Navigating the Research Approval Process

1. National Naval Medical CenterDirectorate for Professional EducationClinical Investigation Department Navigating the Research Approval Process Sheila I. Gaines Research Administrator “The National Naval Medical Center is an approved provider of continuing nursing education by the Navy Medicine Manpower, Personnel, Training and Education Command, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.”

2. Disclosure Statement This CE/CME activity does not have commercial support, and has no conflicts of interest. Research Course

3. Learning Objectives 1. Discuss the Responsible Conduct of Research Service (RCRS) and how it can assist the researchers with the protocol application process. 2. Familiarize researchers with the protocol flow, review and approval process of conducting research at the National Naval Medical Center. 3. Explain to researchers the Federal and Naval requirements. Research Course

4. Learning Objective 1: Discuss the Responsible Conduct of Research Service (RCRS) and how it can assist the researchers with the protocol application process Research Organization SRP Administrative support Research Course

5. Where to go for help…… • Your department • RCRS Web page (NNMC Intranet) • Stitt and Darnell libraries • Librarian to help with literature searches • CID Center staff • Dental Research – Dr. Bertrand • Learning Resources – LCDR Higginson • Scientific Review – CDR Wanko, LCDR Bustamante, Dr. M. Haigney • Institutional Review Board – CDR Donahue • Nursing Research – CDR Kane • Responsible Conduct of Research – CAPT Lenert, Ms. Gaines Research Course

6. Formats and Forms • The proposal itself • Use the Research Proposal Outline on the IRBNET • Include data collection sheets, flyers, advertisements, questionnaires, surveys • Consent and HIPAA forms • Other supporting forms, such as letters of support, approvals from other institutions Research Course

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8. What Is a CIP Number? • CIP = Clinical Investigation Program • Tracking number, unique identifier • Does not mean protocol is approved • Number has three parts • Location – Fiscal year submitted – Sequence number EXAMPLE : NNMC.2010.0001 NNMC = Institution 10 = Fiscal Year 0001 = First research proposal submitted in FY10 Research Course

9. Learning Objective 2: Familiarize researchers with the protocol flow, review and approval process of conducting research at the National Naval Medical Center. Principal Investigator Protocol Flow Department Chair Darnell Library Submit Proposal to RCRS RCRS Reviews Proposal For Completeness Statistician SRP Review Required Revisions And/or Additional Review PI Revisions To IRB Research Course

10. IRB Review Expedited Review (IRB Member + Chair Full Board Requires Revision and/or Additional Review Approved IRB Reviews Revisions Command Approval You May Not Begin Your Research Until You Have received an Approval Letter From the Commander, NNMC. IRB Approved Forward to Radiation Safety or FDA as Needed Annual Review Less frequently than 365 days BUMED-HRPP Review Approved Research Course

11. Usual Sequence for Human Subject Research • RCRS receives the proposal and assigns a CIP number • Scientific Review Panel reviews proposal • IRB reviews the proposal • Expedited/Exempt review if allowable -- or -- • Full IRB review at its monthly meeting • If approved by IRB and Commander, RCRS prepares approval letter • Letter is signed By Direction of the Commander • Investigator may not begin until she/he has the approval letter signed By Direction Research Course

12. What is Exempt or Expedited Review? Research proposals that meet specific criteria: Exempt Review: 32 CFR 219.101- categories • Existing records, pathologic specimens • Educational testing, surveys Expedited Review: 32 CFR 219.110 – must be minimal risk AND in one or more categories from the list • Existing records, pathologic specimens • Data from voice, digital, image recordings, surveys NNMC IRB Chair or designee determines if a research proposal meets exempt or expedited review criteria. Research Course

13. Pitfalls for New Protocols • Typos • Subject enrollment does not match between the protocol and consent form • All documents not included in the submission package • Table of Contents does not match text • Missing references • Coercion not addressed • If enrolling a vulnerable population (children, pregnant women) not including additional safeguards for this group) Research Course

14. Pitfalls for Consent Form • Not using current consent form format • Typos • Not in lay terms – must be in a 6th grade reading level • All procedures not included in the consent • Sample size does not match protocol • Explain what part of the procedure is experimental • Not including all the possible risks Research Course

15. Scientific Review Panel • Reviews all protocols, including those which do not include human subjects • Examines relevance to Navy Medicine • Examines scientific merit • Rates scientific merit for funding • SRP’s review template is available on the RCRS website Research Course

16. Institutional Review Board Criteria for IRB approval: • Risks to subjects are minimized • Risks are reasonable in proportion to benefits • Selection of subjects is equitable • Informed consent is sought appropriately • Informed consent is documented appropriately • When appropriate, research plan includes data monitoring to ensure safety • When appropriate, provisions to protect privacy and confidentiality are adequate IRB disapproval cannot be overruled Research Course

17. Informed Consent • The Belmont Report Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose whether to participate in research. • Types of Consent • Written • Implied • Complete waiver of informed consent is difficult to achieve in DoD and can only be granted by the IRB Research Course

18. What’s an MOU? • Memorandum of Understanding • Collaboration between Federal institutions • Transfer of funds • Sharing of services • Mutual expectations • RCRS drafts the MOUs Research Course

19. What’s a CRADA? • Cooperative Research and Development Agreement • Collaboration between a Federal institution and a civilian institution • Transfer of technology • Sharing of services • Issues regarding patents • RCRS drafts and routes CRADAs that are not sponsored from drug/device companies. Research Course

20. What’s the Henry M. Jackson Foundation and how could it help me? • Assists investigators with writing research protocols, IRB submission, and protocol amendments/changes • Handles negotiations between investigators and sponsors • Monitors the regulatory aspects of research protocols • Manages research funds Research Course

21. Learning Objective 3: Explain to researchers the Federal and Naval requirements. Command Approval of Research • Command Approval Letter • Required by DoD Directive for all research involving NNMC “funding, personnel, facilities, and all other resources”; applies to trainee research elsewhere • Research being done at NNMC gets IRB review/approval or SRP approval if not human subject • Research elsewhere also must have IRB/SRP review and approval; NNMC may accept the other institution’s review under a DoD Institutional IRB Review Agreement • SOPs are posted on RCRS web site Research Course

22. Approval of research is specific • Enrollment dates and number of subjects are specified in the Approval Letter and must be either followed or amended • Protocol specifics such as data elements and analysis plan must also be either followed to or amended • Amendments must have IRB review but this is often expedited and does not require full committee • All amendments must have an specific Amendment Approval Letter Research Course

23. Continuing Review Interval is at least once every 365 days, determined by the IRB Purpose To ensure that human subject protection continues Annual Report replaces continuing review for research not involving human subjects Completion Report Due after data collection and analysis; does not have to wait until after publication Purpose To ensure that research is completed and disseminated Should include a brief account of the important findings: ABSTRACT Ongoing Research Obligations Research Course

24. Documents the PI Must Keep • Research protocol (original and all subsequent versions) • Amendments - extensions, investigator changes, etc. • Records of all IRB communication – Initial approval, continuing review approval, amendment approval etc. • IRB approvals from other institutions Research Course

25. Documents the PI Must Keep • Materials used in recruiting subjects (e.g. flyers, telephone scripts, posters) • Subjects’ research file • IRB approved and stamped consent form • Original signed consent forms and HIPAA forms • Instruments – surveys, questionnaires, interviews • Agreements Research Course

26. Documents the PI Must Keep • Investigator Brochure, if applicable • Case Report Forms, if applicable • FDA form 1571 and FDA Form 1572, if applicable • Drug and device receipt, accountability, and return records, if applicable • Correspondence with Sponsor and FDA, if applicable Research Course

27. Amending or Changing a Research Protocol • Your research proposal - plan for what you intend to do • The IRB expects it to be followed • If changes are need: • Submit amendments to approved protocols by a memo addressed to the SRP/IRB Chairs via RCRS Identify the principal investigator, the CIP#, & protocol title • Describe and justify the requested amendment Research Course

28. Amending or Changing a Research Protocol • State whether there is any change in the risk-benefit assessment • Highlight or underline amended sections • If MTMR – medical monitor must review and endorse • Submit amended protocol through IRBNET • Don’t implement changes until they are approved! Research Course

29. How Does Continuing Review Work? • Continuing review occurs at least once every 365 days from initial IRB approval date • The IRB determines the frequency of continuing review (any interval less than 1 year) • IRB members and investigator receive a memo from RCRS 6 to 8 weeks prior to the scheduled IRB meeting • IRB members are responsibility for contacting the principal investigator to arrange a convenient time to meet to conduct the audit Research Course

30. What do I have to do for Continuing Review? • Investigators must have available for the review: • Research protocol file • Number of subjects enrolled • List of enrolled subject (de-identified) and date of enrollment • List of withdrawn subjects, date, and reason they withdrew • Original signed consent forms and HIPAA forms • Any amendments since the last review • Records of adverse events, unanticipated problems Research Course

31. What do I have to do for Continuing Review? • Following IRB approval of continuing review, RCRS will send the following: Results of the continuing review audit, Newly stamped consent form, HIPAA form, New IRB approval expiration date • Approximate date of next scheduled review Research Course

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33. Regulatory Pitfalls • Beginning enrollment before the date of the Commander’s approval letter • Not using the latest IRB-approved version of the consent form (check for the IRB stamp) • Enrolling more patients than the IRB approved (see the approval letter) • Acquiring collaborators without adding them to the protocol via update with RCRS • Not reporting protocol deviations to the IRB Research Course

34. More Regulatory Pitfalls • Presenting research without RCRS/PAO clearance • Submitting research for clearance after it has already been accepted for a conference or a journal (better than no clearance at all, but not encouraged) • Engaging in research elsewhere without notifying RCRS • Engaging in research under the umbrella of Process Improvement without notifying RCRS • Implementing changes to protocol without IRB-approved amendments Research Course

35. NNMC Research Protocols Data • Publications for FY 08 based on research protocols are 76 52 Staff members 24 residents • Publications for FY 09 based on research protocols are 84 59 Staff members 25 residents Research Course

36. References DeRenzo E, Moss J. Writing Clinical Research Protocols: Ethical Elsevier Academic Press, 2006 Websites: • Office for Human Research Protections (OHRP). Available at: http://ohrp.osophs.dhhs.gov • Office of Research Integrity. Available at: http://ori.dhhs.gov/ • Food and Drug Administration . Available at http://www.fda.gov/oc/oha/irb/toc.html • Department of the Navy Human Research Protection Program. Available at: http://navymedicine.med.navy.mil/humanresearch/ NNMC Websites: • Responsible Conduct of Research Service (RCRS). http://www.bethesda.med.navy.mil/Professional/Research/Responsible_Conduct/index.aspx Research Course

37. Questions? Research Course

38. Thank You! • My contact Information: Ms. Sheila I. Gaines Email: Sheila.Gaines@med.navy.mil Phone: 301-295-6512 Fax: 301-295-1490 Research Course

39. Exempt from IRB Review Which of the below may determine whether a research protocol meets the criteria for exemption: a. investigator b. research study nurse c. IRB Chair or designee Research Course

40. Survey Research What is the principal risk posed by survey research? a. physical harm b. privacy/confidentiality c. coercion d. legal claims Research Course

41. Research Protection Program The primary responsibility of the investigator is to the welfare of: a. the institution b. the IRB c. society d. the human subject in the investigation Research Course