IRB HUMAN SUBJECTS PROTECTION PROGRAM STANDARD OPERATING PROCEDURES INSTITUTIONAL REVIEW BOARD

Transcription

1 IRB INSTITUTIONAL REVIEW BOARD HUMAN SUBJECTS PROTECTION PROGRAM STANDARD OPERATING PROCEDURES REVISED: OCTOBER,

2 Table of Contents Page # INTRODUCTION... 1 CONTACT INFORMATION... 2 PRINCIPLES, ROLES AND RESPONSIBILITIES 1.0 Regulatory and Ethical Mandate The Nuremberg Code The Declaration of Helsinki The Belmont Report Department of Health and Human Services (DHHS) Regulations Federal Policy (Common Rule) for the Protection of Human Subjects. Food and Drug Administration (FDA) Regulations at 21 CFR 50 and Federalwide Assurance IRB Mission and Authority IRB Purpose Definition of Human Subjects Research Research Agreements to provide IRB review of research conducted by unaffiliated investigators Human Research Activities Performed at Other Institutions Requirements for Approval of Research at Non-USA Facilities IRB Approval of Research to be Done at a Non- USA Institution... 8 IRB ORGANIZATION AND ADMINISTRATION 3.0 IRB membership Duties of IRB Members Chairperson responsibilities Vice-Chair(s) responsibilities Committee member appointment /removal Attendance Requirements & Meeting Schedule Non-voting members Termination of appointment Confidentiality agreement Orientation and training of IRB members Member conflict of interest Investigator conflict of interest IRB Administrative Support Other Committee/Administrative Reviews Education and training of staff Investigator and Key Research Personnel Training... 12

3 5.0 IRB Record keeping and Reporting Documentation and Retention of IRB documents Access to IRB records IRBNet Online Management System IRBNet Electronic Signatures IRBNet Forms and Templates Meeting Materials and Documentation Meeting minutes Review by convened IRB IRB review procedures IRB meeting materials IRB Actions/Project Status Approved Modifications required Information Required Pending follow-up of receipt and review of serious adverse event Deferral Disapproval Suspension and termination of research study by IRB Closed - Expired Closed Project Completion Closed Notification of IRB actions Appeal of IRB decisions IRB RESEARCH EVALUATIONS, PROCEDURES, CRITERIA AND ACTIONS 7.0 Determination of Type of Review Expedited Review of Research Types of research eligible for expedited review IRB review materials Exemption from Continuing Review Types of research eligible for exempt continuing review Modifications to exempt studies Modifications to Previously Approved Projects Continuing Review of Approved Applications Criteria for requiring review more often than annually Reminders/Notices

4 11.3 Lapsed studies Study Closure or Completion When can a project be submitted to the IRB for study closure Voluntary completion by investigators Administrative Closure Termination of a study by the IRB Expiration of approval period Adverse Events and Unanticipated Problems in Research Definitions Special requirements for research involving gene therapy studies Internal vs External Reporting Requirements IRB responsibilities following receipt of SAE/follow-up report Safety Alerts, IND Safety Reports, MED Watch Reports Protocol Violations and Deviations Definitions Reporting procedures Review by IRB committee Actions that may be taken during or after the investigation of non-compliance Continuity of care of research participants when study is suspended Final outcome IRB Protocol Audits Recruitment and Advertisement Methods Recruitment methods Recruitment incentives Promotional materials External investigators and recruitment of student population Informed Consent Basic elements of informed consent Additional elements of informed consent Exceptions to informed consent requirements Research related injury Audio/video recordings Consent for mail and telephone surveys Short form consent procedures Waiver of written consent Consent form templates

5 18.10 Assent by minors Parental permission Surrogate consent for subjects who are decisionally impaired Obtaining consent from non-english speaking subjects Translation and informed consent Consent for use of stored samples and genetic Revised Informed Consent and Reconsenting Stamped Copies of Consent Forms Record retention of informed consent documents HIPAA and IRB Review HIPAA authorization and informed consent HIPAA Security / Use of ephi Behavioral and Social Science Research Types of risk found with Social/Behavioral research Research involving deception or withholding of information Debriefing Oral histories Review of Research Using Data and Specimens Prospective use of existing materials Retrospective use of existing materials Research using data or tissue banks Data Safety Monitoring Data Safety Monitoring Plan (DSMP) Data Safety Monitoring Board (DSMB) IRB Responsibilities CONSIDERATIONS FOR FDA-REGULATED PRODUCTS 23.0 Research involving an investigational drug/device Determination of need for an IND Determination of significant vs non-significant for non-exempt medical devices Controlling distribution and disposition of devices Submitting applications Submitting reports Device studies in pediatric populations Emergency Use of an Investigation Drug or Biologic Exceptions from informed consent requirements for emergency research Emergency use of unapproved medical devices

6 27.1 Requirements for emergency use After-use procedures Reporting the use of a test article to the IRB Treatment use of an investigational drug/device Single patient (non-emergency use) Humanitarian use device Biologics SPECIAL POPULATIONS 30.0 Definitions Elements to consider in research involving vulnerable subjects Decisionally impaired subjects Surrogate permission with subjects judged incompetent to consent Research involving pregnant women, human fetuses and neonates Neonates Placenta, fetal material Neonates of uncertain viability Nonviable neonates Viable neonate Research involving prisoners Issues to address in reviewing prisoner research Categories of research in which prisoners may participate Required findings Certification of prisoner research Research involving minors Research in school settings Categories of research involving minors that may be approved by the IRB IRB review of research involving minors Students and Employees APPENDICES: Appendix A: The Belmont Report Appendix B: Unaffiliated Investigator Agreement Appendix C: Confidentiality Agreement Appendix D: Requirements for Humanitarian Use Device Appendix E: Involvement in Clinical Research for Non-Health Care Providers

7 INTRODUCTION Intended Audience and Distribution The purpose of the Institutional Review Board (IRB) Standard Operating Procedures (SOP) is to provide direction to members of the IRB and the IRB staff in carrying out duties assigned to the IRB, and to provide a best practices reference guide. This SOP comprehensively summarizes existing policy as well as the regulatory expectations found in the Common Rule (45 CFR 46) and the Food and Drug Administration (21 CFR 50 and 56). The SOPs provide valuable guidance, in conjunction with the Investigator s Handbook, to principal investigators, research professional and administrative staff, and others conducting or involved in research. Maintaining a Current SOP These SOPs are considered to be a living document that will be updated or reviewed annually or more often as changes in statutes, regulation, guidance, practice or policy occur. The SOP is the primary location for compiling, organizing, integrating, and pointing to the rules, policies, practices, and guidance encompassing the University s Human Subjects Protection Program. At least once every three years the Offices of the IRB and Research Compliance and Assurance initiate a comprehensive review of the SOPs. Revisions may be made at any time, however, as required by changes in law, ethical standards, institutional policy, quality assurance activities, or other considerations. Non-substantive revisions (e.g., to correct typographical errors, update links, or incorporate summaries of new or revised laws or regulations governing the IRB) may be made upon approval of the Office of Research Compliance and Assurance with written notice to the IRB. The Office of Research Compliance and Assurance would appreciate receiving your questions, comments, and suggestions for improving this first version by to dlayton@southalabama.edu

8 CONTACT INFORMATION AND LINKS OFFICE OF RESEARCH COMPLIANCE AND ASSURANCE Dusty Layton, Executive Director Website: IRB OFFICE: SuzAnne Robbins IRB Compliance Specialist Website: INSTITUTIONAL OFFICIAL: Lynne Chronister VP for Research and Economic Development INSTITUTIONAL REVIEW BOARD CHAIR: Dr. Hamayun Imran Chair, IRB USEFUL LINKS: DHHS Office of Human Research Protections (OHRP): OHRP guidance documents: OHRP compliance references : Food and Drug Administration (FDA): FDA guidance documents: FDA compliance references : 2

9 PRINCIPLES, ROLES AND RESPONSIBILITIES 1.0 Regulatory and Ethical Mandates The mission of the USA Human Subjects Protection Program is to ensure that: 1. the rights and welfare of human subjects are paramount in the research process; 2. the highest standards of ethical conduct are employed in all human subjects research activities; 3. research investigators are properly trained in the ethical and regulatory aspects of research with human subjects; 4. research investigators inform human subject participants fully of procedures to be followed, and the risks and benefits of participating in research; and 5. research using human subjects at USA conforms with all applicable local, state and federal laws and regulations and the officially adopted policies of the University. The regulation of human subjects research by the U.S. Department of Health and Human Services is codified in 45 CFR 46. Because Subpart A of 45 CFR 46 has been adopted for human subjects research by many federal agencies it is known as the Common Rule. The Common Rule requires that every institution performing federally supported human subjects research file an assurance of protection for human subjects. This research should be guided by the ethical principles adopted in the Belmont Report and, additionally, should conform to the guidance documents described below: 1.1 The Nuremberg Code The modern history of human subject protections begins with the discovery after World War II of numerous atrocities committed by Nazi doctors in war-related human research experiments. The Nuremberg Military Tribunal developed ten principles as a means of judging their research practices, known as The Nuremberg Code. The significance of the Code is that it addressed the necessity of requiring the voluntary consent of the human subject and that any individual who initiates, directs, or engages in the experiment must bear personal responsibility for ensuring the quality of consent. Additionally, the Nuremburg Code, more than other counterparts listed here, is a recitation of participants legal rights, and has been used as a basis for decisions made in adjudicating the cases involving human research. 1.2 The Declaration of Helsinki Similar principles to The Nuremberg Code have been articulated and expanded in later codes, such as the World Medical Association Declaration of Helsinki: Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects (1964, revised 1975, 1983, 1989, 1996, 2000, 2013), which call for prior approval and ongoing monitoring of research by independent ethical review committees. 1.3 The Belmont Report Revelations in the early 1970s about the 40-year United States Public Health Service Study of Untreated 3

10 Syphilis in the Negro Male at Tuskegee and other ethically questionable research resulted in the 1974 legislation calling for regulations to protect human subjects and for a national commission to examine ethical issues related to human subject research (i.e., the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research). The Commission s final report, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, defines the ethical principles and guidelines for the protection of human subjects. Perhaps the most important contribution of The Belmont Report is its explanation of three basic ethical principles: Respect for persons (applied by obtaining informed consent, consideration of privacy, confidentiality, and additional protections for vulnerable populations); Beneficence (applied by weighing risks and benefits); and Justice (applied by the equitable selection of subjects). The Belmont Report is attached to this document as Appendix A. 1.4 Department of Health and Human Services (DHHS) Regulations Federal regulations require specific protections for human subjects. In May of 1974, the Department of Health, Education, and Welfare (later renamed DHHS) codified its basic human subject protection regulations at 45 CFR 46, Subpart A. Revised in 1981, 1991, 1996 and 2005, the DHHS regulations presently include additional protections for fetuses, pregnant women, and human in vitro fertilization (Subpart B), prisoners (Subpart C), and children (Subpart D). The DHHS regulations are enforced by the Office for Human Research Protections (OHRP). 1.5 Federal Policy (Common Rule) for the Protection of Human Subjects. Food and Drug Administration (FDA) Regulations at 21 CFR 50 and 56 When DHHS revised its regulations in 1981, the FDA codified almost identical informed consent regulations at 21 CFR 50 and IRB regulations at 21 CFR 56. Additional FDA regulations that are relevant to the protection of human subjects are: (1) Investigational New Drug Applications (IND) (21 CFR 312) (2) Radioactive Drugs (21 CFR 361) (3) Biological Products (21 CFR 600) (4) Investigational Device Exemptions (IDE) (21 CFR 812) (5) Additional Safeguards for Children (21 CFR 50, Subpart D). 1.6 Federalwide Assurance The Common Rule requires that every institution engaged in federally supported human research file an Assurance of protection for human subjects. The University of South Alabama conducts human use research under the terms specified in its Federalwide Assurance (FWA), the legally-binding agreement to ensure that all human subjects research complies with the requirements of the governing Federal Department or Agency head and its policies. All human subjects research activities, regardless of funding source, will be guided by the ethical principles in the Belmont Report and all other appropriate ethical standards recognized by Federal Departments and Agencies which have adopted the Federal Policy for the Protection of Human Subjects. All research studies will comply with subparts of DHHS regulations as codified in Title 45 CFR Part 4 and its Subparts A, B, C, and D. The Office of Research Compliance and Assurance will submit the FWA and all updates to the federal Office of Human Research Protections at least every three years. The Common Rule Terms of Assurance are listed on the OHRP website. USA conducts human research under FWA #

11 2.0 IRB Mission and Authority The basic principles that govern the IRB in assuring the rights and welfare of subjects are protected are contained in Ethical Principles and Guidelines for the Protection of Human Subjects of Research (The Belmont Report), and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. These principles apply to all research regardless of funding, including student projects. The Institutional Review Board (IRB) has the authority to ensure that all human subjects research conducted at the University of South Alabama complies with regulations of the Department of Health and Human Services (DHHS) 45 CFR 46, applicable Alabama state statues and regulations, the principles of the Belmont Report and the Federalwide Assurance {FWA } of the University of South Alabama. The Human Subjects Protection Program serves their purpose by: 1. Administratively supporting the University s IRB 2. Reviewing all research involving human subject s research before it is initiated, regardless of the funding source 3. Working to protect the rights and welfare of human subjects by fostering and advancing the ethical and professional conduct of persons engaged in research 4. Providing education to researchers and staff 5. Conducting periodic reviews of research involving human subjects, and 6 Serving as the institutional HIPAA Privacy Board The IRB has the authority to place restrictions on, suspend or terminate approval of any human subjects research study. All human subjects research activities must be reviewed, prospectively approved and subject to continuing oversight (at least annually) by the IRB to ensure the safety and welfare of participants, pursuant to the regulation provided in 45 CFR 46. The IRB conducts review and approval for all human subjects research activities conducted under its jurisdiction. This jurisdiction includes research conducted or directed: By USA faculty, staff, students, affiliates or outside researchers and occurs on the property of the University of South Alabama regardless of funding sources By an outside researcher involving USA faculty, staff, students, or affiliates. The VP for Research and Economic Development is the Institutional Official for the institution for IRB purposes through the Federalwide Assurance Agreement. 2.1 IRB Purpose The IRB is responsible for the review and prior approval processes of research activities involving the use of human subjects by engaging in deliberations to adequately provide a comprehensive review of the proposed research activity, assess the risks and benefits to the subjects, ensure the research is 5

12 conducted ethically in an ongoing manner, and maintain communications with research personnel. Duties of members including reviewing IRB application materials in advance of convened meetings and being prepared to discuss issues related to human subjects protection, serving as primary reviewer or secondary reviewer when assigned, and having an understanding of the specific requirements of human subjects regulations. Duties include: 1. Conduct initial and continuing review of research involving human subjects at intervals appropriate to the degree of risk, but at least once a year and report IRB findings and actions to the investigator and the institution. 2. Determine which projects require review more often than annually and which projects need verification from sources other than the investigators that no material changes have occurred since previous IRB review. 3. Review proposed changes in research activities to insure that changes in approved research, during the period for which IRB approval has been given, has not been initiated without IRB review and approval. 4. Require or waive documentation of informed consent. 5. Follow procedures to insure that the IRB and Office for Human Research Protections (OHRP) of the Department of Health and Human Services (DHHS) receive reports of unanticipated problems involving risks to subjects and others. 6. Monitor additional safeguards when vulnerable subjects (minors, mentally incompetent, prisoners, economically and educationally disadvantaged, pregnant females) are involved in the research in order to protect against coercion or undue influence. 7. Conduct its review of research, except when an approved exempt review procedure is used, at convened meetings at which a quorum of the members of the IRB are present. 8. Conduct reviews of all adverse event reports 9. Approve research only with the concurrence of a quorum of those members in attendance. 10. Report to the institution and OHRP any continuing or serious matters of non-compliance by investigators with the requirements and determination by the IRB. 11. Have authority to suspend or terminate approval of research that is not in compliance with the IRB s determinations or has been associated with unexpected serious harm or risks to subjects. 12. Determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review. 2.2 Definition of Human Subjects Research In order to ensure the rights, welfare, and protection of all subjects, all human subjects research, and all other activities, which in part involve human subject research, regardless of sponsorship, must be reviewed and approved by the IRB prior to initiation. This includes all interventions and interactions with human subjects for research, including advertising, recruitment and/or screening of potential subjects. Human subjects research is any research or clinical investigation that involves human subjects. Note: The DHHS definition of human subjects will generally apply to all human research conducted by investigators at the University of South Alabama unless the research involves a test article. Those investigations involving a test article will also be subject to FDA definitions. DHHS regulations define a human subject as a living individual about whom an investigator conducting research obtains (1) data through intervention or interaction with the individual; or (2) identifiable private information. 6

13 Intervention includes both physical procedures by which data are gathered (e.g., venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject or legal representative in the case of minors or other vulnerable populations. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. FDA regulations define human subject as an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient Research DHHS regulations define research as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. A systematic investigation is an activity that involves a prospective plan that incorporates data collection, either quantitative or qualitative, and data analysis to answer a question. FDA regulations define a clinical investigation as any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the FDA, or is not subject to requirements for prior submission to the FDA under the Federal Food, Drug, and Cosmetic Act, but the results of which are intended to be submitted later to, or held for inspection by, the FDA as part of an application for a research or marketing permit. A test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the Federal Food, Drug, and Cosmetic Act. 2.3 Agreements to Provide IRB Review of Research Conducted by Unaffiliated Investigators USA may be asked to provide IRB review for investigators who are unaffiliated with the University of South Alabama. Circumstances in which this arrangement might be considered would typically involve a study based at USA in which the unaffiliated investigator is collaborating in the study. It will generally not be considered appropriate to extend IRB oversight to research by unaffiliated investigators in which USA is not otherwise engaged. All requests for USA to serve as the IRB of record for an unaffiliated investigator should be referred to the Institutional Official. This referral should include an Unaffiliated Investigator Agreement based on the USA approved template attached as Appendix B, together with a recommendation from the USA IRB with responsibility for that given study and/or group of investigators. Usually, this agreement will apply to a single research project. Copies of the agreement will be provided to the unaffiliated investigator and maintained in the Offices of the IRB and Research Compliance and Assurance. 7

14 2.4 Human Research Activities Performed at Other Institutions All research activities performed by, or under the direction of, USA personnel or which use University resources or facilities, must comply with applicable USA policies and procedures, regardless of funding and whether performed in USA facilities or at offsite locations Requirements for Approval of Research at Non-USA Facilities Any human subjects research conducted in whole or in part outside of USA facilities must be reviewed and approved by USA IRB prior to initiation if it satisfies any of the following criteria. It is conducted by or under the direction of USA personnel in connection with his or her USA responsibilities. It uses USA property, facilities, or resources to support or carry out the research. The name of the University of South Alabama is used in applying for funds (intra or extramural). The name of the University of South Alabama is used in explanations and/or representations to subjects. The investigator plans to use his/her University of South Alabama association in any publication or public presentation resulting from the research. Non-public information from USA will be used to identify or contact human research subjects or prospective subjects IRB Approval of Research to be Done at a Non- USA Institution The researcher will need to obtain approval from the Non-USA IRB in addition to the USA IRB for any research done at a Non- USA Institution unless a cooperative review agreement has been executed in advance of the study. IRB ORGANIZATION AND ADMINISTRATION 3.0 IRB Membership At least five members of sufficiently diverse backgrounds, including consideration of racial and cultural backgrounds of members and sensitivity to issues such as community attitudes; Persons who are able to ascertain the acceptability of research applications in terms of institutional commitments, applicable law, and professional standards; Members of both sexes; At least one member whose primary area of expertise is with children; At least two members whose primary concerns are in behavioral disciplines; At least one member whose primary concerns are in non-scientific areas; Members representing more than one profession; A member who is not affiliated or related to a person who is affiliated with the institution; Persons who are primarily concerned with the welfare of vulnerable subjects (minors, prisoners, terminally ill, etc.); When needed, individuals with competence in special areas to assist in the review of complex issues; Participants in the initial or continuing review of projects who do not have a conflicting interest; The standards described above represent minimum requirements which the USA IRB typically exceeds. In many instances, an IRB will have 15 or more members with varied expertise and speciliaization in 8

15 order to meet the research review requirements. IRB membership is recorded on a roster that is submitted to the Office of Human Research Protections (OHRP) and is filed in the IRB office Duties of IRB Members / Criteria for IRB Approval Duties of members include reviewing human subject application materials in advance of meetings and being prepared to discuss issues related to human subjects protections, serving as primary reviewer when requested by the chair, and having an understanding of the specific requirements of human subjects regulations. Duties include: Protecting rights and welfare of human subjects Determining risks are minimized Ensuring that investigators: o use of procedures are consistent with sound research design and that do not expose subjects to risks o when appropriate, use procedures already being performed on the subjects for diagnostic o or treatment purposes, and ensuring that the investigator follows a procedure for properly documenting informed consent Determining that risks to subjects are reasonable in relation to anticipated benefits to subjects Determining that selection of subjects is equitable. In making this assessment, the following should be considered: o o purpose of the research and setting in which the research is conducted IRB members should be cogniz2ant of special problems of research involving vulnerable populations Determining if informed consent is sufficient and includes all mandated elements, if not, request clarifications and changes in consent document Determining that the research plan includes adequate provisions for ensuring the safety of subjects Determining if adequate protections are afforded to protect the privacy of subjects and maintain confidentiality of data If applicable, documenting requirements for wavier of informed consent have been met Ensuring additional safeguards are in place to protect rights and welfare of subjects that are more likely to be vulnerable to coercion or undue influence, such as students, children, prisoners, educationally and economically disadvantaged, etc. 3.1 Chairperson Responsibilities Chairs convene meetings Call special meetings when necessary Make decisions in emergency situations to protect subjects and remain in compliance with regulations Confirms primary/secondary reviewer assignments made by IRB staff as requested Conducts review of all protocols discussed at convened meetings Conducts expedited review of biomedical research studies Reviews policies and procedures on an ongoing basis Serves as an advisor/educator in the institution s research community 3.2 Vice-Chair(s) Responsibilities Performs duties of the chair in his/her absence Assists chairperson, IRB staff as need 9

16 3.3 Committee Member Appointment Committee members are identified by the Office of Research Compliance and Assurance, and recommendations made by the College of Medicine Dean s Office. Commmittee members are appointed by the Vice President for Research and Economic Development. Prospective members may also be identified by the IRB chair and staff who review the nature and demands of the IRB. IRB members are appointed for three year terms which are renewable. If a member resigns prior to the end of their term, a person may be appointed to complete the original term. Members have liability insurance coverage as part of their IRB membership in their capacity as agents of the University of South Alabama Attendance Requirements & Meeting Schedule IRB meeting dates are scheduled a year in advance and provided to members during IRB orientation, as well as posted on the human subjects website. Additional meetings may be scheduled on an ad hoc basis. Members are expected to regularly attend meetings. When a situation arises which results in an unanticipated absence, the member is expected to inform the IRB office so that assignments will not be designated for review. 3.4 Non-voting Members Non-voting members from among the academic or administrative staff of the University are appointed to aid the IRB in conducting its duties. These members may take part in all meetings of the IRB, participate in discussions and make recommendations, but they may not vote on the decisions. Nonvoting members are not included in determining or establishing a quorum at the meetings. IRB meeting minutes reflect the presence of non-voting members. 3.5 Termination of Appointment: Appointment to the IRB may be terminated before the expiration of the three-year term. The Institutional Official may remove an IRB member if he/she, in consultation with the IRB chair or other parties, determines that the member fails to perform his or her duties as a member. The Institutional Official or designee may remove IRB members, IRB chairs, and if used, other officers (i.e., vice-chairs) with consultations from the Executive Director, Research Compliance and Assurance and IRB chair(s). 3.6 Confidentiality Agreement: Upon appointment to the IRB or attendance at an IRB meeting, members (voting or otherwise), consultants, guests, etc., will sign a confidentiality agreement attached as Appendix C. 3.7 Orientation and Training of IRB Members: Following appointment of new members, the Offices of the IRB and Research Compliance and Assurance conducts an orientation session to include topics such as: research compliance, processing of protocols, meeting process and expectations of an IRB member. Additionally, a new member will receive a binder of reference materials and a IRB member handbook (including these SOPs). All members complete the online educational module entitled Protecting Human Subject Research Participants provided by the NIH Office of Extramural Research or comparable training. Members are provided with continuing education opportunities within the institution, and receive continuing 10

17 education materials at regularly held IRB meetings. 3.8 Member Conflict of Interest: No IRB or consultant may participate in the IRB initial or continuing review of any project in which he/she has a conflict of interest, except to provide information requested by the IRB. Examples of such conflicts of interest could include: a member of the IRB who serves as an investigator or sub-investigator on research under review by the IRB, or a member who holds a financial conflict of interest in a sponsor or product under study. In cases where the assigned initial reviewer has a conflict of interest, the review must declare that conflict of interest and the protocol will be re-assigned to another reviewer. The IRB member will indicate a conflict of interest in IRBNet (i.e., recusal or abstention) and is recorded in the minutes as a recusal or abstention. 3.9 Investigator Conflict of Interest It is University policy that individuals conducting human subjects research have a paramount responsibility to ensure that any conflicting interests of the researchers do not compromise the welfare and rights of those human subjects. Identification of possible conflicts of interest is an important step to protect human participants and maintain the integrity of the IRB process. The University requires submission of an annual conflict of interest disclosure form by all faculty members and Employees in an administrative position at or above a director level, as well as disclosure throughout the year of changes that may either: (a) give rise to a potential conflict of interest; or (b) eliminate a potential conflict previously disclosed. In addition the IRB application includes questions that probe for potential conflict of interest in relation to the specific study. Investigators, Co-Investigators and any study personnel are required to disclose Financial Conflicts of Interest or other interests that are, or may be perceived to be related to the study on the application for initial IRB review and approval. If there is a potential or perceived conflict related to the study, the Investigator is asked if the conflict has been disclosed and/or managed. Conflict of Interest disclosure forms are reviewed by the department chair/supervisor and forwarded to the Office of Research Compliance and Assurance. If warranted, the IRB will verify that a management plan has been executed. A management plan template for human subjects research may be used for documenting and identifying appropriate actions to eliminate, reduce or resolve financial conflicts of interest or conflicts of commitment. These matters may be referred to the University Conflict of Interest Committee and the reporting employee shall be notified of the referral. In instances where a conflict of interest involving human subjects research is allowed, it is essential that research subjects and other interested parties be informed of the conflict of interest. If an investigator is participating in a multicenter trial and has been allowed to conduct human subjects research while possessing a financial interest, that fact should be made known to the Investigator or sponsor by the coordinating center. Notification of research subjects falls within the purview of the applicable IRB, which will determine whether and how the conflict of interest should be disclosed to the relevant human research subjects. This may include a description in the consent form of the conflict of interest. 4.0 IRB Administrative Support The IRB staff supports the function of the IRB infrastructure and all activities engaged in human subjects research at the direction and under the supervision of the Director of the Office of Research Compliance and Assurance (ORCA). The Director, ORCA is responsible for directing and overseeing all IRB support functions and operations; training, supervising and evaluating IRB staff; and developing and implementing procedures to facilitate efficient document flow and maintenance of all IRB records. 11

18 The IRB administrative staff: Maintain up-to-date knowledge of policies/procedures and regulations regarding human subjects research and IRB operations. Perform administrative duties to assure systematic flow of work through the IRB. Prepare and distribute review materials to members and consultants. Maintain files Prepare and distribute minutes Send out notification of IRB decisions, requests for additional information and correspondence to investigators in a timely manner. Assist in the conduct of educational workshops IRB forms are used to ensure that polices are integrated into the day to day research and review operations. This enables execution of functions in which the IRB can manage, review, track and notify in a consistent manner. 4.1 Other Committee / Administrative Reviews Human subject s research involving specific risks require additional committee or administrative oversight. The USA IRB communicates between various offices, as appropriate and may rely upon oversight monitoring by these groups in lieu of monitoring at the study site conducted by the IRB. Institutional Biosafety Committee (IBC) The IBC is responsible for ensuring that recombinant DNA activities comply with the NIH guidelines. Projects involving human gene therapy must be reviewed by the IBC. The IRB and the IBC communicates regarding committee deliberations. Radiation Safety Committee If a study requires radiation outside the standard of care, the Radiation Safety Committee must review the study prior to USA IRB granting final approval. This committee reviews any research that involves use of X-ray, radioisotopes or lasers. and provides expertise with regards to accepted radiation protection practices and regulations. The USA IRB allows concurrent review between both committees and defers the release of the study contingent upon the Radiation Safety Committee determinations. Sponsored Projects Administration / Clinical Trials The Director, Clinical Trials and Sponsored Projects Administration each provide additional oversight of human subject s reseach during their reotine review of grants and contracts. These offices communicate with the IRB to resolve issues regarding IRB review of human subject s research, including conflict of interest issues. Sponsored Projects Administration processes all human research with external support that is funding from governmental agencies via evisions and requires the appropriate institutional office(s) review research proposals. HIPAA Privacy and Security Office The USA HIPAA Privacy and Security Office is assigned IRB protocols for review/comment where protected health information is used for the conduct of medical chart reviews, and other protocols involving the use of electronic protected health information. Additionally, a Business Associate Agreement may be needed for data transactions of protected health information. 12

19 Business Office A w-9 is required to be issued to a study participant for completion before payments are made to participants. This W-9 form is completed and returned to the proper University Business Office. A 1099 will be issued to any subject that is paid $600 or more in a calendar year. 4.2 Education and Training of Staff: Staff members will initially receive the same orientation as IRB members with an introductory lecture and orientation to IRB and office procedures. Further training is provided by working in close interaction with other staff members. Staff members should be provided with continuing education opportunities and resources should be made available for them to attend regional or national human subject protection meetings, as deemed appropriate by the Director of the Office of Research Compliance and Assurance in consultation with the Institutional Official. Credentials as a Certified IRB Professional (CIP) will be encouraged for IRB staff. A variety of resource materials (i.e., newsletters, textbooks, meeting materials, etc.) are available. The administrative staff will make every effort to ensure prompt and through review of all submissions to ensure the safety and welfare of research subjects. In addition, it is the responsibility of the IRB chair, Director, ORCA and administrative staff for educating the members of its research community in order to establish and maintain a culture of compliance with regulations and institutional policies relevant to human subject protections. 4.3 Investigator and Key Research Personnel Training Investigators and research personnel must complete human subjects research training as a condition of the University s Federalwide Assurance of Compliance. In addition to human subjects training, all investigator(s) and key research personnel within USA s HIPAA covered entity must complete USA s HIPAA in Research tutorial. Completion of training is a condition for IRB approval. The Human Subjects Protection Program has ongoing educational programs for both IRB members, investigators and study staff. Examples of educational opportunities that are offered include: Clinical research coordinators/nurses forum In-service educational presentations scheduled as a component of convened IRB meetings Workshops tailored and presented for specific research/departments IRB 101 for Students which includes class presentation to students conducting research as part of their class assignment 5.0 Record keeping and Reporting: The Common Rule and, when applicable, Food and Drug Administration (FDA) regulations require written policies and procedures to govern the operations and direct the activities of the IRB. Record keeping and documentation requirements for IRB operations are as follows: Generally, IRB records shall include: (1) Written standard operating procedures (2) IRB membership rosters a. list of members is identified by name, earned degrees, representative capacity 13

20 (3) Training records (4) IRB correspondence (5) IRB research application (protocol) files (6) Research (protocol) tracking system (7) Documentation of exemptions, exceptions or waiver of informed consent (8) Documentation of expedited reviews (9) Documentation of convened IRB meetings minutes (10) Documentation of review for adverse events (11) Documentation of review for protocol deviations/violations (12) Documentation of review by another institution s IRB when appropriate (13) Documentation of cooperative review agreements, e.g., Memoranda of Understanding (MOUs) for multi-site research, or as otherwise appropriate (14) Federal Wide Assurances (FWA) The study-specific records as outlined above relating to research that is conducted shall be retained for at least 3 years after completion of the research. For studies that the IRB has exempted from continuing review, study-specific records shall be retained for at least three years after the exemption is granted. Annually, the IRB will make an inquiry with the investigator regarding the current status of the project until the investigator reports that the study is complete. Authorized persons shall be able to access records for inspection and copying at reasonable times and in a reasonable manner. Investigators may be required to follow different record retention policies depending on study sponsorship. 5.1 Documentation and Retention of IRB Documents At a minimum, retention of records is required by 45 CFR 46 for a period or three years after a research project is completed. USA retains the following documents in accordance with this requirement. Records will be retained longer if required by applicable FDA or DHHS regulations or by the study sponsor. (1) Copies of all research protocols reviewed, evaluations, approved consent documents, applications for initial approval, continuing review, amendments, advertisements, adverse events reports and protocol deviations and any other correspondence from investigators related to the research study. (2) Minutes of convened IRB meetings. (3) Copies of audit reports (4) Training of IRB members, staff, investigators and key research personnel (5) Correspondence with government officials concerning unanticipated problems (6) Correspondence with government officials that could reasonably be expected to affect the status of USA s FWA. 5.2 Access to IRB Records Ordinarily, access to IRB records is limited to the IO, the IRB chairperson, IRB members, IRB staff, Office of Research Compliance and authorized USA representatives, and officials of Federal and state regulatory agencies, including the Office for Human Research Protections (OHRP), and, if applicable, the Food and Drug Administration (FDA). Investigators shall be provided reasonable access to files related to their research. All other access to IRB records is limited to those who have legitimate need for them, as 14

21 determined by the IRB Chairperson, the Director, Research Compliance, University Counsel and the Institutional Official. 5.3 IRBNet Online Management System The IRB utilizes IRBNet, an online management system for submission, review, and approval of human subjects research studies. Principal Investigators submit the applicable study documents (6.2.2 IRB Meeting Materials) via IRBNet for review by the IRB. IRB members use the IRB Review Form to document review of assigned research studies and is uploaded IRBNet. Additionally, adverse events, protocol deviations, and PI conflicts of interest are electronically tracked. IRBNet resources, including login instructions, creating new project submissions, etc., can be found on the IRBNet resource webpage at: IRBNet Electronic Signatures The USA IRB standard operating procedure continues to require the signature of the Principal Investigator on IRB new project submissions. Student Investigator s must obtain signature of his/her faculty advisor before IRB approval is granted. This requirement transitioned from paper submission to electronic submission via IRBNet. This process is simple by logging in IRBNet and clicking the Sign this package button on the left tool bar. Choose your project role from the drop down menu by clicking the arrow on the box, then click the sign button. The PI cannot delegate another person to sign on their behalf IRBNet Forms and Templates The IRB has adopted the IRBNet management system, accessible via the internet, for bringing a comprehensive on-line submission for protocol management. The USA IRB application forms, templates, and guidance documents are posted under Forms/Templates within the IRBNet online portal. MEETING MATERIALS AND DOCUMENTATION 6.0 Meeting Agenda The IRB meets the second Tuesday of each month at 7:00 am. The meeting agenda outlines human subject research activities subject to review by a convened meeting of board members under the jurisdiction of the IRB. Submission of a research protocol will satisfy all of the procedural requirements necessary for the comprehensive review of all of the relevant materials prior to the convened meeting. Additionally, the agenda provides a listing of any discussion items relevant to the operations of the human subject protection program. The IRB Compliance Specialist prepares the meeting agenda. Additionally, relevant materials for review is distributed via IRBNet to all board members a week in advance of the scheduled meeting. The agenda shall include the following items: Date of meeting Approval of minutes from previous meeting Adverse Events Protocol Deviations 15