The new EU Clinical Trials Regulation (CTR) becomes applicable not earlier than on 28th of May 2016. It introduces a number of changes in the clinical trial’s application, operations, documentation, and assessment. Although CTR is not taking the direct reference on RbM, it refers to principles of Good Clinical Practice (GCP) and Quality by Design (QbD). These principles are the underlying in RbM as well. Therefore, the author offers to apply RbM as a practical mechanism and process in order to embrace the new EU regulation.
The regulation underlines the interest of subjects and assigns to them an ultimate priority over all other interests.
What tools are available in order to help us in the implementation of the new regulations? The RbM approach offers large flexibility and control for these purposes.
The identification of risks, which appear if the regulation is not correctly implemented, helps to avoid them. How to achieve that? Apply several key risk indicators (KRIs) within the digital infrastructure, which can help to monitor automatically the clinical trial and free your time for the real research.
RbM can be defined rather “narrow” following the FDA’s definition:
or “broader”, following the EMA’s definition:
RbM is “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.”1
In the EMA reflection paper the RbM is more as a risk management, which goes beyond the CRA’s responsibilities. The author is an advocate of the second point of view (broader), which can be seen as a part of Quality by Design (QbD) approach.
Such broad view on RbM opens it as an ideal framework for helping to embrace the new EU regulation. Data connection to EDC, CTMS and other clinical trial recording systems helps in applying the KRIs relevant for regulation:
CTR demands “A clinical trial may be conducted only if (…) compliance with the condition is constantly monitored”. Additionally CTR stresses the patient’s benefits and safety.
The RbM is a tool, where one can adequately monitor the compliance, and trigger the monitoring team if a risky situation occurs. What does the term “patient’s benefits and safety” include?
The patient’s benefits and safety assume the following:
The RbM risk indicators can control many sides of the patient’s safety and by means of that help by embracing the CTR:
When risks triggered, a risk-mitigation mechanism should come in place:
Still there are some risks, which are hard to control with RbM, e.g.: Manufacturing compliances (labeling requirements, completeness and the adequateness of the investigator brochure)
Professional with vast experience in development of software for pharmaceutical industry for ERT, Carefusion, Cardinal Health.
Originally comes from programming and mathematical statistics, obtained rich experience in clinical data quality, managed a R&D team of ERT, and was responsible for clinical data quality. Long time developed the software solutions for clinical trials. In 2013 founded an innovative company with the strong team for development of risk based monitoring approaches.
Graduated as Software Engineer, obtained PhD in mathematical methods and software complexes and Executive Master of Business Administration at Cass Business School (City University of London).