CRediT contribution statement
Martin J Llewelyn (https://orcid.org/0000-0002-6811-1124): Conceptualisation, Funding acquisition, Investigation, Project administration, Resources, Supervision, Validation, Writing – original draft, Writing – editing and reviewing.
Eric P Budgell (https://orcid.org/0000-0002-6148-9378): Data curation, Formal analysis, Investigation, Methodology, Software, Visualisation, Writing – original draft, Writing – editing and reviewing.
Koen B Pouwels (https://orcid.org/0000-0001-7097-8950): Data curation, Formal analysis, Investigation, Methodology, Software, Visualisation, Writing – original draft, Writing – editing and reviewing.
Liz Morrell (https://orcid.org/0000-0001-6382-1795): Data curation, Formal analysis, Investigation, Software, Writing – editing and reviewing.
Laurence SJ Roope (https://orcid.org/0000-0001-9098-9331): Data curation, Formal analysis, Investigation, Methodology, Software, Visualisation, Writing – original draft, Writing – editing and reviewing.
Katy Sivyer (https://orcid.org/0000-0003-4349-0102): Data curation, Formal analysis, Investigation, Writing – editing and reviewing.
Marta Santillo (https://orcid.org/0000-0001-6345-7612): Data curation, Formal analysis, Investigation, Writing – editing and reviewing.
Fiona Mowbray (https://orcid.org/0000-0002-3297-4163): Data curation, Formal analysis, Investigation, Writing – editing and reviewing.
Elizabeth LA Cross (https://orcid.org/0000-0002-7462-8330): Data curation, Formal analysis, Investigation, Writing – editing and reviewing.
Magda Laskawiec-Szkonter (https://orcid.org/0000-0002-0123-5616): Data curation, Investigation, Project administration, Writing – editing and reviewing.
Maho Yokoyama (https://orcid.org/0000-0001-6490-4162): Data curation, Formal analysis, Investigation.
Emma Hedley (https://orcid.org/0000-0002-2444-6280): Investigation, Project administration, Supervision, Writing – editing and reviewing.
James Buchanan (https://orcid.org/0000-0003-2528-0638): Investigation, Writing – editing and reviewing.
Kieran S Hand (https://orcid.org/0000-0002-3834-2415): Conceptualisation, Funding acquisition, Writing – editing and reviewing.
Louella Vaughan (https://orcid.org/0000-0002-7626-0779): Conceptualisation, Funding acquisition, Writing – editing and reviewing.
Melissa Dobson (https://orcid.org/0000-0002-4906-3956): Investigation, Project administration, Supervision, Writing – editing and reviewing.
Nicola Jones (https://orcid.org/0000-0003-0468-9282): Investigation, Resources, Writing – editing and reviewing.
Susan Hopkins (https://orcid.org/0000-0001-5179-5702): Conceptualisation, Funding acquisition, Writing – editing and reviewing.
Christopher C Butler (https://orcid.org/0000-0002-0102-3453): Conceptualisation, Funding acquisition, Writing – editing and reviewing.
Clifford Gorton: Conceptualisation, Funding acquisition, Writing – editing and reviewing.
Derrick W Crook (https://orcid.org/0000-0002-0590-2850): Conceptualisation, Funding acquisition, Writing – editing and reviewing.
Sarah Wordsworth (https://orcid.org/0000-0002-2361-3040): Conceptualisation, Funding acquisition, Supervision, Writing – editing and reviewing.
Timothy EA Peto (https://orcid.org/0000-0003-3477-8307): Conceptualisation, Funding acquisition, Supervision, Writing – editing and reviewing.
Lucy Yardley (https://orcid.org/0000-0002-3853-883X): Conceptualisation, Funding acquisition, Supervision, Validation, Writing – original draft, Writing – editing and reviewing.
Ann Sarah Walker (https://orcid.org/0000-0002-0412-8509): Conceptualisation, Funding acquisition, Project administration, Supervision, Validation, Visualisation, Writing – original draft, Writing – editing and reviewing.
Igho Onakpoya: Data curation, formal analysis, Writing – editing and reviewing.
Patient data statement
This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it is important that there are safeguards to make sure that they are stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation
Data-sharing statement
All data requests should be submitted to the corresponding author for consideration. Access to data may be granted following review, and appropriate agreements being in place. Anonymised patient-level electronic health records and hospital-level antibiotic data were obtained from individual hospital organisations, and can be requested either directly from the participating organisations, or through NHS Digital. Access to anonymised data may be granted following review.
Ethics statement
Ethical approval was obtained for different studies within the ARK-Hospital research programme as follows:
WP 2: The original study plan for the hospital-level analysis was approved by the Health and Social Care Information Centre (now NHS Digital), whose guidance at the time was that the use of de-identified routine electronic health record data for secondary data analysis did not require Ethics Committee review. Similarly, for the retrospective analysis of individual patient-level de-identified routine electronic health records, guidance from the Head of Research and Development (Governance) at the University Hospitals Birmingham NHS Foundation Trust was that Ethics Committee review was not required.
WPs 3 and 4: Ethical approval for the qualitative studies with healthcare professionals was obtained from the London–Westminster Research Ethics Committee (REC: 16/LO/0789) (date of approval 24 May 2016). All participants provided written informed consent.
WPs 4, 5 and 6: Ethical approval for the feasibility, non-randomised internal pilot and randomised main trial, including cost-effectiveness analysis, patient experience qualitative study and faecal microbiome sub-study (one protocol), was obtained from the South Central Oxford C Research Ethics Committee (17/SC/0034) (date of approval 7 February 2017) and the Confidentiality Advisory Group (17/CAG/0015) (date of approval 20 February 2017) without individual patient consent since electronic health records were de-identified and no personal identifiable data was collected other than date of death.
WP 6: The online choice survey received ethical approval from the University of Oxford Central University Research Ethics Committee (R56654/RE001, date of approval 27 March 2018); written informed consent was obtained from all study participants.
Information governance statement
Oxford University Hospitals NHS Foundation Trust is committed to handling all personal information in line with the UK Data Protection Act (2018) and the General Data Protection Regulation (EU GDPR) 2016/679. Under the Data Protection legislation, Oxford University Hospitals NHS Foundation Trust is the Data Controller for the ARK-Hospital programme. You can find out more about how we handle personal data, including how to exercise your individual rights and the contact details for our Data Protection Officer here: information.governance@ouh.nhs.uk. All other organisations are Data Processors.
Disclosure of interests
Full disclosure of interests: Completed ICMJE forms for all authors, including all related interests, are available in the toolkit on the NIHR Journals Library report publication page at https://doi.org/10.3310/GJAW4014.
Primary conflicts of interest: Martin J Llewelyn, Lucy Yardley, Derrick Crook, Tim EA Peto, Ann Sarah Walker, Magda Laskawiec-Szkonter, Melissa Dobson, Laurence SJ Roope, Katy Sivyer, Fiona Mowbray, Elizabeth LA Cross, Emma Hedley, Sarah Wordsworth, Koen B Pouwels, Liz Morrell, James Buchanan, Marta Santillo, Christopher C Butler, Nicola Jones, Kieran Hand and Susan Hopkins declare funding from the National Institute for Health Research (NIHR) for the ARK-Hospital programme. Ann Sarah Walker and Lucy Yardley are NIHR Senior Investigators. Lucy Yardley is partly supported by NIHR Applied Research Collaboration (ARC)-West and NIHR Health Protection Research Unit (HPRU) for Behavioural Science and Evaluation. Ann Sarah Walker is partly supported by the NIHR HPRU in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford and the Oxford Biomedical Research Centre. EPB declares funding from Antibiotic Research UK (ANTRUK) (grant number ANTSRG 02/2018). Martin J Llewelyn, Lucy Yardley and Ann Sarah Walker declare funding from NIHR for a development grant to translate the ARK intervention into electronic medication prescribing systems (NIHR206517). Martin J Llewelyn and Koen B Pouwels declare funding from NIHR for a trial of the optimal duration of antibiotic treatment in urinary tract infection using a randomised trial (NIHR134854). Susan Hopkins has a leadership role on the UKHSA Executive Committee. Kieran Hand has a leadership role as the NHS England AMR national clinical lead for pharmacy and prescribing. Ann Sarah Walker has had leadership roles as a member of funding committees for NIHR PGfAR (Panel D: 2012–7) and the Health Technology Assessment (HTA) (2023–). Lucy Yardley has had leadership roles as a member of funding committees for the HTA Antimicrobial Resistance Themed Call (1 December 2013–3 June 2014), HTA Efficient Study Designs (1 November 2015–31 July 2016) and the Public Health Research (PHR) Research Funding Board (16 June 2015–15 June 2017). Christopher C Butler has had leadership roles as a member of funding committees for NIHR’s Efficacy and Mechanism Evaluation (EME) (1 October 2011–1 October 2016) and the Prophylaxis Platform Study Funding Committee (2022). Tim EA Peto has had leadership roles as a member of the funding committees for the HTA Antimicrobial Resistance Themed Call Board (10 December 2013–3 June 2014). Kieran Hand and Koen B Pouwels are members of the UK Scientific Advisory Board on Antimicrobial Prescribing, Resistance and Healthcare-Associated Infection (APRHAI). All other authors declare no competing interests.
Copyright and credit statement
Every effort has been made to obtain the necessary permissions for reproduction, to credit original sources appropriately and to respect copyright requirements. However, despite our diligence, we acknowledge the possibility of unintentional omissions or errors and we welcome notifications of any concerns regarding copyright or permissions.
Publications
Peer-reviewed publications
Work package 1
Onakpoya I, Walker A, Tan P, Spencer E, Gbinigie O, Cook J, et al. Overview of systematic reviews assessing the evidence for shorter versus longer duration antibiotic treatment for bacterial infections in secondary care. PLOS ONE 2018;13:e0194858. https://doi.org/10.1371/journal.pone.0194858
Work package 2
Budgell EP, Davies TJ, Donker T, Hopkins S, Wyllie DH, Peto TEA, et al. Impact of antibiotic use on patient-level risk of death in 36 million hospital admissions in England. J Infect 2022;84:311–20. https://doi.org/10.1016/j.jinf.2021.12.029
Work packages 3 and 4
Santillo M, Sivyer K, Krusche A, Mowbray F, Jones N, Peto TEA, et al. Intervention planning for Antibiotic Review Kit (ARK): a digital and behavioural intervention to safely review and reduce antibiotic prescriptions in acute and general medicine. J Antimicrob Chemother 2019;74:3362–70. https://doi.org/10.1093/jac/dkz333
Islam J, Ashiru-Oredope D, Budd E, Howard P, Walker AS, Hopkins S, Llewelyn MJ. A national quality incentive scheme to reduce antibiotic overuse in hospitals; evaluation of perceptions and impact. J Antimicrob Chemother. 2018;73:1708–13. https://doi.org/10.1093/jac/dky041
Mowbray F, Sivyer K, Santillo M, Jones N, Peto TEA, Walker AS, et al. Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the ‘review and revise’ experience. Pilot Feasibility Stud 2020;6:43. https://doi.org/10.1186/s40814-020-00590-5
Cross ELA, Sivyer K, Islam J, Santillo M, Mowbray F, Peto TEA, et al. Adaptation and implementation of the ARK (Antibiotic Review Kit) intervention to safely and substantially reduce antibiotic use in hospitals: a feasibility study. J Hosp Infect 2019;103:268–75.46 https://doi.org/10.1016/j.jhin.2019.07.017. Freely available here.51
Work package 5
Llewelyn MJ, Fitzpatrick JM, Darwin E, Tonkin-Crine S, Gorton C, Paul J, et al. The antibiotic course has had its day. BMJ 2017;358:j3418.73 https://doi.org/10.1136/bmj.j3418. Freely available here.74
Walker AS, Budgell E, Laskawiec-Szkonter M, Sivyer K, Wordsworth S, Quaddy J, et al. Antibiotic Review Kit for Hospitals (ARK-Hospital): study protocol for a stepped-wedge cluster-randomised controlled trial. Trials 2019;20:421. https://doi.org/10.1186/s13063-019-3497-y
Llewelyn M, Budgell E, Laskawiec-Szkonter M, Cross E, Alexander R, Bond S, et al. Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial. Lancet Infect Dis 2023;23:207–21. https://doi.org/10.1016/S1473-3099(22)00508-4
Yokoyama M, Peto L, Budgell EP, Jones N, Sheridan E, Liu J, et al. Microbial diversity and antimicrobial resistance in faecal samples from acute medical patients assessed through metagenomic sequencing. PLOS ONE 2023 March 1;18:e0282584. https://doi.org/10.1371/journal.pone.0282584
Work package 6
Roope LSJ, Buchanan J, Morrell L, Pouwels KB, Sivyer K, Mowbray F, et al. Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey. BMC Med 2020;18:196. https://doi.org/10.1186/s12916-020-01660-4
Conference abstracts
Work package 2
(Poster) Budgell EP, Davies TJ, Llewelyn MJ, Wyllie DH, Peto TEA, Gill MJ, et al. Are Shorter Antibiotic Courses Associated with Increased Mortality or Readmission Risk in Acute/General Inpatients? ECCMID, 24 April 2017, Vienna, Austria, abstract 1711.
(Poster) Budgell E. The Impact of Reduced Antibiotic Use: An Observational Analysis of Hospital Episode Statistics. ANTRUK Annual meeting, 24 October 2019.
Work packages 3 and 4
(Oral) Sivyer K, Santillo M, Krusche A, Mowbray F, Cross E, Islam J, et al. Optimising Implementation of the ARK (Antibiotic Review Kit) Intervention: Addressing Antibiotic Overuse in Hospitals. EHPS 2018.
(Oral) Sivyer K, Santillo M, Krusche A, Mowbray F, Peto TEA, Walker AS, et al. Using Stakeholder Engagement and Person-based Approaches in Health Psychology Research: The Benefits and Challenges. EHPS 2019.
(Oral) Cross E on behalf of the ARK-Hospital team. Antibiotic Review Kit – Hospital (ARK-hospital). Society for Acute Medicine Autumn conference September 2017.
(Oral) Cross E on behalf of the ARK-Hospital team. ARK – Feasibility of a Complex Behaviour Change Intervention in Secondary Care to Safely and Substantially Reduce Antibiotic Use. FIS November 2017.
(Poster) Cross E, Islam J, Mowbray F, Peto TEA, Santillo M, Sivyer K, et al. ARK-Hospital (Antibiotic Review Kit-Hospital) – A Complex Behaviour Change Intervention in Secondary Care to Safely and Substantially Reduce Antibiotic Use. BIA spring meeting 2018.
Work package 5
(Oral) Llewelyn M, Budgell EP, Laskawiec-Szkonter M, Cross E, Alexander R, Bond S, et al. Antibiotic Review Kit for Hospitals (ARK-Hospital): A Stepped-wedge Cluster-Randomised Controlled Trial. ECCMID, 25 April 2022, Lisbon, Portugal, abstract 04959.
Work package 6
(Poster accepted for ECCMID 2020, but the conference was subsequently cancelled due to the COVID-19 pandemic) Roope LSJ, Buchanan J, Morrell L, Pouwels KB, Sivyer K, Mowbray F, et al. Why Don’t Hospital Prescribers Stop Antibiotics When It Would Be Safe to Do So? Results of a Discrete Choice Experiment. ECCMID, 18–21 April 2020, Paris, France.
Additional outputs
Llewelyn MJ, Nagg S, Garcia-Arias V, Jones N. It’s time to put a hard stop to antibiotic over prescribing in hospitals. Thebmjopinion. 6 March 2019. URL: https://blogs.bmj.com/bmj/2019/03/06/its-time-to-put-a-hard-stop-to-antibiotic-overprescribing-in-hospitals/ (accessed 22 October 2025).
A non-research SCORM-compliant version of the ARK tools and implementation guidance have been made available through the British Society for Antimicrobial Chemotherapy (BSAC) with support from Health Education England (HEE).84 The new ARK resources website also includes a more user-friendly non-research focused forum with frequently asked questions (FAQs) based on previous forum postings in the trial.
Disclaimers
This article presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, CCF, PGfAR or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, the PGfAR programme or the Department of Health and Social Care.