Anders Granholm1,2, Olav Lilleholt Schjørring2,3,4, Aksel Karl Georg Jensen5, Benjamin Skov Kaas-Hansen5,6, Marie Warrer Munch1,2, Thomas Lass Klitgaard2,3,4, Elena Crescioli2,3,4, Maj-Brit Nørregaard Kjaer1,2, Thomas Strøm7,8, Anders Perner1,2, Bodil Steen Rasmussen2,3,4, Morten Hylander Møller1,2. 1. Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. 2. Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark. 3. Department of Anaesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark. 4. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 5. Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 6. Clinical Pharmacology Unit, Zealand University Hospital, Roskilde, Denmark. 7. Department of Anaesthesia and Critical Care Medicine, Odense University Hospital, Odense, Denmark. 8. Department of Anaesthesia and Critical Care Medicine, Hospital Sønderjylland, University Hospital of Southern Denmark, Odense, Denmark.
Abstract
BACKGROUND: Mortality is often the primary outcome in randomised clinical trials (RCTs) conducted in critically ill patients. Due to increased awareness on survivors after critical illness and outcomes other than mortality, health-related quality of life (HRQoL) and days alive without life support (DAWOLS) or days alive and out of hospital (DAAOOH) are increasingly being used. DAWOLS and DAAOOH convey more information than mortality, are easier to collect than HRQoL, and are usually assessed at earlier time points, which may be preferable in some situations. However, the associations between DAWOLS-DAAOOH and HRQoL are uncertain. METHODS: We will assess associations between DAWOLS-DAAOOH at day 28 and 90 (independent variables/predictors) and HRQoL assessed using the EuroQol EQ-5D-5L questionnaire (EQ-VAS and EQ-5D-5L index values) at 6 or 12 months (dependent variables) in two RCTs: the COVID STEROID 2 RCT conducted in adult patients with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) RCT conducted in adult intensive care patients with acute hypoxaemic respiratory failure. We will describe associations using best-fitting fractional polynomial transformations separately in each dataset, with the resulting models presented and assessed in both datasets graphically and using measures of fit and prediction adequacy (i.e., internal performance and external validation). We will use multiple imputation if missingness exceeds 5%. DISCUSSION: The outlined study will provide important knowledge on the associations between DAWOLS-DAAOOH and HRQoL in adult critically ill patients, which may help researchers and clinical trialists prioritise and select outcomes in future RCTs conducted in this population.
BACKGROUND: Mortality is often the primary outcome in randomised clinical trials (RCTs) conducted in critically ill patients. Due to increased awareness on survivors after critical illness and outcomes other than mortality, health-related quality of life (HRQoL) and days alive without life support (DAWOLS) or days alive and out of hospital (DAAOOH) are increasingly being used. DAWOLS and DAAOOH convey more information than mortality, are easier to collect than HRQoL, and are usually assessed at earlier time points, which may be preferable in some situations. However, the associations between DAWOLS-DAAOOH and HRQoL are uncertain. METHODS: We will assess associations between DAWOLS-DAAOOH at day 28 and 90 (independent variables/predictors) and HRQoL assessed using the EuroQol EQ-5D-5L questionnaire (EQ-VAS and EQ-5D-5L index values) at 6 or 12 months (dependent variables) in two RCTs: the COVID STEROID 2 RCT conducted in adult patients with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) RCT conducted in adult intensive care patients with acute hypoxaemic respiratory failure. We will describe associations using best-fitting fractional polynomial transformations separately in each dataset, with the resulting models presented and assessed in both datasets graphically and using measures of fit and prediction adequacy (i.e., internal performance and external validation). We will use multiple imputation if missingness exceeds 5%. DISCUSSION: The outlined study will provide important knowledge on the associations between DAWOLS-DAAOOH and HRQoL in adult critically ill patients, which may help researchers and clinical trialists prioritise and select outcomes in future RCTs conducted in this population.
Keywords:
critical care; critical illness; days alive and out of hospital; days alive without life support; health-related quality of life; outcome selection; randomised clinical trials
Authors: Anders Granholm; Waleed Alhazzani; Lennie P G Derde; Derek C Angus; Fernando G Zampieri; Naomi E Hammond; Rob Mac Sweeney; Sheila N Myatra; Elie Azoulay; Kathryn Rowan; Paul J Young; Anders Perner; Morten Hylander Møller Journal: Intensive Care Med Date: 2021-12-02 Impact factor: 41.787