A Practical Adaptive & Novel Designs and Analysis (PANDA) toolkit

Challenges

Researchers across disciplines, research funders, regulators, and the public acknowledge the need to streamline the conduct of randomised trials to address research questions as efficiently as possible for safe and effective treatments to reach patients swiftly and to avoid unnecessary use of resources. Lessons from pandemics (eg COVID-19) reinforce this.

Adaptive designs can improve efficiency by adding controlled flexibilities to the design and conduct of the trial. They are increasingly being used or at least considered at the design stage by researchers. However, adaptive designs are not routinely used in practice as they should be. The lack of practical education and experience, especially among multidisciplinary researchers, is one of the leading obstacles hampering the uptake of adaptive designs.

Recent initiatives to address the skills and knowledge gap in adaptive designs include research fellowships; the development of educational publications, reporting guidance and software resources; and outreach activities to support UK CTUs, many of which were led by the MRC-NIHR TMRP Adaptive Designs Working Group (ADWG).

However, a few courses focused on practical issues in adaptive designs were available, some of which are expensive, infrequently offered, and focused on statistical audiences. Therefore, accessible education resources that include practical guidance and software recommendations, and can readily be updated, are needed to improve practical knowledge and adaptive designs use, especially among diverse stakeholders in clinical trial research (e.g., trialists, clinicians, statisticians, funders, and ethics committees). 

Therefore, we developed an online, open-access, comprehensive, flexible, and practical educational toolkit on adaptive designs for a broad audience including statisticians, clinicians, grant development support staff, proposal developers, trial managers, trialists, and data managers. We primarily focused on adaptive designs in randomised trials, intending to extend to other trial types in the future.

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Research

The Practical Adaptive and Novel Designs and Analysis (PANDA) toolkit is hosted on the University of Sheffield (UoS) servers and was developed in collaboration with a UoS software development company (epiGenesys) using “Ruby on Rails” with a React frontend. Ethics approval (ref: 012041) was granted by the ScHARR Research Ethics Committee at the UoS.

The project team members had diverse practical knowledge and experience in adaptive and non-adaptive trial designs. This team brainstormed the structure of the online toolkit via face-to-face and online meetings and email correspondence including extensive discussions with software developers.

The educational needs were informed by the experiences of the project team, prior work on barriers and facilitators to the use of adaptive designs, and qualitative feedback from surveys of multidisciplinary stakeholders during the Adaptive designs CONSORT Extension (ACE) project.

The scope and breadth of content to be covered with a more practical focus were brainstormed through face-to-face and online meetings and email correspondence. Educational content was drafted and reviewed iteratively by the project team. Formal and informal feedback was gathered throughout the development process of the portal and content.

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Results

This open-access toolkit allows self-paced practical learning that is easily accessible to anyone involved in clinical trial research. Users can learn remotely about adaptive designs at a time that suits them, and they can easily find content relevant to them at different stages of a trial. The search tool also facilitates ease of access to relevant content.

To ensure long-term sustainability, the PANDA toolkit can be updated to include new and emerging content such as new types of adaptive designs, trial examples, and new software resources to implement them. 

The PANDA toolkit is a globally accessible educational resource that will evolve in response to research needs and feedback from users. The intention is for the PANDA toolkit to be a “one-stop shop” repository hosting essential resources on adaptive designs with a practical flavour from other related emerging work. We hope it will be a vital educational resource to help improve practical knowledge and appropriate uptake of adaptive trials for years to come.

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Impact

The PANDA toolkit oral presentation by Dr Munya Dimairo won the CTU Directors' Award at the International Clinical Trials Methodology Conference (ICTMC, 2022) held in Harrogate (UK) for the most innovative presentation with the most potential future impact. This talk was titled "A practical adaptive designs toolkit: making adaptive designs more accessible." 

A dedicated Wikipedia webpage on adaptive designs cited the PANDA toolkit as an important educational resource on adaptive designs. In addition, the toolkit is already being cited by related peer-reviewed publications, such as point estimation for adaptive trial designs.

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Publications

The PANDA toolkit is an open access online educational resource.

Access the PANDA toolkit

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Project team

Name	Organisation
Dr Munya Dimairo	Sheffield Clinical Trials Research Unit, University of Sheffield
Dr Philip Pallmann	Centre for Trials Research, Cardiff University
Prof Thomas Jaki	Lancaster University
Mike Bradburn	Sheffield Clinical Trials Research Unit, University of Sheffield
Dr Graham Wheeler	Cancer Trials Centre, University College London
Laura Flight	Health Economics and Decision Sciences, University of Sheffield
Prof Cindy Cooper	Sheffield Clinical Trials Research Unit, University of Sheffield
Dr Julie Marsh	Telethon Kids Institute, University of Western Australia

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References

1. Hatfield I, Allison A, Flight L, Julious SA, Dimairo M. Adaptive designs undertaken in clinical research: a review of registered clinical trials. Trials. 2016;17(1):150. doi:10.1186/s13063-016-1273-9
2. Bothwell LE, Avorn J, Khan NF, Kesselheim AS. Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov. BMJ Open. 2018;8(2):e018320. doi:10.1136/bmjopen-2017-018320
3. Hartford A, Thomann M, Chen X, et al. Adaptive Designs: Results of 2016 Survey on Perception and Use. Ther Innov Regul Sci. December 2018:216847901880771. doi:10.1177/2168479018807715
4. Dimairo M, Julious SA, Todd S, Nicholl JP, Boote J. Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials. Trials. 2015;16(1):585. doi:10.1186/s13063-015-1119-x
5. Dimairo M, Boote J, Julious SA, Nicholl JP, Todd S. Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials. Trials. 2015;16(1):430. doi:10.1186/s13063-015-0958-9
6. Love SB, Brown S, Weir CJ, et al. Embracing model-based designs for dose-finding trials. Br J Cancer. 2017;117(3):332-339. doi:10.1038/bjc.2017.186