In a highly competitive landscape where funding and resources are often limited and the timely execution of clinical trials can make or break a biotech’s success, every sponsor is chasing faster start-ups for their clinical studies, which take approximately eight months to initiate on average.[i]

But while the prevailing industry pressure to hit early milestones can be overwhelming, the overall success of the trial rests largely on a well-designed, user-friendly protocol and an ongoing openness towards its implementation. In this context, taking enough time to elicit holistic, comprehensive feedback from candidate sites at the earliest opportunity can be instrumental in ensuring a smoother start-up later down the line.

Site-informed protocol design

While protocol design and risk assessment are rarely handled in a silo, outside perspectives have often been limited to the inclusion of principal investigators (PIs) and key opinion leaders (KOLs), meaning the subsequent protocol risks being difficult to implement.

Sites may experience challenges that hinder their ability to execute the protocol effectively or meet a key early milestone. If a protocol fails to reflect the practical considerations and day-to-day realities of its sites and participants, drug sponsors can face costly setbacks – protocol amendments cost sponsors an average of $141,000 for Phase II trials and $535,000 in Phase III.[ii] 

According to John Kennett, Director of Global Marketing at Fortrea, the ideal scenario is to incorporate diverse site perspectives into initial protocol design discussions – or at least share a draft protocol with key sites before it is submitted for approval. “The industry can often end up with protocols that are wonderful on paper but difficult to actually deploy,” he notes. “Success happens when there is a greater level of collaboration, and the opportunity to invite multiple voices into the early formation of a protocol is very useful.”

Incorporating site feedback into protocol design can streamline workflows while also enhancing the participant’s experience. With their lived understanding of patients’ struggles, sites are more likely to identify unnecessary selection criteria tests, inappropriate use of digital technologies, or overly detailed and complex consent forms that could alienate neurodiverse individuals, for instance. They may also suggest important accommodations that should be made for certain types of participants, helping sponsors and CROs strike a better balance between study requirements and participant burden. This insight ultimately leads to more inclusive trial designs, better enrolment, and improved participant retention. 

Why early engagement means speedier start-up

Timely engagement enables sites to start preparing their team and facility for the trial at the earliest. At the end of the day, sites have a business to run too; giving them a good line of sight with which to forecast their operations is a great way to set the relationship off smoothly.

“Engaging sites early is respectful to them as well,” says Kennett. “The ideal being that the protocol is going to work, the sites are primed and ready to go with everything that they need, and the study team are available to start that study immediately. That’s kind of the holy grail.”

Close collaborations at this early stage provide opportunities for the CRO and sponsor to determine what is needed to ensure a speedy activation of each site. As the trial moves closer to initiation, open conversations help the CRO assess the site’s overall readiness – something which may be particularly important for sites with little or no trial experience. If gaps are identified, an experienced CRO can continue to work with the site closely, formulating a plan that better sets them up for success. 

This collaborative preparation can include dry runs, particularly useful for assessing a site’s readiness ahead of complex patient visits or large cohort days. These simulations help to clarify requirements, test logistical capacity, and enhance the patient experience, ultimately enabling smoother start-ups. Crucially, such efforts depend on open, consistent communication between the sponsor/CRO and site stakeholders, helping to understand local limitations and align on solutions before they become a problem.

Final thoughts

In the race to accelerate clinical trial starts, it can be tempting for sponsors and CROs to prioritise speed above all else. True efficiency, however, comes from thoughtful collaboration with sites during protocol design and start-up preparations, helping teams anticipate and address hurdles together, reduce the risk of amendments, ensure site readiness before the trial begins, and build protocols that are more patient-centric and operationally feasible.

To learn more about addressing site-specific challenges to improve site engagement, please download the whitepaper below

[i] The Association of Clinical Research Professionals. Reducing Study Start-up Times: Quality Improvement Practices at a Site Management Organization. https://acrpnet.org/2025/02/04/reducing-study-start-up-times-quality-improvement-practices-at-a-site-management-organization

[ii] Getz KA, Stergiopoulos S, Short M, Surgeon L, Krauss R, Pretorius S, Desmond J, Dunn D. The Impact of Protocol Amendments on Clinical Trial Performance and Cost. Ther Innov Regul Sci. 2016 Jul;50(4):436-441. doi: 10.1177/2168479016632271. PMID: 30227022.