Monitoring in accordance with the sponsor’s requirements and monitoring plan should generally include the following activities across the clinical trial life cycle, as applicable.
(a) Establishing and maintaining a line of communication between the sponsor and the investigator and other parties and individuals involved in the trial conduct (e.g., centrally performed activities). In general, each site should have an assigned monitor as their contact point.
(b) Informing the investigator or other parties and individuals involved in the trial conduct of relevant deviations from the protocol, GCP and the applicable regulatory requirements and, if necessary, taking appropriate action designed to prevent recurrence of the detected deviations. Important deviations should be highlighted and should be the focus of remediation efforts as appropriate.
(c) Informing the investigator or other parties and individuals involved in the trial conduct of entry errors or omissions in source record(s) and/or data acquisition tools and ensuring that corrections, additions or deletions are made as appropriate, dated and explained (if necessary) and that approval of the change is properly documented.
(d) Actions taken in relation to the deviations, errors or omissions should be proportionate to their importance.
(a) Selecting the site and confirming that the investigator and individuals or parties involved in the trial conduct have adequate qualifications, resources (see sections 2.1, 2.2 and 3.7) and facilities, including laboratories, equipment and investigator site staff, to conduct the trial safely and properly.
(b) Confirming, with consideration of their delegated activities and experience, that the investigator, investigator site staff and other parties, and individuals involved in the trial conduct are adequately informed about the trial and follow the current approved protocol and other protocol-related documents, such as the current Investigator’s Brochure and relevant information related to the investigational product.
(c) Confirming that the investigator is maintaining the essential records (see Appendix C).
(d) Confirming that informed consent was obtained before participation in the trial (see section 2.8) for trial participants at the site.
(e) Determining whether adverse events are appropriately reported within the time periods required by the protocol, GCP and the applicable regulatory requirement(s).
(f) Confirming the protocol requirements for source records and the site’s location of such data.
(g) Verifying that the blinding is maintained, where applicable.
(h) Reviewing and reporting the participant recruitment and retention rates.
(i) Confirming that the investigator provides the required reports, notifications or other information in accordance with the protocol and trial procedures.
(j) Confirming the arrangement for the retention of the essential records and the final accountability of the investigational product (e.g., return and destruction or alternative disposition, if appropriate) during site close-out activity.
(a) Confirming, for the investigational product(s):
(i) That storage conditions are acceptable and in accordance with the storage requirements specified in the protocol or other relevant documents;
(ii) That supplies are sufficient throughout the trial and are used within their shelf life;
(iii) That the correct investigational product(s) are supplied only to participants who are eligible to receive it at the protocol-specified dose(s) and, where appropriate, in accordance with the randomisation procedures;
(iv) That the participants, investigator, investigator site staff and other relevant parties and individuals involved in the trial conduct are provided with
necessary instruction on properly storing, using, handling, returning and destroying, or alternative disposition of the investigational product(s);
(v) That the receipt, storage, use, handling, return and destruction or alternative disposition of the investigational product(s) are controlled and documented adequately;
(vi) That the disposition of unused investigational product(s) complies with applicable regulatory requirement(s) and is in accordance with the sponsor requirements;
(vii) Where product available on the market is dispensed and used in accordance with applicable regulatory requirements, some of the previously outlined considerations may not be applicable.
(a) Verifying that the investigator is enrolling only eligible trial participants.
(b) Checking the accuracy, completeness and consistency of the reported trial data against the source records and other trial-related records and whether these were reported in a timely manner. This can be done on the basis of using samples and supported by data analytics, as appropriate. The sample size and the types of data or records may need adjustment based on previous monitoring results or other indications of insufficient data quality. Monitoring should:
(i) Verify that the data required by the protocol and identified as data of higher criticality in the monitoring plan are consistent with the source;
(ii) Identify missing data, inconsistent data, data outliers, unexpected lack of variability and protocol deviations;
(iii) Examine data trends, such as the range, consistency and variability of data within and across sites;
(c) Identifying significant errors in data collection and reporting at a site or across sites, potential data manipulation and data integrity problems.