Monitoring

Sponsors should implement a proportionate and risk-based approach to clinical monitoring. The strategy must align with the risk control measures identified to minimise/mitigate risks related to participant safety, data quality and reliability of the trial results during the initial and ongoing trial risk assessment as documented in the trial-specific Risk Assessment & Management Plan. See Risk Assessment for further information.

The monitoring strategy is to be documented in a formal Clinical Monitoring Plan (CMP) and include parties involved, activities, methods and tools used, and rationale for their use. The scope includes Investigator Site Monitoring as well as centralised monitoring. Refer to MCTC047 Template | Clinical Monitoring Plan for IITs for the template to write a CMP.

The Sponsor-Investigator is responsible for appointing site monitors and qualified persons performing centralised monitoring activities.  

Monitors should be trained and have the scientific and/or clinical knowledge needed to monitor the trial adequately.

For MCRI-sponsored IITs that will not be used to submit a regulatory submission, site monitoring may be performed by a member of the trial team but only for sites that are external to Melbourne Children's. In the case where RCH or MCRI is a participating site, the site monitoring must be performed by a Monitor who is independent of the trial team. CRDO recommends outsourcing the monitoring to a CRO if the clinical trial data from the trial will be used to support a regulatory submission. 

Monitors should be familiar with the trial-specific Clinical Monitoring Plan, investigational product/intervention, the protocol, written Participant Information & Consent Form (PICF), Sponsor SOPs, relevant site SOPs, GCP and applicable regulatory requirements.

Monitoring of clinical trial site activities is conducted in person and/or remotely. 

In accordance with the Clinical Monitoring Plan, Monitors will check that the Investigator and site staff are suitably qualified and trained for the trial activities they are undertaking, check site facilities are adequate, and verify that the source data matches the data collected into the trial case report form (CRF).

Important

The Sponsor should ensure that the protocol and each site Clinical Trial Research Agreement (CTRA) specify that the site is to provide direct access to source records for trial-related monitoring, audits and regulatory inspections.

The Sponsor should ensure that trial participants have consented to direct access to source records for the purpose of monitoring, audits and inspections.

Some monitoring activities may be done remotely if agreed by both the Sponsor and the site.  Remote monitoring is dependent on the capability of the site to provide remote access to its systems in a manner that protects trial participant confidentiality and is in accordance with the site’s policies and applicable regulatory and data security standards.  

At a minimum, Monitors can only access PHI through the use of systems that are 21 CFR Part 11 compliant and that means:

• Restricted, read only access
• Audit trail
• Back up of data, recovery & retention
• Validated

When this is not possible, monitoring must be done in person and involve providing access to certified paper copies of the medical record and/or supervised access to the source documents.  Monitors are not permitted to remove any identifying patient information from the site. Monitors are bound by confidentiality and personal accountability to data governance standards via their employment contracts, signed Non-Disclosure Agreements (NDAs) and the conditions of the signed site CTRA.

For information about how to plan, conduct and report on site monitoring visits, refer to MCTC046 SOP | Monitoring Visit Activities for Clinical Trials of Investigational Products.  

Centralised monitoring is the ongoing, timely review of centralised data. It is performed by qualified and trained persons in the Sponsor-Investigator’s Central Coordinating Team. Roles involved in centralised monitoring include medical monitor, data manager and the biostatistician. As such, these persons should be involved in identifying the Critical to Quality Factors during the trial planning stage and developing the Monitoring Strategy and the Monitoring Plan. 

Data managers can review the CRF data to identify and raise data queries with the site in relation to missing data, inconsistent data, data outliers, and protocol deviations that may indicate significant errors in data collection and/or reporting at site.

Centralised monitoring may involve statistical monitoring, where patterns of accumulating data are examined using statistical approaches or modelling.  These approaches can help identify higher risk clinical sites, those with higher frequency of errors, protocol deviations or serious safety events.  Centralised monitoring can provide and assist with early identification and mitigation of data quality issues which may compromise the study results.

The activities of Trial oversight committees, e.g. Data Safety Monitoring Boards/Data Safety Committees, are also considered centralised monitoring.

CRDO runs a training course for campus staff and students who are keen to learn how to monitor IITs. More details, including how to register are available on the Training page.   

For all MCRI-sponsored IITs where the intervention is either a medicine, biological or device, the Sponsor-Investigator, PI and internal (employee of RCH or MCRI) Monitor must be trained on the Melbourne Children’s procedure, MCTC046 SOP | Monitoring Visit Activities for Clinical Trials of Investigational Products.  This SOP provides the rationale and procedures for monitoring.  MCTC046 SOP may also be used as guidance for non-investigational drug/device clinical studies where monitoring is required at the discretion of either the Sponsor-Investigator or the approving HREC or Research Governance Office.

Internal Monitors must use MCTC068 Template | Monitoring Visit Report to document the findings from site monitoring visits and it is recommended the MCTC093 Template | Participant-Level Monitoring Form for IITs is used to record the following outcomes:

• Informed consent document/process review
• Source data verification and CRF review
• Expedited reporting of safety events and serious breaches
• Investigational Product Accountability

Other monitoring tools located on METIS and via links below:

MCTC072 Factsheet | Using Teams for Trial Monitoring

MCTC185 Template | Remote Monitoring Visit Confirmation Letter

MCTC186 Template | Remote Monitoring Visit Follow Up Letter

MCTC073 Factsheet | Access Parkville Connect for Trial Monitoring