Early engagement in site selection relies on the involvement of high-performing investigators from the start. Every successful clinical trial requires an investigator who believes in the study and a site that feels committed to it. Even groundbreaking studies may stall without dedicated sites and investigators, forcing patients to wait and timelines to be exceeded. Early engagement in site selection ensures timely study initiation and ultimately leads to stronger trial outcomes. Sponsors who act early gain a competitive advantage over their competitors, ensuring their trials move forward. 

Competition among clinical trials for the same patient population is a common occurrence. When patient pools are limited, trials effectively compete for participants. Increased competition is associated with lower accruals and a higher risk of recruitment shortfalls.

In high-demand fields like cardiology, oncology, and rare diseases, finding the right sites becomes increasingly difficult. There are limited qualified investigators and dependable sites in these specialties, and they tend to be occupied months in advance. 

According to Tufts CSDD’s report New Insights on the Clinical Trial Industry, nearly 4 out of 10 sites in North America never even make it to the starting line. Some get stuck in contracting and budgeting, while others stall waiting for IRB approval. 

Without proactive site selection strategies, sponsors risk missed enrolment targets, stalled sites, and costly delays that jeopardize study timelines. It can cost sponsors up to $8 million in lost revenue for each day a trial is delayed.

The following article discusses the risks of delaying site selection, how early engagement accelerates site start-up, proven early engagement strategies, a case study from the RadComp Trial, and practical recommendations for sponsors.

The risks of delaying site selection

Site selection, either after feasibility or just before a trial begins, frequently results in sponsors missing out on the best sites. Why? Because by then, the top investigators are typically already committed, so sponsors are forced to compete for sites with less experience or those that are overburdened. 

Site performance can vary widely. The Tufts CSDD study examined 16,000 sites participating in 150 trials and found that approximately 11% of these sites did not enroll a single patient. This shows a big difference between the expected and actual performance of sites. 

Amendments to the protocol that occur during the early stages of site activation can significantly prolong the timeline for initiating a study. These modifications often require supplementary reviews by the Institutional Review Board (IRB) and may lead to extended discussions with investigators to ensure that all aspects of the study align with the new changes. 

Moreover, budget negotiations for contracts can take more than 100 days, and regional variations in patient availability, costs, & operations can further increase uncertainty.  These factors highlight the importance of early identification and engagement of high-performing sites to ensure timely enrollment and trial success.

How does early engagement accelerate site start-up?

According to research, it usually takes 5 to 6 months to complete the site start-up process, which includes finding possible sites and engaging them. Sites that have previously worked with sponsors move faster because they are more familiar with the procedures and expectations. 

Interestingly, research shows CROs complete site-related activities 6–11 weeks faster than sponsors, largely due to disciplined planning, technology use, and streamlined operations. This highlights how systematic approaches and expert planning can significantly accelerate trial progress. Here’s how:

Early engagement strategies

Sponsors can employ the following three ways to implement early involvement:

1. Strategic intelligence: Identifying premium sites

Today, sponsors use historical performance indicators, predictive modelling, and real-world data to determine which investigators consistently deliver clean data, retain patients, and enrol well.

• Predictive modelling with real-world data: Using patient registries, claims databases, and Electronic Health Records (EHRs) to forecast the location of eligible patients. For example, a study by Köpcke et al. evaluated predictive modeling algorithms to assess patient eligibility for clinical trials using routine data from electronic health records (EHRs). 
• Historical performance metrics: A study presented in Perspectives in Clinical Research examines the application of artificial intelligence (AI) and machine learning (ML) within clinical trial processes. By analyzing historical data, AI algorithms can effectively identify sites with the highest potential for successful trial execution and completion. 
• Indicators of organisational readiness: Determining if a location has sufficient infrastructure, seasoned coordinators, and reliable IRB procedures.
• Connected-intelligence feedback loops and feasibility analytics: Future site selection improves if a site begins to perform poorly during feasibility or even early in the trial. This establishes a learning system in which the choice of sites for subsequent trials gets better with each experiment.

2. Relationship-building tactics

Once high-performing sites have been identified, the next step is to cultivate connections rather than simply share protocols. This requires the following:

• Co-developing feasibility: Inviting sites to comment on protocol design so they feel ownership.
• Engaging investigators in the study development phase to assist in:
  • Scientific advice on clinical development strategy and protocol design.
  • Advice on therapeutic area priorities and treatment regimen considerations.
  • Participation in development councils to improve research planning and implementation.
• Constant communication and responsiveness: Keeping continuous contact with investigators across the whole study preparation process, & not only during the feasibility phase.
• Support for capacity-building: To improve site performance, provide training sessions, streamlining patient identification procedures, and take into account the pooled coordinator resources.

3. Feasibility, pre-training, and MCTAs as commitment tools

To improve investigator commitment and encourage early participation, these are useful strategies:

• Ongoing site feasibility tracking record: Instead of doing a single feasibility study right before choosing a site, sponsors keep a continuous, dynamic log of the feasibility findings from the sites they have interacted with. Typically, this memorandum contains the site’s operational capacity, historical performance statistics, and infrastructure and technological readiness.
• Pre-training and site readiness support: Sponsors who train staff before trial launch avoid early protocol deviations. They also accelerate FPI and boost site confidence.
• Master Clinical Trial Agreements (MCTAs): These agreements simplify negotiations by reducing repetitive cycles.

These strategies are demonstrated in action in the case study that follows: 

Case study: RadComp trial

The RadComp Trial is an extensive, multi-site, randomized study comparing proton and photon radiation treatments for non-metastatic breast cancer. The University of Pennsylvania coordinates the trial to assess cost-effectiveness, clinical outcomes, and patient-reported outcomes.

Method: Early engagement techniques

RadComp included structured site engagement early on in the planning stage. Among the crucial tactics were:

1. Preliminary feasibility studies and site surveys.
2. Feedback from stakeholders throughout protocol design.
3. Regular updates, learning networks, feedback loops, and continuous two-way communication. 

Key findings supporting early engagement:

• High enrollment success: RadComp enrolled 1,239 patients, showing that early engagement enabled sites to meet recruitment targets.
• Broad multi-site participation: Over 50 U.S. proton therapy facilities participated. Their involvement showed that proactive engagement helps access top-performing centers in a resource-limited area.

Practical recommendations for sponsors

• Consider specialized partners: Working with service providers often saves time and lets sponsors focus on strategic priorities.
• Use site risk scoring to optimize resource allocation: Provide extra staff, training, and support to sites facing greater challenges with protocol execution. Maintain close engagement with their investigators to strengthen feasibility and performance.
• Engage in early problem anticipation: Use past trial data to identify common problems at sites, including lab turnaround delays and patient non-participation. Create plans to address these issues before they happen.
• Foster peer networks among sites: Sponsors should hold regular talks among site investigators to help create collaborative networks.
• Integrate digital tools for remote oversight: Use electronic case report forms (eCRFs), telemonitoring, and virtual visits to keep track of site performance in real time. This reduces the need for frequent in-person visits and helps resolve issues faster.

Conclusion for early engagement in site selection

For emerging or mid-sized biotech firms, it may appear impossible to compete with industry giants in terms of securing top sites. Sponsors obtain high-performing sites by starting outreach months before the study. They engage investigators in protocol design, offer pre-study support, and track study progress.

Initial involvement effectively drives enrollment and improves data quality, giving trials a real competitive advantage. The benefits include faster trials, more efficient operations, and earlier patient access to potentially life-changing drugs. The takeaway? Start early, develop relationships, and leverage site selection as a strategic point. 

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Are you facing challenges in securing investigational sites for complex trials? Let’s discuss how early engagement in site selection & tailored strategies can enhance collaboration.

Engaging investigational sites early is crucial in complex therapeutic areas like rare diseases or oncology, where limited site availability creates challenges. Sponsors can benefit from tailored strategies that enhance operational feasibility and investigator engagement.  Fill in the form below to learn more and get expert guidance.

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