Definition of Risk-based Monitoring

Risk-based Monitoring (RBM) is becoming an essential concept in pharmaceutical clinical research today, which has potential to reduce clinical costs and improve data quality, and time-to-market of a medicine.

In August 2011 FDA underlined its wish to support risk-based monitoring in clinical trials with the publication of its guidance “Oversight for Clinical Investigations — A Risk-Based Approach to Monitoring.”[1]

The idea is not to monitor sites “flat”, but to do it wisely. I.e. to have risk KPIs in order to understand the pain points of the study. Additionally, it would be reasonable to reuse the information from the previous studies in order to benefit the next ones.

Risk-based Monitoring Strategies according to FDA:

As it is shown above the RBM Strategies are:

  • Centralized Monitoring.
    An integrated approach based upon the perceived risk at each Site.
  • Remote Monitoring.
    Use of Iow-cost resources to execute work, which does not require on Site resource.
  • Reduced Monitoring.
    E.g. Targeted SDV.
  • Triggered Monitoring.
    Based upon pre-defined trigger points e.g. Ration of patients enrolled: SAEs reported.

Graphics RbM Strategies

Thus, RBM is the way, where the pharma company produces most remote monitoring and remote view of the source.
FDA: “It’s going to be more centralized and not 100 percent site-specific quality control. There are numerous cost benefits to centralized monitoring, including earlier identification of problems that might not be picked up.”

Still, there is some discrepancy in the understanding of the RBM concept among regulatory agencies:


FDA’s Definition:

RBM — is the adequate mix of strategies including centralized and on-site monitoring practices with the goal of human subject protection and trial integrity [2].


EMA’s Definition:

RBM – is an important part of a preventive clinical trial management approach, which aims to identify, assess, control, communicate and review the risks associated with the clinical trial during its lifecycle in order to guarantee the protection of trial subjects’ rights, well-being, integrity and safety and the assurance of quality of data and the trial credibility [3].

EMA and FDA set only a target, but do not describe a path towards it, therefore a number of burning questions appeared in the industry in the recent time [2], e.g.:

  1. Is it true that only larger pharma or device companies can apply a risk-based approach?
  2. Do I need sophisticated IT tools to implement a risk-based approach?
  3. Is it true that we need to change the way we write protocols and set up trials to implement successfully a risk-based approach?
  4. What are KRIs and KPIs, and how can they support a risk-based approach?
  5. Will a risk-based approach make site selection/qualification and patient recruitment into my trials any easier, and will it help to get better data faster and cheaper?
  6. Will a risk-based approach allow me to stop SDV (source document verification) and reduce the burden of on-site monitoring?
  7. How much money do I save by implementing a risk-based approach?
  8. How will Health Authorities react if they discover a major or critical finding that was not detected or not addressed through your risk management approach?
  9. How does a risk-based approach impact on my organization, i.e., study site, Quality Assurance, Data Management, Clinical Operations, Drug Safety, Biometrics, etc.?
  10. What is the best implementation strategy for a risk-based approach?

And many others. To see our answers to them, see this article.

RBM Components

By application of Risk-based Management, we are speaking about the following components:

Cyntegrity - RBM components

Protocols need to be based on a clear rationale reflecting the needs of prescribers, patients and payers and on one or maximum two primary study objectives. These, as well as inclusion and exclusion criteria, study schedule and other critical protocol elements, need to be verified by means of real-life data in order to meet expectations and capabilities of investigators and patients. Such careful planning is the key in avoiding unnecessary protocol amendments.

Major RBM Pitfalls

All the above described components are essential for the achieving the RBM objectives. Still, by the implementation of the RBM strategy, we should be aware about some major RBM Pitfalls. Among them are:

Pitfall #1. SDV is reduced without any other action. A major risk, when under an RBM flag no other actions except the SDV reduction is taken.

Pitfall #2. Risk evaluation is not objective. This may happen if a human factor is involved in risk evaluation

Pitfall #3. Risk evaluation is biased. Bias is when an interested party is involved in the evaluation. In the economic science, this is called an “agency problem”.

Pitfall #4. Risk evaluation becomes outdated. The risk landscape changes during a trial.

Pitfall #5. Late data arrival. When the data, which is essential for such analysis arrives so late that no corrective action can help to mitigate the risk. Danger – patient safety.

Pitfall #6. Sites ignore RBM and do not improve. Today sites are hardly involved in the RBM initiative.

Pitfall #7. Monitoring team does not accept the new procedure. Why does this happen? Everybody has her/his own reasons; mostly it is scariness, lack of information and lack of involvement. Result – RBM stops working.

Electronic data management (eCTMS, eEDC, etc.) has developed for already more than 30 years and penetrating the clinical research more and more. It gets a new role in the risk management, introducing eRBM, where new system serves the purpose to guarantee early risk identification by providing a centralized location where risk data are saved, managed, monitored, and reported.

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