Courtney McBean

	If you've spent time researching risk-based monitoring (RBM) over the past year, you know dozens of academics, CROs, clinical trial practitioners, and statisticians have proposed varied approaches based on sponsor needs and trial designs. Unfortunately, despite an abundance of theoretical perspectives on RBM, clinical trial teams soon discover a significant gap still exists between perspectives and actual tools to enable real-world 

. The challenge for sponsors remains how to translate theory and methodologies of risk-based monitoring to their unique setting.

		Often overlooked in early evaluation of RBM are the tools and technologies required for successful implementation. Without the right tools to track and prioritize the shift from traditional monitoring to RBM, successful implementation is doubtful, posing detrimental consequences not only for the monitors, but also the overall trial.

		For successful risk-based monitoring program implementation, here are the five must-have capabilities of an effective RBM tool:

1. Ongoing and Continuous Performance Tracking

		Trials never go exactly as planned. The best-intentioned RBM strategy implemented at the beginning of the trial is unlikely to be optimized over the life of the trial. Some sites will not perform as well as expected, while others will surpass projections. Primary investigators and research staff churn, impacting site performance. A static, one-time RBM plan/strategy simply will not be able to account for the dynamics of a real-world clinical trial. An optimal risk-based tool will adjust by incorporating real-time site performance, site status changes, and sponsor profile changes.

		Data in clinical trials are complex and dynamic. The tremendous amount of data collected in a trial offers valuable insight − if harnessed correctly. A solid RBM strategy includes feedback and input from multiple data sources. EDC, CTMS, IVR/IRT, and other study databases contain rich data that when viewed correctly, provide valuable information about how a site is performing and can even predict problem areas. Performance metrics contained in these databases are critical to catching such problems early and preventing significant compliance issues.

		Without question, RBM tools must incorporate data from clinical trial databases such as EDC and CTMS. This data however paints only a partial picture of what's really going on in a trial. One of the most valuable, yet underutilized, resources for tracking and adapting an RBM plan is direct feedback from the monitors themselves. Who knows better what is really going on at a site than the monitors? The leading RBM tools include a mechanism to capture input from the monitors on the RBM strategy implementation at specific sites.

		Sponsors have widely varying needs, strategies and risk tolerances and with no two clinical trials the same. Each trial is designed from the ground up with specific endpoints and objectives. Te tool you choose to implement your RBM strategy needs to accommodate the vast and varying needs of sponsors. During technology evaluation, keep in mind the importance of flexibility and customization unique to your organization's needs.

		Clinical trial teams are inundated with data from EDC, CTMS, in-house systems, e-mail, phone, and other sources. When implementing an RBM strategy, it's critical the technology provide targeted, actionable information. RBM tools must provide sustained, meaningful reporting that enables trial teams to take action on the issues detected.

		Theories rarely live up to their promises to deliver value or return on investment without diligent and careful thought as to implementation – and RBM is no different. RBM demands leading-edge tools to help integrate new monitoring theories, whether in new or existing clinical trials.

		RBM has the potential to deliver on the promise of more efficient use of the ever-shrinking pool of funds and resources dedicated to clinical trials while at the same time improving overall monitoring effectiveness. With the right RBM enabling technologies, clinical trial monitoring groups will, for the first time, be able to "do more with less".

http://www.bioclinica.com/blog/risk-based-monitoring-technology-5-essential-capabilities

Articles

Often overlooked in early evaluation of RBM are the tools and technologies required for successful implementation. Without the right tools to track and prioritize the shift from traditional monitoring to RBM, successful implementation is doubtful, posing detrimental consequences not only for the monitors, but also the overall trial.

5 Essential Cornerstones of RbM Technology

	When I speak on the topic of risk-based monitoring (RBM) at industry events, someone invariably comes up afterward to say how nice it is we finally stopped talking about risk-based monitoring!

	That's because the discussion shifted away from one focused on changing monitoring methods and doing reduced source document verification (SDV) to 'intelligent monitoring.' This is a term that describes a 

unique approach to RBM used by our Compass team

. It's a concept that resonates strongly with clinical trial professionals as noted in an earlier Trial Blazer blog.

	Let's take a closer look at what I mean by intelligent monitoring and why it's smarter than risk-based monitoring alone.

	There are thousands of data points in a trial. Are you focusing on the right ones, or will you be in for a surprise when your trial ends?

	Sad but true, pouring over audit inspections and findings has become a hobby of mine. In 15+ years of managing clinical trials and monitoring teams, I've been able to narrow in on what regulators care about most in determining trial performance. My research shows regulatory bodies prioritize five key areas when they review clinical trials:

	The challenge then becomes: How do you get an accurate view of performance across all of these areas? I've seen first-hand too many examples where over-reliance on clinical data falls short. Even today when RBM is taking a foothold, many sponsors' strategies include objective clinical trial data as their sole source to inform them on trial performance.

	While clinical trial data can indeed give some insight into safety and data quality, clinical trial data alone may miss certain issues. This is especially true with key indicators of site performance such as regulatory compliance and site engagement. All too often trial teams are caught off-guard by a site monitor's findings − when in fact − the issues could have been predicted using the right data analytics!

	Intelligent monitoring is specifically designed to account for those five factors the FDA is looking at most closely. A combination of three sources of data is required to get a complete picture of site performance: operational metrics, clinical outcomes, and qualitative feedback from the sites.

	Keeping the Monitor in Risk-Based Monitoring

	Relying on statistical analysis (e.g.; data anomalies, outliers, etc.) is not enough as shown by numerous examples of informed consent fraud, patient screening issues, absent Investigators, and other difficult-to-catch issues. What commonly ends such a problem is the "gut" feeling of an experienced monitor. His or her eagle-eye and perspective sharpened on hundreds of sites, is capable of seeing poor quality or misleading data that can be traced back to poor site engagement and site performance in the study.

	Because the input of skilled site monitors is so invaluable, their qualitative feedback continues to be an important part of monitoring. These clinical trial professionals capture the softer site performance measures surrounding investigator engagement, staff knowledge, site resources, patient recruitment efforts, and other areas.

	Regular feedback from site monitors is essential and can be a key component of analytics used by trial managers to predict performance issues. Likewise, well-planned feedback gathered from site staff can provide valuable data to complete the site performance picture.

	Rather than zeroing in on a singular data point in time, intelligent monitoring looks at data in new and meaningful ways. This smarter approach lets sponsors know how a trial is performing over the short-, mid- and long-range.

		Short-term – You have the assurance of knowing what is happening at sites, whether physically located there or off-site.

		Mid-term −You are able to pinpoint exactly where a site performance problem is. This enables an emerging trend to be identified and addressed before it becomes a long-term performance issue.

		Long-term – You are able to understand how sites are performing relative to one another over the course of the study.

	Equipped with this intelligence in a digestible format, sponsors are able to consistently take the right action. Monitoring this way can go a long way to assure regulators you are in control of your trial and those five critical areas (Patient Safety; Regulatory Compliance; Data Quality; Site Engagement; and Protocol Integrity).

	Intelligent monitoring also establishes consistency among site monitors and helps ensure that any compliance and performance issues are handled the right way. These are just a few of the ways intelligent monitoring helps sponsors improve quality management in clinical trials.

	While a technology-enabling tool like Compass can speed RBM implementation and help with adjusting monitoring, more importantly, such a tool enables decisions for management of a clinical trial in the most intelligent and quality way possible. With these benefits, more and more people are gravitating toward the intelligent monitoring concept.

	http://www.bioclinica.com/blog/why-intelligent-monitoring-even-smarter-risk-based-monitoring

That's because the discussion shifted away from one focused on changing monitoring methods and doing reduced source document verification (SDV) to 'intelligent monitoring.'

An Alternative to Risk-Based Monitoring May Prove to be Beneficial

Risk-Based Monitoring – Beyond Theory In-Depth Review

With so many sponsors and CROs focused on finding the right technology solution for implementing risk based monitoring, a key element often gets overlooked—the risk assessment. For a clinical research program and protocol, a comprehensive risk assessment is essential to ensuring your risk based strategy is a success.

Here’s why: to appropriately define a risk based strategy, you must identify the key data, define the appropriate performance thresholds, and determine the appropriate monitoring levels for a specific protocol. To do this adequately, you must first identify 

 unique to the investigational product, the program and the protocol. 

 only solves part of the equation. The missing link is understanding 

. No trial is exempt from the challenges of an underperforming site. With a comprehensive risk assessment that focuses on site risk factors, a sponsor can set each site up for success by defining a focused risk mitigation strategy.

A risk assessment that includes the evaluation of each site will add a number of benefits, including:  1) Improving site selection by stratifying sites based on key risk factors; 2) Establishing early mitigation plans for sites with higher risk; 3) Determining a site-specific monitoring level (prior to the study start) that is based on actual data; and 4) Assigning monitors and site managers appropriately, based on site risk. 

At Blueprint, we help clients implement our risk assessment methodology for risk based monitoring strategies as well as for optimizing site selection in traditionally monitored clinical trials.  The Blueprint Clinical methodology looks at site risks in an objective and logical way that is easily communicated throughout the clinical trial organization with concise visualizations and reporting.

With so many sponsors and CROs focused on finding the right technology solution for implementing risk based monitoring, a key element often gets overlooked--the risk assessment.

Courtney McBean

Articles

5 Essential Cornerstones of RbM Technology

An Alternative to Risk-Based Monitoring May Prove to be Beneficial

Is Your RBM Strategy Missing a Critical Link?