1. Lifespan 1 A short course Institutional Review Boards (IRBs) and Human Subjects Research Protection Programs (HRPP) A short course

2. Lifespan 2 Course Content Part 1: Brief Description of the IRB and Research at Lifespan Part 2: IRB Support Staff Function Part 3: Researcher Responsibilities Part 4: How to submit items for review by the IRB Part 5: Brief discussion about Informed Consent

3. Lifespan 3 Part 1 Brief overview of the IRB and Research at Lifespan

4. Lifespan 4 What is an IRB? IRB = Institutional Review Board at least 5 members at least 1 must have a scientific background at least 1 must be a non-scientist (this member must attend a meeting to achieve quorum) at least 1 non-affiliated member (not affiliated with the institution) Members should have expertise in the research that will be reviewed.

5. Lifespan 5 IRBs are regulated by State and Federal Regulations Federal: FDA (Food and Drug Administration, Title 21 CFR ) and OHRP (Office for Human Research Protection, Title 45 CFR Part 46) State of Rhode Island: Section 16, Rules and Regulations for Licensing Hospitals.

6. Lifespan 6 Why is research so heavily regulated? The history of Research has not always been one of ethics and regulations – Nazi war crimes; Tuskegee syphilis study; Yale Milgram experiments (obedience to authority, 1961-62); tea room experiments (homosexual behavior in public restroom – mid 60’s)

7. Lifespan 7 1974- National Research Act mandated specific requirements for institutional review committees which became known as Institutional Review Boards (IRBs) 1979- The Belmont Report provided guidance as to how the new rules should be applied. The Belmont Report defined the three philosophical principles relevant to research:  Respect to persons – must provide adequate information and obtain voluntary consent  Beneficence – Minimize harm maximize benefits  Justice – Selection of subjects must be fair and justified The Modern IRB is Born

8. Lifespan 8 The Primary Concern of the IRB is the Rights and Welfare of the Research Participants

9. Lifespan 9 The Main Purpose of IRB Review To assess the risk/benefit ratio. To ensure that informed consent is obtained in an appropriate manner To verify that the recruitment methods/materials are not misleading or coercive To ensure that the selection of subject is equitable and justified

10. Lifespan 10 Research at Lifespan Lifespan has three IRBs (2 at RIH and 1 at TMH) Researchers at Lifespan may submit to any of the 3 IRBs. The exception is prison protocols which must be submitted to TMH IRB. The Lifespan Research Program is considered to be of medium size when compared across the country. Currently we have:  1,250 active protocols;  TMH has 335 and the RIH IRBs have 915

11. Lifespan 11 Lifespan’s HRPP hierarchy Dr. Arthur Klein, Sr.VP– Institutional Official oversight responsibilities for the HRPP, delegated to Dr. Klein through the Presidents at each Lifespan Affiliate Peg McGill -Director Lifespan Office of Research Administration Pat Houser- Manager Research Review Committees

12. Lifespan 12 Who are the members of Lifespan’s IRBs? Lifespan’s IRBs are made up of physicians, PhDs, pharmacists, nurses, clergy, retirees, and community members who VOLUNTEER their time to review human subject research proposals. Members typically spend 2 hours per month reviewing protocols and 2+ hours at the IRB meeting. Chairpersons spend considerably more time in service to the IRB.

13. Lifespan 13 Accreditation of the Human Research Protection Program Lifespan is seeking accreditation of our human research protection program This accreditation seeks to accredit the entire human research protection program for all of Lifespan not just the IRBs. That means we’re all in this together.

14. Lifespan 14 Part 2 Research Review Committee Office

15. Lifespan 15 Who Are We? The Research Review Committee Office is made up of the following: IRB Manager-  Responsible for the management of research activity and IRB support staff involved in the daily activities of processing research.  Assures regulatory compliance of IRB’s as well as researchers and protocols  Assists the research community with information needed to ensure compliance Committee Assistants-  Provide administrative support to the IRB, researchers and coordinators.  Process, maintain, and update the database, paperwork and files of all research projects. Committee Coordinators-  Review initial IRB applications, continuing review, adverse events and amendments  Act as a communication liaison between the committees and the Investigator  Review all submissions to the IRB for appropriate documentation  Transcribes the IRB meeting minutes and follows up with the investigator with IRB requests for approval.

16. Lifespan 16 What Do We Do? Review all submissions for completeness and accuracy Make a preliminary determination of whether the submission qualifies for exempt, expedited, or full board review Process new applications, revisions to current protocols, adverse events, continuing reviews, and protocol deviations/exception reports Prepare the agenda and distribute review materials to IRB members Prepare meeting minutes and communicate with researchers as to what the IRB requires Serve as resource to the research community Maintain the database

17. Lifespan 17 Part 3 Researcher Responsibilities

18. Lifespan 18 Responsibility of the PI Is to know and understand the regulations and policies prior to initiating any human research. Acknowledge and accept their role to protect the rights and welfare of the research subjects by complying with all of the regulations.

19. Lifespan 19 GCP and the PI When a principal investigator receives an approval letter from the Lifespan IRB, they are notified that this institution and the investigator complies with ICH GCP guidelines as they correspond to the FDA/DHHS regulations. Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conduction, recording and reporting trials that involve the participation of human subjects. Compliance with GCP standards provides public assurance that the rights, safety and well being of trial subjects are being protected and that clinical trial data is credible.

20. Lifespan 20 GCP and the PI The investigator’s responsibility according to ICH GCP guidelines:  4.1 Investigator qualifications and agreements  4.2 Adequate resources  4.3 Medical care of trial subjects  4.4 Communication with IRB  4.5 Compliance with the protocol  4.6 Investigational product  4.7 Randomization procedures and unblinding  4.8 Informed consent of trial subjects  4.9 Records and reports  4.10 Progress reports  4.11 Safety reporting  4.12 Premature termination or suspension of a trial  4.13 Final report by the investigator

21. Lifespan 21 So what are some of the other PI requirements? Ensure that research activities are carried out according to the IRB approved protocol Protect subject confidentiality by storing electronic research data on password protected computers, and paper data in locked cabinets within locked offices Follow HIPAA regulations when the research involves the use or disclosure of PHI -obtain authorization from prospective subjects. Ensure that only IRB approved recruitment materials and research authorizations are used Provide signed copies of consent and authorization forms to research subjects and keep the originals in secured research files When appropriate, place copy of the consent form and authorization in the subject’s medical record.

22. Lifespan 22 So what are some of the other requirements for PIs? Human Subject Protection (HSP) Training is required for all research personnel who interact with human subjects or their identifiable data. Re-certification is required every 3 years. Each PI must also sign a HIPAA Security Assurance annually. HIPAA for Research training is an annual requirement. Each department in Lifespan must provide this training to their employees. HSP and HIPAA training can be done on-line at http://www.citiprogram.org http://www.citiprogram.org

23. Lifespan 23 Part 4 Process for Submission to the IRB

24. Lifespan 24 Process for Submission to the IRB This section will cover: 1. New Applications 2. Continuing Review (progress reports) 3. Requests for Revision to Protocol 4. Adverse Events/Unanticipated Problems

25. Lifespan 25 IRB forms and Instructions are posted at www.lifespan.org/research/

26. Lifespan 26 IRB forms and Instructions are posted at www.lifespan.org/research/irb/irb.asp From the ORA web page, select Human Subject Research

27. Lifespan 27 IRB forms and Instructions are posted at http://www.lifespan.org/research/irb/irbformslist.htm From the IRB web page, select Human Subject Committee forms

28. Lifespan 28 IRB forms and Instructions are posted at http://www.lifespan.org/research/irb/irbformslist.htm Each of the forms are available as hyperlinks on the forms list. The new application form includes a checklist that details each of the IRB forms that are required for your new application. Form specific instructions are also available for download by clicking on the LINK in the third column

29. Lifespan 29 When in doubt- read the instructions Instructions and helpful tools are available for download. From the IRB forms page, select the first item on the list, How do I submit an IRB application – and other guidance

30. Lifespan 30 How to submit an application to the IRB 1. Develop a research plan/grant application or obtain a study protocol from the sponsor 2. Obtain required forms for IRB review from the ORA website http://www.lifespan.org/research/ refer to IRB application checklist and instructions for further informationhttp://www.lifespan.org/research/ 3. Determine when the application is due  Deadlines are posted on the IRB web page and are labeled “Deadline/Meeting dates”  In most * cases, any of the three Lifespan IRBs can review an application for use at a Lifespan affiliate. * Special circumstances for research to be conducted at Bradley or Newport, and research involving prisoners

31. Lifespan 31 How to submit an application to the IRB 4. Do you need Full Board, Expedited, or Exempt review? Reminder: Expedited/exempt projects do not have a deadline and only require 2 complete copies. 5. Financial Considerations before you submit your application  provide Dept cost center if internally funded,  submit business forms to Grants and Contracts Office if externally funded 6. Submit the completed application, with the required number of copies, to Review Committee staff by the due date.

32. Lifespan 32 What happens Next? 1.Research Review Committee staff review the submitted application for completeness. After the application is accepted, it is processed for review. 2.Expedited/Exempt projects – Research Review Committee staff will contact the PI when the item comes back from the reviewer 3.Full Board Review -Applications that are accepted for full board review are placed on the agenda for the next committee meeting. Principal Investigators, or their representatives, are required to appear before the committee to address any questions or concerns raised by the reviewers.

33. Lifespan 33 What happens Next? 3. After the IRB meeting, Review Committee staff prepare the minutes from the meeting and send a summary of the application discussion and comments to the investigator. 4.Investigators make the committee required changes and return any requested information/clarifications to Review Committee staff. 5.Review Committee staff verify that the requested corrections have been made and process approval as appropriate.

34. Lifespan 34 What happens Next? 6. If the study is funded by an external source (grant/contract), then the approval letter will specify that the project is approved but not activated and that no activity is allowed until the activation is in place. When the grant/contract has been finalized, an activation notice with the new cost center will be sent to the investigator from the Grants and Contracts Office. If the project will use Dept. funds, and a cost center has been provided, then the IRB approval letter will also include an activation notice. Investigators cannot begin any project involving human subjects until IRB approval and financial activation have been received.

35. Lifespan 35 Congratulations, Your Study Has Been Approved! Now What? Projects are approved for a period up to 12 months. The IRB may require more frequent review depending on the level of risk. Before IRB approval expires, Review Committee will send a progress report to be completed by the PI. It is ultimately the PIs responsibility to submit the continuing review report in a timely fashion to ensure a lapse in IRB approval does not occur.

36. Lifespan 36 Congratulations, Your Study Has Been Approved! Now What? Be sure to answer all questions. Follow the checklist at the back of the progress report to ensure that all required documents have been included. Progress reports are processed and reviewed in the same manner as new applications. Please note the following: Continuation of the project beyond the anniversary date is contingent upon submission of this report. If the progress report is not received by the due date, approval will expire and no work will be allowed until the report is submitted, reviewed, and approved.

37. Lifespan 37 Steps to submitting a Request for Revision to Protocol for review by the IRB 1. Determine which aspects of the project will be revised (e.g. protocol, consent forms, advertisements, personnel, etc) 2. Obtain required form for IRB review from the ORA website and submit with all required attachments www.lifespan.org/research/irb/irbformslist.asp

38. Lifespan 38 Steps to submitting a Request for Revision to Protocol for review by the IRB If the revision includes information that must be communicated to currently enrolled subjects (such as altered schedules, revised compensation, newly identified side effects), then you must describe the plan for notifying enrolled subjects and attach any documentation that will be used for this purpose.

39. Lifespan 39 Steps to submitting a Request for Revision to Protocol for review by the IRB Most minor revisions can be processed for expedited review. Changes which substantially alter the protocol, or change the Risk:Benefit ratio require review by the convened IRB (full board review). Contact the IRB Coordinator/Manager for guidance. Please Note: The IRB Chairperson has the authority to refer any item to the full board for review.

40. Lifespan 40 Reporting Unanticipated Problems The principal investigator must report to the IRB those unanticipated problem/adverse events occurring locally or at another site, that are: specific to a study approved by a Lifespan IRB, and that: involve risk to human subjects or others (i.e. subject family members, research staff) and are: Unanticipated, serious, and related to the research activity; Or, are Expected but occurring at greater frequency or severity than anticipated. Or, The AE indicates an increase in the risk to participants, regardless of severity

41. Lifespan 41 Reporting Unanticipated Problems The principal investigator must also report to the IRB: any deviations from the protocol or an accidental or unintentional change to the protocol taken without prior IRB approval to eliminate apparent immediate hazard to a research participant (submit a deviation report for this event as well); a breech in confidentiality that may involve risk to that individual or others; a complaint of or from a participant that indicates an unanticipated risk or which cannot be resolved by the research staff.

42. Lifespan 42 Reporting Unanticipated Problems Adverse Event and Deviation Reporting forms are posted on the IRB webpage at www.lifespan.org/research/irb/irbformslist.asp

43. Lifespan 43 Part 5 Informed Consent It’s a Process …not a form

44. Lifespan 44 Historical Background The requirement that researchers obtain informed consent from research subjects originates with Principal 1 of the Belmont Report: Respect for Persons

45. Lifespan 45 Respect for Persons Individuals are treated as autonomous agents. This means that the subjects are not controlled by others and are able to make independent decisions Persons with diminished autonomy are given protection (e.g. vulnerable subjects such as children, prisoners, mentally disabled) Consent to participate in research is voluntary and informed

46. Lifespan 46 Informed Consent - Process Informed consent is a process that begins when you first approach the potential research subject and continues throughout the course of the study.

47. Lifespan 47 Informed Consent- Process The first contact with research subjects may be through any of the following: direct advertising medical record review to screen for eligible subjects physician referral

48. Lifespan 48 Informed Consent - Process Obtaining Informed Consent involves: Providing information to the subject in a language that is understandable to the subject or their representative Ensuring that the subject understands what they are being asked to do Answering any questions that the subject may have Allowing enough time for the person to think about the research before consenting to participate Obtaining voluntary agreement of the subject to participate in the study

49. Lifespan 49 Informed Consent - Process The consent process continues each time that an investigator has contact with a research subject. The consent dialogue is renewed every time that the study is revised, or if new information becomes available that would impact upon a subject’s decision to participate,

50. Lifespan 50 Informed Consent - Elements Elements of informed consent: 1. Information that the study involves research 2. Risks or discomforts 3. Benefits 4. Alternatives 5. Confidentiality 6. Compensation/treatment offered 7. Contact for additional information 8. Contact information for research subject rights 9. Statement that participation is voluntary

51. Lifespan 51 Informed Consent - Waivers Federal regulations allow for some types of research to be conducted without obtaining written informed consent from research subjects. Typically, waivers are only granted for studies that present no greater than minimal risk. The most frequent types of studies that are eligible for waivers are chart reviews and surveys.

52. Lifespan 52 Want to learn more about research and the IRB? The Office of Research Administration has an online Human Subjects Protection course through the CITI program. www.citiprogram.org www.citiprogram.org This site also offers: A good clinical practice course (GCP) A Recombinant DNA course For information and instructions go to: http://www.lifespan.org/research/irb/ma ndatoryedguidance.asp http://www.lifespan.org/research/irb/ma ndatoryedguidance.asp

53. Lifespan 53 Contacts for IRB Questions If you have any questions you can contact: Patricia Houser, Manager Research Review Committees and Communication at phouser@lifespan.org 444-2099phouser@lifespan.org Adrienne McParlin, Coordinator Research Review Committees at amcparlin@lifespan.org 444-3527 amcparlin@lifespan.org Jacqui Poore, Coordinator Review Committees and Compliance at jpoore@lifespan.org 444-2093 jpoore@lifespan.org Dawn Roux, Coordinator Research Review Committees at droux@lifespan.org 444-7547 droux@lifespan.org Deb Temple, Manager Compliance and Training at DTemple@lifespan.org 444-5843 DTemple@lifespan.org