Author:
Granholm Anders,Kaas-Hansen Benjamin Skov,Lange Theis,Munch Marie Warrer,Harhay Michael O.,Zampieri Fernando G.,Perner Anders,Møller Morten Hylander,Jensen Aksel Karl Georg
Abstract
AbstractBackgroundDays 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.MethodsWe 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.ResultsIn 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.ConclusionsThis 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.Trial registrationCOVID STEROID 2 trial, ClinicalTrials.gov: NCT04509973, ctri.nic.in: CTRI/2020/10/028731.
Funder
Sygeforsikringen "danmark"
Novo Nordisk Foundation
The Research Council at Rigshospitalet
Royal Library, Copenhagen University Library
Publisher
Springer Science and Business Media LLC
Subject
Health Informatics,Epidemiology
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