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. 2023 Jun;20(3):307-318.
doi: 10.1177/17407745231151842. Epub 2023 Mar 22.

Heterogeneity of surrogate outcome measures used in critical care studies: A systematic review

Rejina Verghis  1 , Bronagh Blackwood  1 , Cliona McDowell  2 , Philip Toner  1 , Daniel Hadfield  3 , Anthony C Gordon  4 , Mike Clarke  5 , Daniel McAuley  1
Affiliations

Heterogeneity of surrogate outcome measures used in critical care studies: A systematic review

Rejina Verghis et al. Clin Trials. 2023 Jun.

Abstract

Background: The choice of outcome measure is a critical decision in the design of any clinical trial, but many Phase III clinical trials in critical care fail to detect a difference between the interventions being compared. This may be because the surrogate outcomes used to show beneficial effects in early phase trials (which informed the design of the subsequent Phase III trials) are not valid guides to the differences between the interventions for the main outcomes of the Phase III trials. We undertook a systematic review (1) to generate a list of outcome measures used in critical care trials, (2) to determine the variability in the outcome reporting in the respiratory subgroup and (3) to create a smaller list of potential early phase endpoints in the respiratory subgroup.

Methods: Data related to outcomes were extracted from studies published in the six top-ranked critical care journals between 2010 and 2020. Outcomes were classified into subcategories and categories. A subset of early phase endpoints relevant to the respiratory subgroup was selected for further investigation. The variability of the outcomes and the variability in reporting was investigated.

Results: A total of 6905 references were retrieved and a total of 294 separate outcomes were identified from 58 studies. The outcomes were then classified into 11 categories and 66 subcategories. A subset of 22 outcomes relevant for the respiratory group were identified as potential early phase outcomes. The summary statistics, time points and definitions show the outcomes are analysed and reported in different ways.

Conclusion: The outcome measures were defined, analysed and reported in a variety of ways. This creates difficulties for synthesising data in systematic reviews and planning definitive trials. This review once again highlights an urgent need for standardisation and validation of surrogate outcomes reported in critical care trials. Future work should aim to validate and develop a core outcome set for surrogate outcomes in critical care trials.

Keywords: Clinical trials; critical care; outcomes.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Study flowchart. AJRCCM: American Journal of Respiratory and Critical Care Medicine; CCM: Critical Care Medicine; ICM: Intensive Care Medicine; LRM: Lancet Respiratory Medicine. Numbers for 2010 are given in brackets.
Figure 2.
Figure 2.
Potential early phase endpoints in respiratory subgroup and classifications (outer circle shows the outcomes, mid-circle represents the subcategory and the inner circle represents the category).
See this image and copyright information in PMC

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