TY - JOUR
T1 - Advancing Delirium Treatment Trials in Older Adults
T2 - Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS)
AU - Network for Investigation of Delirium: Unifying Scientists (NIDUS) Writing Group
AU - Devlin, John W.
AU - Sieber, Frederick
AU - Akeju, Oluwaseun
AU - Khan, Babar A.
AU - MacLullich, Alasdair M.J.
AU - Marcantonio, Edward R.
AU - Oh, Esther S.
AU - Agar, Meera R.
AU - Avelino-Silva, Thiago J.
AU - Berger, Miles
AU - Burry, Lisa
AU - Colantuoni, Elizabeth A.
AU - Evered, Lis A.
AU - Girard, Timothy D.
AU - Han, Jin H.
AU - Hosie, Annmarie
AU - Hughes, Christopher
AU - Jones, Richard N.
AU - Pandharipande, Pratik P.
AU - Subramanian, Balachundhar
AU - Travison, Thomas G.
AU - van den Boogaard, Mark
AU - Inouye, Sharon K.
AU - Brown, Charles
AU - Whitehead, Jan Busby
AU - Campbell, Noll
AU - Duprey, Matt
AU - Fick, Donna
AU - Helfand, Ben
AU - Hshieh, Tammy
AU - Hwang, Ula
AU - Khan, Sikander
AU - LaHue, Sara
AU - Lindroth, Heidi
AU - Neufeld, Karin
AU - Palanca, Ben
AU - Reed, Nicholas
AU - Sanders, Robert
AU - Schmitt, Eva
AU - Wu, Ting Ting
AU - Zhongcong, Xie
N1 - Publisher Copyright:
Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - OBJECTIVES: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults. DESIGN: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs). METHODS: To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews. RESULTS: We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key. CONCLUSIONS: By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.
AB - OBJECTIVES: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults. DESIGN: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs). METHODS: To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews. RESULTS: We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key. CONCLUSIONS: By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.
KW - clinical trials
KW - delirium
KW - methods
KW - older adults
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85210383048&partnerID=8YFLogxK
U2 - 10.1097/CCM.0000000000006514
DO - 10.1097/CCM.0000000000006514
M3 - Article
AN - SCOPUS:85210383048
SN - 0090-3493
VL - 53
SP - e15-e28
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 1
ER -