A structured methodology review showed analyses of functional outcomes are frequently limited to survivors only in trials enrolling patients at high risk of death

Objective: This structured methodology review evaluated statistical approaches used in randomized controlled trials (RCTs) enrolling patients at high risk of death and makes recommendations for reporting future RCTs. Study design and setting: Using PubMed, we searched for RCTs published in five general medicine journals from January 2014 to August 2019 wherein mortality was >= 10% in at least one randomized group. We abstracted primary and secondary outcomes, statistical analysis methods, and patient samples evaluated (all randomized patients vs. survivors only). Results: Of 1947 RCTs identified, 434 met eligibility criteria. Of the eligible RCTs, 91 (21%) and 351 (81%) had a primary or secondary functional outcome, respectively, of which 36 (40%) and 263 (75%) evaluated treatment effects among survivors only. In RCTs that analyzed all randomized patients, the most common methods included use of ordinal outcomes (e.g., modified Rankin Scale) or creating composite outcomes (primary: 41 of 91 [45%]; secondary: 57 of 351 [16%]). Conclusion: In RCTs enrolling patients at high risk of death, statistical analyses of functional outcomes are frequently conducted among survivors only, for which conclusions might be misleading. Given the growing number of RCTs conducted among patients hospitalized with COVID-19 and other critical illnesses, standards for reporting should be created. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

This structured methodology review assessed statistical approaches used in randomized controlled trials with patients at high risk of death and provided recommendations for reporting future RCTs. The study found that statistical analyses of functional outcomes in these trials are often conducted only among survivors, potentially leading to misleading conclusions. Standards for reporting should be established due to the increasing number of RCTs conducted among patients hospitalized with COVID-19 and other critical illnesses.