September 6, 2018
Risk Based Monitoring – A state of the art approach for your clinical investigation
Factory CRO witnesses and is part of a new trend in the clinical investigation landscape: Risk Based Monitoring (RBM). In this novel approach, focus lies on specific risks related to your clinical investigation, thereby more efficiently using resources, which improves investigation conduct and quality.
Under the guidance and regulation of ISO 14155, MDR, TGA and the FDA, the rights and safety of subjects are ensured while maintaining the integrity of data. However, the extent and nature of the monitor activities can be determined by the sponsor. The FDA’s guidance for RBM and the ICH-E6 (R2) addendum are both recommending the sponsor to develop a systematic, prioritized, risk-based approach for monitoring. In the same context, risk management of clinical studies (ISO 14971) and RBM itself will get a more prominent role in the next version of the ISO 14155 (2020?). With this, RBM starts to infiltrate the clinical landscape.
How does it work?
The aim of RBM is to improve subject safety by focusing on oversight and key aspects of a clinical investigation. This can be considered a result of the increased complexity of clinical investigations, as well as technological advances over the past decades. The approach focuses on the early detection of possible risks in study specific critical data and processes, which are essential to achieve study objectives.
One option to early detect critical data is by implementing centralized monitoring to your clinical investigation. Electronic Case Report Forms (eCRFs) have widely replaced its paper predecessor and the integration of centralized monitoring offers multiple opportunities. Clinical Research Associates, Data Managers, or Statisticians can enter Electronic Data Capture (EDC) systems remotely without having to visit the site. This allows for continuous data monitoring. Benefits of this approach are the early detection of missing or inconsistent data, potential protocol deviations, or other errors. Furthermore, statisticians can analyze the data on a continuous basis, detecting early trends and differences between sites. Thus, this decreases the necessity of on-site monitoring per site or remote calls between site and monitor.
Traditional monitoring vs. RBM
Traditionally, Source Document Verification (SDV) of 100% of the data and frequent on-site monitoring visits are expected from a regulatory point of view. In RBM, SDV is only conducted for certain predefined data, such as Informed Consent signatures, primary endpoints, and safety data. Additionally, on-site monitor visits are only scheduled after a predefined trigger, such as occurrence of a specific event or a predefined incident frequency. Centralized monitoring is a useful tool for early detection of irregularities. As such, RBM allows for a quicker resolution compared to the traditional approach, thus improving patient safety and being cost-efficient simultaneously.
With SDV consuming a lot of budget and time, sponsors might want to focus on adapting the RBM approach. In contrast, from site perspective, RBM may feel like a burden: less on-site with more remote activities from the monitor might suggest more preparation from the sites while a reduction of SDV might imply a lower budget per site. It is, therefore, important to maintain good communication and clearly explain site the benefits of an RBM strategy prior to study start.
“The future of clinical investigations will benefit from a risk-based approach to monitoring, as it addresses subject safety, data integrity, and protocol compliance in a more effective and time efficient way.” Thijs Wervelman – Factory CRO
Setting up a risk-based clinical investigation
To conduct RBM in your clinical investigation, preparation is key. The items mentioned below will help you in the process of developing such an approach:
A. Identify Critical Data and Processes to be Monitored
First, you should identify ‘your’ critical data and processes which are called Key Risk Indicators (KRIs). Examples are verification of the Informed Consent procedures, adherence to the protocol eligibility criteria, timely entering of data in the EDC system, timely correction of any data-queries, level of experience of the user of the device (e.g. surgeons), number (or lack of) Adverse Events, device accountability, and coherence to Good Documentation Practice.
B. Risk Assessment of a Clinical Investigation
Second, you should perform a risk assessment to identify the consequences of errors related to these KRIs. A risk assessment should predefine certain thresholds, setting triggers that request corrective action. This process might take more time during the startup phase of the clinical investigation, when compared to traditional monitoring. However, if well executed, these triggers enable quicker and more adequate corrective actions, of which you may benefit the entire study duration.
C. Developing an Risk Based Monitoring Plan
To conduct and efficient investigation, a tailor-made monitoring plan should be prepared that describes the monitoring methods, responsibilities, and requirements for the investigation (see box). The plan should also focus on preventing or mitigating specific risks an investigation is tied to. Escalation procedures defined in the plan should help to quickly and adequately react to occurred events.
In short, you can say that RBM has a huge potential in increasing the safety and effective performance of clinical investigations, supporting every stage of a study. Whether you have a small study population with a complicated protocol design, or your study aims to confirm the safety of a medical device that has already been released on the market, or if you need to comply to the MDR (for everything you need to know as a medical device manufacturer, read our MDR blog here), RBM might just be what you are looking for.
Factory CRO is an expert medical device CRO with broad experience in performing risk-based medical device clinical investigations in the United States, Australia, and Europe. Our experts are available to help you with questions and define your RBM needs for pre- and post-market clinical investigations.