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. 2022 Oct 1;50(10):e759-e771.
doi: 10.1097/CCM.0000000000005637. Epub 2022 Jul 27.

Patient-Important Outcomes Other Than Mortality in Contemporary ICU Trials: A Scoping Review

Anders Granholm  1 , Carl T Anthon  1 , Maj-Brit N Kjær  1 , Mathias Maagaard  2 , Benjamin S Kaas-Hansen  1   3 , Praleene Sivapalan  1 , Olav L Schjørring  4   5 , Lars W Andersen  6   7   8 , Ole Mathiesen  2   9 , Thomas Strøm  10   11 , Aksel K G Jensen  3 , Anders Perner  1 , Morten H Møller  1
Affiliations

Patient-Important Outcomes Other Than Mortality in Contemporary ICU Trials: A Scoping Review

Anders Granholm et al. Crit Care Med. .

Abstract

Objectives: Randomized clinical trials (RCTs) conducted in adult ICU patients increasingly include patient-important outcomes other than mortality. This comes with challenges regarding outcome choices/definitions, handling of deceased patients and missing data in analyses, and choices of effect measures and statistical methods due to complex distributions. This scoping review aimed to characterize how these challenges are handled in relevant contemporary RCTs.

Data sources: We systematically searched 10 selected journals for RCTs conducted primarily in adult ICU patients published between 1 January 2018 and 5 May 2022 reporting at least one patient-important outcome other than mortality, including "days alive without"…-type outcomes, functional/cognitive/neurologic outcomes, health-related quality of life (HRQoL) outcomes, and ordinal/other outcomes.

Study selection: Abstracts and full-texts were assessed independently and in duplicate by two reviewers.

Data extraction: Data were extracted independently and in duplicate by two reviewers using predefined and pilot-tested extraction forms and subsequently categorized to facilitate analysis.

Data synthesis: We included 687 outcomes from 167 RCTs, with 32% of RCTs using a patient-important outcome other than mortality as a (co-)primary outcome, most frequently "days alive without"…-type outcomes. Many different functional/cognitive/neurologic (103) and HRQoL (29) outcomes were reported. Handling of deceased patients varied, with analyses frequently restricted to survivors only for functional/cognitive/neurologic (62%) and HRQoL (89%) outcomes. Follow-up was generally longer and missing data proportions higher for functional/cognitive/neurologic and HRQoL outcomes. Most outcomes were analyzed using nonparametric tests (31%), linear regression/ t tests (27%), chi-square-like tests (12%), and proportional odds logistic regression (9%), often without presentation of actual treatment effects estimates (38%).

Conclusions: In this sample of RCTs, substantial variation in practice and suboptimal methodological choices were observed. This calls for increased focus on standardizing outcome choices and definitions, adequate handling of missing data and deceased patients in analyses, and use of statistical methods quantifying effect sizes.

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Conflict of interest statement

Dr. Granholm’s institution received funding from Sygeforsikringen “danmark,” and he disclosed that this study is part of the Intensive Care Platform Trial research program ( www.incept.dk ), which has received funding from Sygeforsikringen “danmark,” Ehrenreich’s Foundation and Dagmar Marshalls Fond. Dr. Granholm also disclosed that the Department of Intensive Care at Rigshospitalet has received funding for other projects from The Novo Nordisk Foundation, Pfizer, and, Fresenius Kabi and conducts contract research for AM-Pharma. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

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