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ICH E6(R3) monitoring strategy
Last updated September 2026

Risk-Based Monitoring (RBM) Training

Centralized monitoring and data-driven oversight as ICH E6(R3) describes them: key risk indicators, remote data review, and site visits targeted where the risks are.
Compare RBM with traditional monitoring

Working definition

Risk-Based Monitoring (RBM) is a clinical trial oversight strategy that uses centralized data analytics and Key Risk Indicators (KRIs) to direct monitoring efforts toward the areas where identified risks warrant attention. ICH E6(R3) describes selecting the extent and nature of monitoring according to trial risk: ICH E6(R3).

Remote monitoring
Centralized
Analytics approach
KRI-driven
Site visits
Targeted

Monitoring strategy

RBM compared with traditional monitoring

The FDA recommends that sponsors consider risk-based approaches; ICH E6(R3) describes monitoring whose extent and nature are selected according to identified risks.

Source data verification
Traditional

Broad, routine verification across many data points

Risk-based

Verification extent justified by critical data and identified risk; no universal percentage FDA RBM guidance

Site visit frequency
Traditional

Fixed schedule (e.g., every 4-6 weeks)

Risk-based

Frequency adapted to identified risk and emerging knowledge

Issue detection
Traditional

Found during next site visit

Risk-based

Timely cross-site review with centralized analytics

Cost efficiency
Traditional

High travel and time costs

Risk-based

Resources directed according to risk; savings remain study-specific

Data analysis
Traditional

Site-by-site, retrospective

Risk-based

Cross-site patterns and timely trend review

Regulatory alignment
Traditional

May remain appropriate when justified for the trial

Risk-based

E6(R3) recommends monitoring extent and nature based on identified risks ICH E6(R3), section 3.11.4

Components

The working parts of risk-based monitoring

Centralized monitoring

Remote review of accumulating data using statistical methods to identify outliers, trends, and patterns across sites.

  • Statistical process control
  • Cross-site comparisons
  • Automated alerts

Key risk indicators (KRIs)

Predefined metrics that signal potential quality issues, triggering investigation or intervention when thresholds are exceeded.

  • Protocol deviation rates
  • Query response times
  • Missing data percentages

Targeted site visits

On-site monitoring visits focused on high-risk activities, triggered issues, and critical verification needs.

  • Risk-prioritized scheduling
  • Issue-driven scope
  • Efficient resource use

Remote data review

Continuous review of eCRF data, safety reports, and site metrics without travel to clinical sites.

  • Timely data access
  • Query management
  • Trend identification

From plan to practice

Putting risk-based monitoring into practice

Six steps for moving a trial to risk-based monitoring.

  1. 01

    Define the monitoring plan

    Document your risk-based monitoring strategy including KRI definitions, thresholds, and response procedures.

    • Identify Critical to Quality factors
    • Define KRI metrics and thresholds
    • Specify centralized review frequency
    • Document escalation procedures
  2. 02

    Configure the systems

    Set up technology infrastructure for centralized monitoring including data visualization and alerting.

    • Implement centralized monitoring platform
    • Configure KRI dashboards
    • Set up automated alerts
    • Integrate data sources (EDC, CTMS, etc.)
  3. 03

    Establish baselines

    Collect initial data to establish normal ranges and refine thresholds for meaningful alerting.

    • Run pilot phase for KRI calibration
    • Analyze historical data if available
    • Adjust thresholds to what the data shows
    • Document baseline metrics
  4. 04

    Train the teams

    Monitors, data managers, and site staff need to know the RBM process and their part in it.

    • Train CRAs on new monitoring approach
    • Educate sites on expectations
    • Train data management on KRI review
    • Document roles and responsibilities
  5. 05

    Monitor and respond

    Execute ongoing centralized review, respond to alerts, and conduct targeted site visits.

    • Conduct regular centralized reviews
    • Investigate KRI threshold breaches
    • Schedule risk-driven site visits
    • Document findings and actions
  6. 06

    Adapt and improve

    Continuously evaluate RBM effectiveness and refine approach based on lessons learned.

    • Review KRI performance quarterly
    • Assess issue detection effectiveness
    • Refine thresholds as needed
    • Update monitoring plan

Signals, not defaults

Illustrative key risk indicator signals

These are categories to consider, not default thresholds. Each trial should pre-specify meaningful ranges or triggers based on its critical-to-quality factors, design, population, and applicable requirements.

Enrollment and retention

Screen failure rateUnexpected variance
Enrollment rateDeparture from plan
Participant withdrawal rateSite-level outlier

Data quality

Query rateCross-site outlier
Query resolution timeStudy-defined delay
Missing critical dataUnexpected pattern

Protocol compliance

Protocol deviation rateEmerging trend
Important deviationsStudy-defined trigger
Visit window adherenceSite-level outlier

Safety reporting

AE reporting timelinessApplicable deadline
SAE reporting timelinessProtocol-defined trigger
AE rateCross-site outlier

Frequently asked questions

Common questions about risk-based monitoring

How RBM works in practice, and what the guidance does and does not require.

What is Risk-Based Monitoring (RBM)?
Risk-Based Monitoring (RBM) tailors monitoring methods, scope, and frequency to identified risks. It can combine centralized review, data analytics, remote activities, and site monitoring so that oversight remains focused on participant protection and the reliability of trial results.
What is the difference between RBM and RBQM?
Risk-Based Monitoring (RBM) is a component of Risk-Based Quality Management (RBQM). RBQM is the broader quality management framework covering the entire trial lifecycle, while RBM specifically focuses on monitoring activities. RBM includes centralized monitoring, remote data review, and targeted site visits. RBQM encompasses RBM plus trial design, vendor oversight, and all quality processes.
What are Key Risk Indicators (KRIs) in RBM?
Key Risk Indicators (KRIs) are predefined metrics used to detect potential quality or compliance issues at clinical sites. Examples include enrollment rate deviations, protocol deviation frequency, query response times, missing data rates, and adverse event reporting patterns. KRIs trigger alerts when they exceed predefined thresholds, enabling targeted intervention.
What is centralized monitoring?
Centralized monitoring is a remote evaluation of accumulating data performed by qualified personnel at a location other than clinical sites. It uses statistical analyses to identify data trends, outliers, and potential issues across sites. This allows sponsors to detect problems early, often before on-site visits, and to target monitoring resources where they're needed most.
Does ICH E6(R3) legally require one RBM model?
No. ICH E6(R3) recommends that the sponsor determine the appropriate extent and nature of monitoring based on identified risks, but it does not prescribe one monitoring model or a universal verification percentage. FDA publishes E6(R3) as nonbinding guidance; binding duties come from applicable statutes and regulations, with additional requirements potentially set by the protocol, contracts, and organizational procedures.
Can RBM completely replace on-site monitoring visits?
Sometimes centralized monitoring may be used on its own; in other trials it complements site monitoring. ICH E6(R3) says centralized monitoring can complement and reduce the extent or frequency of site monitoring, or be used on its own. The sponsor should select and document the mix that fits the trial's design, risks, site capabilities, and monitoring objectives.
Does RBM set a standard Source Data Verification percentage?
No. Neither ICH E6(R3) nor FDA's 2013 risk-based monitoring guidance sets a universal SDV percentage. Source data review and verification are tools within a broader monitoring strategy; their extent should be justified by the trial's identified risks, critical data and processes, and applicable requirements.
Is RBM training included in MyTrial Academy's free course?
Yes, RBM training is included in our free ICH E6(R3) GCP course. Module 4 covers risk-based monitoring as proportionate oversight within its Quality by Design, proportionality, protocol design, and practical RBQM lessons.

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