IS IT ETHICAL??
IRB AND Human Subjects
Challenges and NIH Grant Updates
Mayra Lomeli, MSRA, CCRC
IRB Specialist
Mary Woo, RN, DNSc, FAAN, FAHA
Professor
UCLA School of Nursing
UNETHICAL CONDUCT
OF RESEARCH
 Tuskegee Syphilis Study (1932 – 1972)
 Guatemala STD Experiments ( 1946 –
1948)
 Nazi Experiments: WWII (1939 – 1945)
 Thalidomide ( 1950s)
Regulatory Resulting from
Unethical Research
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Nuremberg Code (1948)
Declaration of Helsinki (1964)
Creation of NIH OPRR leading to IRBs (1966)
National Research Act (1974)
Belmont Report (1978)
Common Rule (1991)
What does the Institutional
Review Board (IRB) do?
 Protect the rights & welfare of human subjects
 Support the University’s research mission
 Review and conduct of UCLA research guided by the
principles set forth in The Belmont Report:
 Respect for persons
 Beneficence
 Justice
www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm
WHEN is IRB Review Required??
 All human subjects research requires prior IRB
review and approval before initiation (New
Studies)
 All modifications or changes made to an IRBapproved study require IRB approval prior to
initiation (Amendments)
 All continuation of an IRB-approved study
beyond its approval period requires IRB
approval (Continuing Review)
WHO/WHEN is Review Required
(continued…)
 All faculty and staff who are conducting studies
involving Human Subjects within the course and
scope of their duties
 UCLA students who are conducting studies
involving Human Subjects within the course of their
studies
 All research studies REQUIRE IRB APPROVAL
regardless of the source of the funding (even if no
funds are involved) WITHOUT EXCEPTION before
Research is initiated.
UCLA’s Research Responsibilities
 The UC is legally responsible for the acts and
omissions of its employees acting in the
course and scope of their University duties
 In the event of a suit against an employee in
connection with an IRB-approved Research
activity using Human Subjects, the University
assumes the employee’s defense and
indemnification
 ONLY IF the employee has IRB approval and
necessary certifications
What are the PI’s (faculty, staff,
student) Research Responsibilities?
 All investigators, co-investigators, collaborators, staff,
and students must obtain IRB/Research certifications
for UCLA
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Health Insurance Portability and Accountability Act (HIPAA)
Collaborative Institutional Training Initiative (CITI)
Animal Research (as needed)
UCLA Certification, Education, and Training Web site
 http://ohrpp.research.ucla.edu/pages/certification
 PI must obtain UCLA IRB approval for the study
 PI must adhere to all UCLA IRB rules and regulations
CONSEQUENCES: What can happen if I
DO NOT get IRB approval/violate IRB
regulations?
 PI’s Reputation
 Adverse job review/letter in personnel file
 Censure/unable to obtain future UCLA IRB approval
 Loss of UCLA employment
 School of Nursing’s Reputation
 All of School’s research data and protocols can be reviewed by
Office of Human Research Protection Program (OHRPP)
 All of School’s research can be suspended until OHRPP review
completed
 UCLA’s Reputation
 All of UCLA research can be suspended until Federal review
completed
RESOURCES
UCLA SON Research Website
http://nursing.ucla.edu/body.cfm?id=10
http://nursing.ucla.edu/body.cfm?id=276
TRAINING
UCLA OHRPP Website
http://ohrpp.research.ucla.edu/
Human Subjects and NIH Grants
 NIH scores INCLUDE evaluation of the
Human Subjects section of the grant
 Human Subjects section of an NIH grant
includes
 Risks and benefits to subjects
 Description of protocols to maximize subject safety
and/or privacy
 Description of women and minorities
 Description of children
 Data and Safety Monitoring Board (DSMB) vs.
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Data and Safety Monitoring Plan (DSMP)
Impact of Inadequate Discussion
of Human Subjects in NIH Grants
 Worse overall scores for NIH grants
 Inadequate discussion of safety protocols can
destroy a grant
 Especially on inadequate subject representation
(women, minorities, children)
 Can prevent funding until NIH questions on
Human Subjects are discussed
 Human Subject “COMMENT”
 Human Subject “CONCERN”
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Safety and Privacy Protocols
MUST BE DESCRIBED
 Most common “red flags” – screening for
inclusion/exclusion criteria
 Emotion/Depression – what are you going to do if
you detect significant depression/anxiety/etc.?
 Physical – what are you going to do if you detect
physical symptoms? – example: sleep problems,
high blood pressure, etc.
 Qualitative data collection/interviews – how will
you insure subject privacy?
 Transmission of data/information about
subjects – security procedures?
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Women and Minorities
 MUST have a separate page/section on Women and
Minorities in NIH grant submissions
 Women and minorities MUST be included in studies
unless they are NOT at risk for a diagnosis (ex: not
many women have prostate cancer)
 “Inconvenience” is NOT an adequate excuse for low
women and minority representation
 Don’t forget to mention HOW you will achieve
adequate women and minority representation
 Don’t forget to include non-patients (such as
families/healthcare providers) to be studied
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Children
 MUST have a separate page/section on Children in
NIH grant submissions
 “CHILDREN” are defined as persons who are < 21
years of age (for NIH grants)
 Children MUST be included in studies unless:
 They are not at risk for the target diagnosis
 Their etiologies and responses to the target diagnosis/disease
or treatment are significantly different from adults
 Incidence of the disease is very low
 “Inconvenience” is inadequate justification for not
including children
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DSMBs vs. DSMPs
 Data and Safety Monitoring Board (DSMB)
 Independent (i.e. should NOT consist ONLY of members of
the research team)
 Must have described/standardized review plan
 What will they review
 When will they review
 REQUIRED for all interventional grants (“clinical trials)
 Data and Safety Monitoring Plan (DSMP)
 Does NOT have to include non-members of the research team
 Must describe standardized review plan
 What will they review
 When will they review
 Good idea to have if there are ANY potential risks associated
with the proposed study
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DSMB and “Clinical Trials”
 Types of “Clinical Trials”
 Phase I
 physiologic, toxicity, and dose-finding studies
 Often has a small number (usually less than 100) of subjects
 Phase II
 Efficacy trials
 Often has a moderate number (usually 100’s of subjects)
 Phase III
 Efficacy, effectiveness, and comparative trials
 Often has thousands of subjects
 All clinical trials require monitoring – including adverse
psychological, physiological, and privacy issues
 DSMB does NOT replace reporting adverse events to IRB
When is a DSMB Required?
(Continued…)
 When the trial has the power to detect statistically
significant differences in tangible outcomes (mortality
and significant morbidity).
 When the risks associated with the therapeutic
components are not known. This is particularly
applicable to pivotal phase 3 trials of investigational
agents.
 When the therapeutic components in either arm are
known to be associated with severe adverse effects.
This includes trials intended to evaluate approved
agents for new medical indications.
NIH Grant Updates
Latest news from NIH
February, 2012
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NIH – Emphasis of Institutes
 Potential new emphasis of expertise areas of
institutes
 May limit the type of science/subject matter for
each institute at NIH
 Still in discussion (with lots of upset reviewers)
 Cover letters – should include BOTH requested
institute AND requested study section
 Standard percentages of grants to be reviewed:
 50% of new investigator/early stage investigator
grants
 40% of all other research grant types
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NIH Requirement That Grants Be
“Different”
 Submitted grant applications must be “significantly”
different (more than 60%) from prior grant
submissions
 How do they (NIH) do this?
 Initial flag by software (comparison to previously submitted
grants by the investigators)
 Primary decision is made by a roomful of human reviewers
 Emphasis appears to be on the Specific Aims page and
the Background pages of the grant
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