Practical guidance for planning resources required to support publicly-funded adaptive clinical trials

Abstract

Adaptive designs are a class of methods for improving efficiency and patient benefit of clinical trials. Although their use has increased in recent years, research suggests they are not used in many situations where they have potential to bring benefit. One barrier to their more widespread use is a lack of understanding about how the choice to use an adaptive design, rather than a traditional design, affects resources (staff and non-staff) required to set-up, conduct and report a trial. The Costing Adaptive Trials project investigated this issue using quantitative and qualitative research amongst UK Clinical Trials Units. Here, we present guidance that is informed by our research, on considering the appropriate resourcing of adaptive trials. We outline a five-step process to estimate the resources required and provide an accompanying costing tool. The process involves understanding the tasks required to undertake a trial, and how the adaptive design affects them. We identify barriers in the publicly funded landscape and provide recommendations to trial funders that would address them. Although our guidance and recommendations are most relevant to UK non-commercial trials, many aspects are relevant more widely.

Characteristics, Progression, and Output of Randomized Platform Trials

“…Evidence from a hypothetical costing study suggested increased costs associated with the planning and setup of platform trials compared with traditional RCTs are due to the complex protocols and longer setup times . These increased costs were mitigated when more arms were added to the trial, which was less time intensive and reduced costs long term . Fourth, a comparison of platform trials with traditional parallel-arm RCTs was possible only on an indirect level.…”

Adaptive trials in stroke: Current use & future directions

“…Adaptive clinical trials may impact research and clinical workforce readiness. Adaptive trials require access to statistical, data and trial management staff who are fluent in their design 42 to manage the potential impact on trial costs. A mock-costing exercise completed with seven UK Clinical Trial Units estimated non-platform adaptive trials with pharmacologic interventions were 2-4% more expensive than a non-adaptive trial equivalent 43 .…”

“…The highest increase was for statistical staff, with lower increases for data and trial management staff 43 . Costings for appropriate statistical staff are highly dependent on the nature of the adaptive feature(s) included 42 . During trial conduct, adaptations that occur at prespecified interim analyses (e.g., sample size reestimation, multi-arm, multi-stage) may require more intensive ongoing input than adaptations that are managed on a day-to-day basis by software that implement methods to adaptively randomise individual participants (e.g., covariate-adjusted, response-adaptive).…”

“…Adaptive designs can impact site clinical and trial management staff. There can be additional costs associated with supplementary training in adaptive trial processes and procedures, and time to gain consent may be longer due to the complexity of transparently discussing adaptive features with potential participants 42 . Countering potential increased costs, trials that can be stopped for futility can create efficiencies that traditional trials cannot offer.…”

“…Other features that are more enduring (e.g., adaptive platform) may offer greater stability for trial staff due to their perpetual nature 46 . As such, the impact on the site workforce varies depending on the adaptive features included in a trial, but may also be impacted by the volume of trials operating at a site, whether the site is part of a network (e.g., NIH StrokeNet) or has an accessible Clinical Trial Unit (e.g., UK centres), and experience of the site 24, 42 . These issues have been largely acknowledged in reports from high-income countries and may be more pronounced in low-middle income countries and rural/regional centres.…”