Research Involving Human Subjects

Research Involving Human Subjects Institutional Review Board (IRB) The Research Office Oakland University

Ethical principles • Belmont Report 1979 • Respect for persons- Informed consent • Beneficence- Favorable benefit-risk ratio • Justice- Selection of subjects • Public Heath Services Act 1985

Human Subject Protection Regulations • HHS Regulations • 45 CFR part 46- Subparts A, B, C, D, & E • FDA Regulations • 21 CFR part 50, Protection of Human Subjects • 21 CFR part 56, Institutional Review Boards • 21 CFR part 312, Investigational New Drug Application • 21 CFR part 812, Investigational Device Exemptions

OU Federal Wide Assurance • Allresearch involving the participation of human subjects must be submitted for review by the IRB (Institutional Review Board for the Protection of Human Subjects).

HHS Definition 45 CFR 46.102(d) • Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

HHS Definition (cntd) • "Systematic investigation“ • Attempts to answer a research question or a hypothesis • Uses scientific methods to collect data • Includes qualitative or quantitative data analysis • Depends upon the discipline • "Including research development, testing, and evaluation“ • Pilot studies, feasibility studies, and other preliminary studies

HHS Definition (cntd) • "Designed to develop or contribute to generalizable knowledge" • Designed means the study methods are adequate to answer the research question • Generalizable means universally or widely accepted to apply to a population beyond the site of data collection or population studied • Dissemination of research results is generally through research/scientific publications; results are expected to contribute to generalizable knowledge by filling a gap in scientific knowledge, or supporting, refining, or refuting results from other research studies.

HHS Definition (cntd) 45 CFR 46.102(f) • Human subject means a 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.

HHS Definition (cntd) • "A living individual“ • Information about deceased individuals would not meet the definition except when Secondary living individuals are affected, (e.g. genetic studies) • "About whom“ • Gathering information about livingindividuals • NOT “from whom” or “about things” (e.g. institutions, organizations, programs, etc.). • "Interactions“ • Includes communication or interpersonal contact between investigator and subject, (e.g. interviews, focus groups, online surveys, telephone interviews, etc.)

HHS Definition (cntd) • "Interventions“ • includes both physical procedures by which data are gathered, (e.g. venipuncture, collection of blood pressure) and • manipulations of the subject or the subject's environment that are performed for research purposes, (e.g. playing a video game, listening to music, watching a movie, etc.)

HHS Definition (cntd) • Private Information: • Information about behavior that occurs in a setting in which the individual can reasonably expect that no observation or recording is taking place • information that has been provided for specific purposes, other than research, where the individual can reasonably expect that it will not be made public (e.g., a medical record.) [45 CFR 46.102(f)]. • Protected Health Identifiers (PHI) • Personally Identifiable Information (PII)

HHS Definition (cntd) • Coded Private Information or Biological Specimens • HHS Office of Human Research Protection (OHRP) policy considers private information or specimens to be individually identifiable when they can be linked to specific individuals either directly or indirectly through coding systems. • HHS OHRP guidance states that only a knowledgeable person or entity is authorized to determine if coded specimen or data are identifiable and constitute research. An investigator cannot make that determination.

“Not Research” or “Not Human Subjects Research” Activities • Class Projects • Program Evaluation • Quality Assurance/Quality Improvement Projects • Service Surveys • Oral History Projects • Biography Research • Case studies involving 3 or less participants • Publically available data • Non-identifiable private information Note: Results may be published or presented as site and population specific. May need a determination letter from the IRB. Complete Nonhuman Subject Determination Form.

Activities Requiring IRB Review • The research is sponsored by OU regardless of the location of the project • The research is conducted by, or under the direction of, any faculty, student, or other agent of OU • OU is “engaged” in the research (collaborative project) • The research involves the use of OU’s non-public information to contact human research subjects or prospective subjects • OU is the recipient of a federal grant • The research is conducted using any OU property or facility (Only needs a permission from the IRB office)

Institutional Review Board • IRB is a review committee established to help protect the rights and welfare of human research subjects. • Authority of the IRB: • Approve, disapprove, or modify research • Conduct continuing reviews • Observe and verify changes • Suspend or terminate approval • Observe the consent process and research procedures

Review Categories • Exempt • Expedited Review • Full board Review • Depends on the Risk Level (physical, psychological, social and economic risk)

What is “minimal risk”? • Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Review Categories (cntd) • May be “Exempt” • Projects that present no more than “minimal risk” to the participants and do not compromise the privacy of the participants or confidentiality of the data • Fits 1 of 6 categories • Reviewed by an IRB member or staff • Common in Educational Research (survey, interview, focus group, educational test, observation of public behavior, etc.)

Research Not Exempt • Some interactions with Children (under 18 yoa) • survey, interviews, PI participate in activities during an observational study • Prisoners are research participants • Deception is used in the research • Audio taping, videotaping or photographing is used for research purposes • Exception: Recording for transcription purposes only • Collection of Protected Health Information (PHI)- HIPAA Regulation

Exempt Rapid Review at OU • In-office Rapid Review by an IRB staff • By appointment only • Must complete the Exempt Rapid Review and the Departmental Liaison Checklists • Mark the submission with “Rapid Review” in the “Your Comments” when submitted in IRBNet

Review Categories (cntd) • May be “Expedited” • Projects that present no more than “minimal risk” to the participants, and for minor changes in approved research • Has to fit 1 of 7 categories • Reviewed and approved by 1 or 2 IRB members • Common in Educational Research [collection audio/visual/digital data, behavioral research, survey, interview, focus group, etc.] • Not Expedited- Surveys about illegal behaviors that could be linked back to participants

Review Categories (cntd) • Full Board Review • Projects involving more than minimal risk • Full Committee meets once per month • Application is first reviewed by primary and secondary reviewers • Researcher may be invited to present the research • Vote is taken (in the absence of the researcher) and recommendations are made

Review Categories (cntd) • Continuing Review • Annually for Expedited or Full Board approved applications. • Email notifications sent at 60 and 30 days prior to approval expiration date. • Must complete Continuing Review Application • Same type of review as the original application with some exceptions. • If intervention/interaction and analysis of identifiable data are completed, the study can be closed. Complete Study Completion/Closure Report Form

Approved Research • Research must be conducted as approved by the IRB. • changes to original application must be approved before implementation by submitting applicable Amendment Form(s) • Continuing Review Application must be submitted to extend the research beyond one year. • Study Completion/Closure Report Form must be submitted to close the research • Adverse Events Related to Research must be reported by using Event Reporting Form All applications, forms and templates are found in the Forms and Template library of the on-line application submission system, IRBNet

Criteria for IRB Approval of Research 1. Risks to subjects are minimized • sound research design which do not unnecessarily expose subjects to risk, • using procedures already being performed on the subjects for diagnostic or treatment purposes. 2. Risks to subjects are reasonable in relation to anticipated benefits, and the importance of the knowledge that may result. 3. Selection of subjects is equitable.

Criteria for IRB Approval of Research (cntd) 4. Informed consent is sought. 5. Informed consent is appropriately documented. 6. Plans for monitoring the data collected to ensure the safety of subjects. 7. Adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. 8. Additional safeguards to protect vulnerable population (children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons).

IRB Requirements • IRB must review: • A complete description of the proposed research • Provisions for the adequate protection of rights and welfare of subjects • Compliance with pertinent federal and state laws/regulations and institutional policies • Qualification of the PI and collaborators • Full description about conflicts of interest if any

HIPAA Requirements • Health Insurance Portability and Accountability Act • Mandated standards for storage and transmission of healthcare information • HHS- The Privacy Rule & Security Rule • The research must be HIPAA compliant • HIPAA language requirement in consent form • Protected Health Information (PHI) - 18 identifiers • Authorization, Limited Data Set (16 ids) and Data Use Agreement • HIPAA only covers personally identifiable health information • NO PHI can be brought to or stored on OU campus

FERPA Requirement • The Family Educational Rights & Privacy Act of 1974. • Has several provisions that protect a student's information: • Prohibiting the disclosure of personally identifiable information without written permission from the student • Prohibiting the inspection of student records without written permission from the student • De-identification of student educational records by a neutral third party or an hornet broker • Google Doc should NOT be used to collect identifiable student data • OU has an agreement with Qualtrics. To create a survey, log into Oakland.qualtrics.com using OU IDNet login

De-Identifying Student Records • Per the US Department of Education Privacy and Technical Assistance Center, • *De-identification of data refers to the process of removing or obscuring any personally identifiable information (PII) from student records in a way that minimizes the risk of unintended disclosure of the identify of individuals and information about them. • *PII includes not only direct identifiers, but also other sensitive information that, alone, or combined with other information that is linked to a specific individual, would allow identification. Therefore, simple removal of direct identifiers from the data to be released does NOT constitute adequate de-identification. • Need to complete Appendix M *Privacy and Technical Assistance Center: Data De-Identification: An Overview of Basic Terms

Informed Consent Process • It is a process and not just a form. • It includes: • Recruitment materials • Verbal instructions (in person or via video, DVD) • Written materials • Q & A session(s) • Documentation of consent by signature • Signed copy must be kept with the research records and a copy should be given to participant

Elements of Informed Consent • Eight Basic Elements • Research, Purpose, Procedures (experimental), Expected duration • Risks and discomfort • Benefit • Alternatives procedures (Treatments) • Confidentiality of records • Medical treatment in case of research related injury • Contact Info: Research Qs, Rights Qs, Injury Qs • Participation is Voluntary

Elements of Informed Consent (cntd) • Additional elements, as appropriate • Unforeseeable Risk (embryo or fetus) • Participation may be terminated by researcher • Additional cost to subjects • Consequences of early withdrawal by subjects • Significant new findings that may affect willingness to continue participation • Approximate number of participants

Informed Consent Process (cntd) • Informative – Participants must understand the nature of the research, purpose, procedures, risks and benefits to make an informed decision • Voluntary participation - free of coercion, undue influence, or exculpatory language • Comprehension – well organized, written in lay language appropriate for subject • Allow ample time for consideration and opportunities for questions

Consent Documents • Researchers MUST use the most recent IRB approved version (date-stamped) of the consent document(s). • The IRB approved date-stamped consent documents are published as Board Documents under Reviews in IRBNet. Researchers need to download and save it for their records. • OU Consent Document Templates found in the IRBNet Forms and Template library are Required. • Note: Sections not related to the research should be deleted.

Waiver or Alteration of Consent • The IRB may approve a waiver or alteration of the consent process provided: • The research involves no more than minimal risk to the subjects; • The waiver or alteration will not adversely affect the rights and welfare of the subjects; • The research could not practicably be carried out without the waiver or alteration; AND • Whenever appropriate, the subjects will be provided with additional pertinent information after participation. • Need to complete the relevant Appendix

Waiver of Documentation of Consent • The IRB may approve a waiver of the documentation of consent (not collecting signatures) provided: • The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality; OR • The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. • Need to complete the relevant Appendix

Review by Institution • Research that has been approved by an IRB may be subject to further appropriate review and approval or disapproval by officials of the institution. • However, institutional officials may not approve the research if it has not been approved by an IRB.

Collaborative Research • Institutions participating in collaborative research may do the following: • Enter into an IRB Reliance Agreement to declare one of the institutional IRBs as the IRB of Record, or • Make special arrangements to avoid duplication of efforts.

Collaborative Research (cntd) Collaborative research that was reviewed by another IRB: • If Exempt, complete the Dual Review Exempt Application • If Expedited or Full Board, complete the IRB Reliance Agreement Application • Provide copies of the IRB of Record exempt or approved application, decision letter, consent form and other documents

Other Agreements • Collaboration Agreement • WBH Research Collaboration Acknowledgement • WBH Student Research Agreement • Data Sharing Agreement • Data Use Agreement • Material Transfer Agreement

How to Apply • Submit an application via IRBNet accessible through the Human Subjects (IRB) link on Research website https://wwwp.oakland.edu/research/compliance/ • All applications, forms, appendices and templates are located in the Forms and Templates library of IRBNet. • IRBNet Training Videos and Presentations at http://www.irbnetresources.org/tresources/training.html The login information- Username: oakland and password: training.

How to Apply (cntd) • Researchers including all key personnel must register with IRBNet. • The most current version of applications, forms, appendices, consent templates (adult, parental permission, child assent, information sheet) MUST be used. • All sections of the forms must be completed. • The submission must include CITI training completion reports for all researchers.

CITI Training- Required • OU Human Subjects CITI Training at https://www.citiprogram.org • Human Subject Research Basic/Refresher Course • Three Leaner Groups: • Faculty • Student and Faculty Advisor • IRB Member • Additional modules/courses as applicable to the research: • Research with Children • Vulnerable Subjects – Research Involving Pregnant Women, Human Fetuses, and Neonate • Research with Prisoners • Health Information Security and Privacy • International Research • Avoiding Group Harms – US Perspectives • FERPAfor Researchers

IRB Important Updates • Updated IRB Forms and Templates • The most current versions of the IRB Applications, Forms, Appendices and Consent Templates are available in the Forms and Templates library in IRBNet • All researchers are requested to download the latest versions from IRBNet before completing any form or application. • EU GDPR • If personal data will be collected from European Union (EU) citizens or residents who reside in an EU country at the time of the research, contact the IRB Office to ensure compliance with consent procedures under the EU General Data Protection Regulation (GDPR).

Who Can Apply • All research must be conducted or sponsored by an OU faculty member. • Non-tenured track professors and staff members may obtain a “Special Permission” to conduct or sponsor research. • Special Permission form is available in the Forms and Template library in IRBNet • Needs a copy of the CV and a support letter

Researcher Responsibilities • Protect the rights and welfare of research participants. • All investigators conducting research involving human subjects must complete CITI Training. • Faculty Sponsor must approve a student application before it can be reviewed by the IRB. • All research must be exempted or approved beforeit can be conducted. • Research must be conducted as described in the approved or exempted application. • Any change to approved research must be approved before it is implemented. • Continuing review must be done before approval is expired.

Researcher Responsibilities (cntd) • Informed consent must be obtained and documented before the subjects are involved in the research. • Save copies of signed consent for 3 yr. after the completion of the study. • All adverse event, unanticipated problems involving risks to subjects or others, noncompliance, and/or subject complaints must be reported to the IRB. • Adequate record keeping and retention • Ensure the confidentiality and security of the research records • Ensure approval from other regulatory compliance committees (IBC, RSC) before initiating the research • Verify that IRB approval has been obtained from all institutions participating in collaborative research.

After Project is Submitted • Pre-review by IRB administrative staff for completeness • Check other regulatory compliance i.e. Biosafety, Radiation Safety • If not exempt, assign to IRB member(s) • Request for modifications, conditional approval, or approval letters are published as Board Documents under Reviews in IRBNet. • IRBNet submission package is unlocked to allow the PI to make changes before approval is issued. • Subsequent submissions (Amendment, Event Report, Continuing Review, Closure) are submitted in “New Packages” in the same IRBNet project.

Review Time-line • Exempt determination 1 day to 2 weeks • Expedited Review • IRB member is given 10 business days to complete a review. • May be approved within 2 to 4 weeks. • Full Board Review • the primary reviewer is given 10 business days for a preliminary review. • You may be asked to attend the meeting if needed. • IRB meets monthly. • May be approved within 1-2 months – Depends on the complexity of the project. • Depends on collaborative efforts from PI and IRB

Research Involving Human Subjects