Consent
Process and Forms
http://www.uth.tmc.edu/orsc/training/vids/informedconsent.html
Informed Consent Overview
• All modern codes of ethics concerning
research with human subjects affirm the
moral importance of a principle of informed
consent.
• “The voluntary consent of the human subject
is absolutely essential”
Overview (2)
• Obtaining consent is an ongoing process of
communication and mutual understanding
• The process is misrepresented as:
• A piece of paper
• A moment in time
• A legal contract
Overview (3)
• Must be obtained for each research subject
• Must be obtained prior to initiation of screening
procedures
• Must be tailored to the level of understanding
• If a medical term is essential, a lay definition is
needed
• Sufficient opportunity must be given for consideration,
no coercion
Four Tenets
1. Accurate Information
2. Understanding
3. Voluntariness
4. Decision Making
Capacity
Practical Benefits
• Increases subject adherence to the protocol
and the quality of the research.
• Provides the benefit of an additional layer of
risk review tailored to the interests of the
individual subject.
• Fosters public trust
Four Reasons to Waive Informed
Consent
• 1) Investigations that do not constitute
research involving human subjects
• 2) Human subjects research that is exempt
from compliance with federal regulations
Four Reasons to Waive Informed
Consent (2)
• 3) Non-exempt human subjects research in
which it is not possible to obtain participants’
written informed consent
– For reasons of age, cognitive impairment, or the
like, some individuals are incapable of providing
informed consent
– Research in emergency medicine
Four Reasons to Waive Informed
Consent (2)
• 4) Non-exempt human subjects research in
which it is not desirable to obtain participants’
written informed consent.
– a signed informed consent document may pose a
risk to subjects, and
– obtaining informed consent may diminish the
scientific merit of the research.
CPHS Reviewer Checklist
Office of Research Support
Website
IRIS
• https://iris.uth.tmc.edu/Login.jsp
• Electronic submission of protocols to the IRB
– Initial submission
– Change requests and amendments
– Continuing reviews
– Adverse Events, etc.
• Electronic routing and review by CPHS
• Notifications are electronic and available via e-mail and
within iRIS
Important Information
• iRIS Web Site: http://iris.uth.tmc.edu
• CPHS Web Site:
http://www.uth.tmc.edu/orsc/index.html
• iRIS assistance: 713-500-7960
• Office of Research Support Committees:
713-500-7943
• Robert Nobles: 713-500-7937
Discussion/Questions