Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review

Trials

Ximin Li¹  Elizabeth Colantuoni²  Michael O. Harhay³  Mohamed D. Hashem⁴  Karin J. Neufeld⁵  Victor D. Dinglas⁶  Mounica Koneru⁶  Narjes Akhlaghi⁶  Dale M. Needham⁷ 

[1] Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA;Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA;Outcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;PAIR (Palliative and Advanced Illness Research) Center Clinical Trials Methods and Outcomes Lab, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Department of Medicine, Marshfield Clinic, Marshfield, WI, USA;Outcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA;Outcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA;Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Outcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA;Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD, USA;

关键词: Systematic review;    Randomized trials;    Critically ill patients;    Delirium;    Outcome definition;    Statistical methods;   

DOI  :  10.1186/s13063-021-05299-1

来源: Springer

【 摘 要 】

BackgroundThere is a growing number of randomized controlled trials (RCTs) evaluating interventions to prevent or treat delirium in the intensive care unit (ICU). Efforts to improve the conduct of delirium RCTs are underway, but none address issues related to statistical analysis. The purpose of this review is to evaluate heterogeneity in the design and analysis of delirium outcomes and advance methodological recommendations for delirium RCTs in the ICU.MethodsRelevant databases, including PubMed and Embase, were searched with no restrictions on language or publication date; the search was conducted on July 8, 2019. RCTs conducted on adult ICU patients with delirium as the primary outcome were included where trial results were available. Data on frequency and duration of delirium assessments, delirium outcome definitions, and statistical methods were independently extracted in duplicate. The review was registered with PROSPERO (CRD42020141204).ResultsAmong 65 eligible RCTs, 44 (68%) targeted the prevention of delirium. The duration of follow-up varied, with 31 (48%) RCTs having ≤7 days of follow-up, and only 24 (37%) conducting delirium assessments after ICU discharge. The incidence of delirium was the most common outcome (50 RCTs, 77%) for which 8 unique statistical methods were applied. The most common method, applied to 51 of 56 (91%) delirium incidence outcomes, was the two-sample test comparing the proportion of patients who ever experienced delirium. In the presence of censoring of patients at ICU discharge or death, this test may be misleading. The impact of censoring was also not considered in most analyses of the duration of delirium, as evaluated in 24 RCTs, with 21 (88%) delirium duration outcomes analyzed using a non-parametric test or two-sample t test. Composite outcomes (e.g., rank-based delirium- and coma-free days), used in 11 (17%) RCTs, seldom explicitly defined how ICU discharge, and death were incorporated into the definition and were analyzed using non-parametric tests (11 of 13 (85%) composite outcomes).ConclusionsTo improve delirium RCTs, outcomes should be explicitly defined. To account for censoring due to ICU discharge or death, survival analysis methods should be considered for delirium incidence and duration outcomes; non-parametric tests are recommended for rank-based delirium composite outcomes.Trial registrationPROSPERO CRD42020141204. Registration date: 7/3/2019.

【 授权许可】

CC BY