Human Subject ApprovalHuman Subject Approval(Institutional Review Board, IRB)(Institutional Review Board, IRB)

Biosafety ApprovalBiosafety Approval(Institutional Biosafety (Institutional Biosafety

Committee, IBC)Committee, IBC)Donald E. MosierDonald E. Mosier

Chair, IBCChair, IBC

Member, GCRC Review CommitteeMember, GCRC Review Committee

IRB Approval ProcessIRB Approval Process• Determine if Human Subjects Approval is Determine if Human Subjects Approval is

necessary (> 8 weeks prior to submission)necessary (> 8 weeks prior to submission)• If If YESYES, submit 17-point IRB form , submit 17-point IRB form with grant with grant

texttext• Fulfill NIH & TSRI training requirements Fulfill NIH & TSRI training requirements

for Key Personnelfor Key Personnel• If GCRC (General Clinical Research Center) If GCRC (General Clinical Research Center)

can supply samples, complete their can supply samples, complete their application formsapplication forms

√

√

ARE YOU CONDUCTING RESEARCH ARE YOU CONDUCTING RESEARCH USING HUMAN SUBJECTS?USING HUMAN SUBJECTS?

A ‘human subject’ is a living individual about whom an investigator obtains either (1) data A ‘human subject’ is a living individual about whom an investigator obtains either (1) data through intervention or interaction with the individual, or (2) identifiable private information. through intervention or interaction with the individual, or (2) identifiable private information. Legal requirements to protect human subjects apply to a much broader range of research than Legal requirements to protect human subjects apply to a much broader range of research than many investigators realize, and researchers using human tissue specimens are often unsure about many investigators realize, and researchers using human tissue specimens are often unsure about how regulations apply to their research. Legal obligations to protect human subjects apply, for how regulations apply to their research. Legal obligations to protect human subjects apply, for example, to research that uses–example, to research that uses–

* Bodily materials, such as cells, blood or urine, tissues, organs, hair or nail clippings, * Bodily materials, such as cells, blood or urine, tissues, organs, hair or nail clippings, even if even if you did not collect these materialsyou did not collect these materials * Residual diagnostic specimens, including specimens obtained for routine patient care that * Residual diagnostic specimens, including specimens obtained for routine patient care that would have been discarded if not used for researchwould have been discarded if not used for research * Private information, such as medical information, that can be readily identified with * Private information, such as medical information, that can be readily identified with individuals, even if the information was not specifically collected for the study in question. individuals, even if the information was not specifically collected for the study in question. Research on cell lines or DNA samples Research on cell lines or DNA samples that can be associated with individualsthat can be associated with individuals falls into this falls into this category.category.

IF SO, YOU MUST...IF SO, YOU MUST...

Comply with your institution’s rules and the requirements of your Institutional Review Board Comply with your institution’s rules and the requirements of your Institutional Review Board (IRB) as well as meeting Federal requirements (1) in order to carry out your research. (IRB) as well as meeting Federal requirements (1) in order to carry out your research.

Key pointsKey points• Any material or information derived from Any material or information derived from

humans is likely to require IRB approvalhumans is likely to require IRB approval

• If you obtain human material from a If you obtain human material from a collaborator, both you and the collaborator collaborator, both you and the collaborator must have IRB approvalmust have IRB approval

• Anonymous samples that are unlinked to an Anonymous samples that are unlinked to an individual may be exempt if the IRB agreesindividual may be exempt if the IRB agrees

TSRI Information about Human TSRI Information about Human Subjects ResearchSubjects Research

• Go toGo to TSRI Website TSRI Website

• Go toGo to Campus Services Campus Services

• Go toGo to Regulatory Committees Regulatory Committees

• Go toGo to Institutional Review Board - Institutional Review Board - Human Subjects Committee & TSRI's Human Subjects Committee & TSRI's Minimum Education RequirementMinimum Education Requirement

Human Subjects Committee & TSRI's Minimum Education RequirementHuman Subjects Committee & TSRI's Minimum Education Requirement

Human Subjects Committee - ContactsHuman Subjects Committee - Contacts

TSRI's Minimum Education Requirement For Human Subject ResearchTSRI's Minimum Education Requirement For Human Subject Research

TSRI has implemented policies and procedures for complying with the National Institutes of TSRI has implemented policies and procedures for complying with the National Institutes of Health mandatory education requirement relating to research involving human subjects and Health mandatory education requirement relating to research involving human subjects and specimens. Beginning October 1, 2000, TSRI is requiring that the minimum education specimens. Beginning October 1, 2000, TSRI is requiring that the minimum education requirement be met prior to the submission to TSRI's Office of Sponsored Programs of any requirement be met prior to the submission to TSRI's Office of Sponsored Programs of any grant application or contract proposal involving human subject research. To access TSRI's grant application or contract proposal involving human subject research. To access TSRI's policies, procedures and links to the two compliance requirement documents, click on the policies, procedures and links to the two compliance requirement documents, click on the heading above.heading above.

Forms For TSRI's Minimum Education Requirement For Human Subject ResearchForms For TSRI's Minimum Education Requirement For Human Subject Research

Identification of Key Personnel Form Human Subject Research - Minimum Education Identification of Key Personnel Form Human Subject Research - Minimum Education Certification Statement Certification Statement TSRI's Requirements And Forms For Grant Submissions With Human Subject ProtocolsTSRI's Requirements And Forms For Grant Submissions With Human Subject Protocols

Forms For Human Subject Committee Approval Of Human Subject ProtocolsForms For Human Subject Committee Approval Of Human Subject Protocols

Scripps/TSRI Supplemental Education Seminar SeriesScripps/TSRI Supplemental Education Seminar Series

NIH And Other Related Links - Resources And EducationNIH And Other Related Links - Resources And Education

A. THE NIH MANDATED EDUCATION REQUIREMENT APPLIES TO ALL KEY A. THE NIH MANDATED EDUCATION REQUIREMENT APPLIES TO ALL KEY PERSONNEL PERFORMING RESEARCH INVOLVING HUMAN SUBJECTS.PERSONNEL PERFORMING RESEARCH INVOLVING HUMAN SUBJECTS.

In order to assure compliance with the mandated NIH minimum education requirements In order to assure compliance with the mandated NIH minimum education requirements relating to human subject research, TSRI has established a "Minimum Education relating to human subject research, TSRI has established a "Minimum Education Requirement for Human Subject Research". This requirement applies to all key Requirement for Human Subject Research". This requirement applies to all key personnel participating in the design and conduct of research on a human subject (human personnel participating in the design and conduct of research on a human subject (human subject research) under any grant or contract.subject research) under any grant or contract.

"Key Personnel" include all individuals responsible for the design and conduct of "Key Personnel" include all individuals responsible for the design and conduct of research under a grant or contract.research under a grant or contract.

"Human Subject" means a living individual about whom an investigator (whether "Human Subject" means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.interaction with the individual, or (2) identifiable private information.

Please note that research using any human specimen, such as tissue or blood, or any data Please note that research using any human specimen, such as tissue or blood, or any data derived from a human specimen, may result in that research being classified as human derived from a human specimen, may result in that research being classified as human subject research. If you have any questions about whether or not a particular research subject research. If you have any questions about whether or not a particular research procedure may be human subject research, please contact the Scripps Office for the procedure may be human subject research, please contact the Scripps Office for the Protection of Research Subjects (SOPRS) by phone at (858) 882-8444 or by email at Protection of Research Subjects (SOPRS) by phone at (858) 882-8444 or by email at hsc@scrippsclinic.com.hsc@scrippsclinic.com.

TSRI'S MINIMUM EDUCATION REQUIREMENT FOR HUMAN SUBJECT TSRI'S MINIMUM EDUCATION REQUIREMENT FOR HUMAN SUBJECT RESEARCHRESEARCH

The TSRI Minimum Education Requirement for Human Subject Research consists of The TSRI Minimum Education Requirement for Human Subject Research consists of completing both of the following:completing both of the following:

(1) The NIH Investigator Training Module (a computer-based training program) entitled (1) The NIH Investigator Training Module (a computer-based training program) entitled "Protection of Human Research Subjects: Computer Based Training for Researchers"."Protection of Human Research Subjects: Computer Based Training for Researchers".

(2) Review of the six page pamphlet published by the NIH entitled (2) Review of the six page pamphlet published by the NIH entitled "Research on Human "Research on Human Specimens".Specimens".

TSRI considers completion of the above materials a minimum requirement and encourages TSRI considers completion of the above materials a minimum requirement and encourages all investigators to expand the curriculum through self-study, particularly in areas where the all investigators to expand the curriculum through self-study, particularly in areas where the researcher may be confronted with a difficult topic, such as consent by a child or genomic researcher may be confronted with a difficult topic, such as consent by a child or genomic testing, or a special patient population. The NIH website on bioethics is replete with testing, or a special patient population. The NIH website on bioethics is replete with resources on a broad range of relevant topics.resources on a broad range of relevant topics.

The TSRI/Scripps Clinic Human Subjects Committee has agreed that completion of TSRI's The TSRI/Scripps Clinic Human Subjects Committee has agreed that completion of TSRI's Minimum Education Requirement for Human Subject Research also meets the training Minimum Education Requirement for Human Subject Research also meets the training requirements it requires investigators to complete before they can submit protocols for HSC requirements it requires investigators to complete before they can submit protocols for HSC review. (TSRI investigators who are physicians acting in their capacity as a physician in review. (TSRI investigators who are physicians acting in their capacity as a physician in performance of an IRB approved protocol must still meet the training requirements for performance of an IRB approved protocol must still meet the training requirements for physicians.)physicians.)

IRB ApplicationIRB Application

• 17-point narrative must be approved 17-point narrative must be approved prior to grant funding, not submissionprior to grant funding, not submission

• However, prior approval is highly However, prior approval is highly recommended for first submissions in recommended for first submissions in case IRG (initial review group/study case IRG (initial review group/study section) has any concerns about human section) has any concerns about human subject utilizationsubject utilization

• Grant text is required with IRB Grant text is required with IRB applicationapplication

Any investigator who receives human tissue for study must have his/her research approved by the Human Subjects Committee. The Any investigator who receives human tissue for study must have his/her research approved by the Human Subjects Committee. The Principal Investigator is the person in whose laboratory the tissue will be studied. The physician who obtains the sample should be Principal Investigator is the person in whose laboratory the tissue will be studied. The physician who obtains the sample should be listed as a sub-investigator. Use this form for protocols that propose ONLY to study tissue obtained from patient samples that listed as a sub-investigator. Use this form for protocols that propose ONLY to study tissue obtained from patient samples that would otherwise be discarded. In addition to this form, the complete application must include:would otherwise be discarded. In addition to this form, the complete application must include:

∑∑ A completed HSC Cover SheetA completed HSC Cover Sheet

∑∑ A current copy of any grant associated with this protocolA current copy of any grant associated with this protocol∑∑ A consent form, if necessaryA consent form, if necessary

2002 17-Point Narrative Form for Tissue Collection and Study2002 17-Point Narrative Form for Tissue Collection and Study

HSC # HSC # �� NewNew Renewal� Renewal� Date Submitted: Date Submitted:

Title of Protocol: Title of Protocol: Principal Investigator: Principal Investigator: Sub-Investigator (s): Sub-Investigator (s):

All sections must be completed. If not applicable, insert "NA" in the space provided.All sections must be completed. If not applicable, insert "NA" in the space provided.

1.1. RATIONALE AND PURPOSERATIONALE AND PURPOSE

[Provide a brief explanation, in lay language, of what you plan to do with the tissue][Provide a brief explanation, in lay language, of what you plan to do with the tissue]

Why does this project require human tissue samples? Why does this project require human tissue samples?

Has this use of human tissue been described in your current grant application? Yes�Has this use of human tissue been described in your current grant application? Yes� No� No�

[If no, attach a letter to the granting agency describing this change in the proposed use of human subjects.][If no, attach a letter to the granting agency describing this change in the proposed use of human subjects.]

2.2. BACKGROUND OF PROJECTBACKGROUND OF PROJECT 3.3. FACILITIES WHERE STUDY WILL BE CARRIED OUTFACILITIES WHERE STUDY WILL BE CARRIED OUT

4.4. ESTIMATED DURATION OF THE STUDYESTIMATED DURATION OF THE STUDY

5.5. SUBJECT POPULATIONSUBJECT POPULATION

6.6. SUBJECT RECRUITMENTSUBJECT RECRUITMENT Will advertisements be used? Will advertisements be used? YES� YES� NO� NO�

[Must be submitted to HSC for approval][Must be submitted to HSC for approval]

7.7. SOURCE OF RESEARCH MATERIALSOURCE OF RESEARCH MATERIAL

8.8. PROJECT PROTOCOLPROJECT PROTOCOL

9.9. POTENTIAL RISKSPOTENTIAL RISKS

10.10. RISK MANAGEMENT PROCEDURESRISK MANAGEMENT PROCEDURES

My laboratory staff has been instructed in My laboratory staff has been instructed in biosafety proceduresbiosafety procedures for safe handling of human tissues. for safe handling of human tissues.

11.11. POTENTIAL BENEFITSPOTENTIAL BENEFITS 12.12. RISK-BENEFIT RATIORISK-BENEFIT RATIO

13.13. ALTERNATIVE TREATMENTSALTERNATIVE TREATMENTS

14.14. SUBJECT PAYMENT/COSTSSUBJECT PAYMENT/COSTS

15.15. INFORMED CONSENTINFORMED CONSENT

16.16. CONFIDENTIALITY OF DATA/PRIVACY OF INDIVIDUALSCONFIDENTIALITY OF DATA/PRIVACY OF INDIVIDUALS

17.17. DISCLOSURE OF FINANCIAL INTERESTSDISCLOSURE OF FINANCIAL INTERESTS

Bloodborne Pathogen ActBloodborne Pathogen Act

• Occupational exposure to bloodborne Occupational exposure to bloodborne human pathogens (hepatitis B virus, human pathogens (hepatitis B virus, HIV, hepatitis C virus, etc.) is regulated HIV, hepatitis C virus, etc.) is regulated by federal, state and local lawsby federal, state and local laws

• Work with human tissues or fluids must Work with human tissues or fluids must be conducted at be conducted at Biosafety Level 2 Biosafety Level 2 http://www.scripps.edu/services/biosafety/

• Hepatitis B immunization is mandated Hepatitis B immunization is mandated

General Clinical Research CenterGeneral Clinical Research Center

• GCRC is an NIH-funded TSRI resource GCRC is an NIH-funded TSRI resource for human studiesfor human studies

• GCRC maintains a normal donor pool GCRC maintains a normal donor pool and provides sample collection by trained and provides sample collection by trained professionalsprofessionals

• Use of the GCRC requires prior approval Use of the GCRC requires prior approval of a protocol by the IRB (1st) and the of a protocol by the IRB (1st) and the GCRC Review Committee GCRC Review Committee

Section E - Section E - Human SubjectsHuman Subjects in NIH grant applicationin NIH grant application

• Six specific questions must be answeredSix specific questions must be answered

• Inclusion of women, children, and Inclusion of women, children, and minorities in study population must be minorities in study population must be addressedaddressed

• Training in human research must be Training in human research must be documenteddocumented

e. Human Subjects

We use the General Clinical Research Center (supported by NIH grant MO1 RR00833) at Scripps as a source of peripheral blood cells for all of our studies.

1. Blood donors are all volunteers. All will be healthy, unmedicated consenting adults. There are no restrictions for blood donors as to age, sex or ethnic background, except that children (see below), mentally disabled individuals and pregnant women will not be used. Blood will be obtained by venipuncture from the subjects and whole blood used for the preparation of PBL. The composition of the donor pool is given in Table 5A. The ages range between 21-64 years of age.

2. Normal humans contribute whole blood (50-400 ml) for research purposes. The blood is obtained specifically for this research project.

3. Consent will be obtained from volunteers before venipuncture after a brief description of how the sample is to be used. The Experimental Subjects Bill of Rights approved by the Scripps Clinic and Research Foundation Human Subjects Committee will be explained and signed by each donor.

4. Volunteers undergoing venipuncture experience slight discomfort upon needle insertion, drawing of blood and needle withdrawal. Some bleeding at the puncture site may follow. No physical risk to the subject, other than a rare syncopal attack, is contemplated. No psychological, social or legal risks are inherent in drawing blood.

5. Venipuncture will be done following standard medical practices using sterile technique and a compression bandage in the area of blood removal. A record of the donor and hematocrit result will be kept on file. Experimental results will not include donor identification and confidentiality will be maintained by the Investigator as to identity of blood donors.

6. There is no direct benefit to be gained by volunteers. The risk of venipuncture are small and the benefit of development of treatments for HIV-1 infection is so great that the risk:benefit ratio is highly favorable.

e. Human Subjects (continued)

Inclusion of women. See targeted enrollment plans (p. 40) and genotype coding information below. Women are fully represented in the Scripps GCRC donor pool.

Inclusion of children: The Scripps Green Hospital that houses the GCRC does not provide pediatric care. Use of donors under 16 years of age is thus prohibited by the IRB because of the absence of medical care for any study-related complications.

Inclusion and recruitment of minorities: Information on the composition of the Scripps GCRC donor pool is given below. We have added a new collaboration (funded by another grant) with Case Western University that will provide PBMC samples from a more ethnically diverse population. The Scripps GCRC Core Laboratory continues to operate an outreach program to recruit new donors that reflect the ethnic diversity of San Diego County. Demographic information is presented on the following page (p. 40).

Training in Research Ethics - All key personnel have completed training in the ethics of human research. Certification of training is attached.

Targeted Enrollment Table Is NowTargeted Enrollment Table Is NowAn NIH RequirementAn NIH Requirement

Institutional Biosafety Committee Institutional Biosafety Committee ApprovalApproval

• IBC approval is required for all work involving IBC approval is required for all work involving recombinant DNA, infectious pathogens, viral recombinant DNA, infectious pathogens, viral vectors, and toxinsvectors, and toxins

• IBC approval is required IBC approval is required PRIOR TO PRIOR TO review of review of animal protocols involving human or animal animal protocols involving human or animal pathogenspathogens

• IBC approval is not required prior to submission IBC approval is not required prior to submission of NIH grants (except for animal work), but is of NIH grants (except for animal work), but is required for AHA and other granting agenciesrequired for AHA and other granting agencies

To obtain IBC approvalTo obtain IBC approval

• Complete online biosafety training Complete online biosafety training (general and pathogen-specific)(general and pathogen-specific)http://www.scripps.edu/services/biosafety/

• Complete online Registration DocumentsComplete online Registration Documentshttp://www.scripps.edu/services/ehs/bioforms/

• Determine if vaccine is available for Determine if vaccine is available for human pathogens, and TSRI human pathogens, and TSRI recommendation for vaccinationrecommendation for vaccination

Planning FlowchartPlanning Flowchart

Human SubjectsHuman Subjects YESYES NONO

IRB Submission (± GCRC)IRB Submission (± GCRC)Human Subject Online TrainingHuman Subject Online TrainingBiosafety Online TrainingBiosafety Online TrainingIBC SubmissionIBC Submission

Vertebrate Animals with infectious organisms Vertebrate Animals with infectious organisms or vectors derived from infectious organismsor vectors derived from infectious organisms

IBC Submission prior to IACUC submissionIBC Submission prior to IACUC submission

GRANT SUBMISSION GRANT SUBMISSION (e.g., June 1st)(e.g., June 1st)

Before April 1stBefore April 1st