Risk-Based Monitoring Insights from the Industry: Jamie O’Keefe

Part Six

In the latest of our eight-part Q&A series, we catch up with Jamie O’Keefe, Vice President, Life Sciences, and R&D Practice at Paragon Solutions to get his thoughts on the latest issues in Risk-Based Monitoring (RBM).

When it comes to the practical implementation of Risk-Based Monitoring, where do you observe differences in current best Risk-Based Monitoring practices between companies and CROs of different size?

Looking at where the industry is now, I think a lot of companies are ‘dipping their toes in the water.’ We have seen much more prevalent implementation of RBM in the large pharma space, particularly by the top two, mainly because there is an availability of funding. We are also seeing some sponsors considering how they can embed RBM within their organizations as a standard capability, rather than as an isolated practice in one off trials, which is promising.

We have spent a lot of time with the smaller pharma and biotech companies where the focus tends to be on how they can actually go about this within an organization of their size. As small pharma companies typically outsource much of their clinical trial management to CROs, there is a question over how they should manage the adoption of RBM. Should they just outsource it? Or should they take certain components on? For example, the central monitoring. In my opinion, much of it comes down to whether they are going to get anything out of it from an efficiency or value perspective. Or are they so small that it’s not worth the transition because of the cost implications of transitioning? Are they going to get an outcome from it over the next couple of years to make it worth it? This is an important consideration for small companies that simply don’t have the same financial support as the larger pharma organizations.

What is apparent to organizations of all sizes is that this is a big change, both in terms of culture and systems, as well as technology. In order to drive RBM adoption efficiently, accurately and compliantly, organizations must make sure the changes are communicated to all the relevant people in the business process, including any third party partners. From a technology view point, it’s about systems being able to meet the needs of all users; giving them access to the information they need, when and how they need it, so they have the knowledge to act accordingly.

How are the regulatory authorities likely to respond to the widespread adoption of Risk-Based Monitoring - are they ready for it and why?

In my experience, the people who are actually performing the assessments at study level are not necessarily as on board with RBM adoption as those at senior level, who are definitely ready for it. Despite this, there has been some strong success with the TransCelerate pilot studies, which have received positive feedback from the regulators.

Success will come down to how well a sponsor is documenting and importantly, following their Standard Operating Procedures (SOPs). As long as there is robust documentation and supporting information to demonstrate their actions, and show how they have managed risk appropriately, I don’t think there will be a significant challenge from a regulatory authority perceptive.

How do you think that the multitude of electronic systems are going to co-exist as Risk-Based Monitoring takes off? Will other systems become obsolete or will they need to evolve too?

There is going to be a big shift from a technology perspective. There will be certain categories of systems which will always be around; EDC is a great example, as there will always be a need to collect data. But in terms of how the EDC technology is used going forward, I think we are at a crossroads. It can either evolve to take on additional necessary capabilities, or it will be relegated. In the long term, I think that we will see some components of many current systems, for example, CTMS or site monitoring technology, integrated to create larger, RBM platforms.

Much of the early work in Risk-Based Monitoring has a focus on relatively simple KRIs and traffic-light dashboards which are easy to understand. There is a growing need to complement this approach with a more sophisticated and comprehensive analysis known as Central Statistical Monitoring (CSM). How are companies likely going to adopt these complementary approaches to ensure data accuracy and integrity?

I think this is where we are going to see a divide between large and smaller companies. It will be much more achievable for smaller organizations to integrate CSM and adopt this new approach across all of their trials. The challenge for big pharma companies will be changing existing complex infrastructure. Trying to drive this change through multi-million dollar, multi-year implementations, will be a huge challenge and have a significant impact on business. For that reason, I think we will see the larger pharma organizations take much smaller steps towards RBM and CSM, as they make this transition slowly.

I also think another interesting discussion point is how far the industry could take this from a technology perspective. For example, is there an option further down the line to evolve CSM technology to become a complete risk management platform, rather than just a risk monitoring system?

Discuss the complexity of defining subjective thresholds using Key Risk Indicators KRIs rather than (or in addition to) the objectivity of comparing one site against the others.

While there needs to be a level of granularity and flexibility for what the literal thresholds will be, based on the therapeutic area, indication type, or study design, setting an objective threshold is fairly straightforward.

Setting subjective thresholds will always be more challenging. Instead of simply taking one opinion, assigning it a score and adding it into the overall calculation, there needs to be a system to facilitate the conversation from a group perspective. For example, the site monitor, the site manager, the study manager and the data manager, etc., all have important interactions with sites from a qualitative perspective, how does a study team bring all these opinions together and set one threshold?

What are your thoughts on the ICH (E6) Addendum, how to implement the parts outlined in the guidelines practically for the respective area (EDC, Risk-Based Monitoring, etc.) and how the changes could impact current practices?

I think this will be the biggest roadblock for the industry. Current systems and tools, and what they are used for, differs greatly across the sector, so for the time being, implementation will be tailored to individual organizations.

As study teams make the transition from current to new systems, it will be important for them to have a clear vision and documented plan detailing how they will approach implementation, which acknowledges timeframes for adoption and any associated risks. The timeframe for implementation will vary depending on the size of the organization. For large pharma companies, the transition could take up to five years, whereas a small biotech business could potentially make the transition within six months.

The biggest impact is going to be defining the roles of the major stakeholders and ensuring teams work together cohesively. Different team members, for example, data monitors and study team leaders, will interact with data and make decisions in very different ways, so it will be crucial to consider how this will impact system capability and/or the flow of information across the team. In my opinion, success will come down to organizations making a plan and sticking to it. RBM is a fairly quickly evolving area so communicating and documenting any changes to the original plan will be crucial in order to increase compliance across the organization.

It is also important to have an active dialogue with the health authorities. A collaborative approach will minimize the chance of challenges and issues when it comes to review by the regulators and ultimately result in more drugs being approved for market.

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