Collaborating for protocol perfection: a holistic approach to protocol design

Across geographies and therapeutic areas, we have observed a notable shift in protocol development trends. Where protocols we reviewed once contained significant gaps, they are now more complete but often more complex than necessary to achieve the underlying scientific goals. In addition to the burden, cost and time associated with the additional complexity, protocols across the board seem to be no less vulnerable to amendments. According to Tufts 2023 data, increasing trial sizes, expanded scopes and the burden of additional endpoints contribute to the growing complexity of protocols. More than 75% of clinical trial protocols require at least one substantial amendment¹.

To navigate these challenges, a consultative, multidisciplinary approach to protocol development is essential. By incorporating a holistic approach from the outset, sponsors can develop protocols that are scientifically sound, operationally efficient, patient-centric and inclusive.

Four facets of protocol perfection

An optimal protocol must balance multiple elements to ensure a study is both scientifically sound and operationally feasible. At ICON, we have developed a structured protocol optimisation process that focuses on four foundational aspects:

Scientific and operational risk: This ensures feasibility and that the endpoints and data collection requirements are achievable within the proposed study population and timeline. It also includes considerations for recruitment, retention and data collection challenges.

Completeness: Protocols today start from a more comprehensive foundation, but completeness should not lead to complacency. A well-structured protocol clearly defines study procedures, assessments and timelines to ensure consistency and avoid ambiguity for site staff.

Complexity: While completeness is critical, excessive complexity creates burden. For example, many protocols include overly restrictive eligibility criteria and excessive assessments that add little scientific value. Simplifying these elements can reduce patient burden, optimise resource allocation and streamline site operations.

Diversity and inclusion: Creating a representative trial population is both an ethical and scientific imperative and it begins at the protocol level. We pressure test the trial’s accessibility by evaluating recruitment criteria, site locations and study procedures. Comparing this to our Patient Voice data, we can identify even small adjustments that will enable more patient-centred trials that produce more representative clinical trial data.

Enhancing individual protocols requires a holistic approach. By balancing these four dimensions, sponsors can develop protocols that align with study goals, regulatory expectations, and operational realities, ultimately maximising the return on investment.

Quantifying protocol quality

A structured, data-driven assessment is key to improving protocol quality. Our process begins with a comprehensive checklist that addresses the four facets of protocol development, to ensure a protocol is on the right track.

Where our approach diverges from industry norms is in quantifying protocol quality. We assign a “percentage to perfection” score, providing sponsors with clear visibility into a protocol’s strengths and weakness, actionable insights on necessary adjustments, and the impact those changes will have on study execution and timelines. Our multidisciplinary three-tiered review goes beyond a surface-level checklist by evaluating the interrelatedness of individual protocol elements across study stages. This in-depth structured review provides robust, cross-functional feedback ensuring scientifically and operationally sound enhancements in as little as five days.

Consultative approach to protocol design

Protocol optimisation can begin as early as the study concept stage, progressing through the development of an ICH-compliant protocol synopsis. We collaborate with sponsors to review and define the research question and identify the most appropriate study, as well as ensure the protocol supports a clinically meaningful treatment effect and aligns scientific rigor with operational feasibility. The resulting protocol synopsis outlines the objectives, methodology, eligibility criteria, variables, statistical methods and study-specific procedures and schedules.

Every recommendation we provide is backed by quantitative analysis and real-world expertise. This evidence-driven approach ensures sponsors understand the rationale behind suggested protocol adjustments, making it easier to implement meaningful changes that align with organisational goals and scientific objectives.

This consultative approach offers a distinct advantage, as sponsors gain insights from a multidisciplinary team that considers clinical, regulatory, operational and patient-focused factors. Ultimately, even small changes can have big impacts. The ability to balance opinions with evidence through ICON’s consultative and data-driven framework for protocol optimisation is especially valuable in helping sponsors develop protocols that will withstand regulatory scrutiny, minimise costly amendments and accelerate study timelines.

Protocol optimisation from square one

A comprehensive, well-designed protocol mitigates unnecessary complications, reduces costs and minimises delays. This is especially true when optimisation is prioritised from the start. At ICON, our experts in protocol development provide an integrated perspective that balances scientific integrity with operational efficiency. Acting as a single point of contact for the multidisciplinary evaluations required for a complete, comprehensive design, we help sponsors develop best-fit protocols from the outset. Starting with an optimised protocol can result in fewer late-stage amendments that contribute to delays, increased costs, and operational inefficiencies. By partnering with ICON, sponsors can streamline the development process and accelerate timelines and optimise outcomes at all phases – ensuring success from square one.

Contact ICON today to learn how we can help you design protocols that drive efficiency, enhance patient engagement and accelerate your clinical development goals.

References:

¹Tufts CSDD. Impact Report, Vol 25, Number 2, Mar/April 2023

Four facets of protocol perfection

Quantifying protocol quality

Consultative approach to protocol design

Protocol optimisation from square one

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