Protocol usability is a critical yet often overlooked factor in clinical trial efficiency. Errors and inconsistencies within protocols and supporting documents can lead to confusion, operational delays, and protocol deviations at research sites. This article explores how a site-centric approach emphasizing clarity, integration, and operational feasibility can significantly reduce these issues and enhance trial execution. Contributing their expert insights areâŻTed Trafford, a veteran executive who has spent nearly 30 years at Probity Medical Research building a global network of over 70 investigative sites across multiple therapeutic areas, andâŻBrad Hightower, founder of Hightower Clinical and host ofâŻNote to File: A Clinical Research Podcast, who brings over 15 years of site-level experience, including leadership at the Oklahoma Heart Hospital Research Foundation.âŻ
The Impact of Protocol Errors and InconsistenciesÂ
Protocol errors and inconsistencies remain a leading source of frustration among investigators and site staff. Discrepancies between protocol sections, or between the protocol and supporting documents such as lab manuals, eCRFs (electronic case report form), or pharmacy manuals, frequently result in confusion and operational delays. Even minor variations in language, such as differing descriptions of prohibited medications across sections can lead to misinterpretation, protocol deviations, or unintended eligibility violations. In many cases, investigators may remain unaware of these inconsistencies until flagged by monitors, often after multiple patients have been enrolled.Â
The fragmented delivery of study materials, typically distributed as unlinked files across multiple platforms, further complicates site operations. Coordinators and site managers are often left to synthesize disparate documents without centralized guidance, increasing the risk of procedural errors. Some sponsors attempt to mitigate this by requiring pre-randomization approvals or additional documentation, which, while burdensome, can reduce downstream compliance issues. A more effective approach involves the inclusion of integrated work instructions within protocols, developed with operational feasibility in mind. Standardized guidance not only reduces variability across sites but also enables early identification of inconsistencies before patient enrollment begins. Proactive document harmonization and clear operational workflows are essential to minimizing protocol deviations and supporting consistent, high-quality trial execution.Â
Protocol Usability and Site EfficiencyÂ
Protocol usability remains a critical factor in site performance and staff efficiency. Current practices often require coordinators to navigate multiple unlinked documents such as protocols, lab manuals, pharmacy manuals, and training slides, without a centralized reference system. This fragmented approach increases the likelihood of procedural errors and consumes valuable time that could otherwise be spent on patient-facing activities. While some vendors have developed integrated platforms to consolidate study materials and enable cross-referencing, adoption remains limited. Sponsors that fail to implement such systems risk overburdening site staff and reducing enrollment efficiency. The absence of intuitive tools and clear guidance often leads coordinators to exclude potentially eligible patients out of caution, particularly in academic settings where risk aversion is high and incentives are limited.Â
Additionally, traditional protocol formats have not evolved to accommodate diverse learning styles or operational realities. Visual tools such as flowcharts and interactive training environments offer effective ways to communicate study design and procedures. Simulation-based onboarding, for example, could allow staff to rehearse enrollment workflows before engaging with real patients, reducing visit duration and improving the participant experience. Streamlining access to information, minimizing ambiguity, and modernizing protocol delivery methods are essential steps toward improving site engagement, reducing errors, and enhancing overall trial efficiency.Â
Streamlining Protocol DesignÂ
Protocol complexity continues to be a significant barrier to efficient site execution. Excessive procedures, footnotes, unclear instructions, and redundant references across protocol sections contribute to confusion and operational delays. In early-phase studies, where visit structures are already intensive, the lack of clarity in procedural tables and supporting documentation can result in prolonged patient visits and increased staff frustration. Coordinators often encounter circular referencing within protocols, where footnotes are directed to other sections that contradict or further complicate the original instruction. Additionally, many footnotes are irrelevant to specific sites due to regional or procedural differences yet remain embedded in the universal protocol. This lack of customization increases cognitive load and the risk of error. A more effective solution would involve the development of adaptive, electronic protocols tailored to site-specific responsibilities. Interactive platforms that guide staff through relevant procedures and eliminate unnecessary content could significantly reduce training time and improve compliance.Â
Improving protocol usability through integrated, site-focused design is essential for minimizing errors, reducing staff burden, and enhancing trial efficiency. By streamlining documentation, embracing adaptive tools, and prioritizing operational clarity, sponsors can better support site performance and ensure more consistent, high-quality outcomes across clinical studies.Â
About the AuthorsâŻ
Ted TraffordâŻ
Ted Trafford is a seasoned clinical research executive with nearly 30 years of experience at Probity Medical Research. He has led the transformation of a single-site operation into a global network of over 70 investigative sites, with a focus on Dermatology, Allergy/Immunology, Cardiology, and Rheumatology.âŻ
Brad HightowerâŻ
Brad Hightower brings over 15 years of site-level clinical research experience, including his tenure as Executive Director of the Oklahoma Heart Hospital Research Foundation. He is the founder of Hightower Clinical, an integrated site network, and the host ofâŻNote to File: A Clinical Research Podcast.âŻ
