Risk-Based Monitoring (RBM) in clinical trials represents a departure from traditional, one-size-fits-all monitoring approaches. This innovative strategy tailors monitoring activities to the specific risks associated with a trial, optimizing resource utilization and enhancing data quality. This article explores the key principles, benefits, and challenges of RBM, illustrating its transformative impact on the landscape of clinical trial oversight. Key Principles: Risk Identification and Assessment: RBM begins with a comprehensive assessment of potential risks to data integrity, patient safety, and study endpoints. These risks are identified based on factors such as study complexity, patient population, and investigational product characteristics.

1. Welcome
RISK BASED MONITORING IN CLINICAL TRIALS
AISHWARYA JANJALE
MSc Analytical Chemistry
CLS_214/102023
10/18/2022
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INDEX
• INTRODUCTION
• WHAT IS MONITORING
• RISK BASED MONITORING
• WHY IS RISK BASED MONITORING ON
RISE?
• WHAT IS CENTRALIZED MONITORING
• BENEFITS OF RISK BASED MONITORING
• QUALITY BY DESIGN IN RBM

3. Introduction
Clinical trials play a critical role in the development and delivery of
breakthrough medical treatments. They evaluate which drugs,
devices and treatments are safe and effective for humans, and
which therapies work best for certain illnesses or patient
populations. Successful trials require quality data, protection of
patient safety, affordability and speed.
This presentation focuses on a modernized, proactive method of
clinical trial monitoring called Risk-based monitoring (RBM),
an adaptive approach that directs monitoring focus and activities to
the evolving areas of greatest need which have the most potential to
impact patient safety and data quality.
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4. WHAT IS MONITORING?
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5. Risk based monitoring
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• Mixture of on site, remote and statistical monitoring based on risk evaluation

6. Risk-based monitoring in clinical
trials
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• Risk-based monitoring is the process of ensuring the quality of clinical trials by identifying,
assessing, monitoring and mitigating the risks that could affect the quality or safety of a study.
• RBM is an approach to clinical trials monitoring that emphasizes focusing monitoring efforts on
areas with the greatest potential risk to data quality and patient safety.
• RBM uses a combination of on site and off site monitoring activities to manage risks effectively
Steps for effective Risk Based monitoring are-
1. Identify critical data and processes. To accurately monitor the quality of a study and the
safety of its participants, the sponsor must know which elements are most important for each
particular study – from informed consent to eligibility screening and tracking of adverse events.
2. Perform a risk assessment. A risk assessment involves determining specific sources of risk
and the effect of study errors on those risks.
3. Develop a monitoring plan. According to FDA's guidance, a monitoring plan should "describe
the monitoring methods, responsibilities, and requirements of the trial." The plan is responsible
for communicating risks and monitoring procedures to everyone involved in monitoring the
trial.

7. WHY IS RISK BASED MONITORING ON
RISE?
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• The cost and complexity of clinical trials have grown dramatically in recent years. Up to
a third of a study's cost can now be attributed to the traditional on-site review of trial
data.
• Because efficient monitoring is critical to protecting the well-being of trial participants
and maintaining the integrity of final results, it is now generally accepted that the
process for clinical trial monitoring needs to change
• A more centralized, risk-based approach is now the preferred method for monitoring
clinical trials, according to several regulatory agencies, including the FDA.

8. What is Centralized Monitoring?
• Centralized monitoring is the process of collecting data from multiple sources, such as multiple
research sites or across patient populations, to a remote, central location that is located away
from the sites.
• Centralized monitoring tools and techniques can help identify Patterns or outliers in data that may
indicate potential risks or risk at site level. These tools can be used to prioritize which site or data
points require more intensive on site monitoring under the RBM strategy.
• By Centralizing data review and analysis, RBM becomes more efficient and targeted, allowing
clinical trials sponsors to allocate monitoring resources where they are most needed
• This data is then evaluated by teams that can include clinical monitors, data managers, and
statisticians.
• Centralized monitoring has been used increasingly over the past decade as clinical research has
been reshaped by increased data sets and the need for collaboration between sponsors
and CRO regarding monitoring plans, and the use of new technologies to facilitate the same.
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9. Centralized Monitoring
Centralized Monitoring began with some potential benefits in mind. It allowed for all the source
data to be collected in one electronic system that could be accessed and monitored remotely.
This has led to a clear set of benefits:
• Increased efficiency through decreased visits for real time monitoring of trial status, data
quality, and compliance with regulatory requirements.
• Increased efficiency for risk based monitoring through real time identification of risks to
patients, outliers, and trend identification.
• Increased ability to implement adaptive trial monitoring because of the availability of near
real time data.
• Increased efficiency in data management through use of digital source data.
• Increased validity of research through the ability to use expanded data sets or involve more
research sites without prohibitively increasing costs.
• Decreased costs associated with less frequent onsite visits by monitors.
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10. Benefits of RBM
• The principles of centralized analytics used extensively in industries have been
observed to have multiple benefits, including improved quality of operations and
product, with an associated lower cost. These principles can be effectively
applied to pharmaceutical development and clinical trial monitoring
through risk-based monitoring (RBM).
• While paper-based data collection is a practice that still occurs in clinical trials,
the industry is increasingly shifting towards processes that digitize clinical
data.
• Digitization specifically impacts the earlier detection of data quality issues,
making possible a string of actions that weren’t feasible in a paper-based
paradigm, most notably, a comprehensive risk-based monitoring
(RBM) approach. RBM can involve the entry and storage of digital data, which
improves quality by bringing data collection and tracking in real-time, and trends
and analytic capabilities to the forefront. Digitization contributes to RBM’s core
goals:
1. Controlling and ensuring that clinical data quality is accurate, complete and
verifiable
2. Enhancing the safety of patients in a clinical trial, ensuring the rights and well-
being of human subjects are protected
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11. What are the specific and important benefits that RBM enables
for investigator sites, sponsor companies and patients?
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12. The monitoring process
As discussed above, the FDA has provided some detailed guidance on how to prepare a monitoring plan, but once
the plan is in place, it's the sponsor's responsibility (or the sponsor's delegate, like a CRO) to execute the plan.
While specifics will differ widely between studies, a risk-oriented monitoring program will typically contain the
following activities, which all flow through a comprehensive risk dashboard built for your particular study:
• Data collection and submission. A centralized approach requires a steady and reliable flow of data from each
study site to the central monitoring system. This may occur either through manual entry and transfer of relevant
data, or through an automated connection between the data entry system and the central dashboard.
• Dashboard monitoring. The function of the dashboard is to provide, at a glance, information about the status of
each study site relative to the specific risk factors in your trial. When a site shows a high risk level, your
monitoring plan should help you decide whether further investigation is appropriate, from in-depth statistical
analysis to on-site data verification.
• Statistical analysis. In addition to monitoring your risk dashboard, it can also be useful to perform
supplementary statistical analyses to help identify problems. Simple histograms and box plots can be
extremely useful for spotting outliers between sites or countries for various risk indicators. More advanced
techniques like clustering can also help identify problematic sites or even fraud.
• Targeted on-site investigation. Dashboard monitoring and further analysis will sometimes signal strongly that
in-person investigation is needed at a particular site. In these cases, it may be appropriate to visit and perform a
more traditional source data verification activity, depending on the nature of your study. The key is that once a
centralized system in place, on-site investigation should be the exception, not the norm.
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Quality by design in RBM
In context of clinical trials and risk based monitoring, QBD principles can be applied to improve the
overall quality and efficiency of the trial. Here’s how QBD relates to RBM.
1. Early planning and Design:
QBD encourages early planning and design to identify factors and potential risks in trials. This aligns with RBM’s risk assessment phase
where risks are identified and prioritized.
2. Risk identification:
QBD helps identify risk associated with trial design, product development, while RBM focuses on risks throughout clinical trial lifecycle.
3. Risk Mitigation:
QBD and RBM work together to develop strategies for risk mitigation, QBD focuses on designing a robust and reliable trial, while rBM adapts
monitoring activities to address identifies risks effectively.

14. Conclusion
• RBM is a dynamic process that involves ongoing evaluation of the study's risk profile and adjusting the
monitoring strategy accordingly. By focusing monitoring efforts on the areas of the study that pose the highest
risk, RBM can improve data quality and participant safety, while reducing monitoring costs and burden.
• The RBM process begins with a risk assessment, which involves identifying potential risks to the study's data
integrity, participant safety, and study conduct. This may include risks related to patient enrollment, data
collection, adverse event reporting, or protocol compliance. Based on the risk assessment, the study team
creates a risk management plan that outlines the monitoring strategy to be employed throughout the trial.
• Overall it’s a great method to reduce cost and increase efficiency for your clinical trials.
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15. Thank You!
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