Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review
Abstract Background There 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 purp...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-05-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-021-05299-1 |
| _version_ | 1819101287112769536 |
|---|---|
| author | Elizabeth Colantuoni Mounica Koneru Narjes Akhlaghi Ximin Li Mohamed D. Hashem Victor D. Dinglas Karin J. Neufeld Michael O. Harhay Dale M. Needham |
| author_facet | Elizabeth Colantuoni Mounica Koneru Narjes Akhlaghi Ximin Li Mohamed D. Hashem Victor D. Dinglas Karin J. Neufeld Michael O. Harhay Dale M. Needham |
| author_sort | Elizabeth Colantuoni |
| collection | DOAJ |
| description | Abstract Background There 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. Methods Relevant 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). Results Among 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). Conclusions To 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 registration PROSPERO CRD42020141204 . Registration date: 7/3/2019. |
| first_indexed | 2024-12-22T01:16:16Z |
| format | Article |
| id | doaj.art-eb590fe231614c0fb8bb5a160b0d824c |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-22T01:16:16Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-eb590fe231614c0fb8bb5a160b0d824c2022-12-21T18:43:52ZengBMCTrials1745-62152021-05-0122111210.1186/s13063-021-05299-1Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic reviewElizabeth Colantuoni0Mounica Koneru1Narjes Akhlaghi2Ximin Li3Mohamed D. Hashem4Victor D. Dinglas5Karin J. Neufeld6Michael O. Harhay7Dale M. Needham8Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins UniversityOutcomes After Critical Illness and Surgery, Johns Hopkins School of MedicineOutcomes After Critical Illness and Surgery, Johns Hopkins School of MedicineDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins UniversityDepartment of Medicine, Marshfield ClinicOutcomes After Critical Illness and Surgery, Johns Hopkins School of MedicineOutcomes After Critical Illness and Surgery, Johns Hopkins School of MedicineDepartment of Epidemiology, Perelman School of Medicine, University of PennsylvaniaOutcomes After Critical Illness and Surgery, Johns Hopkins School of MedicineAbstract Background There 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. Methods Relevant 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). Results Among 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). Conclusions To 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 registration PROSPERO CRD42020141204 . Registration date: 7/3/2019.https://doi.org/10.1186/s13063-021-05299-1Systematic reviewRandomized trialsCritically ill patientsDeliriumOutcome definitionStatistical methods |
| spellingShingle | Elizabeth Colantuoni Mounica Koneru Narjes Akhlaghi Ximin Li Mohamed D. Hashem Victor D. Dinglas Karin J. Neufeld Michael O. Harhay Dale M. Needham Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review Trials Systematic review Randomized trials Critically ill patients Delirium Outcome definition Statistical methods |
| title | Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review |
| title_full | Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review |
| title_fullStr | Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review |
| title_full_unstemmed | Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review |
| title_short | Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review |
| title_sort | heterogeneity in design and analysis of icu delirium randomized trials a systematic review |
| topic | Systematic review Randomized trials Critically ill patients Delirium Outcome definition Statistical methods |
| url | https://doi.org/10.1186/s13063-021-05299-1 |
| work_keys_str_mv | AT elizabethcolantuoni heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT mounicakoneru heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT narjesakhlaghi heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT ximinli heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT mohameddhashem heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT victorddinglas heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT karinjneufeld heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT michaeloharhay heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview AT dalemneedham heterogeneityindesignandanalysisoficudeliriumrandomizedtrialsasystematicreview |