Contributions of authors
Lucy E Bradshaw (https://orcid.org/0000-0001-8382-6040) (Medical Statistician) contributed to the conception and design of the trial and the acquisition, analysis and interpretation of the data; was responsible for statistical analysis; drafted, reviewed and edited the final report; and was a member of the Trial Management Group (TMG).
Laura A Wyatt (https://orcid.org/0000-0002-9817-5356) (Trial Manager) supported the conduct of the trial; drafted, reviewed and edited the final report; and was a member of the TMG.
Sara J Brown (https://orcid.org/0000-0002-3232-5251) (Professor of Dermatology, and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis, or interpretation of the data, and was responsible for the genetic analysis. Sara also contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report and was a member of the TMG.
Rachel H Haines (https://orcid.org/0000-0001-7924-0602) (Senior Trial Manager) contributed to the conception or design of the trial and the acquisition, analysis, or interpretation of the data and supported the design and conduct of the trial; reviewed and edited the final report and was a member of the TMG.
Alan A Montgomery (https://orcid.org/0000-0003-0450-1606) (Professor of Medical Statistics and Clinical Trials, Senior Statistician and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data and was responsible for statistical analysis; reviewed and edited the final report and was a member of the TMG.
Michael R Perkin (https://orcid.org/0000-0001-9272-2585) (Consultant in Paediatric Allergy and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data; supported the food allergy assessment and reviewed and edited the final report.
Tracey H Sach (https://orcid.org/0000-0002-8098-9220) (Professor of Health Economics, and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and was responsible for the health economic design and analysis; drafted, reviewed and edited the final report; and was a member of the TMG.
Sandra Lawton (https://orcid.org/0000-0002-6163-5822) (Nurse Consultant Dermatology and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report; and was a member of the TMG.
Carsten Flohr (https://orcid.org/0000-0003-4884-6286) (Professor of Dermatology) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report.
Matthew J Ridd (https://orcid.org/0000-0002-7954-8823) (NIHR Clinical Trials Fellow and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report.
Joanne R Chalmers (https://orcid.org/0000-0002-2281-7367) (Senior Research Fellow and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and supported the design and conduct of the trial; reviewed and edited the final report; and was a member of the TMG.
Joanne Brooks (https://orcid.org/0000-0003-2456-0160) (Trial Coordinator) contributed to the conduct of the trial (data collection and management).
Richard Swinden (https://orcid.org/0000-0001-9877-8301) (Trial Coordinator) contributed to the conduct of the trial (data collection and management).
Eleanor J Mitchell (https://orcid.org/0000-0002-6998-4533) (Associate Professor) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data and supported the design and conduct of the trial; reviewed and edited the final report.
Stella Tarr (https://orcid.org/0000-0001-8990-4425) (Data Manager) contributed to the conduct of the trial (data collection and management).
Nicola Jay (https://orcid.org/0000-0003-1388-192X) (Consultant Paediatrician Respiratory and Allergy and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and supported the food allergy assessment; reviewed and edited the final report.
Kim S Thomas (https://orcid.org/0000-0001-7785-7465) (Professor of Applied Dermatology Research and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data and supported the design and conduct of the trial, and contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report.
Hilary Allen (https://orcid.org/0000-0002-7013-0308) (General Practitioner) contributed to additional analysis of the food allergy data; reviewed and edited the final report.
Michael J Cork (https://orcid.org/0000-0003-4428-2428) (Professor of Dermatology and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and provided expertise in emollients and the skin barrier; reviewed and edited the final report.
Maeve Kelleher (https://orcid.org/0000-0002-3764-0461) (Honorary Consultant in Paediatric Allergy) supported the food allergy assessment, reviewed and edited the final report.
Eric L Simpson (https://orcid.org/0000-0003-0853-0252) (Associate Professor in Dermatology, and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis or interpretation of the data, and contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report.
Stella T Lartey (https://orcid.org/0000-0001-9519-7886) (Lecturer) contributed to the health economic analysis and reviewed and edited the final report.
Susan Davies-Jones (Research Nurse) contributed to the conception or design of the trial and the acquisition, analysis, or interpretation of the data, and contributed clinical experience of eczema or eczema trials, or both; reviewed and edited the final report.
Robert J Boyle (https://orcid.org/0000-0002-4913-7580) (Consultant in Paediatric Allergy and co-applicant) contributed to the conception or design of the trial and the acquisition, analysis, and interpretation of the data, and led the food allergy assessments; reviewed and edited the final report; and was a member of the TMG.
Hywel C Williams (https://orcid.org/0000-0002-5646-3093) (Professor of Dermato-Epidemiology and Chief Investigator). Hywel conceived the trial, contributed to the design of the trial and the acquisition, analysis and interpretation of the data; drafted, reviewed and edited the final report; and was a member of the TMG.
Acknowledgements
Additional funding for the food allergy and sensitisation tests was obtained from Goldman Sachs Gives and the Sheffield Children’s Hospital Research Fund (reference CA15008). Research nurse support was provided by the NIHR Clinical Research Networks.
The trial was developed with and supported by the UK Dermatology Clinical Trials Network (UK DCTN). The UK DCTN is grateful to the British Association of Dermatologists and the University of Nottingham for financial support of the Network.
We would like to thank the parents and infants who took time to participate in this trial, and the patients who contributed to trial design by providing helpful feedback at different stages of trial development.
We would like to thank the independent members of the Trial Steering Committee: Sarah Meredith, (Chair, Medical Research Council Clinical Trials Unit at University College London), Angela Crook (Statistician, Medical Research Council Clinical Trials Unit at University College London), Paula Beattie (Dermatologist, Royal Hospital for Children, Glasgow), Kirsty Logan (Paediatric Epidemiologist, King’s College London) and Emma Thomas (patient representative). Michael Perkin (St George’s, London) was previously an independent member of the TSC prior to becoming part of the team involved in the food allergy assessment.
We would also like to thank the following for their work on BEEP at the Nottingham Clinical Trials Unit:
- Jim Thornton for work on the grant application during his time as deputy director of the NCTU.
- Clinical Research Facilitator: Trish Hepburn.
- Senior Trial Manager: Rebecca Haydock.
- Trial Managers: Amy Moody, Angela Pushpa-Rajah, Sandip Stapleton.
- Trial Co-ordinators: Margherita Carucci, Louisa Gray, Juliet Jackson.
- Trial Administrators: Jennifer White, Andrew Jadowski, Gurmit Dhanjal, Aneesa Mehmood.
- Database Programmers: Daniel Simpkins, Keith Whitaker, Chris Rumsey.
- Data Management: Sarah Walker, Jessica Haywood, Lisa Evans.
- Statisticians: Reuben Ogollah (assistance with CACE analysis), Chris Partlett (independent validation of primary outcome, main food allergy outcome and skin infection outcome) and Grace Holt (independent validation of the UKWP AD tertiary outcome).
We would like to acknowledge and thank Dr Charlotte Davies (RAND corporation) who contributed to earlier versions of the health economic evaluation analysis undertaken using the 24-month data.
The genetic analysis work was co-ordinated by SJB at the Skin Research Group, School of Medicine, University of Dundee. During this time SJB also worked clinically at the Ninewells Hospital and Medical School, Dundee. We would like to thank Sheila C Wright (Skin Research Group, Division of Molecular and Clinical Medicine, University of Dundee, UK) for cataloguing and processing the saliva samples for DNA analysis.
Data-sharing statement
All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.
The study protocol, SAP and HEAP are available on the trial website and the NIHR journals library. All other related documents are available on request to Prof. Hywel C Williams as chief investigator of the BEEP trial, at any point.
Ethics statement
The trial was approved by the NRES Committee West Midlands – Solihull (REC reference 14/WM/0162) on 9 June 2014 prior to the start of recruitment.
Information governance statement
The University of Nottingham 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, the University of Nottingham is the Data Controller, and 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: https://www.nottingham.ac.uk/governance/records-and-information-management/contact.aspx.
Disclosure of interests
Full disclosure of interests: Completed ICMJE forms for all authors, including all related interests, are available in the toolkit on the report publication page of NIHR Journals Library at https://doi.org/10.3310/RHDN9613.
Primary conflicts of interest: Sara Brown holds a Wellcome Trust Senior Research Fellowship in Clinical Science (reference 106865/Z/15/Z and 220875/Z/20/Z). Alan Montgomery was a member of NIHR HTA Clinical Trials and Evaluations Funding Committee 2015–21 but had no part in the decision-making for funding this study. Tracey Sach was a member of NIHR HTA Efficient Study Designs – 2, HTA Efficient Study Designs Board, HTA End of Life Care and Add-on-Studies, HTA Primary Care Themed Call Board and the HTA Commissioning Board between 2013 and December 2019. She is a steering committee member of the UK Dermatology Clinical Trials Network and Chair of the NIHR Research for Patient Benefit Regional Advisory Panel for the East of England. Tracey had no part in the decision-making for funding this study. Carsten Flohr is Chief Investigator of the UK NIHR-funded TREAT (ISRCTN15837754) and SOFTER (ClinicalTrials.gov: NCT03270566) trials as well as the UK-Irish Atopic Eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and the Principal Investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (www.biomap-imi.eu/). He also leads the EU Joint Program Initiative Trans-Foods and the UK Medical Research Foundation-funded consortia. His department has received funding from Sanofi-Genzyme and Pfizer for skin microbiome work. Carsten received a grant from the EU IMI grant scheme (Horizon 2020), outside of the submitted work. Maeve Keller holds an NIHR Transitional Research Fellowship (TRF-2017–10–003). Matthew Ridd holds a Post-Doctoral Research Fellowship from NIHR (PDF-2014–07–013). Matthew Ridd was a member of HTA General Committee and ESP Evidence Synthesis Programme Advisory Group. Michael Cork received institutional research grants and personal consulting fees from Hyphens Pharma, L’Oréal and Perrigo (ACO Nordic). Michael is on the advisory board for L’Oréal and was a member of the Board of the European Academy of Dermatology and Venereology (EADV) and is a voluntary medical advisor to the National Eczema Society, UK. Eric Simpson reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Boston Consulting Group, Collective Acumen LLC (CA), Dermira, Eli Lilly, Evidera, ExcerptaMedica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, Leo Pharm, Medscape LLC, Merck, Pfizer, Physicians World LLC, Regeneron, Roivant, Sanofi-Genzyme, Trevi therapeutics, Valeant, WebMD. Eric Simpson also reports grants (or Principal investigator role) from AbbVie, Amgen, Arcutis, Aslan, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Hakko Kirin, Leo Pharmaceuticals, Pfizer, Regeneron, Sanofi, and TARGET-DERM. These potential conflicts of interest have been reviewed and managed by OHSU. Robert Boyle received personal fees from Cochrane, Wiley, British Society of Allergy and Clinical Immunology for editorial work and fees for expert witness work, outside of the submitted work. Robert’s employing institution Imperial College London has a formal research and innovation partnership with Nestlé, who manufactures and markets nutritional products for managing food allergy and sponsor infant nutrition research related to eczema and food allergy. Hywel Williams was director of the NIHR Health Technology Assessment Programme from 2015 to 2020. Hywel Williams was a member of the HTA Antimicrobial Resistance Themed Call Board, HTA Commissioning Sub-Board, HTA Efficient Study Designs – 2, HTA Efficient Study Designs Board, HTA Funding Teleconference Member, HTA Surgery Themed Call Board, NIHR CTU Standing Advisory Committee, NIHR Journals Library Board, PGfAR EOIs – HTA projects Remit meeting, Pre-Exposure Prophylaxis Impact Review Panel, HTA Remit and Competitiveness Group, HTA General Committee, HTA Post-Funding Committee teleconference, HTA Funding Committee Policy Group and HTA Commissioning Committee. Hywel had no part in the decision-making for funding this study. All other authors declare no competing interests.
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
Publications
Bradshaw LE, Haines RH, Thomas KS, Chalmers JR, Irvine AD, Williams HC, Brown SJ. Clinical examination for hyperlinear palms to determine filaggrin genotype: a diagnostic test accuracy study. Clin Exp Allergy 2021;51:1421–28. https://doi.org/10.1111/cea.14025. Epub 18 October 2021. PMID: 34608691.
Bradshaw LE, Montgomery AA, Williams HC, Chalmers JR, Haines RH. Two-by-two factorial randomised study within a trial (SWAT) to evaluate strategies for follow-up in a randomised prevention trial. Trials 2020;21:529. https://doi.org/10.1186/s13063-020-04373-4. PMID: 32546180; PMCID: PMC7296963.
Bradshaw LE, Wyatt LA, Brown SJ, Haines RH, Montgomery AA, Perkin MR, et al. Emollients for prevention of atopic dermatitis: 5-year findings from the BEEP randomized trial. Allergy 2023;78:995–1006. https://doi.org/10.1111/all.15555. Epub 3 November 2022. PMID: 36263451.
Chalmers JR, Haines RH, Bradshaw LE, Montgomery AA, Thomas, KS, Brown SJ, et al. Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial. Lancet 2020;395:962–72. https://doi.org/10.1016/S0140-6736(19)32984-8
Chalmers JR, Haines RH, Mitchell EJ, Thomas KS, Brown SJ, Ridd M, et al. Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial. BMC Trials 2017;18:343. https://doi.org/10.1186/s13063-017-2031-3
Kelleher MM, Cro S, Van Vogt E, Cornelius V, Lodrup Carlsen KC, Ove Skjerven H, et al. Skincare interventions in infants for preventing eczema and food allergy: a cochrane systematic review and individual participant data meta-analysis. Clin Exp Allergy 2021;51:402–18. https://doi.org/10.1111/cea.13847. Epub 25 February 2021. PMID: 33550675.
Overgaard LEK, Main KM, Frederiksen H, Stender S, Szecsi PB, Williams HC, Thyssen JP. Children with atopic dermatitis and frequent emollient use have increased urinary levels of low-molecular-weight phthalate metabolites and parabens. Allergy 2017;72:1768–77. https://doi.org/10.1111/all.13157. Epub 4 April 2017. PMID: 28281298.
Perkin MR, Logan K, Marrs T, Radulovic S, Craven J, Boyle RJ, et al.; EAT Study Team. Association of frequent moisturizer use in early infancy with the development of food allergy. J Allergy Clin Immunol 2021;147:967–76.e1. https://doi.org/10.1016/j.jaci.2020.10.044. PMID: 33678253.
Van Vogt E, Cro S, Cornelius VR, Williams HC, Askie LM, Phillips R, et al. Individual participant data meta-analysis versus aggregate data meta-analysis: a case study in eczema and food allergy prevention. Clin Exp Allergy 2021. https://doi.org/10.1111/cea.14085. Epub ahead of print. PMID: 34939249.
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, the HTA programme 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 HTA programme or the Department of Health and Social Care.