Institutional Review Board (IRB) Overview for Medical, Behavioral and Educational Research

1. Institutional Review Board (IRB) Overview for Medical, Behavioral and Educational Research Jack Medendorp M.S., B.S.N., CIP. Office of Regulatory Research Compliance Drexel University

2. DISCUSSION POINTS • Regulatory Oversight • What is Research? • Levels of IRB Review • Qualifications and Training • Application Process • Investigator Responsibilities

3. Regulatory Research Environment • The last few years have witnessed increased public and governmental scrutiny of research involving human subjects resulting in a move towards significant enhancement in regulatory and ethical standards to ensure that researchers, sponsors and funding agencies operate in accordance with all applicable regulations • Therefore, in this enterprise, researchers, institutions and funding agencies have the heavy responsibility to keep research subjects out of harms way. • An important consideration in this environment is: • Grasp of regulatory issues • Compliance by researchers and others involved in this enterprise • Gain public acceptance and confidence

4. Consequences of Improper Conduct • Reputational damage to: • Research focus and advancing research • Researcher and his/her institution = financial hardship (loss of funding, etc.) • Litigation • Regulatory sanctions • Fundamentally unethical All of the above force us to reexamine concepts of: - Personal responsibility - Ethical or legal culpability

5. Office of Regulatory Research Compliance (ORRC) Objectives Operate in accordance to all Federal, State, local regulations • Office for Human Research Protections (OHRP) guidelines CFR 45.46 HHS/NIH supported clinical and non-clinical research • Food and Drug Administration (FDA) Code of Federal Regulations (21 CFR Part 50, 54, 56, and 312) Drug, Devices, Biologicals, Radiological • Health Insurance Portability and Accountability Act (HIPAA) Protection of personal, identifiable health information • Drexel University policies and IRB guidelines Encompass all areas of research

6. ORRC Objectives • Oversight of all Investigator research activities: • Provide assistance and guidance to investigators • Ensure ethical conduct and compliance in performance of research in the following areas: • Human subject protection • Adults, Children and Vulnerable Populations • Promote responsible conduct of research • Consideration for subject safety, ethics, and integrity • Oversight of Behavioral, Educational and Medical research • Conflict of Interest (determination and avoidance)

7. What Is Research? • Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities. HHS regulations define research at 45 CFR 46.102(d)

8. Types of Research Requiring IRB Review STUDIES INVOLVING: • Human subjects or information derived from human subjects that is about that subject (sensitive surveys and questionnaires) • Human tissues and specimens specifically, and prospectively collected for purposes of research • Data and confidential information from human subjects which is identifiable • Any type of research that may place the subject at minimal to more than minimal risk • Studies involving vulnerable populations • Prisoners, pregnant women and fetuses, children, emotionally challenged or deficient.

9. Who decides whether an IRB review and approval is required? • OHRP has recommended that investigators not be given the authority to make an independent determination that research does not involve human subjects • Therefore, all investigators irrespective of whether their study involves human subjects or not, must submit their application to the ORRC for a determination to be made whether the proposed study is research and whether it involves humans subjects • The individuals who are authorized to make this decision at Drexel University and Drexel University College of Medicine are: • IRB Chairs or Chair’s designees • Vice Provost for Research Compliance • Assistant Director for Research Compliance

10. What is an IRB? • Usually, a voluntary administrative board which has the authority to approve, request modifications to, or disapprove research involving human subjects or information derived from human subjects. • IRBs are federally mandated to ensure that human subject research is conducted in accordance with federal regulations (Common Rule) and rights of subjects are protected. • Federal regulations require that all research involving human subjects or analysis of data gathered from human subjects including data mining, surveys, clinical records and charts, regardless of funding source/status be reviewed by the IRB PRIOR to the implementation of any research activity.

11. Drexel University College of Medicine IRB Committees DUCOM research oversight is registered with DHHS under the Assurance for Drexel University College of Medicine. Four separate IRBs: IRB #1- Adult Medical/Psychological Trials IRB #3- Adult Behavioral/Educational/Social IRB #4- Children Medical/Psychological Trials Western IRB (WIRB)- Multicenter Sponsored Clinical Trials

12. Meeting Dates DUCOM IRB’s • IRB #1 meets every 1st and 3rd Wednesday of each month, alternating between 1601 Cherry St. and Hahnemann University Hospital/NCB. • IRB# 3 meets every 3rd Thursday of each month scheduled at Drexel University and 1601 Cherry St. • IRB#4 meets every 3rd Wednesday of each month at St. Christopher’s Hospital for Children. • WIRB has 14 committees and meets weekly

13. IRB MEETING DEADLINES • Meeting dates and deadlines for submission for full board meetings are posted on the Office of Regulatory Research Compliance Website www.research.drexel.edu/compliance • There are NO deadlines for Exempt and Expedited review applications. • WIRB deadlines: Contact WIRB directly at www.WIRB.com

14. IRB Levels of Review • Study may fall within the guidelines of one of the following levels of review: • Case study or case review • Exempt from IRB review (less than minimal risk) • Expedited review (minimal risk) • Full review (more than minimal risk) requiring rigorous review of risks and benefits by convened IRB

15. IRB Levels of Review • Case study and Case reports • Three or fewer patients, are prepared for the purpose of illustrating some points in the care of a patient, to educate and formulate new research questions which may eventually lead to generalizable knowledge. • Examples: • Uncommon observations • Report of a new condition, treatment and follow up • Report of a familial condition with a proposed mode of inheritance • Questions regarding a new theory • Unusual combination of conditions or events that cause confusion • Adverse responses to therapies

16. IRB Levels of Review • Exempt: Categories 1-6 • Category 1: Research involving normal educational practices • Category 2: Educational tests, surveys, questionnaires • Category 3: Survey and interview of public officials • Category 4: Use of existing records/data/biological samples • Category 6: Taste and food quality evaluations • Rarely will involve consent of subject, may require use of HIPAA waiver of authorization (biologic samples/specimens)

17. IRB Levels of Review • Expedited Review • No more than minimal risk to the human subjects, • According to Health and Human Services, 45 Code of Federal Regulations, Part 46.102i, "minimal risk" means that the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater in and of themselves from those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. "Minimal Risk" does not include administration of medication or use of any device placed inside the body.

18. IRB Levels of Review • Types of Expedited Review: • Retrospective chart review with waiver of consent and HIPAA waiver • Prospective collection of health information with informed consent inclusive of HIPAA • Minimally invasive collection of human specimens (venipuncture, prospective collections of discardable tissue) • Questionnaires and surveys of a sensitive nature or with identifiers (may qualify for full)

19. IRB Levels of Review • Full IRB review: • Projects for which the level of risk is determined by the principal investigator or Chair of the IRB to be greater than minimal. (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 examination(s) or test(s). • Examples: projects which involve deception, sensitive or protected populations; e.g. minors, prisoners, fetuses, mentally disabled, test subjects for new drugs or clinical devices, pregnant women, illegal behavior, or legally incompetent persons • Investigational New Drugs • Investigational Devices

20. QUALIFICATIONS AND TRAINING • Who can be a PI? • Policy at DU/DUCOM requires a PI to be • Attending Physician • Faculty • Staff • Who can be a sub-investigator? • Fellows • Residents • Students • Research assistants

21. Mandatory Training • Every Investigator, faculty member, staff or student directly involved in the proposed research activity must complete the appropriate Collaborative Institutional Training Initiative (CITI) training modules before a research protocol is approved. • Beginning July 1st 2010, CITI training specific to your type of protocol is required regardless of the type or level of IRB review and approval. • Approval letters for new applications to the IRB, Periodic renewals for continued enrollment or data analysis, and amendments to protocol to add new personnel will not be released until the necessary CITI training modules are complete.

22. CITI Training Courses DUCOM offers four (4) CITI training courses • CITI Human Subject Research (HSR) Training • (All Investigators/Key Personnel) • CITI Good Clinical Practice (GCP) • (drug, device or conducting clinical trials) • CITI Responsible Conduct of Research (RCR) • (required for applicants to National Science Foundation) • CITI Health Information Privacy and Security (HIPS) • (All personnel accessing PHI) All applicable CITI training courses require recertification every two (2) years.

23. Training Requirements • The required CITI training courses may be found at: • www.research.drexel.edu/compliance or • www.citiprogram.org DUCoM specific guidance and FAQs may be found at http://drexel.edu/research/compliance/training • Personnel with CITI training certificates completed at non-DU/DUCOM institutions will be honored, though additional modules may be required, and be renewed every 2 years.

24. Drexel Core Training Modules • Additional training courses may be required depending upon: • Use or access to Protected Health Information (HIPAA I & II) • Use of surrogate, substitute or proxy consent process • DUCOM Core HIPAA and Surrogate consent training do not require recertification • Collection and processing of human specimens/tissues, (blood borne pathogen, laboratory safety training) • Shipping of human or animal specimens/tissues off campus, • Blood borne pathogen, Lab safety, and Shipping courses require annual recertification • These Drexel Core training modules may be found at www.research.drexel.edu/compliance OR http://drexel.edu/research/compliance/training/

25. The Process • Who can Assist you? • Each committee has a specifically assigned IRB Coordinator • Office of Regulatory Research Compliance • www.research.drexel.edu/compliance • Phone: 215 255-7857 • Address: 1601 Cherry Street, 3 Parkway Bldg., Suite 10-444 Philadelphia, Pa 19102

26. Working with the IRB • Pre-submission questions • Set up an appointment with ORRC • Attend monthly “lunch and learn” workshops, 2nd Tuesday of every month with Jack Medendorp at 12 noon • Request for departmental meeting • Ask questions • Obtain information on how to complete forms • Obtain information on levels of review • Review status and follow up assistance for assistance with your IRB Coordinator

27. What does an IRB expect of an application? • Consideration of how the substantive issues & methods fit with ethical guidelines & IRB requirements • Clarity in statement of problem, Research Questions & Methods of data collection • Consistency in content of all documents • Completeness of all materials

28. What Forms Do I Submit? • Case Study: (Original) • CS application, HIPAA waiver, copy of the Case Study • Exempt: (Original and 1 copy) • Checklist • Category 1-6 application • Written proposal • Data collection tool/survey/questionnaire • Any advertisement/announcement • Letter of approval from the “Owner” of data/material when the data is owned by an individual or entity other than DU/DUCOM/Tenet

29. What Forms Do I Submit? • Expedited Review: All applications must include the following (Original and 3 copies) • Checklist • Transmittal form (ONLY IF FUNDED) • Written proposal • Full review/Expedited review form • Expedited certification form • Data collection tool/survey/questionnaire • Any advertisement or announcement • Internal indemnification form • SPECIAL NOTE: • If your application is for pathologic samples, or chart review, use their specific application form and NOT the combined form

30. What Forms Do I Submit? • Expedited special circumstances: • If your interaction and/or data collection is in any way prospective you MUST consent the subject by use of a consent form inclusive of HIPAA authorization • If your data collection is ONLY retrospective then you MUST include a consent waiver and HIPAA waiver of authorization • Minors? Consent/Permission form and Assent form

31. What Forms Do I Submit? • Full Review: (Original and 3 copies) • Checklist • Transmittal form (ONLY IF FUNDED) • Written proposal • Investigator Brochure • Full review/Expedited review combined form • Consent for with HIPAA authorization • Minors? Consent/Permission form and Assent Form • Data collection tool/survey/questionnaire • Any advertisement or announcement • Internal indemnification form

32. Investigator Initiated Clinical Trials and Research • New Committee: Investigator Initiated Study Advisory (IISA) Committee • IISA reviews Investigator Initiated Clinical Trials and Research proposals independently in advance of an IRB application • Committee evaluates investigator initiated protocols and provides guidance to the investigator and university related to: • Risk and or need for university indemnification • Conflict of Interest • Funding and Cost Analysis • Need for infrastructure or manpower • Identify possible need for FDA/OHRP registrations (IND, IDE, Certificate of Confidentiality) • May recommend Drexel IRB vs. WIRB review Contact Jack Medendorp at 215-255-7859 for additional clarity.

33. Investigator Initiated Clinical Trials and Research • IISA guidelines and application instructions/forms may be found at http://www.research.drexel.edu/compliance/IRB/iisa.aspx • The IISA membership: • Clinical Research Group (CRG) • Office of General Counsel • Office of Regulatory Research Compliance • Additional experts/consultants as necessary • This process: • Should be done in advance of an IRB application, • The PI is invited to take part in the review, • The IISA is not an editorial review, and • IISA is independent of the IRB review process.

34. How Long Does IRB Approval Take? • IT DEPENDS upon the level of review and the investigator’s responses to IRB conditions. • Exempt and Expedited reviews generally take less time than full board reviews. • In general, the turn around time may be improved if investigators respond to IRB/ORRC questions. • Need assistance in responding to questions or clarifications on questions, contact ORRC so the office can help you resolve those questions

35. WHEN CAN I BEGIN MY RESEARCH? NO RESEARCH ACTIVITIES MAY COMMENCE UNTIL: • YOU HAVE RECEIVED YOUR IRB LETTER OF APPROVAL, AND IF APPLICABLE, • YOUR APPROVED AND STAMPED CONSENT FORM

36. WHO CAN ASSIST WITH MY RESEARCH ACTIVITIES AND CONSENTING OF SUBJECTS? • Only investigators, sub-investigators and research coordinators or assistants who have been approved by the IRB for the study, and have completed all relevant training requirements.

37. WHO IS PERMITTED TO OBTAIN A RESEARCH SUBJECT’S CONSENT? • ONLY THOSE QUALIFIED INDIVIDUALS WHO: • HAVE COMPLETED THEIR HUMAN SUBJECTS RESEARCH TRAINING, • HAVE SIGNED A CONFLICT OF INTEREST STATEMENT, • HAVE BEEN APPROVED BY THE IRB, AND • WHOSE NAMES APPEAR IN THE SIGNATURE SECTION OF THE CONSENT FORM.

38. WHO IS RESPONSIBLE OF FOR THE RESEARCH ACTIVITIES AND OUTCOMES? • THE PRINCIPAL INVESTIGATOR IS RESPONSIBLE FOR ALL ACTIONS AND ACTIVITIES OF ALL INDIVIDUALS WHO CONTRIBUTE TO THE STUDY. • ANY MISCONDUCT, FAILURE TO FOLLOW THE APPROVED PROTOCOL OR FAILURE IN COMPLIANCE AND REPORTING IS THE PI’s RESPONSIBILITY!

39. What happens after initial Approval? • How can I change the protocol after it is approved? • Researcher submits for review all modifications or amendments (if any and however trivial they may be) • Every project is approved for the duration of one year; Yearly (at least) continuing review and approval is required for the continuation of the research • Protocol Expiration: 364 Days after date of approval • If continuing review is not done, the project expires on the expiration date, no new subjects should be enrolled into the study, (reporting obligations to the ORRC remain). • Expired protocols for reactivation requires brand new review.

40. Reports, Records and Continuing Reviews • Activation notice sent by the PI to the IRB once the study begins enrollment • Continuing Reviews are done as often as necessary, but not less than once per year • Adverse Event reporting • Reporting non-compliance and suspensions to regulatory authorities, Institutional Officer and funding agencies • Accurate record keeping is critical (all documents related to the study must be kept in the regulatory binder) • Final reports

41. Non-complianceConsequences • Serious Noncompliance Human subject research being carried out without IRB review and approval by institution’s IRB. Serious noncompliance also includes substantive modifications to IRB-approved research without IRB approval. • Continuous Noncompliance This involves a principal investigator making the same mistake several times repeatedly, particularly after an IRB has informed him or her and his/her team member(s) of the problem. Continuous noncompliance also includes if the principal investigator has multiple problems with noncompliance over a long period of time or has a problem with multiple projects. • Suspension or Termination The IRB and the Signatory Official and the Humans Subject Protection Administrator have the authority to suspend or terminate approval of human subject research that is not being conducted in accordance with the IRB’s requirements

42. In Summary • When in doubt, ask questions; seek help • Remember: consideration for clarity, consistency, completeness • On-going process – keep dialogue open • All committees use “reasonable person” standard to ensure high standards of ethical research • These committees help facilitate responsible of conduct of research

43. Questions? Contact the Office of Regulatory Research Compliance at 215-255-7857