The ICH E6 R2 Addendum is starting to have a significant, positive impact on clinical trial design – offering a real opportunity to inject efficiencies into clinical research and development. We do not need to be fearful of the updated ICH E6 R2 guidance as it is actually designed to support becoming more efficient despite the ever growing complexity in trials. We’re all striving for significantly better outcomes and this is exactly what this unified standard is seeking to achieve. By adopting these guidelines we can achieve improved and more efficient approaches to clinical trial design, conduct, oversight, recording and reporting. And more importantly continue to ensure reliability of trial results and crucially human subject protection.

Quality Outcomes, Savings and Shorter Study Timeframes
As clinical research organizations are being compelled to implement a compliant Risk-Based Approach to Study Execution (RBx), many still seem reluctant to do so. There are many advantages to be gained as we shift towards RBx implementation – and it’s about more than ensuring compliance – we’re talking about improving the operational success rate of clinical research, including three key dimensions of value:

• Higher quality
• Shorter timelines
• Greater operational efficiency

RBx can have a positive impact on quality outcomes across the business, resulting in more successful marketing submissions and faster time-to-market. It also offers a pragmatic opportunity to reduce on-site monitoring that can lead to significant and direct savings in the cost of clinical trial budgets. Effective centralized monitoring can also result in shorter study timeframes.
 
Improve Site Quality Control and Protocol Risk Assessment
There are many drivers behind an effective RBx strategy and now is the time to review the updated guidelines to determine what is needed for compliance. New investment options may drive companies to rethink their sourcing options, with some shifting monitoring from a CRA-centric, site visit model of monitoring to incorporate more data-driven, statistical approaches. Crucially, organizations need to revise their current strategies and operating models in a bid to improve on inefficient traditional methods of managing clinical trial quality.
 
Steps to take include:

• Work with technology departments to incorporate algorithms and account for the sensitivity of smaller trials
• Perform risk assessments and gap analyses of organizational procedures to identify where the company stands
• Determine areas that have the most impact on the credibility of data and that will be most impacted

RBx is Straightforward to Implement
Many people may have some concerns surrounding RBx but there are strategies to eliminate any potential issues.

• Work collaboratively with the correct study partners
• Identify and implement the right tools that will help manage the change in the most effective way
• Once implemented, study teams should ensure clear communication with all involved in the change
• Create an environment of openness where discussion about the new approach is encouraged
• Avoid information overload
• Continuously checking understanding to ensure correct processes are being followed

Effective Quality Oversight
Central Statistical Monitoring (CSM) is key to compliance with ICH E6 R2 and organizations can  ensure a successful implementation of RBx driven by CSM. It can help sponsors and CROs manage the shift towards RBx, while achieving compliance with the new regulatory guidelines. By supporting organizations in bringing significant improvements to the quality and integrity of their data, and therefore the success rates of their trials, it will be a vital tool in optimizing operational quality monitoring within this exciting new paradigm for clinical research.
 
CSM uses statistical methods to identify unexpected or unusual patterns in clinical data, and is ideally composed of at least the following four components:
 
1. Overall Data Quality Assessment (DQA) / Data Surveillance
2. Key Risk Indicators (KRIs)
3. Quality Tolerance Limits (QTLs)
4. Patient Profiles (PP)
 
The combination of DQA, KRIs, QTLs and PP can provide a very powerful, comprehensive approach to operational quality and risk monitoring. When designed and implemented effectively, CSM not only drives significantly better-quality outcomes, but does so with much greater operational resource efficiency – enabling a significant reduction in the reliance on SDV and related on-monitoring reviews.
 
Any Limitations?
While there may be change management and logistical challenges to overcome, the benefits of enhanced efficiency and quality and the chance to transform risks into returns really outweigh any perceived limitations. Where do I see RBx in the next 10 years? I think it will become the new normal. Traditionally, CROs tend to be very conservative with respect to trying new technologies and new paradigms, and RBxis no exception.However, since the guidelines came into effect, there is a real sense from pharmaceutical companies that ICH E6 R2 has validated the RBx approach, accelerating a faster adoption cycle than would have otherwise occurred.

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Responsible for leading global sales, product, marketing, operational and technical teams throughout his career, Patrick is a Senior Executive with over eighteen years international commercial experience within life sciences, healthcare and telecommunications. In the past, Patrick consulted on corporate and commercial strategy for various life sciences companies and was responsible for successfully positioning ClinPhone as the leading Clinical Technology Organization during his 10-year tenure with the company. Patrick holds a Marketing degree from the University of Newcastle-upon-Tyne, UK, and a post-graduate Marketing diploma in Business-to-Business Marketing Strategy from Northwestern University – Kellogg School of Management, Chicago, IL.