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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.

Additional file 1. Brief overview of each scenario used in the Costing Adaptive Trials mock costing exercise.

Additional file 1. Trials whose staff experiences added to this paper.

Additional file 1. Scenarios and guidance pre-revision.

Background: The ethical basis of randomised controlled \ud trials is \ud equipoise, \ud whether \ud at the collective or individual level. Neonatal intensive \ud care \ud trials \ud are \ud therefore \ud conducted in a context of clinical uncertainty as \ud well as stress \ud and trauma. \ud The \ud theoretical literature suggests that tensions \ud exist \ud in the trials \ud situation \ud between the \ud aims of care and research. \ud Objectives: To improve understanding \ud of \ud decisions that \ud clinicians \ud and \ud parents make \ud about neonatal trial collaboration, participation \ud and \ud non-participation. \ud Methods: Semi-structured interviews were conducted \ud with \ud 30 \ud neonatologists \ud and \ud 63 \ud parents from 5 UK hospitals who \ud were \ud offered enrolment \ud in the INNOVO \ud and/or \ud CANDA trials. Qualitative analysis \ud was aided \ud by ATLAS-ti. \ud Results: The neonatologists' interviews suggested an \ud intermediate level \ud of equipoise. \ud A therapeutic orientation operated \ud for the INNOVO Trial \ud but \ud not \ud for the \ud CANDA \ud Trial. Neonatologists often did not \ud connect trial \ud participation and trial-related \ud postmortem pathology studies. Most parents made very \ud rapid \ud decisions \ud about trial \ud participation. Perception of risk was \ud independent \ud of the trial \ud under \ud consideration \ud but \ud associated with a slower decision-making process. \ud The 'therapeutic \ud misconception' \ud was present for parents in both trials. Many \ud supported \ud contributing to \ud research. \ud For \ud some of the bereaved parents, this extended \ud to \ud contribution to trial-related \ud pathology \ud studies. Parents who declined the \ud CANDA \ud Trial \ud saw \ud risks \ud in the trial \ud situation. \ud Conclusions: Decisions were complex \ud and \ud multi-tiered. \ud The \ud boundaries \ud between \ud care \ud and research were often unclear for neonatologists \ud and \ud parents. \ud Clarification \ud of the \ud nature of decisions at the heart of clinical trials is \ud needed, \ud so that those \ud associated \ud with \ud research might be willing collaborators and \ud participants, \ud fully \ud cognisant \ud of the \ud activity \ud in which they are engage