Use of days alive without life support and similar count outcomes in randomised clinical trials – an overview and comparison of methodological choices and analysis methods

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Background
Days alive without life support (DAWOLS) and similar outcomes that seek to summarise mortality and non-mortality experiences are increasingly used in critical care research. The use of these outcomes is challenged by different definitions and non-normal outcome distributions that complicate statistical analysis decisions.

Methods
We scrutinized the central methodological considerations when using DAWOLS and similar outcomes and provide a description and overview of the pros and cons of various statistical methods for analysis supplemented with a comparison of these methods using data from the COVID STEROID 2 randomised clinical trial. We focused on readily available regression models of increasing complexity (linear, hurdle-negative binomial, zero–one-inflated beta, and cumulative logistic regression models) that allow comparison of multiple treatment arms, adjustment for covariates and interaction terms to assess treatment effect heterogeneity.

Results
In general, the simpler models adequately estimated group means despite not fitting the data well enough to mimic the input data. The more complex models better fitted and thus better replicated the input data, although this came with increased complexity and uncertainty of estimates. While the more complex models can model separate components of the outcome distributions (i.e., the probability of having zero DAWOLS), this complexity means that the specification of interpretable priors in a Bayesian setting is difficult.

Finally, we present multiple examples of how these outcomes may be visualised to aid assessment and interpretation.

Conclusions
This summary of central methodological considerations when using, defining, and analysing DAWOLS and similar outcomes may help researchers choose the definition and analysis method that best fits their planned studies.
OriginalsprogEngelsk
Artikelnummer139
TidsskriftBMC Medical Research Methodology
Vol/bind23
Udgave nummer1
Antal sider12
ISSN1471-2288
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The Department of Intensive Care at Copenhagen University Hospital – Rigshospitalet has received funding for other research projects from the Novo Nordisk Foundation, Pfizer, and Fresenius Kabi, and conducted contract research for AM-Pharma.

Funding Information:
Open access funding provided by Royal Library, Copenhagen University Library This project was conducted as part of the Intensive Care Platform Trial (INCEPT) research programme ( www.incept.dk ), which aims to establish an adaptive platform trial conducted in a broad population of acutely ill adult admitted to participating ICUs. The INCEPT programme has received funding from Sygeforsikringen “danmark”, Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond, and Dagmar Marshalls Fond. The COVID STEROID 2 trial was funded by the Novo Nordisk Foundation and supported by the Research Council at Rigshospitalet. MOH is funded by the United States National Institutes of Health, National Heart, Lung, and Blood Institute (grant number R01-HL168202).

Publisher Copyright:
© 2023, The Author(s).

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