What strong site enablement really looks like: Lessons from Sano’s site expert
Trial sponsors often assume that site enablement is largely complete once a trial launches. Feasibility assessments, training materials, and startup timelines are expected to translate directly into enrollment. In practice, these inputs rarely account for how sites actually operate once a trial is live, leading to slow recruitment and disengagement.
To better understand why, we sat down with a Site Engagement Manager at Sano who works directly with clinical and referring sites across multiple regions and disease areas. Her role involves daily communication with sites, addressing concerns as they arise, and adapting trial support in real time.
Drawing from that firsthand experience, several consistent lessons emerge about effective site enablement and the actual role of sites once a trial is underway.
Lesson 1: Enrollment projections rarely reflect reality
Across trials, enrollment almost always comes in lower than projected. A shortfall of 20% compared to feasibility estimates is common. In some cases, enrollment is far lower, and occasionally a site that appeared promising during selection does not enroll any patients at all.
This gap is rarely due to bad intent or poor planning on the part of sites. Instead, it reflects the reality of clinical environments. Healthcare systems are overburdened, clinicians are balancing multiple priorities, and trial participation often competes with routine patient care. Forecasts tend to assume steady capacity, while real-world conditions are far more variable.
What matters most is ongoing feedback throughout the trial. Challenges frequently arise after activation, and without regular check-ins and course correction, small issues can quietly derail enrollment. Enrollment forecasts need to be managed as living inputs that are revisited throughout the trial, rather than treated as fixed feasibility commitments.
Lesson 2: Referral pathways are a critical component of enablement
Another recurring pattern is the difference between sites that are selected for a trial and those that actually drive enrollment. Referring clinicians play a critical role, especially in rare and complex diseases. A strong referral network can substantially increase recruitment.
However, referrals require effort. Participating sites already juggle numerous platforms and portals, which contributes to tech fatigue and can lead to a site refusing to navigate yet another interface. Adding another system without a clear benefit is often unrealistic. Even modest logistical barriers can prevent referrals from happening at all. For referring sites, staff must manage core responsibilities with limited time, which introduces the need for rewarding extra time dedicated to trial activities.
Small incentives can make a meaningful difference. In some cases, even symbolic reimbursement acknowledges the time and effort involved and signals that referrals are valued. Streamlining the referral process and handling administrative steps centrally also reduces friction and increases participation. This suggests referral enablement should be resourced separately from site startup.
Lesson 3: There is no standard site experience
Despite the prevalence of standardized training materials and workflows, no two sites operate in the same way. Training needs vary widely. Some sites require detailed discussions around ethics and audits. Others focus on operational logistics or data flow.
As a result, one-to-one engagement matters. Introductory calls that create space for questions, clarify expectations, and surface concerns early often set the tone for the entire collaboration. Tailoring the approach based on each site’s structure, experience level, and regional context is far more effective than applying a single process across all sites.
Differences also emerge by geography and seniority. Communication norms vary by country, and responsiveness can differ substantially. Younger healthcare professionals may show greater openness to new systems and research participation, while more established clinicians may be more selective due to time constraints.
Effective enablement depends on flexible, site-specific approaches instead of uniform training models applied across regions and institutions.
Lesson 4: Responsiveness shapes trust and engagement
One of the clearest differentiators in site engagement is responsiveness. Quick follow-up signals presence and support. Responding within hours rather than days changes how sites perceive the relationship and whether they feel comfortable raising issues as they arise.
When sites become unresponsive, structured escalation pathways are essential. Involving the CRA when a CRO is present, aligning with sponsors on next steps, and clearly defining when a site should be considered inactive helps prevent prolonged uncertainty. In some cases, disengagement reflects lack of interest rather than logistical issues, and recognizing that early allows resources to be redirected.
Across conversations with sites, a recurring frustration with other vendors is lack of communication. Clear expectations, consistent follow-up, and transparency are repeatedly cited as reasons sites prefer one partner over another. Clear ownership of site communication, defined escalation paths, and rapid response expectations are critical components of sustained site engagement.
Lesson 5: Ethical and emotional considerations are central, especially in rare disease
In rare and high-burden diseases, site enablement extends beyond operations. Clinicians frequently express concern about raising patient expectations when eligibility is uncertain. This is particularly challenging when there is only one available trial or when inclusion and exclusion criteria are complex. Screening initiatives that sit adjacent to, but separate from, trial criteria can create tension if not carefully explained.
Some sites raise the need for psychological support, especially when patients undergo genetic testing that may not ultimately lead to trial participation. These concerns shape the willingness to engage and require thoughtful, empathetic handling. Enablement strategies should explicitly address ethical risk and patient impact, particularly in high-burden indications where eligibility uncertainty is high.
Lesson 6: Motivation is often social, not just financial
While reimbursement matters, motivation is often driven by recognition and relationships. Friendly competition between hospitals can encourage engagement. Simple gestures such as newsletters highlighting enrollment milestones or acknowledging early participation can make sites feel part of a broader effort.
Personal connection also plays a role. Sites that feel supported, appreciated, and understood are more likely to go beyond minimum requirements. In rare cases, this even includes clinicians conducting additional assessments out of pocket, motivated by commitment to their patients and trust in the collaboration.
Sites that are already active in clinical research often adapt more quickly, but enthusiasm and engagement are not limited to experienced centers. Attitude, responsiveness, and personal investment frequently matter more than prior trial volume. Site engagement is likely to improve when enablement efforts reinforce a sense of participation and progress, not just contractual or financial obligations.
Conclusion
Through ongoing work supporting sites across precision medicine and genetic trials, Sano’s in-house site expert has observed consistent patterns in how site enablement succeeds or breaks down.
For sponsors, effective site enablement requires treating site engagement as a continuous operational responsibility rather than a phase that concludes at activation. Enrollment variability, referral dynamics, communication responsiveness, and ethical considerations need to be designed into enablement strategies from the outset, particularly in trials with complex eligibility and high patient impact.
In precision and genetic trials, sites operate within constrained clinical environments while managing heightened patient expectations. Enablement approaches that account for these realities support more reliable referral activity, sustained site participation, and clearer communication between sponsors, CROs, and sites.
Sponsors that design enablement around how sites actually work, rather than relying solely on planning assumptions, are better positioned to achieve consistent enrollment and execution outcomes.
To see how these site enablement principles translate into practice, explore our site enablement case study from a precision medicine trial.