Clinical monitoring

• Phase I–IV studies on drugs
• Bioequivalence and bioavailability studies
• Clinical studies on food supplements
• Clinical studies on medical devices
• Clinical studies on vaccines

The Convex monitoring team consists of full-time Clinical Research Associates who guarantee up-to-date knowledge of the clinical trial’s status at each clinical site. Our monitoring procedures include:

• Evaluation of the study progress
• Review of the staff and facilities at the clinical sites
• Review of protocol compliance
• Review of CRFs and performance of SDV
• Review of investigator’s file
• Review of biological sample handling
• Review of the investigational product(s)
• Identification of issues and implementation of corrective actions
• Maintenance of frequent and direct communication plan
• Maintenance of tracking reports

CRA Visits

Convex CRO monitoring visits are generally referred to as pre-study visits, initiation visits, monitoring visits, and close-out visits. A pre-study visit may not be required when a study site is well known to the sponsor; initiation visits may be replaced by an Investigator Meeting attended by the PI and Clinical research staff.

Pre-Study Visit

A pre-study visit takes place after a potential PI indicates interest in a specific clinical trial. The purpose of this visit is to determine the site’s ability to conduct the study. Before the visit, the PI should review the protocol and Investigator’s Brochure and sign the Confidentiality Agreement. During the visit, the Convex CRA will meet with the PI and CRC to verify that they have adequate time to devote to the study, have access to the appropriate subject population, and are not involved with competing clinical trials. The CRA will tour the facility to evaluate its adequacy and determine the availability of protocol-required equipment. The CRA will also evaluate the facility’s suitability for subject enrollment and follow-up, investigational product storage, and data form storage. Other study-specific requirements, such as access to an ECG laboratory or the facility where study-required scans will be performed, will be evaluated as well.

Topics for the Pre-Study Visit:

• PI responsibilities and qualifications (summarized in the investigator’s CV);
• Qualifications of the CRC and other site personnel;
• Study objectives, protocol-required procedures, eligibility criteria, and subject recruitment;
• RB and informed consent requirements;
• AE reporting, source documentation, and record retention;
• Space requirements, availability of a secure area for storing investigational drugs, biologics, or devices;
• Availability of required equipment.

In some cases, such as when the investigative site is already known to the sponsor/CRA, the sponsor may allow a pre-study evaluation to be performed over the telephone instead of on-site. An overall pre-study visit is meant simply to assess the fаsibility of conducting the study at the site and determine whether the site can manage protocol-specific requirements, this visit does not obligate the PI or the sponsor to work together on the trial.

Initiation Visit

Once the PI agrees to participate in the study and signs the contract with the sponsor, regulatory documents are accepted by the sponsor, the protocol and consent form is approved by the RA/EC, and clinical supplies are shipped to the site, a study in initiation visit can be initiated. This visit verifies that the investigator and other site study personnel understand the investigator’s obligations, the protocol, and the investigational product being studied. During the initiation visit, the CRA meets with the PI, sub-investigators, the CRC, and other personnel related to the study, such as pharmacy and laboratory staff.

Topics for the Initiation Visit:

• study overview, including eligibility criteria, procedures, and access to a suitable subject population;
• review of regulations and GCP guidelines, including informed consent requirements, EC obligations, AE reporting, and investigational product accountability;
• review of data forms and data recording; review of regulatory documents and study file organization.

Monitoring Visits

After one or more subjects are enrolled in the study, a monitoring visit is scheduled to evaluate how the study is being conducted and to perform source document verification. The number of visits will be determined by several factors outlined in the monitoring plan, including the number of subjects enrolled and the percentage of records that require on-site review and source document verification.

Topics for Periodic Monitoring Visits

• the PI and other trial personnel are fulfilling their obligations as set forth by regulations and GCP guidelines;
• the trial is being conducted according to the protocol and any deviations are appropriately documented;
• enrolled subjects meet study eligibility criteria;
• informed consent was properly obtained before study participation;
• subject data are accurate and complete when compared with source documents;
• investigational product accountability procedures are being followed;
• SAEs and unanticipated problems involving risks to subjects or others are documented and reported appropriately;
• the PI and CRC are providing the EC/RA with timely reporting of study progress and safety;
• proper filing and storage of study documents are maintained.

When contacting the CRC to schedule a periodic monitoring visit, the CRA will request that subject data forms and SAEs forms for subjects enrolled since the previous monitoring visit be made available. Signed consent forms and source documents should be available as well for review and source document verification. To prepare for an aperiodic monitoring visit, the PI and CRC should confirm that the following activities have been completed to ensure a productive monitoring visit takes place:

• complete all applicable subject data forms before the visit;
• confirm that SAEs have been documented and reported, and are available for review during the visit;
• obtain necessary source documents for study subjects who require source document verification of data. Medical records and transfer records from external medical offices and hospitals may be needed;
• organize study file documents for review;
• confirm that signed consent forms for all enrolled subjects are available;
• schedule an appointment for the CRA to meet with the pharmacist, if requested;
• schedule time for the CRC to meet with the CRA to review all data forms monitored during the visit and to discuss the trial’s general progress trial;
• schedule a meeting between the CRA and the PI to review the findings.

Checking data against source documents, clarifying discrepancies and misinterpretations on data forms, and observing and providing practical ideas for implementation of the protocol at specific sites make periodic monitoring visits an integral aspect of a successful clinical trial. The Periodic Monitoring Visit Checklist on the following page is an example of one that may be used by a CRA when conducting a site monitoring visit.

Close-Out Visits

Topics for a Close-Out Visit:

• discuss timelines and strategies for completing outstanding data and queries;
• oversee the return or destruction of unused test products;
• collect outstanding subject data forms and study forms such as the Site Visit Log and Screening Logs;
• perform a final review of study file documents;
• discuss plans for record retention;
• ddiscuss plans for notifying PI and subjects of final study results.

Site Visit Report

Upon monitoring visit completion, CRA submits a comprehensive site visit report to the sponsor or sponsor-designee. This report lists all findings at the site. Any issues, protocol violations, or other tasks will be described, as well as proposed corrective actions and timelines for making the changes.

Follow-up Letter to the PI

Findings from the site visit are summarized in a follow-up letter to the PI. He/she reviews the letter to make sure they agree with the stated findings and suggestions to resolve deficiencies or corrective actions. The follow-up letter should then be kept in the site study file.