Evidence map›Paper›PMID 34016134›Full record

SynthesisTrials2021

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

Elizabeth Colantuoni, Mounica Koneru, Narjes Akhlaghi, Ximin Li, Mohamed D Hashem, Victor D Dinglas, Karin J Neufeld, Michael O Harhay, Dale M Needham

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Trials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Elizabeth ColantuoniDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. ejohnso2@jhu.edu.ORCID http://orcid.org/0000-0002-0091-9434
Mounica KoneruOutcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Narjes AkhlaghiOutcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Ximin LiDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Mohamed D HashemDepartment of Medicine, Marshfield Clinic, Marshfield, WI, USA.
Victor D DinglasOutcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Karin J NeufeldOutcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Michael O HarhayDepartment of Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dale M NeedhamOutcomes After Critical Illness and Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Funding

Improving Long-Term Outcomes Clinical Research for Acute Respiratory FailureR24HL111895 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI NEEDHAM, DALE MURRAY · 2013 to 2017
$5.4M
Supplement to Network for Investigation of Delirium across the U.S (NIDUS)R24AG054259 · NIA · HEBREW REHABILITATION CENTER FOR AGED · PI INOUYE, SHARON K. · 2016 to 2020
$4.3M
Improving the statistical design and analysis of randomized controlled trials of delirium prevention and treatment for critically ill older adultsR01AG061384 · NIA · JOHNS HOPKINS UNIVERSITY · PI COLANTUONI, ELIZABETH · 2019 to 2022
$1.5M
Improving the measurement and analysis of long-term, patient-centered outcomes following acute respiratory failureR00HL141678 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI HARHAY, MICHAEL OSCAR · 2020 to 2022
$747k
Foundation for the National Institutes of Health R24AG054259Foundation for the National Institutes of Health R24HL111895Foundation for the National Institutes of Health (US) R0HL141678National Institute on Aging (US) R01AG061384NHLBI NIH HHS R00 HL141678NHLBI NIH HHS R24 HL111895NIA NIH HHS R01 AG061384NIA NIH HHS R24 AG054259
6 · The paper itself

Abstract

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.

Indexed as

DeliriumAdultCritical IllnessHumansIntensive Care UnitsRandomized Controlled Trials as TopicCritically ill patientsDeliriumOutcome definitionRandomized trialsStatistical methodsSystematic review

Identifiers

PMID34016134
PMCPMC8136095

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.