Section 2

How Does Clinical Trial Site Monitoring Work Under a Risk Based Monitoring Approach?

The TransCelerate Model Approach

People, Process and Technology

RBM Stakeholders: Research Sites and Regulatory Authorities

The TransCelerate Model Approach

Download a PDF of the RBM Interactive Guide

The TransCelerate RBM Initiative was one of the first five initiatives established in 2012 for creating more effective and efficient solutions in research and development (R&D). What sets it apart from other efforts, lies in its development of a model RBM framework that can be successfully deployed and scaled in a collective manner.

TransCelerate’s methodology shifts away from dependence on an On-site monitor to instead primarily enact monitoring duties through an emphasis on Centralized monitoring and/or Off-site activities. It’s an adaptive approach that focuses on the evolving areas of greatest need which have the most potential to impact patient safety and data quality, and implements Source Data Review (SDR) as a fundamental practice.

TransCelerate’s RBM methodology can be adopted by any size organization, and any type or phase of a clinical trial. It incorporates According to the US FDA, quality risk management is a systematic process for the assessment, control, communication and review of risk to the quality of the drug product across the product lifecycle.quality risk management1 as a foundation for ensuring subject safety and data quality. TranCelerate’s RBM methodology predicates on several key practices and values that have been defined by TransCelerate and include:


Scroll over the bolded terms below to learn more about key practices.

  • Building Systematically building quality into a clinical trial design to ensure that processes are focused on what is critical, and are performed in a way that mitigates errors that would have the greatest impact on subject safety and data quality.Quality by Design (QbD) into trials
  • Early and ongoing The process by which potential risks that could affect subject safety, data quality or regulatory compliance are examined. Includes categories such as study phase and subject population.Risk Assessment
  • A focus on Processes that are critical to the reliability of the study findings, and those related to ensuring subject safety.Critical Processes and Data that are critical to the reliability of the study findings, specifically those data that support primary and key secondary endpoints, as well as data that are related to subject safety.Critical Data
  • Use of Risk indicators are metrics used to monitor identified risk exposures over time.Risk Indicators and The level, point, or value associated with a Risk Indicator that will trigger an action such as increased data scrutiny or site follow-up.Thresholds
  • Ongoing adjustment of monitoring activities based on
    the issues and risks that may arise throughout the study

What are the steps a sponsor might take to adopt a RBM model to a clinical trial?

Click on each step to learn more about how to adopt a RBM model
  • Teams can conduct a cross-functional risk assessment at the program level, which means identifying the relevant risks that could impact subject safety and/or data quality.
  • Teams can also assess risk at the protocol level, which invariably expands the initial list of risks and examines risk in greater detail, as protocol-level assessment typically mandates an even closer examination.
  • Sponsors can use TransCelerate’s Risk Assessment and Categorization Tool (RACT) which provides categories of risk, questions for discussion and considerations specific to risk categories. The RACT helps determine risks that could affect subject safety, data quality and regulatory compliance, and provides guidance on how and by which function the risks may be managed.
  • Studies are assigned a high, medium or low Overall Risk Level, which may vary across the different stages of the study. The type and amount of monitoring activities applied are based on the determined Overall Risk Level.
  • The second stage of implementing TransCelerate’s RBM methodology lies in defining Critical Data and Critical Processes.
  • What are some examples of Critical Data and Processes?
    • Data critical to subject safety, such as serious adverse events
    • Data that supports primary and key secondary trial objectives
    • Processes that reinforce subject safety and ethical treatment
    • Processes that strengthen data quality
    • Data and processes that help the trial obtain reliable results
  • Critical Data and Processes are defined by the sponsor at the program level, reassessed at the protocol level and monitored throughout the lifecycle of the trial.
  • Teams can create potential Risk Indicators and associated Thresholds.
  • Teams enacting a RBM plan can develop an Integrated Quality Risk Management Plan (IQRMP), a tailored and integrated strategy for each specific clinical trial that will define the actions that each function takes to proactively identify, assess and manage risk through the entire clinical trial. The IQRMP may or may not be an actual document, it may be a concept to ensure the various functional plans align at the IQRMP level. Some companies combine all the functional plans to create the IQRMP, but others do not.
  • What are examples of inputs to the IQRMP?
    • Clinical development plan
    • Regulatory strategy
    • The RACT tool
    • Critical Data
    • Any existing program or product risk management plans
  • To bring the preceding steps to a cohesive place, study-specific plans should be created for each function.
  • The monitoring plan should include trial-specific instructions for all team members, which include not just the Monitors but also Protocol and Project Managers, Data Managers, Statisticians and sometimes clinical operations groups, to monitor and proactively mitigate risk.
    • Instructions enable key players to make sure that the clinical trial is conducted, recorded and reported in accordance with the protocol, standard operating procedures, Good Clinical Practice (GCP) and applicable regulatory requirements
  • The monitoring plan should define what activities will be conducted Off-site and Centralized, as well as those that must be performed On-site.
  • Monitoring activities are aligned with the Overall Risk Level assigned at the protocol level; if Overall Risk Level changes at various stages of the study, the monitoring activities may change accordingly.

Additional Considerations:

The pharmaceutical industry is working to improve safety and quality in clinical trials. TransCelerate’s RBM methodology has the potential to help identify and proactively manage emerging risks to avoid obstructing a trial’s success. This is due to the methodology’s proactive quality and risk management approach into the scientific design and operational conduct of clinical trials.

1. US FDA, “Guidance for Industry: Quality Risk Management”

Section 2: How Does Clinical Trial Site Monitoring Work Under a Risk Based Monitoring Approach?

People, Process and Technology