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Challenges

Adaptive designs can provide efficiency in the conduct of clinical trials. These flexible designs have already been deployed successfully to address multiple research objectives quickly to identify effective or ineffective treatments sooner than could have been achieved using traditional fixed trial designs. Also, they are increasingly being used in clinical trials research. However, despite their appealing features, the fact that adaptive designs allow prespecified changes to be made to an ongoing trial based on interim results also creates the potential for biases to be introduced at different stages of the trial. This brings additional demands for transparency and adequate reporting of adaptive trials so that consumers of research findings can make informed judgements about the validity and trustworthiness of results.

Inadequately reported adaptive trials are difficult to interpret their results and reproduce methods, results, and inference. This can severely undermine public confidence in research findings to influence clinical practice resulting in research waste. In addition, poorly reported adaptive trials are not useful for practical knowledge transfer, which is essential for innovative and complex trial designs. 

This project was initiated to address the poor and inconsistent reporting of adaptive trials found in previous research by developing a consensus-driven and international reporting guidance in the form of an extension to the CONSORT 2010 statement.   

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Research

We followed the guidance for developing reporting guidelines as recommended by the CONSORT Group and EQUATOR Network as detailed in this . In summary, the process involved a two-stage Delphi process that included cross-sector (public and private) and multidisciplinary key stakeholders in clinical trials research from 21 countries (such as trialists, journal editors, regulators, and funders). Delphi survey response rates were 94/143 (66%), 114/156 (73%), and 79/143 (55%) in round one, round two, and across both rounds, respectively. A consensus meeting attended by 27 cross-sector delegates from Europe, Asia, and the US followed this. Members of the CONSORT Group provided oversight throughout the process. The ACE Consensus Group and Steering Committee approved the final checklist that included the abstract and contributed to the final Explanation and Elaboration (E&E) document

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Results

The resultant ACE checklists and E&E document has been co-published in the and journals and accessible via other platforms such as the , , MRC-NIHR Network of , and .  Researchers are encouraged to read the E&E text with examples in the ACE guidance to help them when reporting their adaptive trial. They can download the checklists to complete when submitting their .

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Impact

We hope ACE guidance will improve the quality of reporting of randomised adaptive trials so that methods used are reproducible and findings are easy to interpret. This will maximise their ability to inform practice and future research and reduce research waste. Finally, the potential benefits of innovative and efficient adaptive trial designs can only be realised when methods and results are well-reported and can also be a useful resource for knowledge transfer.  

The ACE guidance is already in use and influencing high-quality reporting of randomised adaptive trials. For example, this that was stopped early for efficacy at the second interim analysis satisfactorily adhered to the reporting guidance and trial methods and results are much easier for readers to understand and interpret. Researchers can now easily access the ACE checklists and guidance document via the .

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Publications

Dimairo M, Pallmann P, Wason J, Todd S, Jaki T, Julious SA, Mander AP, Weir CJ, Koenig F, Walton MK, Nicholl JP, Coates E, Biggs K, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG; ACE Consensus Group. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ. 2020 Jun 17;369:m115.  

Dimairo M, Pallmann P, Wason J, Todd S, Jaki T, Julious SA, Mander AP, Weir CJ, Koenig F, Walton MK, Nicholl JP, Coates E, Biggs K, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG; ACE Consensus Group. The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials. 2020 Jun 17;21(1):528.  

Dimairo M, Coates E, Pallmann P, Todd S, Julious SA, Jaki T, Wason J, Mander AP, Weir CJ, Koenig F, Walton MK, Biggs K, Nicholl J, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG. Development process of a consensus-driven CONSORT extension for randomised trials using an adaptive design. BMC Med. 2018 Nov 16;16(1):210.  

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Additional information

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Funder

The NIHR Clinical Trials Unit (CTU) Support Funding (NIHR129671) and MRC Network of HTMR (MR/L004933/1-R/N/P/B1) jointly funded the project.

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Project team

• Dr Munya Dimairo
• Ms Katie Biggs
• Dr Daniel Hind
• Prof Susan Todd
• Prof Steven Julious
• Prof Jon Nicholl
• Dr James Wason
• Dr Adrian Mander
• Prof Christopher Weir
• Prof Thomas Jaki
• Dr Franz Koenig
• Prof Doug Altman
• Prof Toshimitsu Hamasaki
• Dr Michael Proschan
• Dr Marc Walton
• Dr John Scott
• Dr Yuki Ando
• Sarah Gonzalez