Office of Human Research
Page Title

SOP No.: 504    ROUTINE MONITORING VISITS

Author:    Office of Human Research

Effective Date:  October 1, 2007

Supercedes document dated:              N/A

Last Reviewed on:     N/A                                 

Results of Review:               N/A

This SOP pertains to:  FDA-regulated human subject research sponsored by faculty (i.e., Investigators) within Thomas Jefferson University. All sites participating in these studies will be monitored according to this procedure.

Responsibility for executing this SOP:  Investigator and Designated Research Personnel

Approved By:

 

J. Bruce Smith, MD

 

Associate Vice President for Research

 

(signature on file at OHR)

Approved By:

 

Steven E. McKenzie, MD, Ph.D.

 

Vice President for Research

 

(signature on file at OHR)

 

1. INTRODUCTION AND PURPOSE

This procedure describes the activities performed during the monitoring of clinical study investigative sites.

2. GENERAL INSTRUCTIONS AND RESPONSIBILITIES

  1. The Investigator is responsible for ensuring that all clinical studies are monitored at appropriate intervals.
  2. The Investigator is responsible for designating a trained and qualified staff member or contractor to serve as study Monitor and for reviewing the results of all monitoring visits.
  3. The Monitor is responsible for preparing for, conducting and documenting periodic clinical site monitoring visits. The objectives of site monitoring are:
    • Document and report on clinical study progress
    • Document that the protocol and associated forms are current
    • Update investigative site personnel of changes in study conduct/documentation
    • Ensure that institutional/Sponsor requirements and Investigator obligations are being met
    • Ensure continued acceptability of the Investigator, his/her key personnel and facility
    • Obtain and review current clinical data, reports and source documents
    • Ensure adequate investigational product inventory, management, and accountability
  4. The Investigator and all other participating Investigators and their key study personnel are responsible for cooperating with the Monitor in all aspects of the monitoring visit

3. SPECIFIC PROCEDURES

3.1 Scheduling/Frequency of Visits

  1. The Investigator, in consultation with the OHR, will determine the number of anticipated monitoring visits for a particular clinical study, based on the complexity of the study design, its phase of development, previous site experience and compliance with study requirements, rate of participant enrollment and any other unique attributes of the study and the site.
  2. Monitoring visits will be conducted at each site throughout the clinical study, with the first occurring after enrollment commences as specified in the study Data and Safety Monitoring Plan.
  3. The clinical protocol and/or associated study Data and Safety Monitoring Plan will outline the anticipated monitoring schedule, however, the number of visits may change as monitoring visit results dictate, to include additional scheduled and unscheduled monitoring visits.
  4. The Monitor will conduct unscheduled monitoring visits as needed based on reports or evidence of potential non-compliance with the protocol, other concerns about the proper conduct of the study or participant safety, and any other Sponsor/regulatory requirements, which may have been noted during a prior scheduled visit or received from any other source, including employees at the site.
  5. Unscheduled visits may also be added due to significant increases in participant enrollment rates, and changes in the protocol or key study personnel.
  6. The Investigator or designated Monitor will contact the Investigator at each study site regarding scheduling and conducting upcoming monitoring visits.
  7. The Monitor will confirm the date and logistics of the monitoring visit in writing and provide the Investigator with a list of source documents and records (e.g., hospital charts, laboratory records, etc.) that will be reviewed during the monitoring visit.

3.2 Preparing for a Monitoring Visit

  1. The Monitor should review the relevant contents of the study and site files in the Regulatory Master File prior to the monitoring visit.
  2. The Monitor also should review previous Monitor's Reports for any outstanding items that must be addressed during the next scheduled visit.
  3. After reviewing all site information, the Monitor should note any questions and issues to be checked against source documents or other documents at the site.

3.3 Conducting a Monitoring Visit

3.3.1 General Monitoring Instructions

  1. The Monitor will document the monitoring visit by signing a Site Visit Log at the investigative site (See SOP 402 Attachment C).
  2. The Monitor will document all findings during the monitoring visit on a Monitoring Visit Report (See SOP 504 Attachment A).
  3. The Monitor will assess whether the key study personnel and facilities continue to be acceptable for the study and that the site's Investigator is appropriately involved in the conduct of the study.
  4. The Monitor will review the contents of the site's study files to ensure that all required documents are on file and current, and that the Investigator routinely files and forwards essential and required information to other required parties appropriately (e.g., Institutional Review Board or IRB).
  5. The Monitor will review any study conduct issues or incidents of non-compliance with the site's Investigator and other key study personnel and document the issues on the Monitoring Visit Report.
  6. If necessary, the Monitor will remind the site's Investigator of the obligation to immediately record and report serious adverse events to the IRB, other appropriate regulatory authorities, and the Investigator (if applicable), and to provide follow-up reports of the final outcome.
  7. The Monitor must confirm that all informed consent forms have been appropriately obtained and documented for all participants, and that informed consent was obtained before any protocol-related procedures were conducted (except those specified in the clinical protocol).

3.3.2 Case Report Form and Source Document Monitoring

  1. The Monitor will compare participant case report forms (CRFs) with the source documents to ensure protocol compliance and that data are accurate. According to the Data and Safety Monitoring Plan, elements of the CRF and source document verification by the Monitor will include:
    • Verification that the CRFs are being completed in a timely manner and according to protocol requirements by inspecting all CRF pages for completeness, accuracy, and internal consistency.
    • Review of key efficacy and safety parameters routinely for all participants
    • Review of inclusion and exclusion criteria and study events routinely for all participants
    • Review of participant Screening and Enrollment Logs (see SOP 603 Attachment A) and Subject Eligibility Checklists (see SOP 603 Attachment B) to ensure they have been signed and dated by the Investigator or qualified designee.
  2. Monitors may not enter data, correct data or write on the CRFs. If a recorded entry on a CRF appears to be aberrant, but after review of the source documents is found to be correct, the Monitor will indicate on the Monitoring Visit Report that the apparently aberrant entry was verified.
  3. The Monitor will immediately notify the Investigator or designee of discrepancies and improper completion of CRFs. Unresolved discrepancies will be documented and followed up.
  4. The following information must be included in the case history (basic medical record or hospital chart) for each participant: notice of participation in the investigational study, medical condition being treated, dosage or amount or type of investigational product being administered or used, the approximate duration of therapy, any concomitant therapy, and study events and other relevant information (as appropriate).
  5. The Monitor will remind the Investigator that all records and reports pertaining to the study must be retained at the study site as required by the Investigator and applicable regulatory requirements.
  6. The Monitor will remind the Investigator to provide all updated information pertaining to the study including changes in key personnel to the Investigator on a timely basis.

3.3.3 Inventory and Storage Monitoring

  1. The Monitor will ensure that investigational product accountability and reconciliation obligations are being followed, and verify all investigational products expiration dates.
  2. The Monitor will examine storage refrigerator, freezers and other storage equipment to confirm they are appropriate for the clinical protocol's requirements and that calibration and temperature logs are maintained in the site's study file.
  3. The Monitor will check the site's inventory of investigational product, forms, or other relevant materials, and arrange to provide additional items as necessary after concluding the visit.

3.3.4 Specimen and Laboratory Monitoring

  1. The Monitor will verify that all specimens for protocol-specific laboratory studies are being stored and forwarded properly and that specimen preparation documentation is maintained.
  2. The monitor will inspect specimen storage equipment as noted above in section 3.3.3.

3.3.5 Concluding the Monitoring Visit

  1. Upon concluding the monitoring visit, the Monitor will report any significant unresolved problems or protocol violations immediately to the Investigator, who may confer with the OHR regarding those findings.
  2. At the end of the monitoring visit, the Monitor should meet with the site Investigator, and Clinical Research Coordinator if appropriate, to review any monitoring findings and discuss management of such findings as applicable.

4. APPLICABLE REGULATIONS AND GUIDELINES

21 CFR 312.50

General responsibilities of sponsors

21 CFR 312.56

Review of ongoing investigations

21 CFR 312.59

Disposition of unused supply of investigational drug

21 CFR 312.60

General responsibilities of investigators

21 CFR 312.62

Investigator recordkeeping and record retention

21 CFR 312.64

Investigator reports

21 CFR 312.66

Assurance of IRB review

21 CFR 312.68

Inspection of investigator's records and reports

September 1993

FDA Compliance Program Guidance Manual 7348.811: Clinical Investigators

September 1994

FDA Compliance Program Guidance Manual 7348.810: Sponsors, Contract Research Organizations and Monitors

January 1988

Guidelines for the Monitoring of Clinical Investigations

5. REFERENCES TO OTHER APPLICABLE SOPs

GA-102

Responsibilities of the Research Team

SS-203

Investigator and Site Initiation Meetings

PM-301

Site-Sponsor/CRO Communications

PM-303

Regulatory Files and Subject Records

PM-305

Study Termination Visit

PM-306

Investigational Drug Accountability, Storage, Dispensing and Return

DM-501

Data Management

6. ATTACHMENTS

A.          Monitoring List Report

7. DEFINITIONS AND GLOSSARY

The following definitions the International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline apply to this SOP.

Case Report Form (CRF): A printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial subject.

Compliance (in relation to trials): Adherence to all the trial-related requirements, good clinical practice (GCP) requirements, and the applicable regulatory requirements.

Contract: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.

Direct Access: Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsors, monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects’ identities and sponsor’s proprietary information.

Documentation: All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records; and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

Essential Documents: Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.

Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

Investigator: A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.

Monitoring: The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement(s).

Protocol: A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents.

Protocol Amendment: A written description of a change(s) to or formal clarification of a protocol.

Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial).

Sponsor: An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

 

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