Trial Site Engagement Models are Poised for Disruption

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We’re witnessing significant changes in how trial sites interact with biopharmaceutical organizations.The adoption of digital tools and platforms has enabled more efficient and effective communication, collaboration, and data collection across different stakeholders. However, challenges such as ensuring that trial sites have the capacity, skills, and incentives to participate in more complex and innovative trials remain. Plus, it’s also important to consider how can we foster a culture of trust and transparency between trial sites and biopharma sponsors—especially when it comes to sharing sensitive data and feedback. One key to solving these challenges may be the clinical research associate (CRA).

The CRA has been the front-line pharmaceutical sponsor resource at trial sites, ensuring clinical trial data reliability, and participant safety for more than 40 years. It has also been the predominant conduit of the training and sharing of information between sites and sponsors and serves an important role as the relationship face of the sponsor. A CRA role has been the career path for many pharmaceutical executives, with the role of the CRA—or study monitors—and the requirement for monitoring evolving over the decades.

There are four key trends affecting the traditional role of the CRA which is leading pharma sponsors to rethink their broader site engagement strategy:

• Since the pandemic, pharma sponsors are increasingly using more efficient ways to monitor sites involved in their studies. Risk-based monitoring (RBM) guidelines that were finalized in 2013 recommend proactive, risk-based approaches to site monitoring as well as tailored monitoring plans that could use centralized monitoring in place of onsite monitoring. There’s also been an increased recognition of the limited value of 100% source data verification (SDV), driving a shift from SDV to source data review (SDR) and reducing the need for previous levels of CRA-led monitoring.
• The site staff crisis has resulted in an increased workload on principal investigators and site staff, creating urgency and pressure on the pharma sector to ensure strong site relationships and reduction of uncoordinated efforts. It’s not uncommon for an investigator to be engaged with not just a sponsor’s CRA, but also with field medical staff—such as medical science liaisons (MSLs)—and regional leaders. As a result, this may complicate the building of a strong single trusted relationship. More than ever, it’s becoming critical for pharma sponsors to have a clear value proposition for sites to participate in their studies and the appropriate level of support to make patient recruiting and engagement successful.
• The rise in AI-enabled co-pilots is creating a world of possibilities in terms of the number of things that CRAs and other site-engaging roles can now support. Through techniques historically reserved for their commercial counterparts, CRAs can now use sophisticated techniques to segment sites, apply personalized messaging, and react to real-time feedback.
• Finally, data acquisition strategies are evolving. An "electronic source data (eSource)-first" future has been in the pipeline for years but now seems to be a growing reality. We’re seeing more point solutions available, tools for electronic health records (EHR) to electronic data capture (EDC) being embedded in traditional data capture platforms and efforts like the HL7 accelerator Project Vulcan showing that the future is much closer than we may think. As such, eSource will join RBM as the next disruptor of traditional "100% SDV" and further refine and refocus the role of the CRA.

Based on these trends, pharma sponsors are evaluating the mix of roles, responsibilities and appropriate sizes to optimally engage with trial sites:

• Can lower-value on-site tasks of CRAs be reduced with the shift to central monitoring, allowing for more valuable activity that ensures data reliability and participant safety while building stronger relationships with site staff?
• With site relationship importance on the rise, how can we insource the CRA roles—if outsourced—and establish site engagement lead roles?
• How does our strategy need to vary by country?
• How does our strategy need to evolve?
• How can we establish a long-term strategy knowing our portfolio of trials will shift?
• Can we strengthen and reimagine our collaboration with our MSL counterparts?

The answers to these questions will vary by organization. Here are a few considerations for pharma sponsors as they look to stay ahead of the curve:

Role design: It’s critical to start with internal buy-in on the roles and activities required to engage with sites. This process allows teams to gain a deep understanding of needs and activities while also ensuring alignment on the roles and objectives. It’s also in this step where an initial understanding of how different roles will collaborate to ensure effective teamwork after implementation. The details of the role can vary by country based on the local needs and on whether the teams are focused on the therapeutic area or on the portfolio.

Individual team sizing: Most often, the size of the team will need to be based on workload buildup. In this step, the activities required per site multiplied by the number of target sites will give an understanding of the number of team members required—efficiencies from AI-enabled co-pilots and benchmarking in relation to others in the industry will also help. We’ve seen some companies experiment with estimating the impact of site visits on outcomes such as recruitment rate or satisfaction scores by adjusting the workload for optimal impact.

Territory design: The last step is to design territories that balance the required workload with the location of the sites. This is where the strategy needs to be achievable to actually work. Site location, personnel location and travel time will all need to be incorporated to create workable territories. Depending on the level of collaboration expected, territory design will also need to ensure maximum overlap of different roles to minimize the number of internal collaborations required.

Alignment with technology strategy: As the CRA strategy evolves, it will be important to align with the technology strategy. Just as we think about role design linked to organization structure, we must think about role design aligned to rapid technological advances across development—such as data capture evolution, adoption of generative AI, automation, or other AI-enabled progress.

Pharmaceutical companies who tap into these approaches to increase their site engagement model sophistication will maximize their chances of success in an increasingly dynamic and crowded global trial landscape.

Mike Martin, principal, clinical development, ZS; Jonathan Rowe, principal, R&D excellence, ZS; Craig Lipset, co-chair, Decentralized Trials & Research Alliance; and Judith Reece, advisor, Reece Advisory