Causal Bayesian machine learning to assess treatment effect heterogeneity by dexamethasone dose for patients with COVID-19 and severe hypoxemia

Bryan S Blette, Anders Granholm, Fan Li, Manu Shankar-Hari, Theis Lange, Marie Warrer Munch, Morten Hylander Møller, Anders Perner, Michael O Harhay

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The currently recommended dose of dexamethasone for patients with severe or critical COVID-19 is 6 mg per day (mg/d) regardless of patient features and variation. However, patients with severe or critical COVID-19 are heterogenous in many ways (e.g., age, weight, comorbidities, disease severity, and immune features). Thus, it is conceivable that a standardized dosing protocol may not be optimal. We assessed treatment effect heterogeneity in the COVID STEROID 2 trial, which compared 6 mg/d to 12 mg/d, using a causal inference framework with Bayesian Additive Regression Trees, a flexible modeling method that detects interactive effects and nonlinear relationships among multiple patient characteristics simultaneously. We found that 12 mg/d of dexamethasone, relative to 6 mg/d, was probably associated with better long-term outcomes (days alive without life support and mortality after 90 days) among the entire trial population (i.e., no signals of harm), and probably more beneficial among those without diabetes mellitus, that were older, were not using IL-6 inhibitors at baseline, weighed less, or had higher level respiratory support at baseline. This adds more evidence supporting the use of 12 mg/d in practice for most patients not receiving other immunosuppressants and that additional study of dosing could potentially optimize clinical outcomes.

Original languageEnglish
Article number6570
JournalScientific Reports
Volume13
Issue number1
DOIs
Publication statusPublished - 21 Apr 2023

Keywords / Materials (for Non-textual outputs)

  • Humans
  • COVID-19
  • SARS-CoV-2
  • Bayes Theorem
  • COVID-19 Drug Treatment
  • Dexamethasone/therapeutic use
  • Hypoxia

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