Title: IS IT ETHICAL?? IRB AND Human Subjects Challenges and NIH Grant Updates
1IS 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
2UNETHICAL CONDUCTOF RESEARCH
- Tuskegee Syphilis Study (1932 1972)
- Guatemala STD Experiments ( 1946 1948)
- Nazi Experiments WWII (1939 1945)
- Thalidomide ( 1950s)
3Regulatory Resulting from Unethical Research
- 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)
4What does the Institutional Review Board (IRB) do?
- Protect the rights welfare of human subjects
- Support the Universitys 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.ht
m
5WHEN 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
IRB-approved study require IRB approval prior to
initiation (Amendments) - All continuation of an IRB-approved study beyond
its approval period requires IRB approval
(Continuing Review)
6WHO/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.
7UCLAs 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
employees defense and indemnification - ONLY IF the employee has IRB approval and
necessary certifications
8What are the PIs (faculty, staff, student)
Research Responsibilities?
- All investigators, co-investigators,
collaborators, staff, and students must obtain
IRB/Research certifications for UCLA - 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
9CONSEQUENCES What can happen if I DO NOT get IRB
approval/violate IRB regulations?
- PIs Reputation
- Adverse job review/letter in personnel file
- Censure/unable to obtain future UCLA IRB approval
- Loss of UCLA employment
- School of Nursings Reputation
- All of Schools research data and protocols can
be reviewed by Office of Human Research
Protection Program (OHRPP) - All of Schools research can be suspended until
OHRPP review completed - UCLAs Reputation
- All of UCLA research can be suspended until
Federal review completed
10RESOURCESUCLA SON Research Website
http//nursing.ucla.edu/body.cfm?id10 http//nurs
ing.ucla.edu/body.cfm?id276
11TRAININGUCLA OHRPP Website
http//ohrpp.research.ucla.edu/
12Human 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. Data
and Safety Monitoring Plan (DSMP)
13Impact 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
14Safety 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?
15Women 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 - Dont forget to mention HOW you will achieve
adequate women and minority representation - Dont forget to include non-patients (such as
families/healthcare providers) to be studied
16Children
- MUST have a separate page/section on Children in
NIH grant submissions - CHILDREN are defined as persons who are lt 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
17DSMBs 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
18DSMB 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 100s 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
19When 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.
20NIH Grant Updates
- Latest news from NIH
- February, 2012
21NIH 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
22NIH 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