Key Risk Indicators

Key Risk Indicator (KRI)

Monitoring Rationale

Actions to be considered when KRI is above High (H) or below Low (L) limits.

Enrolment Rate

High enrolling sites make an important contribution to a trial and the quality and integrity of the data they generate must be ensured.

Low enrolling sites represent cost-inefficient contributions to a trial and site-specific recruitment problems must be addressed.

H- Ensure sufficient resources are available at the site to support the protocol’s workload. Ensure the site’s personnel have received sufficient training.

L- Verify the enrolment process and site’s motivation.

Screen Failures / Enrolment

A high screen failure/enrolment ratio can indicate a deficient screening process.

A low screen failure/enrolment ratio is ideal but the absence of screen failures might also indicate a deficient screening process.

H- Analyze the primary reason for screen failure. Ensure proper screening process.

L- Verify the screening process.

Withdrawal / Enrolment

A high withdrawal/enrolment can indicate problems related to an improper screening process or the safety of subjects. Inadequate patient retention affect the cost-effectiveness of sites.

H- Analyze the primary reason for discontinuation. Retrain the site’s personnel regarding the protocol’s inclusion/exclusion criteria.

Out of Range Visit Rate

Visits occurring out of the planned visit range represent protocol deviations which affect the endpoint analysis. A high occurrence of out of range visits may indicate site management problems.

H- Investigate root cause. Review visit scheduling process with the site’s personnel. Ensure sufficient resources are available at the site to support the protocol’s workload.

Missed Doses Rate

Missed doses have an impact on the analysis of the treatment’s safety and efficacy.

H- Investigate reason for missed doses. Verify drug distribution process and instructions given to subjects regarding drug administration and diary keeping.

Missing Endpoint Data

Missing endpoint data reflect poor protocol compliance and can compromise a trial’s integrity. Missing data can indicate problems with the training received by the site’s personnel or the instructions given to subjects. It can also indicate problems with the instruments used to collect data.

H- Investigate reason for missing endpoint data. Review instructions received by site’s personnel and given to subjects. Assess potential problems with the instruments used for the collection of endpoint data.

Time to Data Entry

Late data entry is indicative of poor site motivation and protocol adherence. It affects the contemporaneity of data used to perform centralized monitoring. Late data entry can indicate problems related to the site’s resource sufficiency and motivation. It can also indicate problems related to the training received by the site’s personnel.

H- Ensure sufficient resources are available at the site to support the protocol’s workload. Reiterate the importance of timely data entry to the site’s personnel. Offer data entry refresher training.

Query Rate

The query rate is a measure of the amount of data entry errors and protocol non-compliance. A high rate may indicates problems with the training received by the site’s personnel which can affect data quality.

H- Retrain the site’s personnel regarding the protocol and the data entry instructions. Increase the required SDV at the site.

Time to Query Resolution

The time to query resolution affects data quality and reflects the ability of the site’s personnel to work with the EDC system and their ability to address data issues in a timely manner. It also affects the quality and the contemporaneity of the data used to perform centralized monitoring.

H- Evaluate the site’s personnel query resolution proficiency. Ensure sufficient resources are available at the site to support the protocol’s workload. Retrain the site’s personnel on query resolution.

Error Rate

The error rate reflects the ability of the site’s personnel to work with the EDC system. A high error rate indicates of data entry difficulties which may translate into poor data quality.

H- Investigate root cause. Retrain site’s personnel with regards to data entry. Increase the required SDV at the site.

Deviation Rate

The deviation rate reflects protocol and GCP compliance which can compromise trial integrity. Deviations linked to study objectives can affect the scientific soundness of the research plan or the rights, safety, or welfare of human subjects. A high deviation rate may indicate poor protocol and GCP compliance but also over-reporting.

A low deviation rate may indicate that deviations are not appropriately reported.

H- Evaluate the root cause of deviations. Ensure deviations are reported adequately.

L- Ensure deviations are properly reported in a timely manner.

Adverse Events Rate

A high Adverse Event Rate may reflect an inadequate protection of subject’s right, safety and welfare.

A low Adverse Event rate may indicate that adverse events are under-reported.

H- Ensure AEs are properly reported. Evaluate the potential risk to subject right, safety and welfare.

L- Review source data (e.g.: concomitant medications, physical exams, vital signs, laboratory results) for unreported AEs.

Monitor’s Site Appreciation Survey

The on-site monitor’s rating represents a qualitative metric which allows for the evaluation of the site’s quality. The ratings of aspects such as the Investigator Involvement, the Trial Master File Maintenance, the Source Documents Quality, and the Resource Sufficiency serve to highlight site difficulties. The survey complements the centralized monitoring effort with real-world observations.

L- Evaluate the root cause and develop mitigation strategies with the assigned CRA and the site’s personnel.