For a long time, research sites have been silent executors. Protocols arrived fully written, and their role was simply to carry them out step by step, without having a real say. But this perspective is starting to shift.
The new ICH E6(R3) guideline radically changes the paradigm: quality must be built from the very beginning, through a participant-centered design and a careful assessment of risks. At the same time, the rise of hybrid and decentralized trials reveals a simple truth: what looks perfect on paper cannot be implemented without local adaptations, shaped together with the sites.
Sponsors and CROs are beginning to recognize an obvious fact: if sites are not involved early in the design phase, trials risk stalling in recruitment, retention, or compliance.
September 2025 marks a turning point. It is the moment when sites can move from being mere executors to becoming strategic partners. Not through a formal declaration, but through the voice and practical intelligence they bring to the design table. Sites that know how to make their voices heard are becoming indispensable in the future architecture of clinical research.
1. What does co-creating trial design really mean in practice
For decades, clinical trial design was shaped almost exclusively by sponsors and CROs, with sites called in only to execute fully written protocols. Today, that reality is shifting.
📌 The ICH E6(R3) – Final 2025 Guideline is explicit: quality must be “built-in” (quality by design) from the earliest stages of planning, through a process that integrates the perspectives of all stakeholders — including research sites. The guideline emphasizes that risk-based management and participant-centered design cannot be achieved without input from those who directly understand patient realities and day-to-day implementation.
In parallel, the IQVIA White Paper (2024) highlights that site involvement brings “site intelligence” — practical insights into feasibility, logistics, and real-world barriers that sponsors often miss when working only theoretically. IQVIA gives concrete examples: a site may anticipate roadblocks such as the lack of infrastructure for virtual visits, unrealistic scheduling timelines, or difficulties for patients traveling from rural areas.
Moreover, the Maturity Model (2023, PMC) shows that a mature clinical trial ecosystem is one where sites are not just executors but active contributors to protocol optimization. What used to be dismissed as administrative details — like patient scheduling or staff availability — are now recognized as critical factors for trial success.
👉 In practice, co-creating trial design means:
The result? Protocols that are more realistic, more efficient, and more likely to succeed. Sponsors gain feasible studies, sites strengthen their status as strategic partners, and patients experience trials that are more accessible and truly centered on their needs.
2. The three forces that make sites indispensable today
2.1. ICH E6(R3) regulations: risk management and participant-centered design
The new ICH E6(R3) guideline (2025) is clear: “Quality should be built into the protocol and trial processes, focusing on critical to quality factors and participant experience.” In other words, quality is no longer something to check at the end; it must be designed from the start, with the participant’s experience at the center.
Anyone who has worked at a site knows how the first cracks appear: scheduling visits that don’t fit patients’ real lives, procedures that look simple on paper but are hard to execute, and eventually, patients who drop out. And all this not because people don’t want to participate, but because the protocol was never designed with them in mind.
That’s why site involvement is no longer a “nice to have,” but a condition for building quality into design. Because, in the end, the patient is both the first and the last link in the chain: the study begins with them and ends with them, when they become the user of the therapy that has gone through so many filters.
2.2. The rise of hybrid and decentralized trials: impossible to implement without local adaptation
The IQVIA White Paper (2024) makes it clear that many protocols fail because “site feedback on operational feasibility is not systematically incorporated during trial design.” In theory, virtual visits and digital data collection look like perfect solutions. In practice, the reality varies greatly from site to site. Some teams have the infrastructure and training to support them, others barely manage with basic technology.
Anyone working in sites has seen this firsthand: a patient in a big city logs into an online visit with ease, while another from a small community struggles to find a stable internet connection. In such situations, only sites can say what works and what doesn’t, before the protocol becomes unworkable.
Their observations are not minor logistical notes — they are warnings that can save months of delays, additional costs, or even an entire study.
2.3. The “site as partner” culture: from provider to strategic ally
According to the Maturity Model (PMC, 2023), a mature clinical trial ecosystem does not treat sites as simple “recruitment centers,” but as design partners. The old models, where sites were excluded from planning, too often led to “trial failure due to poor feasibility assessment.”
The truth is that many protocols hinge on seemingly small details. A single observation from a site — “this procedure takes longer than you think” or “our patients cannot come at 8 a.m.” — can make the difference between a workable protocol and one doomed to remain on paper.
📌 The E6(R3) regulations, the explosion of hybrid trials, and the emergence of the “site as partner” culture all point to the same conclusion: sites are no longer silent executors. They are indispensable partners, without whom trial design can no longer be feasible, sustainable, or truly patient-centered.
3. How a site moves from executor to strategic partner
Transformation doesn’t happen overnight, nor through a single meeting with a sponsor. It is a path that begins with simple but clear steps.
The first step is for a site to document its expertise. Not just with a list of completed studies, but with real stories from practice: situations where the team anticipated problems, found solutions, or adapted a process to save a trial. These examples become tangible proof of the value added.
The second step is feedback on protocols. This is where the difference between an executor and a partner begins. A site that raises its hand and says, “this visit schedule isn’t realistic for our patients” or “this procedure can’t be done with current resources” is not blocking the project — it is making it stronger.
The third step is preparing the team. Investigators, coordinators, and even administrative staff need to feel comfortable discussing not just recruitment numbers with sponsors, but also feasibility and solutions. Sponsor trust is earned when the site can argue clearly, realistically, and constructively.
And perhaps most importantly, partnership is not earned through one isolated example. A single observation can save a protocol, but true recognition comes from consistency: repeated feedback, repeated solutions, the same reliable voice from trial to trial.
Because a site becomes a strategic partner only when sponsors know they can rely on it not just to execute, but to think together.
In conclusion, research sites can no longer be seen as mere executors. They are the voice that makes the difference between a feasible protocol and one doomed to fail. The reality of recent years makes it clear: without their involvement, clinical trials cannot be feasible, sustainable, or truly patient-centered.
ICH E6(R3), the rise of hybrid trials, and the culture of “site as partner” all point in the same direction: without sites, there is no quality, no relevance, and ultimately, no trust.
A site that raises its voice is not speaking only for itself. It speaks for the patients, for the teams carrying the daily burden, for the sponsors who seek real outcomes, and for a research system that can no longer afford costly failures.
The true transformation of the industry does not lie in spectacular technologies or new regulations, but in the courage to recognize that partnership with sites is the only path to trials that serve their ultimate purpose: the patient.
The real issue is not just who has a seat at the table. The real issue is whether we can build, together, a research model that starts not from assumptions, but from the lived reality of sites and the voice of the patient.
Because, in the end, the truth about what works and what doesn’t lies where it matters most: in the field, in front of the patient, in the hands of the team that turns a protocol from a document into reality.
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