Growing Emphasis on Risk-Based Monitoring - A Strategy for Quality Improvement


21 June 2017

regulatory risk management line of defence

Risk-based monitoring (RBM) is gaining acceptance as the proactive method of choice for monitoring clinical trials. Rather than sticking to the traditional stance that a study monitor must engage in the costly and time-consuming practice of 100% source data verification (SDV), the tide is turning to the more insightful and targeted RBM approach. This is happening because RBM is playing a major role in the industry’s trend toward data-driven techniques that identify and mitigate risk and optimize the quality of study oversight. In particular, problems linked to protocol complexity, adverse events and cycle-time challenges can be identified through the use of data and predictive analytics. This information may trigger site visits in an effort to flag issues prior to or during study conduct. And as more data are analyzed as the study unfolds, RBM strategy may change in order to focus attention on the most critical elements.

An industry-wide survey on RBM uptake, conducted in 2016 by Metrics Champion Consortium (MCC), documented the significant rise in RBM use.[1] According to the survey, 50% of respondents reported using RBM in pivotal trials, a big jump from only 30% in 2013, when MCC’s first RBM survey was conducted. This shift is supported by a growing body of research on the subject, which questions the expense and impact of continuing with 100% SDV,[2] a process that tends to focus on correcting existing errors rather than preventing them.[3]

The expanding use of RBM aligns with the strong interest expressed by regulatory authorities in identifying and mitigating risk in clinical trials. In particular, a risk-based approach to monitoring is featured in the recent Good Clinical Practice (GCP) guideline released by the International Conference on Harmonisation (ICH) in November 2016, the first update in 20 years.[4] As described in the guideline, known as ICG-GCP E6(R2), RBM is made possible due to evolutions in technology and risk management processes, which are the driving forces behind new opportunities to increase efficiency in clinical trials.

As part of this effort, the guideline dedicates an entire section to Quality Management that:

 

 

 

  • Recommends that sponsors develop a systematic risk-based approach to monitoring clinical trials
  • Details elements of a risk-based system, including risk identification, risk evaluation, risk control, and other factors
  • Highlights the importance of quality processes throughout a clinical trial


RBM is here to stay, but as explained in the guideline, and as is widely known in the industry, it is not the only option. There is also remote monitoring, which can complement and reduce the frequency of onsite monitoring. If remote monitoring is conducted centrally, a secure virtual workspace can be used to identify data that are missing, inconsistent, or are outliers. It can also examine data trends such as the range, consistency and variability of data within and across sites.

So, how exactly does it differ from RBM?

The key difference is that remote monitoring may or may not be part of a risk-based strategy. Specifically, it is possible to have an RBM study that includes limited onsite monitoring visits, usually due to data triggered or event triggered activity. Alternatively, an RBM trial can also have remote monitoring visits. The two monitoring styles are related, but not necessarily correlated. Making the choice is a function of where stakeholders are in the embracing of a proactive approach to monitoring.

For more on this subject, watch this webinar replay, “Reinventing Remote Monitoring: The Implications of Innovation.”


[1] An Updated Look at Risk Assessment and Risk-based Management Practices. MCC Industry Practices Insight Reports. Metrics Champion Consortium. Available at: http://metricschampion.org/rbm/. Accessed June 14, 2017.

[2] Koreith K. The High Cost and Questionable Impact of 100% SDV. The CenterWatch Monthly. 2011;18(2):1,15-17.

[3] Ansmann EB, Hecht A, Henn DK, et al. The future of monitoring in clinical research – a holistic approach: Linking risk-based monitoring with quality management principles. German Medical Science. 2013. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563312/. Accessed June 14, 2017.

[4] Integrated addendum to ICH E6(R1): guideline for Good Clinical Practice E6(R2). ICH Harmonised Guideline. 2016. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4.pdf. Accessed June 15, 2017.

 



Andrew Mitchell

Andrew Mitchell

Director of Strategy and Product Marketing for Life Sciences

Andrew Mitchell is the director of strategy and product marketing for life sciences at Intralinks. Andrew has many years of experience working in and with the Life Sciences industry, delivering innovative software solutions through his time with Covance, Relsys, Medidata and BioPharm Systems (Oracle Gold implementation partner). With a focus on Software as a Service, he has a strong belief in providing solutions that simplify and improve the user experience and the relevant subject matter expertise to ensure delivery of real benefits and enhanced compliance.