UUSOP-10: Monitoring Visits for Externally Sponsored Clinical Trials

Version Date: November 28, 2023

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1. Introduction and Purpose
2. Definitions and Acronyms
3. Procedure
   1. Monitoring Expectations
   2. Scheduling Monitoring Visits
   3. Monitoring Visit Preparation
   4. On-Site Monitoring Visit Expectations
   5. Central/Remote Monitoring Expectations
   6. Monitor Visit Follow-up
   7. Additional Considerations
4. Materials Required
5. References
6. Document Approval
7. Revision History

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Introduction and Purpose 

The sponsor of a clinical research study is responsible for quality assurance throughout all stages of the trial process by ensuring trials are adequately monitored. The purpose of monitoring is to ensure:

• Human subject protection: The rights and well-being of human subjects are protected.
• Reliability of trial results: The reported trial data are accurate, complete, and verifiable from the source documents.
• Compliance with the current Institutional Review Board (IRB) approved protocol/amendment(s), with International Council for Harmonization (ICH) Good Clinical Practice (GCP), and with applicable regulatory requirements.

Externally sponsored clinical research studies are studies sponsored by an entity other than the University of Utah. All externally sponsored studies are subject to monitoring by the sponsor. The sponsor may delegate some or all of the quality oversight to a Clinical Research Organization (CRO).

The Principal Investigator (PI) is required to make available the requested trial-related material for the monitor, auditor, or regulatory authorities.

 

Definitions and Acronyms 

Clinical Research: Clinical research includes all research involving human participants. It does not include secondary studies using existing biological specimens or data collected without identifiers or data that are publicly available.

Clinical Trial: Clinical trials are clinical research studies involving human participants assigned to an intervention in which the study is designed to evaluate the effect(s) of the intervention on the participant and the effect being evaluated is a health-related biomedical or behavioral outcome.

CFR:	Code of Federal Regulations
CRO:	Contract Research Organization
EHR:	Electronic Health Record
ERICA:	Electronic Research Integrity and Compliance Administration
FDA:	United States Food and Drug Administration
GCP:	Good Clinical Practice
ICF:	Informed Consent Form
ICH:	International Council for Harmonization
IDS:	Investigational Drug Services
IRB:	Institutional Review Board
LAR:	Legally Authorized Representative
PI:	Principal Investigator
SOP:	Standard Operating Procedure
VPR:	Office of the Vice President for Research

Procedure 

1. Monitoring Expectations
   
   1. Monitoring will be performed as determined by the sponsor’s requirements. The extent and nature of monitoring visits (e.g., scope, method, frequency, duration, etc.) should be based on trial complexity and risk.
      1. Sponsors may conduct either in-person or remote/central monitoring, or could utilize a combination of monitoring techniques and methods.
   2. Monitoring activities should be performed in accordance with the monitoring plan to confirm the trial is being conducted and documented properly.
   3. The monitor is responsible for communicating between the sponsor and the investigator.
2. Scheduling Monitoring Visits
   1. The assigned monitor is expected to schedule the monitoring visit with appropriate advanced notice (i.e., minimum of 4-weeks).
   2. The assigned monitor can “visit” (either physically or virtually) for a mutually agreed upon number of consecutive days per month for each protocol the monitor is assigned. The monitor must inform the study team of the expected number of days required to conduct the monitoring review.
   3. Monitors assigned to multiple active studies are encouraged to monitor one study at each “visit”. Exceptions may be made for multiple studies to be monitored in one visit if accommodations are prearranged.
      1. Participant charts and regulatory files for multiple studies cannot be provided at the same time.
      2. Separate confirmation and follow-up letters should be drafted for each trial monitored.
   4. Monitoring visits must be scheduled at a reasonable and mutually agreed upon spaced interval. Exceptions can be made in rare cases, if the PI and study team can accommodate. Potential exceptions may include a Phase 1, first-in-human clinical research study.
   5. The monitor must communicate if an additional monitor(s) will be participating in the monitoring visit. Depending on space availability, the study team may or may not be able to accommodate multiple monitors for one in-person visit.
   6. The assigned monitor is expected to inform the study team of the following:
      1. The clinical research study to be reviewed.
      2. The participant research charts to be reviewed.
      3. Regulatory documents required to be reviewed.
      4. Investigational product required to be reviewed.
         1. Study monitors are not allowed to enter and physically inspect any University of Utah pharmacy. According to the Utah Pharmacy Practice Act Rule, Utah Administrative Code R156-17b, allowing unauthorized personnel into a pharmacy is unprofessional conduct. Monitors qualify as unauthorized personnel.
         2. For studies utilizing Investigational Drug Services (IDS):
            1. IDS uses remote monitoring practices in alignment with monitoring requirements stated in Guideline for good clinical practice E6(R2).
            2. Monitors will be provided access to the web-based investigation drug service system, Vestigo. Vestigo pharmacy monitoring appointments are requested here: https://pharmacyservices.utah.edu/investigational-drug-service/appointments 
            3. If IDS’ remote monitoring practices are unable to meet a monitor’s needs, a request identifying a legitimate business need may be submitted to the Pharmacy Manager for an onsite monitoring visit. The Pharmacy Manager will assess the need and send the request and assessment to the IDS Medical Director and Chief Pharmacy Officer for approval/disapproval. The request can be submitted by email to investigational.pharmacy@hci.utah.edu.
      5. Possible dates for the visit; including total number of days required.
      6. For in-person monitoring: Times of arrival and departure for scheduled visit (acceptable monitoring hours are workdays between 8:00am and 5:00pm).
   7. Monitors are expected to bring/use their own laptops and cell phones.
   8. In case of cancelations, the monitor should provide at least 48 hours notice of cancellation of the monitoring visit.
3. Monitoring Visit Preparation
   1. The study team is expected to identify mutually available dates, reserve necessary space for the monitor (for in-person monitoring), grant monitor access to electronically stored study records (for both central/remote monitoring), and schedule meetings with required parties (e.g. PI, IDS, etc.), as appropriate.
   2. The study team will notify potentially affected individuals of the upcoming monitoring visit.
   3. The study team will prepare the requested documentation for the monitoring visit, including but not limited to:
      
      1. Organize research charts for easy of identification of source documents.
      2. Obtain and file any missing source documentation.
      3. Confirm data and case report forms (CRF) are complete and resolve any missing or inaccurate data.
      4. Confirm all essential documents are filed.
      5. Ensure training and delegation logs are current.
      6. Resolve any queries from the prior monitoring visits.
   4. All monitors external to the University are required to complete a HIPAA training module and sign a confidentiality agreement to gain access to electronic systems, for both on-site and remote-based monitoring. The confidentiality agreement only needs to be completed once, unless the University makes substantial changes to the agreement and requires re-signature, and the HIPAA training must be completed annually for each external monitor.
      1. Confirmation of appropriate documentation must be performed prior to granting external monitors access to electronic systems. For monitoring through eReg and EpicLink (see sections 6.4.1 and 6.4.2 below), the confirmation is performed atomically. However, for all other electronic systems (see section 6.4.3 below), study teams are responsible for confirming appropriate monitor documentation prior to granting access.
      2. The Research Study Monitor Confidentiality and Non-Disclosure Agreement is available here: https://pulse.utah.edu/dc/Documents/Confidentiality%20Agreement%20-%20Research%20StudyMonitor.docx?d=w2d738af39015499fae84f34f3d0257cf 
      3. The HIPAA Training is available here: https://healthcare.utah.edu/patient-privacy/students.php 
4. On-Site Monitoring Visit Expectations
   1. The monitor should notify the study team upon arrival for the visit. A “sign-in” and “sign-out” sheet may be used as the study specific monitoring log.
   2. The study team will familiarize the monitor with their surroundings, including any office policies.
      1. Monitors may be physically located in shared space with other site monitors.
   3. Monitors are expected to demonstrate professional and ethical behavior while performing the monitoring visit.
   4. The monitor may only review the study materials initially requested during the monitoring site visit set-up.
   5. Electronic Health Records (EHR) may be reviewed by external monitors through physical and/or electronic means:
      
      1. Printed EHR records may be added to the participant research chart. Audit trails, electronic signatures, etc. are tracked within the EHR. Printed records will indicate the date, time, and individual who printed the record. Additional records can be printed from the EHR as needed.
      2. Digital EHR records may be electronically provided and reviewed in accordance with UU-SOP-06, Study Records Management: Monitoring & Auditing of Study Records.
   6. Monitors are not allowed within secured areas without the assistance of accompanied authorized personnel. This may include labs or other clinical workspaces.
   7. All materials provided to the monitor for review must be returned to secured areas at the end of each business day to ensure privacy and confidentiality of the research records. Monitors may not duplicate the research records in any format. Any request for duplication of study documents must be made to the study team.
   8. The monitor is expected to complete the monitoring visit within the scheduled timeframe for the visit.
   9. At the conclusion of the monitoring visit, the monitor may request a close-out meeting with the study team.
5. Central/Remote Monitoring Expectations
   
   1. Requests for centralized/remote monitoring must be approved and arranged in advance, adhering to the same principles and processes used to schedule in-person monitoring visits.
   2. A monitoring visit log may be completed and electronically signed by the monitor.
   3. Digital EHR records may be electronically provided and reviewed in accordance with UU-SOP-06, Study Records Management: Monitoring & Auditing of Study Records.
   4. The monitor may only review the study materials initially requested during the monitoring site visit set-up, regardless of unintended access to other documentation within electronic folders.
      1. Study teams are advised to limit monitor access to those materials requested during visit set-up.
   5. The monitor is expected to complete the monitoring visit within the scheduled timeframe for the visit.
   6. At the conclusion of the monitoring visit, the monitor may request a close-out meeting with the study team.
6. Monitor Visit Follow-up
   1. The monitor should provide a summary of their review in the form of a monitoring report and/or follow-up letter. These typically include details of monitoring activities, documents reviewed, findings, and recommended corrective actions.
   2. The monitoring summary may be submitted to the PI following the monitoring visit.
   3. The PI and study team should promptly address all outstanding findings and data queries, as well as develop and implement appropriate corrective action to prevent future recurrences of similar findings.
   4. The monitoring visit report should be maintained with other essential study documents in the regulatory record.
7. Additional Considerations
   1. The monitor is expected to schedule close-out monitoring visits, “data crunches” or “data locks” with appropriate advanced notice.
   2. Any changes to sponsor assigned monitoring personnel must be communicated to the study team.

 

Materials Required 

• Current IRB approved protocol/amendment(s)
• Current IRB Approved Consent Form(s)
• Participant research charts
• Access to electronic data capture (EDC) system
• Access to essential documents / regulatory binders
• Access to Vestigo

 

References 

• 21 CFR Part 50 Subpart B: Protection of Human Subjects
• 21 CFR Part 312 Subpart D – Investigational New Drug Application, Responsibilities of Sponsors and Investigators
• ICH Guidance for Industry E6(R2): Good Clinical Practice
• UUSOP-06 – Study Records Management
• Investigational Drug Service SOP - Auditor and Monitor Visits

 

Document Approval 

Erin Rothwell, Ph.D.
Vice President for Research, University of Utah
DATE: December 7, 2023

 

Revision History