Why Early Site Engagement Matters

Early site engagement plays a critical role in the success of clinical trials, especially during the planning and protocol development stages. By involving sites early, sponsors and CROs can gain valuable insights into the standard of care (SOC) across different regions, assess the appropriateness of comparator arms, and better understand site interest and capacity to participate. This proactive approach not only enhances protocol feasibility but also strengthens site relationships and improves overall trial execution.

Early site engagement helps sponsors build strong relationships with investigators and research sites from the start, ensuring better understanding of the study requirements, faster site activation, and improved patient recruitment. By addressing potential challenges early and aligning expectations, sponsors can enhance trial efficiency, reduce delays, and increase the likelihood of achieving enrollment targets.

What is early site engagement?

Early site engagement means bringing clinical trial sites into the conversation before the protocol is set in stone. It’s about listening, really listening, to the people who care for patients every day. By asking for their input early on, we gain valuable insights into what’s practical, what aligns with standard care, and what might make a trial more or less feasible. More than anything, early engagement shows that their voice matters. It builds trust, encourages collaboration, and helps shape trials that work better for both the teams running them and the patients who rely on them.

Understanding the standard of care (SOC): A local perspective

The Standard of Care (SOC) refers to the routine treatment practices that physicians follow for a specific condition in a given setting. While clinical trials often rely on global protocols, SOC can vary significantly from country to country, region to region, and even between institutions. That’s why understanding the local SOC early in the trial planning phase is crucial for designing realistic and feasible studies.

Here’s how early site engagement helps uncover the local SOC:

1. Reveals real-world practice patterns

Sites can provide insights into what treatments are commonly used in routine care.
This helps sponsors align protocol expectations with what is actually feasible at the site level.

2. Avoids protocol-design misalignment

A treatment considered “standard” globally may not be accessible or approved in certain regions.
Misalignment with local SOC can result in poor recruitment, protocol deviations, or ethical concerns.

3. Supports ethical and regulatory compliance

Protocols must respect local medical norms and ethics.
Regulators often require justification when deviating from the local SOC, especially in placebo-controlled or comparator-arm trials.

4. Improves patient enrollment and retention

If the investigational product or comparator is vastly different from the SOC, patients may be less willing to participate.
Aligning with local SOC makes the trial more acceptable to both physicians and patients.

5. Improves comparator selection

Understanding what’s currently used helps in choosing comparators that are relevant, ethical, and acceptable in the target regions.

Engaging sites early allows sponsors to gain accurate insights into the local SOC, which helps avoid major feasibility issues down the line. This step not only strengthens trial design but also shows respect for the clinical realities of each site involved.

Site feedback on comparator arms

Selecting the right comparator arm is one of the most critical and sensitive aspects of clinical trial design, especially in therapeutic areas like oncology or rare diseases, where treatment options are evolving, and ethical considerations are high. While sponsors may choose comparators based on global trends or regulatory expectations, those choices aren’t always aligned with what is considered relevant or acceptable in real-world clinical settings.

This is where early site feedback becomes invaluable.

When sites are consulted early:

They highlight what’s clinically meaningful: Investigators can share what treatments their patients are actually receiving, and whether a proposed comparator reflects the real standard of care in their region.
They can flag ethical concerns: For example, in some cases, using a placebo or outdated therapy as a comparator may be seen as unethical when more effective treatments are locally available. Sites help sponsors avoid such missteps before protocol approval.
They offer insights into patient acceptability: Sites understand what patients are likely to accept or refuse. If a comparator isn’t seen as beneficial, patients may decline participation, affecting both enrollment and retention.
They guide regulatory alignment: In some countries, regulators expect comparators to reflect the local treatment landscape. Early feedback from experienced sites ensures the protocol meets those expectations, minimizing the risk of delays or rejections.

Incorporating site feedback into comparator selection not only improves the ethical and clinical relevance of a study but also increases trust, buy-in, and long-term site engagement. Ultimately, informed choices about comparator arms lead to more meaningful outcomes and smoother trial execution.

Gauging site interest and operational fit

Just because a site is qualified on paper doesn’t always mean it’s the right fit for a particular trial. That’s why early conversations with sites are so important—they help uncover not only whether a site can take on a study, but whether they want to.

When we engage with sites early, we learn a lot more than what a feasibility form can tell us. We understand:

What truly interests them: Is this study aligned with what they’re passionate about? Are they familiar with the condition? Do they see this as a priority, or just another protocol on their desk?
What else are they balancing: Many sites are already managing multiple studies. A quick check-in can reveal whether they have the time and resources to give your trial the attention it deserves.
Whether they’re operationally ready: Do they have the right staff in place? Are their systems set up to handle what the protocol demands? Sometimes, even a motivated site needs support to be fully ready.
If the study fits their context, Cultural, regional, and institutional realities can all affect whether a trial feels appropriate and doable at a given site.

At the end of the day, early engagement helps identify sites that are not only capable but committed. And when you work with sites that are truly on board, the entire trial runs smoother for the team, the sponsor, and most importantly, the patients.

Incorporating site feedback into protocol design

One of the biggest benefits of early site engagement is the chance to shape the protocol with real-world input. Sites are on the front lines; they understand what works for patients, what challenges staff face, and what’s realistic within their daily routines. When their feedback is woven into the protocol design, it makes a huge difference.

Sites can highlight things like visit schedules that are too demanding, eligibility criteria that are too narrow, or procedures that may be hard to perform consistently. They can suggest adjustments that make participation easier and more comfortable for patients, which in turn boosts recruitment and retention.

More importantly, involving sites early sends a message: their experience matters. This fosters a sense of partnership and ownership, making them more invested in the trial’s success.

Incorporating site feedback doesn’t just improve the protocol—it helps avoid costly amendments and delays down the road, saving time and resources. It’s a win-win that leads to smoother trials and better outcomes for everyone involved.

ICH Good Clinical Practice Guideline (ICH E6(R3))

The ICH GCP (E6) guidelines stress the value of involving investigators and sites early, making sure they have the right qualifications, resources, and a clear understanding of the trial before it starts. The latest E6(R3) update takes this further, encouraging sponsors to work closely with investigators from the very beginning on protocol design and risk planning. This early collaboration helps spot potential challenges, keeps participants safe, and supports the collection of high-quality data.

The strategic benefits of early site engagement

Early site engagement offers key advantages that can make clinical trials run more smoothly and successfully. It helps improve protocol feasibility by aligning with real-world practice, boosts patient recruitment through motivated sites, and reduces costly delays by addressing challenges early. It also builds stronger partnerships and ensures compliance with local standards.

Investing in early site engagement sets the foundation for more efficient trials and better outcomes.

For more details, please refer to our full article on the strategic benefits of early site engagement.

Conclusion: Build better trials by listening early

To wrap things up, involving sites early on isn’t just a box to check—it’s a game changer. When you take the time to understand the local standard of care, get honest feedback on comparator arms, and really gauge site interest, you’re setting the stage for a trial that actually works in the real world. It helps build trust, makes collaboration smoother, and most importantly, leads to better experiences for patients and everyone involved. Taking that extra step early can save a lot of headaches down the road—and that’s something everyone can appreciate.

Do you have any further questions regarding site engagement and how it can benefit your clinical trial?

Would you like to learn more about how early site engagement can support your clinical trials, or do you need our assistance in conducting early engagement with sites and investigators? Fill out the form below to reach out to us and speak with our expert team.