Protocol predictability: Refocusing through the lens of site and patient engagement

Longer trial timelines, higher drug development costs and increased burden on sites and patients can often be traced back to study protocols.

Growing complexity in protocols is a pervasive problem. Between 2001-2005 and 2011-2015, the number of endpoints in pivotal phase 3 clinical trials almost doubled from seven to 13, according to Tufts.¹ Over the same period, there was also a 70% increase in the total number of procedures performed in typical phase 3 pivotal studies. This surge in required time and effort makes it harder to recruit patients and keep them engaged throughout the trial, which in turn may have a substantial impact on research outcomes and costs.²

Optimising protocol development with a focus on site and patient perspectives can facilitate faster recruitment, boost engagement, reduce burden and create more predictable outcomes during the critical start-up phase of clinical trials.

Starting with endpoints that matter

Reducing unnecessary complexity has a direct impact on site and patient burden, improving start-up speed and predictability. Avoiding unnecessary endpoints that add operational burden prevents overcomplicating the research. According to the Center for Information & Study on Clinical Research Participation (CSCRP) in 2017, an estimated 30% of all data gathered in trials has no direct influence on subsequent stages of drug development.³ This represents a significant amount of logistical and execution effort for irrelevant data.

Selecting the right endpoints will prevent unnecessary medical costs and keep the quality of data higher to reduce follow-up periods and better inform decision making. Regulators expect that all study assessments be clearly justified and essential, which will accelerate approval timelines and reduce the risk of amendments. Similarly, leveraging direct feedback and patient voice data helps ensure that the selected endpoints are scientifically sound, compliant and representative of patients’ real-world priorities.

Reducing burden improves recruitment and retention

Streamlining protocols also positively impacts patient recruitment and retention. Reducing unnecessary endpoints limits the number of procedures per visit and the associated time commitment per visit, thereby reducing patient burden. Tufts found that less burdensome protocols in later stage trials show better retention rates, shorter trial durations and less protocol amendments.⁴

In addition, since responsibility for patient engagement falls largely on the site investigator, reducing their operational burden frees up their time to focus more effort on recruitment and communication. Protocols developed with a site-friendly approach ensure that research plans are more appropriate, manageable and productive.

Designing protocols that make it easier for sites and patients to participate can also reduce potential amendments and the often substantial time and costs associated with their implementation. Regulators initiate a significant portion of protocol amendments, and their priorities remain focused on reducing patient burden and maintaining data integrity. A proactive approach to patient-centric protocol can mitigate the potential disruption of costly regulator-driven amendments while maintaining compliance and efficiency.

41%
Sites fail to meet planned enrolment
30%
Patient drop-out rate across on average
30%
Sites that fail to enroll a single patient

Better feasibility drives effective site activation

Strong feasibility planning is the foundation for effective site activation. Identifying the right sites and supporting them well with dedicated teams and centralised tools enables them to reach their full potential. Smaller sites or those new to a therapeutic area can perform exceptionally with the right tools, information and engagement from day one. Strategic selection and support means sites recruit faster, stay active longer and accelerate start-up timelines while contributing more meaningfully to overall study success.

A well-structured feasibility assessment helps avoid costly missteps by identifying risks, refining trial design and setting realistic expectations with the best-fit sites. Open communication with sites and including investigator perspectives during protocol development provides a more complete design that can be executed more efficiently and effectively. This feedback acts as a pressure test, generating insight into how sites and patients might respond to the protocol to help refine its operational feasibility. A holistic approach to feasibility ensures protocols are tailored to answer the right scientific questions, while also empowering investigators to recruit the most suitable and engaged patients, which can increase enrolment rate predictability across sites.

Putting patients at the centre of protocol development

Patients are the reason we are dedicated to developing meaningful therapeutics. Beyond being the reason why we conduct this research, patients are also how – without participants and volunteers, there is no measurable endpoint data to drive development. As such, a patient-centric recruitment strategy that focuses on motivation and engagement will support more positive outcomes.

Working closely with sites to gather patient feedback through surveys and focus groups helps sponsors better understand perceptions of clinical trial burden and the overall patient experience. This input can potentially lead to amendments in the protocol during earlier stages of trial design, improving feasibility, accessibility and appeal.

Time in motion studies and burden analyses can help quantify the impact of each procedure on patients. Mapping this data into a comprehensive matrix that specifies the time commitment for each element of the protocol, with accompanying recommendations, can enhance the patient journey and allow for a more balanced protocol.

Further surveys of the target patient demographic can explore attitudes to symptoms, study procedures and visit lengths, as well as how these factors influence their willingness to participate. This layered understanding of the patient perspective enriches recruitment strategies and helps ensure that the trial design is truly aligned with patient needs. Coupling insights from patients and investigators with historical data can result in significant increases in participant numbers and site compliance.

Predictability is the foundation of success

Protocol development is a core driver of start-up speed and predictability, which in turn impacts other important aspects of development success. Optimising the protocol for patient and site engagement generates more predictability in enrolment, improves engagement and data quality, and sets sponsors up for smoother regulatory review.

Strong protocol design also reduces waste, saving time and resources at every stage, particularly during study site start-up and activation, which is a critical step in the success of the broader study plan. Refocusing protocol optimisation around sites and patients can help counter the trend towards overly complex design, leading to faster, more efficient and cost-effective clinical trials with meaningful outcomes.

Contact us to learn how we can help you reduce patient burden, optimise resources and drive faster, more cost-effective study start-up.

References:

¹ Tufts: Clinical trials face tough going as data densities grow. Marie Powers. BioWorld. July 2018.

² https://www.ciscrp.org/wp-content/uploads/2019/06/2017-CISCRP-Perceptions-and-Insights-Study-Participation-Experience.pdf

³ https://www.tandfonline.com/doi/abs/10.1080/10543406.2015.1052497?journalCode=lbps20

⁴ Tufts Center for the Study of Drug Development, Participation burden for patients in clinical trials is rising, especially in non-oncology studies, Impact Report, Vol 26, Number 5, Sep/Oct 2024