IRB History, Ethical Foundations, & Researcher Responsibilities

IRBIRBHistory, Ethical Foundations, & History, Ethical Foundations, &

Researcher ResponsibilitiesResearcher Responsibilities

Michael MahoneyMichael Mahoney Asst. Director - IRBsAsst. Director - IRBs

WIRB LiaisonWIRB Liaison

mmahoney@ufl.edu

http://irb.ufl.edu/http://irb.ufl.edu/

Considerations

• Basis for review

• What is reviewed

• Process and other issues

• Resources

IRBIRB ==

Institutional Review BoardInstitutional Review Board

MissionMission

Protect Protect rightsrights and and welfarewelfare of human of human research subjects / research subjects / participantsparticipants

People harmed by researchPeople harmed by research• Nazi experimentationNazi experimentation• Milgram’s Obedience Study Milgram’s Obedience Study (1963)(1963)

• Willowbrook Willowbrook (1963-66)(1963-66)

• Radiation experiments Radiation experiments (1930s-60s)(1930s-60s)

• Stanford Prison Experiment Stanford Prison Experiment (1971)(1971)

• Tuskegee Syphilis Study (Tuskegee Syphilis Study (1932-1972)1932-1972)

• More….More….http://irb.ufl.edu/ethics/

http://www.ushmm.org/research/doctors/indiptx.htm

Nazi Nazi ExperimentationExperimentation

Tuskegee Syphilis Study1932-1972

http://www.cdc.gov/nchstp/od/tuskegee/time.htm

Belmont Report Cornerstones

http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm

1. Respect for Persons– Informed Consent process– Privacy and Confidentiality

2. Beneficence– Risk/Benefit Analysis– Scientific Merit

3. Justice– Review of subject selection

Federal Regulations

OHRP 45 CFR 46(1976)

FDA 21 CFR 50, 54, 56, 312, 812 (1980)

OCR HIPAA(2003)

VA 1200.5 + 38 CFR 16

(2003)

Problems protecting subjects continue…

• U Penn – gene therapy 1999

• Hopkins – hexamethonium bromide 2001

• Stratton VA – eligibility falsification 2002

– Criminal conviction in Feb 2006

– http://ori.dhhs.gov/misconduct/cases/Kornak.shtml

Nuremberg Trials 1940s

US Scandals

Tuskegee 1972

Jesse Geslinger

Stratton VA

1940

1950

1960

1970

1980

1990

2000

Nuremberg Code

Declar. Helsinki

OPRRNatl Rsch Act

Belmont ReportFDA Regs

HIPAAVA Accreditation

Human Subject

Living individual about whom an investigator (whether professional or student) conducting research obtains:

1. data through intervention or interaction with the individual, or

2. identifiable private information.45 CFR 46.102.(f)

Research

A systematic investigationA systematic investigation, , including research development, including research development, testing and evaluation, testing and evaluation, designed designed to develop or contribute to to develop or contribute to generalizable knowledgegeneralizable knowledge..

45 CFR 46.102.(d)45 CFR 46.102.(d)

Examples of research

• Clinical Trials (therapeutic research) • Survey, observational, or educational

research

IRB APPROVAL REQUIRED

• Review of medical records or databases• Tissue or data

– Identifiable vs coded vs anonymous– Exisiting?

REQUIRED: All Research

• Research must be approved before being conducted

Review Process

IncreasingIncreasingInvolvementInvolvementOr RiskOr Risk

IncreasingIncreasingProtection, Protection, Requirements,Requirements,& Paper Work& Paper Work

4. 4. Full BoardFull Board

3. 3. ExpeditedExpedited

2. 2. ExemptExempt

1. 1. Non-HumanNon-Human

Indefinite Plans / Non-human

• Research involves human tissue, data, etc., but

– NO interaction or intervention with living person,

AND– NO exposure to or collection of privately

identifiable data

Exempt

• Interaction/intervention with living individual or their identifiable data

1. Survey, observational, educational research

• Either no risk to subject, or• If potential risk recorded anonymously

• Survey does not collect identifiers

Exempt

2. Review of existing data, documents, records or specimens that is recorded anonymously :

– All data exists BEFORE submission– Researcher sees identifiers, but collects

data such that it cannot be linked back to subject• 17 HIPAA identifiers apply • No codes or links, permanent or temporary

Expedited

• Interaction/intervention with living individual or their identifiable data

• Prospective minimal risk research– Collection of data from voice, video, digital, or image

recordings made for research purposes.– Research on individual or group characteristics or behavior

(including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.

Expedited

• Approved for a maximum of 1 year– must obtain approval for Continuing

Review – Adverse Events

• Researcher can do more, so more protection needed.

Full Board

• Required if Greater than Minimal Risk• Use of vulnerable populations*• Data collection on:

– Conditions that can affect insurability, employability, reputation

– Criminal activity, drugs, sexual misconduct• Therapeutic research / Radiation / X-ray / Genetics

Full Board

• Approved for a maximum of 1 year– must obtain approval for Continuing

Review – Adverse Events

• Researcher can do more, so more protection needed.

Full Board vs Expedited

•Full Board – IRB-01 = 1st and 3rd Wednesday of

each month– IRB-02 = 3rd Thursday of each month– Deadline prior

•Expedited – forwarded “daily” to chairs

REQUIRED: All Research

• Any changes, no matter how minor, must be approved before implementation

• Unanticipated Problems – Adverse Events– Loss of data– Breach of confidentiality

“Outside” Issues

• Secondary subjects: anyone you collect data on is a subject

• Conducting research at other locations– International Research

• Involving outsiders in research• Conflict of Interest

Privacy & Confidentiality• Privacy

– Subject’s ability to control how other people see, touch, or obtain information about the subject.

• Confidentiality – the ways identifiable information will be

stored and shared

Non-compliance• Conducting research

prior to initial approval• Conducting research

after approval expires• Implementing revisions without prior IRB

approval• Over-enrolling• Enrolling subjects not approved by IRB

– Vulnerable populations

Non-compliance

• Enrolling subjects who do not fit enrollment criteria in protocol

• Need approval from Sponsor & IRB

• Failure to obtain/document consent• Losing copies of signed consents• Failure to document procedures

“If it’s not documented it didn’t happen”

Regulatory non-compliance is reported Regulatory non-compliance is reported bybythe institution to the appropriate Federalthe institution to the appropriate Federalagenciesagencies

Local Info: IRB-01Local Info: IRB-01

• 352-846-1494352-846-1494• irb1@grove.ufl.edu irb1@grove.ufl.edu

http://irb.ufl.edu/irb01/http://irb.ufl.edu/irb01/

Local Info: IRB-02Local Info: IRB-02

• 352-392-0433352-392-0433• irb2@ufl.eduirb2@ufl.edu

http://irb.ufl.edu/irb02/http://irb.ufl.edu/irb02/

Other Offices:

•VA R&D•IBC•HURRC•Pharmacy•CTSI

Other Offices:

•VA R&D•IBC•HURRC•Pharmacy•CTSI

Research at• UF• Shands• NF/SG VHS

HELP! PageHELP! Page

http://irb.ufl.edu/irb01/help/http://irb.ufl.edu/irb01/help/

Researcher “To do”Researcher “To do”

• Required ReadingRequired Reading http://irb.ufl.edu/education/trainreq.htm

– Belmont ReportBelmont Report– 45 CFR 4645 CFR 46– IRB-01 Policies & ProceduresIRB-01 Policies & Procedures

• Researcher responsibilitiesResearcher responsibilities – http://irb.ufl.edu/irb01/researcherresponsibilities.htm

• HIPAAHIPAA – required training – required training every every yearyear

ResourcesResources

• IRB researcher listservIRB researcher listserv– http://irb.ufl.edu/irb01/april04announce.htm

• NewsletterNewsletter– http://irb.ufl.edu/education/InvestiGATORS.htm

• Ethics LinksEthics Links– http://irb.ufl.edu/ethics/

• Assistance with NEW studiesAssistance with NEW studies– Renee Collins Renee Collins rbcollins@ufl.edu 273-8788 273-8788

DSRDSR

• Division of Sponsored ResearchDivision of Sponsored Research– http://rgp.ufl.edu/research/ – Grants & ContractsGrants & Contracts

• Judy HarrisJudy HarrisGrinter Hall room 207Grinter Hall room 207(352) 392-9267 (352) 392-9267 jaharris@ufl.edu

HURRCHURRC

• Human Use of Radioisotopes and Human Use of Radioisotopes and Radiation CommitteeRadiation Committee– http://www.ehs.ufl.edu/Rad/RCGuide/HURRC.htm – http://www.ehs.ufl.edu/Rad/

• Don MunroeDon MunroeBox 118340Box 118340Gainesville, FL 32611-8340Gainesville, FL 32611-8340(352) 392-7359 (352) 392-7359 don@ehs.ufl.edu

Shands PharmacyShands Pharmacy

• UF - Susan Beltz, PharmD UF - Susan Beltz, PharmD Box 100316Box 100316Gainesville, FL 32610-0486Gainesville, FL 32610-0486beltze@shands.ufl.edu

IBCIBC

• Institutional Biosafety CommitteeInstitutional Biosafety Committee– Studies involving Human Gene TherapyStudies involving Human Gene Therapy– http://www.ehs.ufl.edu/Bio/default.asp

• Dr. Phillip S. CollisDr. Phillip S. CollisBox 112190 Box 112190 (352) 392-1591(352) 392-1591pcollis@ehs.ufl.edu

CTSICTSI

• Clinical and Translation Science InstituteClinical and Translation Science Institute– Variety of resources open to all researchersVariety of resources open to all researchers

– http://www.ctsi.ufl.edu/

• Kathryn St. CroixKathryn St. CroixBox 100219 Box 100219 (352) 273-8770(352) 273-8770stcroixk@ufl.edustcroixk@ufl.edu

NF/SG VHSNF/SG VHS

• North Florida / South Georgia Veterans North Florida / South Georgia Veterans Health SystemHealth System– R&D = Research & Development CommitteeR&D = Research & Development Committee– SCI = Subcommittee for Clinical InvestigationsSCI = Subcommittee for Clinical Investigations– http://www1.va.gov/visn8/nfsg/Research/

• Separate submission requirementsSeparate submission requirements

• Hattie GrantHattie Grant376-1611 ext 4956376-1611 ext 4956 Hattie.Grant@va.gov

SummarySummary

IRBIRB = =

Protect rights Protect rights and welfare of and welfare of

subjectssubjects

SummarySummary

• IRBIRB = protect rights and = protect rights and welfare of welfare of subjectssubjects

• Need approval BEFORE starting Need approval BEFORE starting researchresearch

• On-going approval requiredOn-going approval required

• Host of requirementsHost of requirements

• We’re here to help!We’re here to help!

Remember

• The ends do NOT justify the means

• Research is a privilege

44

Institutional Animal Care & Use Committee

IACUCwww.iacuc.ufl.edu

Dorian LuceyCoordinator, Training & Quality Assurance

IACUC, University of Floridaluceydg@ufl.edu

Main office: Communicore Bldg CB-151B

Main number: (352) 392-9917

Fax: (352) 392-9919

Email: iacuc@grove.ufl.edu

Web site: www.iacuc.ufl.edu

List-serv: http://www.iacuc.ufl.edu/IACUCmail.htm

IACUC contact information:

Outline

• History• Role of the IACUC• Animal Care & Use Protocols• Protocol Review• Training• Inspections• Quality Assurance• Questions?

• From Mid 1800s on, increased use of animals in medical research

Public concerned about animal welfare

• British Cruelty to Animals Act of 1876

• Establishment of several Antivivisection Societies (late 1800’s-early 1900’s)

• Following World War IIEconomic boom, large increase in scientific researchHygienic Laboratory renamed National Institutes of

Health (NIH)Huge Increase (approx 40x) in NIH budget

Setting the stage

• 1961, “The Guide” was created which was supported by National Institutes of Health. http://grants.nih.gov/grants/olaw/olaw.htm

• 1963, The Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) was formed. UF has been AAALAC accredited since 1965.

IACUC History

• 1966, article in Life magazine prompted creation of the Laboratory Animal Welfare Act (USDA).

• Established minimum standards in 8 areas: housing, feeding, watering, sanitation, shelter, separation of species, ventilation, & adequate veterinary care.

IACUC History (cont.)

• 1970 amendment

report animals by pain category

require appropriate use of anesthetics

include all warm-blooded animals except rats of the genus Rattus, mice of the genus Mus, and birds bred for research.

IACUC History (cont.)

• Made into law by the 1985 Health Research Extension Act and is applicable to all PHS-supported activities involving animals conducted in any US territory. It includes all vertebrate animals.

• The Office of Laboratory Animal Welfare (OLAW) at the NIH has the responsibility of enforcing PHS Policy

• Require an Institutional Animal Care & Use Committee (IACUC) composed of at least 5 members (must include a veterinarian, scientist, non-affiliated member)

Public Health Service (PHS) Policy on Humane Care & Use of Laboratory Animals

• PHS requires use of the Guide, USDA refers to the Guide, AAALAC uses the Guide as a standard.

• PHS guidelines required by CDC, FDA, NIH. Last year, UF received $580M for sponsored research (over half from federal sources, half of this from the NIH)

• Ag Guide: “Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching”

The Guide for the Care and Use of Laboratory Animals

• 19 members at UF: Ph.D., D.V.M., community members, consultants (J.D., EH&S, D.V.M.)

• 6 alternate members• Support Staff (Office & Coordinators)• Meet 1st & 3rd Tuesday of each month for Full-Committee

protocols & any IACUC business• ~450 researchers, over 1300 active protocols

IACUC at UF

The IACUC at the University of Florida is

committed to ensuring that all animals used for experimental purposes are treated humanely and that pain and stress are minimized.

Why are we here?

• Oversight and evaluation of all aspects of animal care and use program

• Assure compliance with all federal, state, and local laws & regulations

• Evaluate animal care & use program (ACS, IACUC, EH&S)

• Inspect facilities• Review Animal Use Protocols• Review animal welfare concerns• Suspend Activity

The role of the IACUC

The role of the IACUC

• Reviews all animal care and use protocols• It is a formal request from the investigator to the university to

use vertebrate animals and tissues in experiments.• It is a contract between the PI and the university• No work on a protocol can be started without approval• All personnel contacting animals must be listed on the

protocol• All changes and/or additions must be approved by the

IACUC

• Original/initial protocol submission (approved for up to 3 years)

• Addendums (minor changes to existing protocol)• Annual review of protocol (report of what has been done in

past year)• Triennial review of protocol (protocols already approved for

3 years, needs to be approved for up to 3 more years)• Major Revision • Administrative (title, room, and/or funding change)• myIACUC login• Veterinary Consultation –

All new protocols, triennial reviews, major revisions, and addendums must be reviewed by a veterinarian.

Animal care and use protocolshttp://www.iacuc.ufl.edu

When reviewing protocols

• Pain, distress and discomfort

• Cat. A – No live animal use, observational field studies or use of cadavers not euthanized for study

• Cat. B – Breeding or observation only

• Cat. C - Minimal pain, distress, discomfort associated with protocol, and no pain relieving drugs or treatments are necessary

• Cat. D – Pain, distress, discomfort associated with protocol and appropriate pain relieving drugs or treatments are provided

• Cat. E - Pain, distress, discomfort associated with protocol, but pain relieving drugs or treatment are withheld because use would interfere with study objectives.

• Alternatives to animal use/duplication (3 R’s)

• Replacement: when non-animal or in-vitro models are available

• Reduction: minimize number of animals used while still being consistent with sound scientific and statistical standards.

• Refinement: procedures should have the least amount of potential pain, discomfort, distress, & morbidity (PDDM). PDDM should be minimized through pharmacological and other means.

• Justification for species used and any deviations from standard practices

• Endpoints and criteria for euthanasia

When reviewing protocols (cont.)

• Post procedural care

• Treatments (doses, volumes, routes of administration)

• Qualifications/training

When reviewing protocols (cont.)

• ACS Vets• IACUC Office checks training requirements,

room inspections, grant correlation• Member Consideration• Administrative, Designated Review (DR) or Full

Committee• Review time-frame

The protocol review process

• All non-human primate studies• All Category 3 studies involving unrelieved pain,

distress or discomfort• Deviations from The Guide• Any member can call any protocol if he/she feels

full committee discussion is required

Full committee review:

**IFAS Food & Fiber research does not need IACUC approval unless the funding agency or journal of publication requires it**

**Tissue studies may or may not need IACUC approval. Funding sources or publishers may require an IACUC approval.**

**Protocols that involve field studies and teaching must be submitted for IACUC approval**

Information to note:

• Complete all UF IACUC training requirements (http://www.iacuc.ufl.edu/training.htm)

• Fill out a Health Risk Assessment from Environmental Health & Safety’s (EH&S) Animal Contact Program (http://www.ehs.ufl.edu/Bio/Animal/acweb.htm).

• If applicable, complete all UF Animal Care Services training requirements (www.acs.ufl.edu)

So, you will be working with animals…http://www.iacuc.ufl.edu/training.htm:

IACUC training requirements

•Working With the UF IACUC modules

•AALAS training modules for specific species and procedures

•Working with IACUC

ACS Requirements

• Animal Awareness Seminar• Blackboard Training & Exams• Contact ACS at 392-2977 or http://acs.ufl.edu/

• USDA, PHS/OLAW, AAALAC require • Semi-annually• What are we looking for?• Deficiencies: Minor or Significant.

Written corrective action or plan of action with a time frame.

• IO & OLAW: receives semi-annual report, IO signs Letter of Assurance

Inspections

• Whistle-blower Policyhttp://www.iacuc.ufl.edu/mistreatment.htm

• Possible Non-Compliance

• Suspension/Corrective Action (Reportable to IO & possibly OLAW…UF fined, AAALAC accreditation).

• Overcrowding/Over animal numbers. Know how many animals are allowed per your IACUC protocol. Watch for cage overcrowding when breeding animals.

Quality Assurance

Useful Links

IACUC: http://www.iacuc.ufl.edu/ IACUC Policies: http://www.iacuc.ufl.edu/links.htm IACUC List-serv: http://www.iacuc.ufl.edu/IACUCmail.htm Animal Welfare Act:

http://www.nal.usda.gov/awic/legislat/usdaleg1.htm USDA Animal Care Policies:

http://www.aphis.usda.gov/animal_welfare/index.sht PHS Policy:

http://grants.nih.gov/grants/olaw/references/phspol.htm OLAW: http://grants.nih.gov/grants/olaw/olaw.htm AAALAC: http://www.aaalac.org/ The Guide:

http://www.nap.edu/readingroom/books/labrats/ Ag Guide:

http://www.iacuc.ufl.edu/AnimalUseGuides/AgGuide.PDF ACS: http://acs.ufl.edu/ EH&S: http://www.ehs.ufl.edu/

Institutional Animal Care & Use Committee

IACUCwww.iacuc.ufl.edu

Dorian LuceyCoordinator, Training & Quality Assurance

IACUC, University of Floridaluceydg@ufl.edu