1. Common Audit Findings UTHSC Institutional Review Board (IRB)

2. Authority to Audit 21 CFR 56.109(f) gives the IRB the authority to observe, or have a third party observe, the consent process and the research. When and if the IRB is concerned about the conduct of the study or the process for obtaining consent, the IRB may consider whether, as part of providing adequate oversight of the study, an active audit is warranted. 45 CFR 46.109(e) An IRB shall conduct continuing review of research covered by this policy at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party observe the consent process and the research.

3. UTHSC IRB Policy The UTHSC IRB will have the authority or may designate a third party to observe the conduct of any research activity, and may review at any time all research records, including but not limited to informed consent documents, regulatory files, IRB files, subjects’ research and medical records, clinical materials, storage and distribution of investigational devices (e.g., drugs, devices, or biologics), record storage, computer files, and results of procedures and tests performed during the course of the research. Research compliance auditing staff will also have the authority to observe the informed consent process and to interview subjects either during or after their participation in research activities.

4. General Goals of Audits Assure protections for human subjects are implemented Verify that protections for human subjects are properly documented Assess compliance with applicable regulations, guidance, and local policies Enable investigator to avoid sanctions for non-compliance Assure that the University and affiliated institutions remain in good standing with federal agencies that have oversight of human subjects research activities Confirm that study data are accurate and reliable

5. How are we doing? Audit program 2014-2015 58% of audited studies exhibited noncompliance in at least one area: 28% Consent Process 26% Accuracy and Completeness of Study Records 25% Adherence with Continuation & Revision Policies 19% Inclusion/Exclusion Criteria 11% Protocol Adherence 9% Enrollment Numbers 6% Data Confidentiality

6. Correcting Problems: General Considerations Start every study with a delegation of responsibilities log and review it with all study team members. Make sure your delegation log matches your IRB study application under Section (415). Our Tools & Guides page includes a Delegation of Responsibilities template: http://www.uthsc.edu/research/research_compliance/IRB/guides. php http://www.uthsc.edu/research/research_compliance/IRB/guides. php

7. Correcting Problems: General Considerations Know the local policy and guidelines. http://uthsc.edu/research/research_compl iance/IRB/policies.php Visit our SOP page: Call the IRB office when you are unsure! Read the document, “Things to Remember When Conducting Research,” and use the Project Checklists found here: http://www.uthsc.edu/research/resear ch_compliance/IRB/guides.php http://www.uthsc.edu/research/resear ch_compliance/IRB/guides.php

8. Documenting is the KEY…

9. Consent Process Problems Enrolled subjects were consented by people not listed as key study personnel or as having the responsibility for obtaining informed consent. Child assent was not obtained on a regular basis and/or no reason was documented for not obtaining assent. Verification of the informed consent interview was not present in the research record. Unapproved/unstamped consent forms were used to consent subjects. Original, signed consent forms were missing.

10. Non-English speaking subjects were enrolled using an English version of the consent form. Adult subjects were enrolled using the LAR’s permission with no documentation about the inability of the subject to give consent. Permission from the LAR was obtained over the phone. (Consenting over the phone constitutes an alteration of the consent process that must be approved by the IRB and must be requested in the application.) Date and/or time of the consent was not recorded in the document. Consent Process Problems

11. How do we correct them? Include a note regarding the consent process ‐ how it was conducted; whether questions were asked/answered; the fact that a signed copy was given to the subject; whether a translator was present (if applicable) Template is available at http://uthsc.edu/research/research_compliance/IRB/guides.php http://uthsc.edu/research/research_compliance/IRB/guides.php Before starting consent process, check to make sure you have latest approved version from IRB. Tip: get the last stamped-approved version directly from iMedRIS each time. An investigator must sign the consent form within 72 hours after the subject and person obtaining consent. You must keep the original, signed consent form in the study files.

12. Problems With Study Records There was no documentation or incomplete documentation regarding: Site study visits Phone call visits Treatment and doses (including drug dispensing) Date and time for lab tests Questionnaires - no record for some subjects The only research record was the CONSENT FORM…yikes!

13. How do we correct them? Read the protocol and IRB study application carefully before starting the study, AND: Make sure you capture necessary study data. Use the approved data collection tools. Set up a regular research team meeting time to review study data. Document, document, document (if it isn’t written, it didn’t happen)

14. Continuation & Revision Problems Accrual of subjects was continued after IRB approval lapses. Changes were made in study interventions, assessment tools, visits, etc. without IRB approval.

15. How do we correct them? If you let IRB approval for your study expire, you: Must cease all study activities on the expiration date May not enroll any new subjects May not obtain any data on current subjects until your study has been approved (again) by the IRB to continue for another year May possibly be required to submit a new application again Caveat: if stopping activities could pose any harm to the subject, make a written request to the IRB for each subject to continue study interventions Any and all changes you wish to make to your project must be submitted to the IRB (via a Form 2) and approved before implementation.

16. Problems with Inclusion/Exclusion Criteria No source documentation confirming eligibility criteria was recorded. Subjects did not meet the inclusion/exclusion criteria for the study.

17. How do we correct them? You and your team READ the protocol and KNOW the eligibility criteria. Use an eligibility checklist. A template is available at: http://uthsc.edu/research/research_compliance/IRB/guides.php When a local investigator receives a protocol waiver from a study sponsor, or the principal investigator of an investigator-initiated study proposes to enroll a subject who does not meet the approved inclusion/exclusion criteria, the details of the proposed waiver, subject identification, and all supporting documentation must be submitted to the UTHSC IRB for review and approval prior to implementation. The IRB will acknowledge receipt of such waiver requests. In case of intentional deviation from approved eligibility criteria:

18. Protocol Adherence Problems More information/data was recorded than described in the application/protocol/consent form. The follow-up visit notes were missing; a visit was scheduled outside of the protocol window; or some tests were not completed (i.e., no documentation exists).

19. How do we correct them? Be sure to use only approved data collection tools that match your IRB- approved protocol, study application, and consent form.

20. How do we correct them? The principal investigator is responsible for reporting all Major Protocol Deviations occurring at the local research site to the IRB. A Major Deviation: Has harmed or posed a significant risk of substantive harm to the subject; Has compromised the scientific integrity of the data collected; Appears to result from willing/knowing misconduct on the part of an investigator/staff; or Appears to involve some other serious or continuing noncompliance with federal, state, or local research regulations. Follow the local policy:

21. How do we correct them? All major deviations should be reported as soon as possible, but no later than 5 working days after the investigator/coordinator becomes aware of the event. Minor deviations do not have to be reported to the IRB; however, a note-to-file should be made in the research record indicating: What the minor deviation was; The reason it occurred; and The communication that took place or plan implemented so that the deviation would not occur again Remember that the continued occurrence of minor deviations could compromise the scientific integrity of the research data collected

22. Enrollment Number Problems More subjects were enrolled than approved by the IRB Enrollment occurs when the consent form is signed, not when the subject is randomized. Therefore, an estimate of screened failures should be incorporated into the target enrollment number submitted to the IRB. Also, the number of subjects who signed the consent form, not just the number of subjects who were randomized, should be included on the renewal application under the number of subjects accrued.

23. How do we correct them? Keep a consent log. A template is available at: http://uthsc.edu/research/research_compliance/IRB/guides.php Check your IRB-approved study application, under section 1400, and know how many subjects you are approved to enroll. If you need more subjects, submit a Form 2: Change Request & Amendments for IRB review and approval before enrolling additional subjects.

24. The IRB recognizes that non-compliance with approved protocols may occur. It is the responsibility of the Principal Investigator to notify the IRB regarding major protocol deviations or to call the IRB when you are unsure of whether you must report an incident. The IRB has the authority to place research activities on hold, as well as to suspend or terminate approval of research that is not being conducted in accordance with the IRB policies or federal regulations for the protection of human subjects. Investigator Noncompliance

25. Summary of Best Practices Perform all and only those research procedures that are specifically described in your IRB-approved application/protocol Use compliance tools & checklists available on the IRB website Use the consent form & research record to carefully document all aspects of the informed consent process Submit continuation applications 3 weeks before your expiration date Secure approval for all study revisions prior to implementation