Even the most well-designed protocols can encounter unexpected challenges once a trial is underway. Procedures that seem straightforward on paper may prove burdensome in practice. Eligibility criteria that appear reasonable may limit enrollment more than anticipated. Small design choices can have a big impact on patient experience and retention.
That’s why early input from research sites can be so valuable. With firsthand knowledge of day-to-day operations, participant needs, and common friction points, sites are in a strong position to support clinical trial protocol optimization from the start.
By asking the right questions upfront, sites can use those insights to help shape a protocol that works well in the real world.
Each additional visit requires time and coordination from study participants and site staff. In some cases, protocols include visits that are focused on a single activity, such as drug resupply or a brief assessment, that may be able to align more closely with other scheduled visits.
During protocol review, sites can look for opportunities to thoughtfully coordinate assessments at the same timepoint, including:
We’ve seen trials where protocols ask participants to return mid-week for a short task that could have been completed during their prior visit with minimal study impact. In other situations, allowing additional study drugs to be dispensed upfront may reduce the need for an extra trip.
When visits are streamlined where appropriate, the study experience can feel more manageable for participants, while also supporting smoother operations and stronger retention over time.
Visit schedules that are too rigid can unintentionally create challenges for participants. While structure is essential in a trial, protocols that allow for a degree of flexibility are better suited to support engagement, especially when they reflect the realities of participants’ day-to-day lives.
During protocol review, it’s beneficial for sites to ask whether the design allows for:
In one study, a required visit was scheduled on January 1st, with no flexibility outlined in the protocol. A simple scheduling allowance for holidays could have prevented the issue.
Adding flexibility helps participants stay on track without feeling like the study is in conflict with other parts of their lives.
Inclusion and exclusion criteria are critical to participant safety and study integrity. But when criteria are more restrictive than necessary, it can make enrollment more difficult and limit the relevance of the study to real-world patient populations.
As part of protocol review, sites should take a close look at the criteria that may unintentionally narrow the eligible population. Examples are:
Rather than excluding entire groups, a risk-managed approach may offer a more balanced path. For example, allowing patients with controlled hypertension to enroll — with additional safety monitoring in place — could preserve safety while broadening eligibility. Similarly, when a commonly prescribed medication is excluded, it’s worth considering whether that exclusion is still necessary or if the potential impact can be mitigated through monitoring.
Adjusting overly narrow criteria where appropriate can improve enrollment feasibility and enhance the generalizability of the trial’s findings while maintaining participant safety and data quality.
Many sponsors prioritize diversity in clinical trials, recognizing the importance of representative data and equitable access. For those goals to be achievable, the protocol needs to support them in practical ways.
Sometimes, certain protocol design elements can create unintentional barriers for participants from underrepresented communities. These may include:
While offering transportation reimbursement is a helpful step, be mindful of the fact that it can still place a temporary financial burden on participants who may not have the means to pay upfront. Alternatives like prepaid ride services or direct stipends can be more accessible.
Fasting lab requirements, meanwhile, are sometimes carried over by default, even when the endpoint doesn’t require them. Re-evaluating those requirements can allow for more flexible scheduling and reduce barriers to participation for those with early morning work or family obligations.
If the goal is to reach a broader and more diverse population, the protocol should be designed with that in mind, offering flexibility and support that make participation more accessible.
Screen failures are common in clinical research, but when they occur more frequently than anticipated — particularly late in the screening process — they can create added burden.
To plan more effectively, it’s useful for sites to ask whether the protocol development process included:
In some scenarios, we’ve seen participants complete multiple steps in the screening process before being ruled out due to something that could have been flagged earlier, like a specific lab value or imaging criteria. These situations can be discouraging for participants and resource-intensive for sites.
By modeling screen failure more closely to real-world scenarios and incorporating early indicators where possible, sponsors and sites can work together to reduce unnecessary procedures and create a more efficient, participant-friendly experience from the start.
Collecting robust data is integral to trial success, supporting safety, efficacy, and potential regulatory pathways. At the same time, it’s worth considering how the volume and frequency of data collection may affect participant engagement and study efficiency.
During protocol review, sites can work with sponsors to thoughtfully assess whether each procedure or data point directly supports trial goals. Questions to consider might include:
There are times when protocols are designed to collect more data than may be required — often to ensure flexibility in the analysis phase. While this can be useful from a statistical perspective, it may also lead to longer visits, increased participant burden, and greater demand on site resources.
Taking a balanced approach to data collection can preserve participant comfort and site efficiency, while capturing the information needed to meet scientific and regulatory objectives.
When it comes to clinical trial success, protocol optimization is one of the most powerful — and often underutilized — opportunities for improvement. Even small adjustments early in the process can make a significant difference in how a study performs in the real world.
With deep experience managing day-to-day operations, engaging participants, and navigating protocol challenges firsthand, sites bring valuable insight into what works and what can be refined. By asking thoughtful, patient-centered questions during protocol review, sites can help sponsors design studies that are practical, inclusive, and more likely to stay on schedule.
At Remington-Davis, we approach every clinical study as a partnership. With over 30 years of experience, a 97% patient retention rate, and a 19,000+ volunteer database, our team understands the operational realities and the strategic opportunities that come with every protocol. You can count on us to bring a hands-on, collaborative approach to support smarter trial design from day one.
To learn how we can help your next trial succeed, contact us.
Protocol amendments can be surprisingly expensive, not just in direct costs, but in time lost. Studies have shown that a single protocol amendment can cost anywhere from $150,000 to over $500,000, depending on its complexity. Beyond financial impact, amendments often result in delays to recruitment, database lock, and trial completion timelines. Engaging research sites early to identify potential operational challenges can help minimize the need for these mid-study changes.
Complex protocols often involve more frequent visits, longer appointment durations, additional assessments, and narrow eligibility criteria — all of which can make it harder for participants to enroll and stay engaged. This can also increase the burden on site staff and reduce overall study efficiency. Simplifying where possible, and aligning study design with real-world patient needs, helps improve both patient recruitment and long-term retention.
Leveraging historical data from similar trials — including screen failure rates, enrollment timelines, and dropout trends — can help sponsors and CROs design more realistic and efficient protocols. Sites can also contribute by sharing local feasibility insights, patient population characteristics, and past screening challenges. Together, this data-forward approach to clinical trial design can reduce waste, streamline workflows, and enhance trial performance from the start.
A patient-centric protocol is one that’s thoughtfully designed with the participant experience in mind. This includes minimizing unnecessary procedures, allowing for flexible scheduling, reducing travel where possible, and incorporating tools like remote visits or home-based assessments. When participants feel that their time, comfort, and real-life responsibilities have been considered, they’re more likely to enroll and stay in the study.
Protocol design directly impacts key performance metrics like enrollment speed, screen failure rate, retention, and timeline adherence. Overly complex protocols or those that don’t align with site workflows and patient realities can lead to delays, deviations, and lower data quality. By involving experienced research sites early and designing scientifically sound, feasible protocols, sponsors can improve trial execution, reduce costly amendments, and accelerate time to completion.