Risk-Based Monitoring, What is It?
Risk-based Monitoring (RBM) is a lean approach to clinical trial monitoring driven by the current ICH E6(R2) Guideline for Good Clinical Practice. The purpose of risk-based monitoring is to help clinical research organizations predict and manage risk at an early stage, so that monitoring resources can be prioritized based on risk and need rather than the traditional 100% SDV approach. A well-implemented risk-based monitoring process should result in significant data quality, patient safety and monitoring cost benefits, and ultimately reduce time to market.
Risk-Based Monitoring Strategies According to the FDA
Prior to the ICH E6(R2) addendum, the FDA underlined its wish to support risk-based monitoring in clinical trials with the publication of its guidance for industry “Oversight for Clinical Investigations — A Risk-Based Approach to Monitoring” in August 2013. 
The FDA identifies the following risk-based monitoring strategies:
- Centralized Monitoring
An integrated approach based on the perceived risk at each study site.
- Remote Monitoring
Use of low-cost clinical resources to execute monitoring activities, that do not require onsite visits.
- Reduced Monitoring
g. targeted Source Data Verification (SDV).
- Triggered Monitoring
Based on predefined trigger points such as patient enrollment rate and reported Serious Adverse Events (SAE).
Risk-based monitoring, the industry’s new gold standard
The time to think about the next stage of the clinical research journey seems to be now:
“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.” [FDA]
Risk-based monitoring interpretation discrepancies between the regulatory agencies
Despite the EMA joining the FDA in the growing risk-based monitoring movement, there are differences between their definitions:
FDA’s definition of risk-based monitoring:
RBM — is the adequate mix of strategies including centralized and onsite monitoring practices with the goal of human subject protection and trial integrity. 
EMA’s definition of risk-based monitoring:
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 life cycle 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. 
The direction is set by the leading pharmaceutical regulatory agencies
Both the EMA, with its reflection paper, and the FDA, with its guidance for industry, have clearly set the direction toward a risk-based approach, leaving the industry with many unanswered questions about how to get there:
- Is it true that only larger pharma or medical device companies can apply a risk-based approach?
- Do I need sophisticated IT tools to implement a risk-based approach?
- Is it true that we need to change the way we write protocols and set up trials to successfully implement a risk-based approach?
- What are KRIs and KPIs, and how can they support a risk-based approach?
- Will a risk-based approach to monitoring make site selection, site qualification and patient recruitment easier? And, will it help to get better data faster and cheaper?
- Will RBM allow me to stop SDV and reduce the burden of onsite monitoring?
- How much money will I save by implementing risk-based monitoring?
- How will Health Authorities react if they discover a major or critical finding that was not detected or not addressed through this new risk management approach?
- How does RBM impact my organization, i.e. study site, quality assurance, data management, clinical operations, drug safety, biometrics, etc.?
- What is the best implementation strategy for risk-based monitoring?
…and more. Continue reading the RBM Consortium’s responses to these burning questions.
The Key Components of Risk-Based Monitoring
key components make up the risk-based monitoring process roll-out:
Study protocols need to be based on a clear rationale reflecting the needs of prescribers, patients and payers, and one or 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 key to avoiding unnecessary protocol amendments.
Major Pitfalls in Risk-Based Monitoring
Besides the essential RBM process implementation components, it is important to be aware of the major pitfalls:
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 critical data, essential to the risk analysis, arrives too late for any corrective action. Danger – patient safety.
Pitfall #6. Sites ignore RBM and do not improve. Engaging and involving sites in the RBM initiative is critical to its success.
Pitfall #7. Monitoring team does not accept the new procedure. Why does resistance happen? Change management is required to get the buy-in of all involved. Risk – RBM implementation discontinues.
Learn more about Cyntegrity and our risk-based monitoring services. Do not hesitate to contact us for a free consultation.