{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:59:24Z","timestamp":1793217564546,"version":"4.5.0"},"reference-count":23,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["16\/93\/01"],"award-info":[{"award-number":["16\/93\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n Choice of sedation of critically ill patients is a core element of intensive care practice. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial tested the effectiveness of two alpha agonist sedatives versus propofol in reducing time on mechanical ventilation in 38 intensive care units in the United Kingdom. To evaluate both how this complex trial was implemented and how this may have influenced trial outcomes, an understanding of the contextual and practice variation across multiple sites was required.<\/jats:p>\n <\/jats:sec>\n \n Aim and objectives<\/jats:title>\n The aim of this process evaluation of the A2B trial was to determine how the intervention was delivered, the extent to which it was delivered as intended and the impact this had on outcomes. Specifically, we aimed to:<\/jats:p>\n \n \n Establish the degree to which the A2B intervention was delivered as intended, specifically in relation to fidelity, dose and reach across patients.<\/jats:p>\n <\/jats:list-item>\n \n Understand factors that impacted on successful delivery of both the A2B intervention and trial, in relation to attitudes and perceptions of staff, including context and standard care.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>\n \n Design and methods<\/jats:title>\n A mixed-methods, multiphase design was used following extensive pre-trial exploration of current practice. Quantitative data were drawn from the main trial database covering 38 sites to assess the intervention\u2019s fidelity, dose and reach in each site. Data were analysed descriptively and provided a low-moderate-high rating. Qualitative data were collected by interviews mid trial (phase 1) and end of trial (phase 2). Participants were recruited from a random sample of 30 intensive care units active at the time of sampling and included the principal investigator, research nurses and clinical staff. Semistructured interviews, informed by the trial\u2019s logic model, lasted 45\u201360 minutes. Data collection focused on whether the intervention could be delivered as intended, factors that impacted upon successful delivery and understanding intervention adherence. Analysis used a framework approach based on the logic model. Data collection and qualitative analyses were completed prior to knowing the primary results of the trial.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Site intervention adherence ratings for fidelity, dose and reach were low (4), moderate (20) and high (14). Participants from 12 intensive care units in each of phase 1 (33 staff) and phase 2 (36 staff) provided qualitative data; participating intensive care units differed between phases. Factors identified in phase 1 focused on intervention delivery and trial conduct and incorporated both organisational and participant-related factors. In phase 2, participant-related factors included clinician preference, individual equipoise, clinician resistance and staff capability and capacity, while A2B trial-related factors included concerns relating to safety and side effects, overnight deep sedation practice, patient comfort and trial documentation. Many of these factors were impacted by the COVID-19 pandemic, particularly in regard to staffing numbers and experience.<\/jats:p>\n <\/jats:sec>\n \n Limitations<\/jats:title>\n Due to the impact of the COVID-19 pandemic, most data collection occurred remotely through video-conferencing rather than planned at site observation and interviews.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Optimal sedation practice is influenced by multiple factors related to clinician perceptions, capacity and capability. Priorities in care focus on short-term safety and comfort. Limitations in staffing mean that longer-term consequences related to recovery and rehabilitation are second tier considerations.<\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n Findings highlight the multiple contextual factors, including both organisational and participant-related characteristics, that should be considered when planning both clinical trials and changes to routine care. Multiple strategies for achieving behaviour change when implementing complex interventions are essential.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16\/93\/01.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/gjtw0620","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T03:53:27Z","timestamp":1750391607000},"page":"1-18","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["An exploration of the factors influencing successful implementation, delivery and outcomes in an intensive care sedation study: process evaluation of the A2B RCT"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-9090","authenticated-orcid":true,"given":"Leanne M","family":"Aitken","sequence":"first","affiliation":[{"name":"School of Health & Medical Sciences, City St George\u2019s, University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-5758","authenticated-orcid":true,"given":"Lydia M","family":"Emerson","sequence":"additional","affiliation":[{"name":"School of Health & Medical Sciences, City St George\u2019s, University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-8230","authenticated-orcid":true,"given":"Kalliopi","family":"Kydonaki","sequence":"additional","affiliation":[{"name":"Faculty of Nursing, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4583-5381","authenticated-orcid":true,"given":"Bronagh","family":"Blackwood","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-1232","authenticated-orcid":true,"given":"Ben","family":"Creagh-Brown","sequence":"additional","affiliation":[{"name":"Department of Critical Care, Royal Surrey NHS Foundation Trust, Guildford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-2779","authenticated-orcid":true,"given":"Nazir","family":"Lone","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Critical Care and Pain Medicine, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-9711","authenticated-orcid":true,"given":"Cathrine","family":"McKenzie","sequence":"additional","affiliation":[{"name":"School of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton, and Perioperative and Critical Care Theme, Department of Pharmacy and Critical Care, University Hospital Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2658-5022","authenticated-orcid":true,"given":"Richard","family":"Parker","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-0707","authenticated-orcid":true,"given":"Michael C","family":"Reade","sequence":"additional","affiliation":[{"name":"Medical School, University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6494-4903","authenticated-orcid":true,"given":"Christopher J","family":"Weir","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2763-4316","authenticated-orcid":true,"given":"Matt P","family":"Wise","sequence":"additional","affiliation":[{"name":"Adult Critical Care, University Hospital of Wales, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-8540","authenticated-orcid":true,"given":"Timothy S","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Critical Care and Pain Medicine, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2025,11]]},"reference":[{"key":"key2026070120360500_ref1-bib1","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1186\/cc8956","article-title":"A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety","volume":"14","author":"Jackson","year":"2010","journal-title":"Crit Care"},{"key":"key2026070120360500_ref2-bib2","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1097\/CCM.0000000000000882","article-title":"Posttraumatic stress disorder in critical illness survivors: a metaanalysis","volume":"43","author":"Parker","year":"2015","journal-title":"Crit Care Med"},{"key":"key2026070120360500_ref3-bib3","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1056\/NEJMoa1906759","article-title":"Nonsedation or light sedation in critically ill, mechanically ventilated patients","volume":"382","author":"Olsen","year":"2020","journal-title":"N Engl J Med"},{"key":"key2026070120360500_ref4-bib4","doi-asserted-by":"crossref","first-page":"e078645","DOI":"10.1136\/bmjopen-2023-078645","article-title":"Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): protocol for a multicentre phase 3 pragmatic clinical and cost-effectiveness randomised trial in the UK","volume":"13","author":"Walsh","year":"2023","journal-title":"BMJ Open"},{"key":"key2026070120360500_ref5-bib5","first-page":"1","article-title":"Clinical pharmacist\u2019s views on the role of alpha-2-agonists in practice and research for the management of agitation, sedation, and delirium (ASD)","volume":"23","author":"Eadie","year":"2022","journal-title":"J Intensive Care Soc"},{"key":"key2026070120360500_ref6-bib6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.anclin.2017.01.009","article-title":"Alpha-2 agonists","volume":"35","author":"Nguyen","year":"2017","journal-title":"Anesthesiol Clin"},{"key":"key2026070120360500_ref7-bib7","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1056\/NEJMoa1904710","article-title":"Early sedation with dexmedetomidine in critically ill patients","volume":"380","author":"Shehabi","year":"2019","journal-title":"N Engl J Med"},{"key":"key2026070120360500_ref8-bib8","doi-asserted-by":"crossref","first-page":"h1258","DOI":"10.1136\/bmj.h1258","article-title":"Process evaluation of complex interventions: Medical Research Council guidance","volume":"350","author":"Moore","year":"2015","journal-title":"BMJ"},{"key":"key2026070120360500_ref9-bib9","doi-asserted-by":"crossref","first-page":"e081637","DOI":"10.1136\/bmjopen-2023-081637","article-title":"Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial","volume":"14","author":"Aitken","year":"2024","journal-title":"BMJ Open"},{"key":"key2026070120360500_ref10-bib10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1001\/jama.2025.7200","article-title":"Dexmedetomidine- or clonidine-based sedation compared with propofol in critically ill patients: the A2B randomized clinical trial","volume":"334","author":"Walsh","year":"2025","journal-title":"JAMA"},{"key":"key2026070120360500_ref11-bib11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.12968\/ajmw.2010.4.2.47612","article-title":"Framework analysis: a method for analysing qualitative data","volume":"4","author":"Furber","year":"2010","journal-title":"Afr J Midwifery Women\u2019s Health"},{"key":"key2026070120360500_ref12-bib12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00134-021-06356-8","article-title":"Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial","volume":"47","author":"Shehabi","year":"2021","journal-title":"Intensive Care Med"},{"key":"key2026070120360500_ref13-bib13","first-page":"e0301","article-title":"A scoping review of implementation science in adult critical care settings","volume":"2","author":"McNett","year":"2020","journal-title":"Crit Care Explor"},{"key":"key2026070120360500_ref14-bib14","first-page":"133","article-title":"Cracking the code of change","volume":"78","author":"Beer","year":"2000","journal-title":"Harv Bus Rev"},{"key":"key2026070120360500_ref15-bib15","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1108\/01443570410552108","article-title":"Emergent change and planned change \u2013 competitors or allies?","volume":"24","author":"Burnes","year":"2004","journal-title":"Int J Oper Prod Man"},{"key":"key2026070120360500_ref16-bib16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1177\/1751143716663749","article-title":"Exploring obstacles to critical care trials in the UK: a qualitative investigation","volume":"18","author":"Pattison","year":"2017","journal-title":"J Intensive Care Soc"},{"key":"key2026070120360500_ref17-bib17","volume-title":"Dexdor \u2013 Direct healthcare professional Communication (DHPC)","author":"European Medicines Agency","year":"2022"},{"key":"key2026070120360500_ref18-bib18","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1164\/rccm.202206-1208OC","article-title":"Dexmedetomidine and propofol sedation in critically ill patients and dose-associated 90-day mortality: a secondary cohort analysis of a randomized controlled trial (SPICE III)","volume":"207","author":"Shehabi","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"key2026070120360500_ref19-bib19","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12913-016-1292-y","article-title":"Implementing research results in clinical practice \u2013 the experiences of healthcare professionals","volume":"16","author":"Kristensen","year":"2016","journal-title":"BMC Health Serv Res"},{"key":"key2026070120360500_ref20-bib20","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2147\/JHL.S221141","article-title":"Creating empowering conditions for nurses with workplace autonomy and agency: how healthcare leaders could be guided by strengths-based nursing and healthcare leadership (SBNH-L)","volume":"13","author":"Gottlieb","year":"2021","journal-title":"J Healthc Leadersh"},{"key":"key2026070120360500_ref21-bib21","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1559827617745479","article-title":"Advocating for behavior change with education","volume":"12","author":"Arlinghaus","year":"2018","journal-title":"Am J Lifestyle Med"},{"key":"key2026070120360500_ref22-bib22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13012-017-0605-9","article-title":"A guide to using the Theoretical Domains Framework of behaviour change to investigate implementation problems","volume":"12","author":"Atkins","year":"2017","journal-title":"Implement Sci"},{"key":"key2026070120360500_ref23-bib23","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1093\/ajhp\/zxab202","article-title":"An examination of sedation requirements and practices for mechanically ventilated critically ill patients with COVID-19","volume":"78","author":"Balakrishna","year":"2021","journal-title":"Am J Health Syst Pharm"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2049178","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/sites\/journalslibrary\/files\/journal_data\/GJTW0620\/GJTW0620.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2049178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:10:53Z","timestamp":1782918653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/published-articles\/GJTW0620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":23,"alternative-id":["10.3310\/GJTW0620"],"URL":"https:\/\/doi.org\/10.3310\/gjtw0620","relation":{},"ISSN":["2046-4924"],"issn-type":[{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"04-2018","name":"contractual_start_date","label":"contractual_start_date","group":{"name":"article_history","label":"Article History"}},{"value":"02-2025","name":"editorial_review_begun","label":"editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"06-2025","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}