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Parsing the (un)necessary
Phase 3 trials are infamously challenging, and we have come to expect a certain increase in protocol complexity at this stage. However, we have perhaps allowed this expectation too much leeway, as some statistics show that approximately 30% of the data collected does not inform future study design and has no influence on the drug development – begging the question of whether these protocol elements were necessary additions.
The most striking data shows that the increased complexity of trials has most significantly impacted phase 1 trials. As more primary, secondary and exploratory endpoints are incorporated at this early stage along with novel methodologies, some in the industry are referring to phase 1 trials as the new phase 2. While these advancements aim to enhance scientific validity and accelerate development timelines, they also introduce significant execution challenges.
Protocol complexity impacts clinical research timelines, efficiency and cost. As the number of procedures, endpoints and eligibility criteria grows, so does the burden on sites and patients, leading to delays in recruitment and lower retention. Furthermore, the increased likelihood of protocol amendments compounds these issues. Industry data indicates that approximately a third of all protocol amendments are avoidable, with most initiating with regulators. These amendments not only incur substantial costs – up to hundreds of thousands of dollars – but also prolong timelines, disrupting the overall development process.
Optimize early
Addressing protocol complexity at the outset is crucial to mitigate these challenges. By evaluating study designs early, sponsors can streamline execution, minimize amendments and reduce the burden on sites and patients to ensure their trials run smoothly. ICON offers a comprehensive approach to optimized protocol design through propriety worksheets, ensuring that sponsors achieve scientifically robust and operationally feasible designs that avoid unnecessary complexities.
As part of ICON’s protocol optimization process, we assess protocols against a set of checklists to create a tangible quantification of their quality, integrating therapeutic expertise, multidisciplinary review and stakeholder collaboration. This approach enables sponsors to design trials that are scientifically sound, operationally efficient and patient-centric and inclusive. It also supports accelerated timelines, with delivery of protocol enhancements within as little as five days of the comprehensive, three-tiered review.
Success in simplification
Our Drug Development Services consulting group provides multidisciplinary perspectives on protocol design, stress-testing through concept development. Comprising clinical, operational and regulatory professionals, the committee balances scientific validity with feasibility to ensure protocols are not only rigorous but also practical to implement. The sheer scope of impact of protocol design means that any small detail can have significant downstream implications. Factors must be weighed across site feasibility to dosing to patient preference and potential enrolment rates.
ICON not only supports the enhancement of individual protocols but takes into consideration the whole development program. In a recent example, a biotech startup had proposed two phase 2 trials, one testing a series of loading doses and validating a composite endpoint, while the other assessed clinical utility. ICON’s drug development experts used PK/PD modelling to determine the most efficient approach to test the hypothesis. We proposed a single, simplified trial design that combined the key elements of the original proposal and avoided the need for loading doses. It also enabled faster study startup, ultimately saving several months and $30m in development costs.
Compounding benefits
A data-driven protocol optimization process enables faster decision-making, while collaboration with therapeutic experts and key opinion leaders (KOLs) maneuvers protocol away from potential design pitfalls and towards more efficient, holistic solutions for the comprehensive development plan. In addition to scientific validity and feasibility, patient burden is a vital consideration at the protocol level, as this directly impacts the trial’s ability to recruit and maintain participants. This in turn impacts the amount of viable data collected or, in many cases, the very success or failure of the trial.
A holistic protocol review considers the patient journey. ICON leverages insights from our Patient Voice program, which actively collects patient and site feedback through multiple channels, to inform protocol design for the end-user, the patient. ICON also quantifies the time needed for each visit, thus prioritizing a patient-centric design. This reduces recruitment challenges and enhances retention, contributing to improved data quality and overall trial success.
Preparing for optimized futures
The deeply interconnected complexity of the clinical development plan and protocol design provides an opportunity for technology like artificial intelligence (AI) to play a major role. With AI, sponsors could leverage advanced analytics and machine learning to identify potential design flaws and predict the impact of complex trial requirements at much faster rates. ICON is consulting with a pharma partner as they develop an internal AI tool trained to improve protocol design. Our experience with developing and using clinical research-specific AI tools and our depth of expertise in protocol design allows us to help train the tools for multilevel, multidisciplinary considerations that would reduce the number of amendments they encounter.
Reversing the complexity trend
Clarke Cyril
Peter Schueler
Will Maier
Clinical trials are inherently complex endeavors, though we can mitigate unnecessary complications, reduce costs and minimize delays through closer attention to protocol design. By combining therapeutic expertise, a multidisciplinary review process and patient-focused strategies, ICON ensures protocols are scientifically robust and operationally sound. Sponsors partnering with ICON gain the advantage of streamlined development processes that accelerate timelines and optimise outcomes at all phases.
Authors:
- Will Maier, Senior Vice President, Drug Development Services, ICON
- Peter Schueler, Senior Vice President, Drug Development Services, ICON
- Cyril Clarke Vice President, Drug Development & Consulting, ICON
Filed Under: clinical trials, Sponsored Content
