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

      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

review and approval before initiation (New Studies) IRB 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)

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   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. Data and Safety Monitoring Plan (DSMP) 12

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” 13

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?

14

    

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 15

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 16

 

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 17

  

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 20

  

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 21

  

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 22