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. 2024 May 28;28(1):184.
doi: 10.1186/s13054-024-04967-3.

Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review

Humphrey G M Walker #  1   2 , Alastair J Brown #  3   4   5   6 , Ines P Vaz  4 , Rebecca Reed  4 , Max A Schofield  4 , Jeffrey Shao  7 , Vinodh B Nanjayya  4   5 , Andrew A Udy  4   5 , Toby Jeffcote  4   5
Affiliations

Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review

Humphrey G M Walker et al. Crit Care. .

Abstract

Background: The use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes.

Methods: A systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included.

Results: 8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2-3). Trials using a COM recruited fewer participants (409 (198.8-851.5) vs 584 (300-1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important.

Conclusions: COM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

Keywords: Critical care; Critical care outcomes; Outcome assessment; Randomized controlled trials as topic.

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Conflict of interest statement

No potential conflicts of interest relevant to this article were reported however AU reports grants (paid to Monash University) from NHMRC Australia, MRFF Australia and the Department of Health, Commonwealth of Australia that are unrelated to this work and the receipt of in-kind support (trial consumables) from Integra Lifesciences for a project outside of the current work.

Figures

Fig. 1
Fig. 1
Showing PRISMA flow diagram of trial selection
Fig. 2
Fig. 2
Showing the trend of COM use as a proportion of all trials included in the systematic review
Fig. 3
Fig. 3
Showing a heatmap of all the components used in COMs within this systematic review. aCirculatory support includes extracorporeal membrane oxygenation (ECMO). bIncludes outcomes assessing both hospital and ICU length of stay. cOperative specific components include outcomes such as re-operation. dDisease specific components includes development of specific diseases or syndromes. For example, myocardial infarction (MI), acute kidney injury (AKI), Acute Respiratory Distress Syndrome (ARDS) or venous thromboembolic event (VTE)
Fig. 4
Fig. 4
Showing the predicted relative effect estimates for COM and Non-COM studies. Error bars are median and IQR
See this image and copyright information in PMC

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