Post Approval Monitoring for Human Subject Research Studies at HSC

All on-going HSC human research projects with IRB approval granted by the NTR IRB are eligible to be audited by the Research Ethics Officer or designee. For the most part, these post-approval audits are considered routine and “not for cause” audits. Such audits are intended to be proactive and focused on educating investigators and research staff about their ethical and regulatory responsibilities regarding human subject research.

Directed compliance audits will be initiated by the Office of Research Compliance/ NTR IRB as a result of a complaint, suspected non-compliance, or questions/concerns regarding the safety and welfare of research participants enrolled in a research study.

The Research Ethics Officer or designee will either perform periodic “routine” or “for cause” directed audits to ensure compliance with the approved IRB protocol, federal and state regulations, as well as NTR IRB procedures associated with the protection of research participants.

For periodic/routine audits protocols can be selected on a random basis from any category of review: exempt, expedited, or convened meeting (“full board”). Selection of a protocol for audit does not imply any suspected noncompliance for routine audits. A risk-based selection process may be utilized or randomly selecting approved protocols reviewed by either expedited or full board procedures (see “Criteria for Compliance Audit Selection” section below) or determined by the NTR IRB to be exempt category.

Investigators are informed in advance of the impending audit, informed of the process, and the type of records to make ready for review (see sections titled, “Documents/Processes that may be selected for reveiw” and “Audit Process”, below). With the cooperation of the principal investigator, it is expected that a routine audit can be conducted, in most cases, in 1 to 5 days or less.

The Office of Research Compliance / NTR IRB may use any one or more of the following criteria for selection of a research project for compliance audit:

• At random (for periodic/routine audits only)
• At the discretion of the IRB
• Risk based selection: high risk studies as designated by the IRB; studies that include vulnerable populations (i.e. pregnant women, children, prisoners, etc.); studies reporting on-site SAEs or protocol violations; studies reporting a high local-site proportional enrollment relative to overall study enrollment; or Investigators who have limited or no prior research experience with human subjects.
• To verify compliance: For those studies in which the Investigator(s) have a previous noncompliance history or concern, or for protocols involving Investigators who have prior FDA 483, “Inspectional Observations”, and / or FDA Warning Letter(s) on file; Report of suspected non-compliance or complaint; Previous suspension of the research protocol (for any reason).
• Research placed on administrative hold or closure by the IRB due to failure by the Investigator to submit a study for continuing review or failure to respond to a request for information from the IRB.
• To verify Continuing Review reports (Progress Reports), if required

• Examination of the protocol and amendments, consent documents, source documents, case report forms (CRF), adverse events, advertisements, recruitment materials, and other research study related documents and correspondences
• Regulatory submissions and correspondences with IRB, Sponsor, Monitor, etc
• Review of subject enrollment log and recruitment practices, as needed
• Key personnel training records and site signature / responsibility log
• Review of research data, data collection tools, and procedures
• Review of serious adverse event reporting
• Examination of consent forms to verify that they are signed and dated correctly
• Examination of proper storage, maintenance, and accountability of study related items (i.e. regulatory files, IRB files, subjects’ research and medical records, clinical materials, computer files, electronic data records and storage, specimens, drugs, devices, equipment, and results of procedures and tests performed during the course of the research, etc.)
• Contacting research participants either during or after their participation in research activities to evaluate their involvement in the research study, and/or,
• Observation of the consent process
• Observation of research interactions/interventions with research participants
• Monitor conflict of interest concerns to ensure that the consent document includes appropriate language and disclosures
• Other relevant research project documents or activities as deemed appropriate by the Office of Research Compliance and/or NTR IRB
• When applicable, an appropriate “Research Recovery Plan and Safety Protocol for COVID-19” was approved and in place (this applies to any in-person research procedures that were conducted during the COVID-19 pandemic, from June 2020 to May 2021, when in-person research interactions at HSC were limited)

1. The Research Ethics Officer or designee will schedule compliance audits of previously IRB-approved research studies.
2. Prior to initiation of a compliance audit, the principal investigator (PI) will be notified by the Research Ethics Officer and/or designee at least 10 working days in advance, by email, telephone (including voice mail), or by hard copy letter, that a compliance audit will be conducted. Once the PI has had time to receive the Notice of Post Approval Monitoring (NPAM), the Research Ethics Officer or designee will finalize the date and time of the compliance audit by phone or email confirmation with the PI, or their designee.
3. If the PI fails to respond to the initial NPAM for any audit within 5 working days, a follow-up email will be sent to the PI requesting verification of date of audit and location of audit (the PI’s Chair or supervisor will be copied on this follow-up email). If the PI fails to reply to the follow-up NPAM email, the Principal Investigator and applicable protocol(s) will be referred to the next convened meeting of the NTR IRB for review and consideration. The NTR IRB may request a for-cause audit to be conducted and/or suspend the Principal Investigator’s protocol(s) as deemed appropriate. In addition, the IRB Chair may exercise his/her authority to notify applicable institutional and other agency official(s) of the PI’s failure to comply with NTR IRB policies and procedures.
4. The notice of compliance audit will identify the PI and the protocol to be reviewed during the on-site compliance audit. The Research Ethics Officer or designee will make every effort to be available via email/phone if the PI has more specific questions as to the nature and/or procedures of the compliance audit.
5. For a directed compliance audit only, in the interest of subject safety, there may be no pre-notification or minimal notification of a compliance audit at the discretion of the Director, Research Compliance. However, it is the intent of the Office of Research Compliance to inform the PI whenever a directed compliance audit is being implemented.
6. The PI need not be present for the compliance audit; however, either the PI or other study personnel associated with the project being reviewed should be available on-site during the audit. If the PI will not be present for the compliance audit, a designated member of the research staff knowledgeable about the conduct of the study must be available to provide access to study records and to answer questions by the Research Ethics Officer or designee.
7. Prior to conducting the compliance audit, the Research Ethics Officer or designee will review the research study file maintained within the electronic IRB submission system (and review any hardcopy/paper files maintained in ORC office, if applicable, as needed) to familiarize himself/herself with the IRB application, protocol synopsis, consent forms, amendments, including (if applicable) correspondence from the sponsor, monitor, and/or other regulatory/federal agencies, etc.
8. During the compliance audit, the Research Ethics Officer or designee will have access to all pertinent study documents, records, processes, etc. Please refer to the above section, which provides a partial list of the items that may be subject to review during the compliance audit. The Research Ethics Officer or designee will document compliance audit findings on the Post Approval Monitoring (PAM) Audit Checklist form.
9. After completion of the compliance audit, the Research Ethics Officer or designee will prepare the Post Approval Monitoring (PAM) Audit Checklist form and written report and submit it to the Director of Research Compliance and IRB Chair for review. If the audit reveals non-compliance, then a close-out meeting will be scheduled with the PI or designee, Director of Research Compliance or designee, and IRB Chair or designee to formally review the audit findings and discuss a compliance plan to ensure compliance.
10. Following the audit close-out meeting the PI will receive the final Post Approval Monitoring (PAM) Audit Checklist and audit report for review and written response. Following receipt of the Post Approval Monitoring (PAM) Audit Checklist / Report, the PI will have 1 week (5 business days) to respond, in writing, to the compliance audit report findings. The PI should sign this response memo, which will also include the Corrective Action Plan (CAP). If comments, acknowledgements, and/or clarifications by the Principal Investigator are not submitted within 1 week (5 business days) to the Office of Research Compliance, a follow-up email will the sent to the PI requesting the written memo/ CAP.
11. If the PI fails to respond to the follow-up email requesting the signed memo/CAP, then the applicable protocol and PI will automatically be brought before the next NTR IRB convened meeting for consideration and follow-up action. Note that the NTR IRB has the authority to suspend or terminate the study in accordance with federal regulations and IRB standard operating procedures until a written response is received from the Principal Investigator. Additionally, the IRB may exercise its authority to notify applicable institutional and outside agency officials of the principal investigator’s failure to comply with NTR IRB policies and procedures.
12. If there are not any documented findings during the compliance audit, the Post Approval Monitoring (PAM) Audit Checklist and written memorandum will still be drafted and sent to the PI for his/her review.
13. If preliminary findings of non-compliance by the Research Ethics Officer or designee so indicate the safety and welfare of subjects is in jeopardy, the Director of Research Compliance can immediately request the IRB Chair to suspend the protocol, including study enrollment and/or activities, and take appropriate action to ensure the safety and welfare of the subjects until this matter can be brought before the next IRB convened meeting for further review and determination. [See “When the safety and welfare of subjects are in jeopardy”, below for further details].
14. If the PI responds to the Post Approval Monitoring (PAM) Audit Checklist / Report with his/her comments and/or acknowledgments, the Research Ethics Officer or his/her designee will compile the documents for IRB review and further recommendations, if needed. IRB review/acknowledgement of the Final Audit Report will be documented in the Meeting Notes/Chair’s Report. 
15. If no further follow-up is necessary, a copy of the Board Action Notice/ Audit Close-Out Memo will be sent to the PI. If the IRB requests further follow-up, the PI will be notified of the IRB’s determinations.