IRB 101IRB 101

An introduction to the An introduction to the federal regulations and federal regulations and how they relate to how they relate to institutional policy and institutional policy and procedures.procedures.

Springfield Committee Springfield Committee for for Research Research Involving Human Involving Human Subjects (SCRIHS)Subjects (SCRIHS)

SCRIHS SCRIHS isis an an Institutional Institutional Review Review Board (IRB)Board (IRB)

Commonly Used Commonly Used AcronymsAcronyms

• Code of Federal Regulations (CFR)Code of Federal Regulations (CFR)• Investigational New Drug number (IND)Investigational New Drug number (IND)• Investigational Device Exemption number Investigational Device Exemption number

(IDE)(IDE)• Primary Investigator (PI)Primary Investigator (PI)• Informed Consent Form (ICF)Informed Consent Form (ICF)• Authorized Study Personnel (ASP)Authorized Study Personnel (ASP)• Adverse Event (AE)Adverse Event (AE)• Amendment Summary (AS)Amendment Summary (AS)• Continuing Review (CR)Continuing Review (CR)• Investigator’s Brochure (IB)Investigator’s Brochure (IB)

REGULATION OF HUMAN REGULATION OF HUMAN SUBJECTS RESEARCH SUBJECTS RESEARCH

DHHS- Department of Health and DHHS- Department of Health and Human ServicesHuman Services

OHRP- Office of Human OHRP- Office of Human Research Research ProtectionsProtections

FDA- Food and Drug FDA- Food and Drug AdministrationAdministration

NIH- National Institute of HealthNIH- National Institute of Health

ORI- Office of Research IntegrityORI- Office of Research Integrity

WhoWho is the IRB? is the IRB? 1 1

• SCRIHS is currently made up of 19 appointed SCRIHS is currently made up of 19 appointed members: physicians & surgeons – including members: physicians & surgeons – including 1 resident member, pharmacists, medical 1 resident member, pharmacists, medical students, nurses, attorneys, and community students, nurses, attorneys, and community membersmembers

• Areas of specialization include: oncology, Areas of specialization include: oncology, surgery, psychology, neurology, cardiology, surgery, psychology, neurology, cardiology, and medicine-as well as other areasand medicine-as well as other areas

• Dr . Elvin Zook, Chief of the Division of Dr . Elvin Zook, Chief of the Division of Plastic Surgery , is the current SCRIHS chairPlastic Surgery , is the current SCRIHS chair

Who ? Who ? 2 2

• 45CFR46.107 regulates IRB 45CFR46.107 regulates IRB membershipmembershipEach IRB must be comprised of at least 5 Each IRB must be comprised of at least 5

members with varying backgrounds, “to members with varying backgrounds, “to promote complete and adequate review of promote complete and adequate review of research commonly conducted by the research commonly conducted by the institution”institution”

1 member -scientific, 1 member –1 member -scientific, 1 member –nonscientific, and 1 member-not affiliated nonscientific, and 1 member-not affiliated with the institution with the institution

WhatWhat is the IRB? is the IRB?

• The IRB is a group of “appropriately The IRB is a group of “appropriately constituted” people which has been constituted” people which has been formally designated to review and formally designated to review and monitor biomedical research monitor biomedical research involving human subjects and involving human subjects and ensure that the appropriate steps ensure that the appropriate steps are taken to protect the rights and are taken to protect the rights and welfare of human participantswelfare of human participants

WhenWhen ? ?

• SCRIHS currently meets once / SCRIHS currently meets once / month, on the 2nd Wednesday month, on the 2nd Wednesday of each monthof each month

• Erin, Alisha, Gary and Susan Erin, Alisha, Gary and Susan are in the office dailyare in the office daily

WhereWhere is the IRB? is the IRB?

• The SCRIHS office is located in room 2049, The SCRIHS office is located in room 2049, 2053 and 2061 on the 2nd floor of 801 N. 2053 and 2061 on the 2nd floor of 801 N. Rutledge (the building with the medical Rutledge (the building with the medical library)library)

• Erin 545-7602 or ecampbell@siumed.eduErin 545-7602 or ecampbell@siumed.edu• Alisha 545-7256 or amirabile@siumed.eduAlisha 545-7256 or amirabile@siumed.edu• Gary 545-2184 or gfifer@siumed.eduGary 545-2184 or gfifer@siumed.edu

• Monthly meetings are held in the Dirksen Monthly meetings are held in the Dirksen Conference Room (in the library) starting at Conference Room (in the library) starting at 5:30p.m.5:30p.m.

WHYWHY ? ?

• Because the government says so:Because the government says so:

45CFR part 4645CFR part 4621CFR parts 50, 56, 312, and 81221CFR parts 50, 56, 312, and 812

Belmont Report: Justice, Beneficence, Belmont Report: Justice, Beneficence, RespectRespect Declaration of HelsinkiDeclaration of Helsinki

Nuremberg CodeNuremberg Code

THE “COMMON RULE”THE “COMMON RULE”

• 45CFRpart46 45CFRpart46 • Subpart A- Basic Policy for Protection Subpart A- Basic Policy for Protection

of Human Subjects of Human Subjects

VULNERABLE POPULATIONSVULNERABLE POPULATIONS• Subpart B- Pregnant Women, Fetuses, Subpart B- Pregnant Women, Fetuses,

In VitroIn Vitro• Subpart C- ChildrenSubpart C- Children• Subpart D- PrisonersSubpart D- PrisonersIRB review of protocols involving prisonersIRB review of protocols involving prisoners

FDAFDA

• 21CFR: 21CFR: part 50 – human subjects protectionspart 50 – human subjects protectionspart 54 – financial disclosurepart 54 – financial disclosurepart 56 – IRB’spart 56 – IRB’spart 312 – IND (drugs)part 312 – IND (drugs)part 600 – Biological Productspart 600 – Biological Productspart 812 - IDE (devices)part 812 - IDE (devices)

• Special Publications:Special Publications:FDA Information SheetsFDA Information SheetsHHS Publication FDA 96-4159 “IDE Manual”HHS Publication FDA 96-4159 “IDE Manual”

What is Research?What is Research?

• 45CFR46.102(d) defines research 45CFR46.102(d) defines research as “a systematic investigation, as “a systematic investigation, including research development, including research development, testing, and evaluation, designed testing, and evaluation, designed to develop or contribute to to develop or contribute to generalizable knowledge.”generalizable knowledge.”

What is a Human Subject?What is a Human Subject?

• 45 CFR46.102(f) defines a human 45 CFR46.102(f) defines a human subject as “a subject as “a livingliving individual about individual about whom an investigator (whether whom an investigator (whether professional or student) conducting professional or student) conducting research obtains…data”research obtains…data”

• Chart ReviewsChart Reviews• Medical Students & ResidentsMedical Students & Residents

Who made you boss?Who made you boss?

• 45CFR.10945CFR.109

“ “An IRB shall review and have An IRB shall review and have authorityauthority to approve, require to approve, require modifications in (to secure modifications in (to secure approval), or disapprove approval), or disapprove allall research activities covered by this research activities covered by this policy” policy”

Ok, so Ok, so nownow what do I have what do I have to do?to do?

• Exempt - the IRB must “certify” Exempt - the IRB must “certify” that the research is indeed that the research is indeed exempt, the PI does NOT get to exempt, the PI does NOT get to make this determinationmake this determination

• Expedited Review - see pages 2-3 Expedited Review - see pages 2-3 on application for approvalon application for approval

• Full Board Review - any study Full Board Review - any study involving greater than minimal riskinvolving greater than minimal risk

Full Board Review Full Board Review (45CRF46.111)(45CRF46.111)

CRITERIA FOR IRB APPROVAL OF RESEARCH:CRITERIA FOR IRB APPROVAL OF RESEARCH:• Risks to subjects are minimizedRisks to subjects are minimized• Risk / Benefit ratio is balancedRisk / Benefit ratio is balanced• Selection of subjects is equitableSelection of subjects is equitable• Informed Consent and HIPAA Authorization will be soughtInformed Consent and HIPAA Authorization will be sought

and documentedand documented• Adequate provisions for monitoring data to ensure safetyAdequate provisions for monitoring data to ensure safety• Privacy and confidentiality will be protectedPrivacy and confidentiality will be protected• Additional safeguards are in place to protect vulnerable Additional safeguards are in place to protect vulnerable

populationspopulations

Full Board ReviewFull Board Review

• Application for approval (SIU vs. Non-SIU)Application for approval (SIU vs. Non-SIU)• ASP formASP form• HIPAA ApplicationHIPAA Application• HIPAA Authorization- 23 copiesHIPAA Authorization- 23 copies• Informed Consent- 23 copies w/ protocol #Informed Consent- 23 copies w/ protocol #• Protocol- 23 copies w/ protocol #Protocol- 23 copies w/ protocol #• Investigator’s Brochure / Tech. Manual- 3 Investigator’s Brochure / Tech. Manual- 3

copiescopies• Billing Papers: unless you are given a waiverBilling Papers: unless you are given a waiver

Common Issues/ Common Issues/ ProblemsProblems

• OBTAIN PROTOCOL NUMBER (and use OBTAIN PROTOCOL NUMBER (and use it)it)

• ENOUGH COPIESENOUGH COPIES• COLLATECOLLATE• MEETING THE DEADLINE (always last MEETING THE DEADLINE (always last

Wednesday of the month)Wednesday of the month)• NIH GRANT REVIEWNIH GRANT REVIEW• PROTECTED CLASSESPROTECTED CLASSES• WAIVER OF CONSENT- 4 pointsWAIVER OF CONSENT- 4 points

NIH Grant Application NIH Grant Application ReviewReview

• 45CFR46.103(f) 45CFR46.103(f)

Requires that each application or proposal Requires that each application or proposal for HHS supported human subject research for HHS supported human subject research be reviewed & approved by the IRB.be reviewed & approved by the IRB.

• 45CFR46.12245CFR46.122

““Federal funds…may not be expended for Federal funds…may not be expended for research involving human subjects unless research involving human subjects unless the requirements of this policy have been the requirements of this policy have been satisfied.”satisfied.”

Vulnerable PopulationsVulnerable Populations“vulnerable to coercion or undue influence”“vulnerable to coercion or undue influence”

• Fetuses and Human In Vitro FertilizationFetuses and Human In Vitro Fertilization• WomenWomen• Children & MinorsChildren & Minors• Cognitively Impaired Persons – new SCRIHS Cognitively Impaired Persons – new SCRIHS

policypolicy• PrisonersPrisoners• Traumatized and Comatose PatientsTraumatized and Comatose Patients• Terminally Ill PatientsTerminally Ill Patients• Elderly/Aged PersonsElderly/Aged Persons• MinoritiesMinorities• Students, Employees, Normal VolunteersStudents, Employees, Normal Volunteers• International ResearchInternational Research

You mean I don’t have to get You mean I don’t have to get Informed Consent? The 4 Informed Consent? The 4 pointspoints

• A PI may seek a waiver or alteration of informed A PI may seek a waiver or alteration of informed consent if the IRB can find that the PI has consent if the IRB can find that the PI has justified (in writing) the 4 points of justification. justified (in writing) the 4 points of justification. 45CFR46.11645CFR46.116• No more than minimal riskNo more than minimal risk• Waiver or alteration will not adversely affect rights / Waiver or alteration will not adversely affect rights /

welfarewelfare• Research could not practicably be carried out without Research could not practicably be carried out without

the waiver / alterationthe waiver / alteration• Subjects will be given additional pertinent information Subjects will be given additional pertinent information

after participation, whenever appropriateafter participation, whenever appropriate

Expedited Review Expedited Review (45CFR46.110)(45CFR46.110)

• Application for approval Application for approval • ASPASP• HIPAA ApplicationHIPAA Application• ICF- 3 copies (unless waived)ICF- 3 copies (unless waived)• Protocol - 3 copiesProtocol - 3 copies• HIPAA Authorization- 3 copies (unless HIPAA Authorization- 3 copies (unless

exempted or waived)exempted or waived)• ALSO, you ALSO, you mustmust submit any questionnaires, submit any questionnaires,

interview questions, etc. that you may be interview questions, etc. that you may be using in your studyusing in your study

Common Issues / ProblemsCommon Issues / Problems

• No monthly deadline for submissionNo monthly deadline for submission• Waiver of Consent and/or Authorization - Waiver of Consent and/or Authorization -

must meet must meet allall points of justification points of justification• 2 committee members assigned to 2 committee members assigned to

review and allowed 2 weeks to return review and allowed 2 weeks to return commentscomments

• See 45CFR46.110 and DHHS “Notice to See 45CFR46.110 and DHHS “Notice to Federal Register” for expedited Federal Register” for expedited categoriescategories

Exempt from Review Exempt from Review (45CFR46.101)(45CFR46.101)

• A letter, addressed to Dr. Elvin A letter, addressed to Dr. Elvin Zook containing the following:Zook containing the following:• title of your research projecttitle of your research project• a brief proposal of what you wish to doa brief proposal of what you wish to do• purpose, why are you doing the research?purpose, why are you doing the research?• state whether any identifiers will be used, or notstate whether any identifiers will be used, or not• Waiver of HIPAA Authorization or HIPAA De-Waiver of HIPAA Authorization or HIPAA De-

Identification FormIdentification Form• any other pertinent information such as surveys any other pertinent information such as surveys

or questionnairesor questionnaires• INCLUDE YOUR NAME AND PHONE NUMBERINCLUDE YOUR NAME AND PHONE NUMBER

Common Issues / ProblemsCommon Issues / Problems

• Submit your letter and information to Submit your letter and information to the SCRIHS office, NOT Dr. Zook’s officethe SCRIHS office, NOT Dr. Zook’s office

• No monthly deadlines for submissionNo monthly deadlines for submission• A letter will be issued to you/PI stating A letter will be issued to you/PI stating

that your proposal has been reviewed that your proposal has been reviewed and is indeed exempt from IRB review, and is indeed exempt from IRB review, DO NOT proceed until you hear from usDO NOT proceed until you hear from us

And so, it continues…And so, it continues…

• Amendment Summaries - if you need to Amendment Summaries - if you need to make a change to your research, informed make a change to your research, informed consent- including the process, protocol, IB, consent- including the process, protocol, IB, Tech. Manual, or wish to advertise for Tech. Manual, or wish to advertise for participantsparticipants• minor changes can be reviewed administrativelyminor changes can be reviewed administratively• other changes other changes maymay by required to go to the full by required to go to the full

board for reviewboard for review AllAll changes must be approved by the IRB changes must be approved by the IRB

prior to implementationprior to implementation

Yes, we Do have written Yes, we Do have written guidelines for AE guidelines for AE submissionsubmission

• Adverse Event Reports: The reporting Adverse Event Reports: The reporting guidelines are in the SCRIHS guidelines are in the SCRIHS procedures manual, pages 41-44, procedures manual, pages 41-44, which outline the “what”(event) is which outline the “what”(event) is required to be turned in “when”(time required to be turned in “when”(time deadlines) deadlines)

• These requirements have changed These requirements have changed and will be updated in the new and will be updated in the new Procedures ManualProcedures Manual

No, the fun is NOT over No, the fun is NOT over YETYET

• Continuing Review Statements: Continuing Review Statements: (45CFR46.109)(45CFR46.109)• This happens at least once/year regardless of This happens at least once/year regardless of

whether your research needed full board or whether your research needed full board or expedited review. The IRB can require that a expedited review. The IRB can require that a project be reviewed on a more frequent basis, project be reviewed on a more frequent basis, usually based on the risk involved. These ALWAYS usually based on the risk involved. These ALWAYS go to the full board for reviewgo to the full board for review

• Letters / monthly deadlines Letters / monthly deadlines • It is the responsibility of the PI to know the It is the responsibility of the PI to know the

continuing review deadline for his/her studies and continuing review deadline for his/her studies and ensure that all necessary paperwork is sumbitted ensure that all necessary paperwork is sumbitted on time to the IRB officeon time to the IRB office

Finally, a light at the end Finally, a light at the end of the research tunnelof the research tunnel

• Termination forms - if your study is Termination forms - if your study is complete, fill one of these out and complete, fill one of these out and submit to our officesubmit to our office

Miscellaneous TopicsMiscellaneous Topics

• Call ahead for a protocol number and USE Call ahead for a protocol number and USE itit

• IND / IDE # is required PRIOR to IRB reviewIND / IDE # is required PRIOR to IRB review• Submission of correct number of copiesSubmission of correct number of copies• Submit verification if the company/sponsor Submit verification if the company/sponsor

is requesting changes with an an is requesting changes with an an amendment summaryamendment summary

• Submit a list of changes to protocol/IBSubmit a list of changes to protocol/IB• Try to use the computer or type your formsTry to use the computer or type your forms

Remind me AGAIN why I Remind me AGAIN why I am doing research!am doing research!

• Please call and ask if you don’t Please call and ask if you don’t know or need help. Contrary to know or need help. Contrary to what you may think we are here to what you may think we are here to help.help.

COMING SOONCOMING SOON

• BRAAN- paperless IRBBRAAN- paperless IRB• Conflict of InterestConflict of Interest• IRB AccreditationIRB Accreditation